Gram negative

Am J Vet Res, 1989 Jan, 50(1), 126 - 30
Humoral recognition of lipopolysaccharide core antigens of gram-negative bacteria in neonatal swine; Tyler JW et al.; Serologic recognition of common lipopolysaccharide core antigens has been related to enhanced resistance to gram-negative bacterial disease in several species . Class-specific titers (IgG, IgM) were determined by direct ELISA, using intact Escherichia coli (J5) as a plate antigen . Serum samples were obtained from 224 neonatal swine between the ages of 36 and 60 hours . The mean (+/- SEM) log10 IgG titer against gram-negative core antigens was 1:1,713 +/- 0.4718 and the mean log10 IgM titer was 1:202 +/- 0.5644 . The IgG titer was directly related with litter size, birth weight, and serum total IgG concentration; IgM titer was directly related with dam parity and serum total IgG concentration.

J Bacteriol, 1989 Jan, 171(1), 321 - 8
Isolation and nucleotide sequencing of an aminocyclitol acetyltransferase gene from Streptomyces rimosus forma paromomycinus; Lopez-Cabrera M et al.; A gene (aacC7) encoding an aminocyclitol 3-N-acetyltransferase type VII {AAC(3)-VII} from Streptomyces rimosus forma paramomycinus NRRL 2455 was cloned in the Streptomyces plasmid pIJ702 and expressed in Streptomyces lividans 1326 . Subcloning experiments located the aacC7 structural gene on a 1.05-kilobase DNA sequence . The direction of transcription of aacC7 was determined by using riboprobes synthesized in vitro from a DNA fragment internal to the gene . A DNA segment encoding the AAC(3)-VII activity and comprising 1,495 base pairs was sequenced . The aacC7 gene was located in an open reading frame of 864 base pairs that encoded a polypeptide of Mr 31,070, consistent with the Mr (32,000) of the AAC(3)-VII enzyme as determined by physicochemical methods . High-resolution S1 nuclease mapping suggested that transcription starts at or near the A residue of the ATG initiator codon . A DNA fragment from the 5' region of aacC7 had promoter activity in the promoter-probe plasmid pIJ486 . The -10 and -35 regions of this fragment showed limited sequence resemblance to other Streptomyces promoters . The primary structure of the AAC(3)-VII enzyme showed strong homology with those of the AAC(3)-III and AAC(3)-IV enzymes encoded by plasmids in gram-negative bacterial genera . Upstream of the aacC7 gene was an open reading frame of 357 nucleotides which did not appear to be involved in controlling the expression of the aacC7 gene.

J Steroid Biochem, 1989 Jan, 32(1A), 27 - 34
Isolation and characterization of a 50 kDa testosterone-binding protein from Pseudomonas testosteroni; Thomas JE et al.; A testosterone-binding protein (Mr = 50,500) has been isolated from the Gram-negative bacterium Pseudomonas testosteroni . The protein was partially purified by a combination of ion exchange chromatography and chromatofocusing . Final purification was achieved by electroelution of the 50 kDa protein from SDS-polyacrylamide gels . Following renaturation from a diluted solution of guanidine-HCl, specific binding of {3H}testosterone to the purified protein was observed . The native protein has a pI of 6.8 . It appears to contain 428 amino acids, 39% of which are hydrophobic . There is only one cysteine residue . Both chymotrypsin and V8 protease were used to produce peptide maps of the protein for use in future identification . The first 10 amino acids situated at the N-terminal of the protein were Ser-Pro-Phe-Asp-Leu-Arg-Pro-Leu-Ser-Gly . Testosterone binding to the protein was saturable at approximately 3.8 nmol/mg protein; the binding constant was approximately 25 nM . Unlabelled testosterone, androstenedione, 5 alpha-dihydrotestosterone and 5 beta-dihydrotestosterone were able to compete for {3H}testosterone bound to the protein; 17 beta-estradiol also competed for {3H}testosterone but to a lesser degree . Neither progesterone nor desoxycorticosterone competed for the testosterone-binding site . Binding of testosterone to the protein was stable at pH's ranging from 5.5 to 9.0 and at various temperatures ranging from 4 to 30 degrees C . The protein was unable to metabolize testosterone in either the presence or absence of the cofactor NAD.

J Trauma, 1989 Jan, 29(1), 109 - 12
Secondary infection of post-traumatic pulmonary cavitary lesions in adolescents and young adults: role of computed tomography and operative debridement and drainage; Carroll K et al.; Secondary infection of post-traumatic cavitary lung lesions is unusual . This report describes the clinical course of four patients who sustained severe blunt chest trauma and developed pulmonary pseudocysts that became foci for systemic sepsis . All four patients were adolescents or young adults . Hemophilus species and aerobic Gram-negative rods were the predominant pathogens recovered . Computed tomography of the chest was instrumental in establishing the diagnosis in each case . Despite appropriate antibiotic therapy, all four patients remained septic for weeks . One of the patients died as a result of this infectious process . One patient underwent successful operative debridement and drainage of the involved lung and pleural space . Because infected traumatic pseudocysts may not respond like typical lung abscesses to appropriate antibiotic management, early exploratory thoracotomy should be considered in those patients with prolonged fever and pulmonary deterioration.

Chest, 1989 Jan, 95(1), 155 - 61
Patterns and routes of tracheobronchial colonization in mechanically ventilated patients . The role of nutritional status in colonization of the lower airway by Pseudomonas species; Niederman MS et al.; Tracheobronchial colonization by Gram-negative bacteria is common in mechanically ventilated patients . Pseudomonas sp are commonly isolated from the lower airways . We hypothesized that Pseudomonas sp would preferentially colonize the lower airway and would be more common in patients with poor nutritional status . We serially collected 75 pairs of upper and lower respiratory tract cultures from 14 patients treated with mechanical ventilation for at least one week, examined patterns of airway colonization and routes of bacterial entry for Pseudomonas sp and other enteric Gram-negative bacteria (EGNB), and related these findings to host-associated factors, including nutritional status . Pseudomonas sp were the most common species isolates taken from the lower airway, found in nine of 14 patients and in 41.3 percent of all cultures . In contrast to other EGNB, Pseudomonas sp were found significantly (p less than or equal to 0.05) more often in the tracheobronchial tree (31 of 75 cultures) than in the oropharynx (18 of 75 cultures) . Primary colonization of the lower airway by Pseudomonas sp was found in four patients, while other EGNB never followed this pattern when subjects were studied with cultures taken every third day . A host-related factor related to lower airway colonization by Pseudomonas species was poor nutritional status, assessed by a multifactorial index (p less than or equal to 0.01) . We conclude that in mechanically ventilated patients, Pseudomonas sp colonize the lower airway in a different pattern and by a different route from those of other EGNB . The findings that Pseudomonas sp preferentially colonize the tracheobronchial tree may be important for the design of strategies to prevent airway colonization . The recognition that poor nutritional status, a potentially modifiable host-related factor, favors lower airway growth of Pseudomonas sp suggests one direction for future infection-control efforts.

Pneumonol Pol, 1989 Jan, 57(1), 29 - 37
{Bacterial infections in pulmonary aspergilloma}; Halweg H et al.; 28 cavernoscopies were carried out in 26 patients . Complete or partial removal of mycetomas was achieved in 18 patients with 20 caverns . Under aerobic conditions Aspergillus fumigatus was cultured from the 28 removed mycetomas in 22 cases (78.6%) and bacterial organisms in 20 (71.4%) . Bacteria were isolated from mycetomas that had demonstrable A . fumigatus organisms as well as from those that did not have them . In all infected mycetomas Gram negative rods were cultured, in only 4 cases Gram (+) cocci were found . Only in two cases of mycetomas under anaerobic conditions Gram (+) cocci were cultured . In most patients the organism could be demonstrated in sputum as well as in mycetomas . In 18 patients the pathogenic organism disappeared from sputum after removal of mycetomas . Also following removal of aspergillomas a decrease of sputum production was noted and it changed its character from purulent to mucoid.

J Intern Med, 1989 Jan, 225(1), 21 - 7
Abnormal proteolysis (DIC)--successful treatment with antithrombin III concentrate and a concentrate containing F XIII and native von Willebrand factor; Delshammar M et al.; Two patients with life-threatening disseminated intravascular coagulation (DIC) syndrome, one caused by Gram-negative bacteria and one by premature separation of the placenta, are described . Specific substitution was given by antithrombin III concentrate and AHF-Kabi, a low purity factor VIII concentrate containing native von Willebrand factor and factor XIII . The treatment quickly returned the extremely low levels of antithrombin III, factor VIII:C, fibrinogen and factor XIII, initially found, to normal, and also returned the multimeric pattern of von Willebrand factor to normal . This resulted in diminished bleeding, enabling surgical treatment of the underlying disease.

J Bacteriol, 1989 Jan, 171(1), 308 - 13
Susceptibility of Rhodobacter sphaeroides to beta-lactam antibiotics: isolation and characterization of a periplasmic beta-lactamase (cephalosporinase); Baumann M et al.; Thirteen strains of the gram-negative, facultative phototrophic bacterium Rhodobacter sphaeroides were examined fro susceptibility to beta-lactam antibiotics . All strains were sensitive to the semisynthetic penicillins ampicillin, carbenicillin, oxacillin, cloxacillin, and methicillin, but 10 of the 13 strains were resistant to penicillin G, as well as a number of cephalosporins, such as cephalothin, cephapirin, and cephalosporin C . A beta-lactamase (EC 3.5.2.6) with strong cephalosporinase activity was detected in all of the resistant strains of R . sphaeroides . With strain Y-1 as a model, it was shown that the beta-lactamase was inducible by penicillin G, cephalosporin C, cephalothin, and to some minor extent, cephapirin . The beta-lactamase was located in the periplasmic space, from which it could be extracted by osmotic shock disruption . By using this fraction, the beta-lactamase was purified 34-fold to homogeneity by steps involving batch adsorption to and elution from DEAE-Sephadex A50, chromatography on Q-Sepharose, and preparative polyacrylamide gel electrophoresis . The molecular masses of the native and denatured enzymes were determined to be 38.5 kilodaltons by gel filtration and 40.5 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively, indicating a monomeric structure . The isoelectric point was estimated to be at pH 4.3 . In Tris hydrochloride buffer, optimum enzyme activity was measured at pH 8.5 . The beta-lactamase showed high activity in the presence of the substrates cephalothin, cephapirin, cephalosporin C, and penicillin G, for which the apparent Km values were 144, 100, 65, and 110 microM, respectively . Cephalexin, cepharidine, and cephaloridine were poor substrates . The beta-lactamase was strongly inhibited by cloxacillin and oxacillin but only slightly inhibited by phenylmethylsulfonyl fluoride or thiol reagents such as iodoacetate and p-chloromercuribenzoate.

Microbios, 1989, 59(238), 47 - 63
Microbiological degradation of quinoline by Pseudomonas stutzeri: the coumarin pathway of quinoline catabolism; Shukla OP; A Gram-negative, oxidase positive, polar flagellated rod, characterised as Pseudomonas stutzeri, has been isolated from sewage by enrichment culture on quinoline . The organism utilizes quinoline as the sole source of carbon, nitrogen and energy, and liberates UV absorbing and phenolic metabolites during its growth on quinoline . 2-Hydroxyquinoline, 2,8-dihydroxyquinoline, 8-hydroxycoumarin and 2,3-dihydroxyphenylpropionic acid have been isolated as the transformation products of quinoline by this bacterium . Quinoline, 2-hydroxyquinoline, and 8-hydroxycoumarin were rapidly oxidised by quinoline-adapted cells; 2,3-dihydroxyphenylpropionic acid oxidation was also demonstrated by Warburg respirometry but 2,8-dihydroxyquinoline was not oxidised . A pathway for quinoline catabolism by P . stutzeri and the probable mechanisms for formation of 8-hydroxycoumarin are suggested.

Vutr Boles, 1989, 28(1), 60 - 5
{The diagnostic significance of antibodies to lipid A in patients with chronic kidney infections}; Altunkova I et al.; The interest in antilipid A antibodies increases in recent years . By means of an immunoenzyme test developed by the authors the frequency, quantity and characteristic of these antibodies were studied in 46 patients with chronic renal infections and in 36 healthy controls . The frequency of antilipid A antibodies class IgM is 5.7% and of class IgG it is 2.8% in the control group (healthy persons) and it is 41.3% and 19% respectively in the renal patients group . Most frequently their presence and quantity correlate with an active infection or with the convalescent period following antibiotic treatment (62.5%) . This allows the use of antilipid A antibodies as a confirming marker for the presence of a heavy Gram negative infection and as a possible index for evaluation the efficacy of the treatment.

Antibiot Khimioter, 1989 Jan, 34(1), 66 - 8
{Antibiotic sensitivity of gram-negative opportunistic bacteria isolated from the feces of newborn infants with intestinal infections}; Litiaeva LA et al.; Antibiotic sensitivity of 136 pure cultures of gram negative aerobic potentially pathogenic bacteria was assayed . The bacteria were isolated from feces of newborns with intestinal infections . It was shown that the majority of the strains were resistant to 4-5 antibiotics widely used in treatment of patients . However, they were sensitive to gentamicin and polymyxin M.

Acta Neurochir (Wien), 1989, 97(3-4), 111 - 3
Stunning device as a suicide weapon; Klun B et al.; Thirteen patients who had attempted suicide with the stunning device, were treated over a time span of eleven years . Five of them died . The survivors made a satisfactory recovery with minor neurological sequelae only . The characteristics of this type of brain injury are: high incidence of infection (all developed meningitis and six of them brain abscesses), with prevalence of gram negative animal strains and technical difficulties in removing foreign bodies from the deeper part of the missile track.

Z Exp Chir Transplant Kunstliche Organe, 1989, 22(1), 3 - 8
{Endotoxin in experimental mesenteric infarction}; Gogler H; After ligation of the mesenteric arteries an intestinal ischaemia was obtained . Endotoxin was measured from the peritoneal cavity, the portal und the peripheral blood . The limulus test for Endotoxin was used after phenol-water-extraction of the plasma . Microbiological investigations were done simultaneously . The endotoxin concentrations correlated to the clinical state of gram negative sepsis.

Sci Prog, 1989, 73(292 Pt 4), 469 - 99
Airborne bacteria and viruses; Cox CS; Coughing, sneezing, talking, bed-making, turning pages of books, etc . all generate microbial aerosols which are carried and dispersed by air movements . Inhalation of these particles may cause allergic responses but whether or not infectious disease ensues depends in part on the viability and infectivity of the inhaled microbes and their landing sites . Desiccation is experienced by all airborne microbes; gram-negative bacteria and lipid-containing viruses demonstrate phase changes in their outer phospholipid bilayer membranes owing to concomitant changes in water content and/or temperature . These changes most likely lead to cross-linking reactions of associated protein moieties principally at mid to high relative humidity (RH) . For lipid-free viruses these reactions of their surface protein moieties occur most rapidly at low RH . Radiation, oxygen, ozone and its reaction products and various pollutants also decrease viability and infectivity through chemical, physical and biological modification to phospholipid, protein and nucleic acid moieties . The extent of damage and the degree of repair together with the efficacy of host defence mechanisms largely controls whether the causative microbes take hold and spread disease via the airborne route . At least indoors, where desiccation is the predominant stress, the general reversibility of membrane-phase changes by vapour-phase rehydration when coupled with efficacious microbial enzymatic repair mechanisms under genetic control, virtually ensures the spread of disease by the aerobiological pathway.

Arkh Patol, 1989, 51(12), 74 - 9
{Pathology of the digestive organs and systemic endotoxinemia}; Permiakov NK et al.; The intestine being a natural depot of the gram-negative bacteria, may be the source of the systemic endotoxinemia in various pathologic processes followed by the increase of bacteria death, mucous membrane damage, pancreas endocrine function deficiency, liver barrier function depression, decrease of the portal circulation speed or its shunting . At the same time, the systemic endotoxinemia in itself may be one of the most important etiological factors of the various digestive organs injury . The authors observations and the literature suggest an important role of the endotoxin-positive granulocytes in the pathogenesis of the haemorrhagic infarct of the intestine, mesenteric vein thrombosis, destructive appendicitis and cholecystitis.

Scand J Infect Dis, 1989, 21(6), 709 - 15
Early fall of circulating iron and rapid rise of lactoferrin in septicemia and endotoxemia: an early defence mechanism; Gutteberg TJ et al.; Total serum iron, plasma lactoferrin and circulating leukocytes were measured in piglets during the early phase of severe gram-negative septicemia and endotoxemia in 3 experimental settings: intravenous (i.v.) infusion of lipopolysaccharide (LPS) (n = 8), i.v . infusion of live Escherichia coli (n = 7) and intraperitoneal (i.p.) infusion of E . coli (n = 6) . Iron dropped significantly during the first 30 min of LPS infusion from a median of 32 microM to 13.4 microM . A similar decrease in serum iron was demonstrated in the 2 other groups with minimum values at 120 min after the start of E . coli infusion . Plasma levels of lactoferrin increased significantly 120 min after the start of LPS infusion (median 6 mg/l) when compared to preinfusion values (0.25 mg/l) . After i.v . infusion of E . coli a significant rise of plasma lactoferrin was demonstrated already 30 min after bacterial infusion (to 2.1 mg/l) compared to preseptic values (0.8 mg/l) . This increase was accompanied with a significant drop of circulating leukocytes (to 7.3 x 10(9)/l) compared to before the infusion (17 x 10(9)/l) in the pigs given E . coli i.v . After i.p . E . coli infusion no significant change of plasma lactoferrin was observed . The rapid fall of total serum iron seen during endotoxemia and E . coli septicemia may in part be explained by the release of lactoferrin from granulocytes and the clearance of iron-bound lactoferrin in the blood or peritoneal cavity.

Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S25 - 35
Current approaches to management of infections in bone marrow transplants; Winston DJ et al.; Infections continue to be common complications of bone marrow transplantation, but recent advances have improved their outcome . Oral chemoprophylaxis with the fluoroquinolones has reduced gram-negative infections during periods of granulocytopenia, while new triazole drugs show promise for improving antifungal prophylaxis . Similarly, recombinant hematopoietic growth factors may reduce infections by shortening the period of post-transplant granulocytopenia . The efficacy of double beta-lactam antibiotic therapy or monotherapy with imipenem has obviated the need to use aminoglycosides in the empiric treatment of febrile patients receiving cyclosporine or other nephrotoxic agents . Treatment of post-transplant interstitial pneumonia associated with cytomegalovirus (CMV) remains problematic, but recent results using the combination of ganciclovir plus intravenous immune globulin have been favorable . In CMV-seronegative patients, CMV infections and pneumonia can be prevented or modified by using CMV-seronegative blood products and intravenous immune globulin . Intravenous immune globulin also has the additional benefits of modifying graft versus host disease and preventing late bacterial infections after marrow engraftment . In CMV-seropositive patients, prophylactic ganciclovir may prevent CMV reactivation and pneumonia and is the subject of an ongoing controlled clinical trial.

Trans R Soc Trop Med Hyg, 1989 Jan-Feb, 83(1), 38 - 41
Antibiotic resistance in the tropics . 1 . The genetics of bacterial ampicillin resistance in tropical areas; Young HK et al.; Ampicillin and its derivatives are the most widely used beta-lactam antibiotics throughout the world . Ampicillin resistance in Gram-negative bacteria is usually manifested by plasmid-encoded beta-lactamases, which hydrolyse the beta-lactam ring of the antibiotic . There are at least 30 different plasmid-encoded beta-lactamases but almost all of them are found very infrequently . The one exception is the TEM-1 beta-lactamase which is found wherever transferable ampicillin resistance emerges and accounts for over 50% of all plasmid encoded ampicillin resistance . In India, the incidence of ampicillin resistance is high (82%) and, amongst Escherichia coli, a significant proportion of the plasmid-encoded beta-lactamases are different from those found in the United Kingdom . Although many Gram-negative species are able to accept the TEM-1 beta-lactamase, certain species have a pre-disposition to their own plasmid beta-lactamase types.

Arkh Patol, 1989, 51(5), 77 - 80
{Role of bacterial lipopolysaccharides in provoking immune conflict in the mother-fetus system}; Bandazhevskii IuI; The paper analyzes the role of lipopolysaccharide (LPS) substances of gram-negative bacteria in occurrence of the immune conflict in the mother-fetus system . Proceeding from experimental evidence, the author advances the hypothesis that the immune conflict between the mother and her fetus is induced by bacterial LPS . In so doing, the bacterial agents play a subsidiary role by replacing T helpers when the mother's organism develops an immune response to antigenic determinants of fetal erythrocytes.

Immunol Invest, 1989 Jan-May, 18(1-4), 187 - 209
The role of antibody, complement and neutrophils in host defense against Actinobacillus actinomycetemcomitans; Wilson ME et al.; A . actinomycetemcomitans is a facultative Gram-negative coccobacillus which has been implicated in the etiology and pathogenesis of localized juvenile periodontitis and has also been recognized for its potential to cause serious extraoral infections, particularly endocarditis . The polymorphonuclear neutrophil has been suggested to play a key role in host resistance to periodontopathic organisms, as indicated by the association between defective production or function of these phagocytic cells and severe periodontal disease . This association has engendered interest in the study of the interaction between neutrophils and A . actinomycetemcomitans, as well as the role of immunoglobulin and complement in facilitating this interaction . The objective of this review is to summarize current knowledge of the nature and consequences of the interaction between A . actinomycetemcomitans and the host defense triad consisting of neutrophils, complement and immunoglobulin.

Clin Exp Pharmacol Physiol, 1989 Jan, 16(1), 1 - 6
Mechanisms of aminoglycoside nephrotoxicity; Bennett WM; Aminoglycosides continue to be widely used for the treatment of serious Gram-negative infections . Ten to fifteen per cent of all courses of therapy are complicated by declines in renal function, despite close monitoring of serum drug levels . The proposed pathogenesis and biochemical mechanisms of renal dysfunction caused by these commonly used therapeutic agents are discussed.

Crit Care Clin, 1989 Jan, 5(1), 151 - 5
Review of corticosteroid treatment in sepsis and septic shock: pro or con; Nicholson DP; The use of glucocorticoids in high dosage for the prevention and treatment of sepsis, septic shock, and ARDS has been controversial . The state of our knowledge has been reviewed, particularly to include some recent critical contributions . It is possible that glucocorticoids have a place in the treatment of gram-negative bacteremia, because the evidence in this situation is equivocal . There is no evidence that such therapy is indicated in other septic states, nor is there evidence that glucocorticoids prevent ARDS or improve the outcome . There are inadequate data to state categorically that glucocorticoid therapy in sepsis is harmful.

APMIS, 1989 Jan, 97(1), 14 - 22
Cloning and expression of the Legionella micdadei "common antigen" in Escherichia coli; Bangsborg JM et al.; To study individual Legionella antigens, a Legionella micdadei genomic library in Escherichia coli SC181 was established . Partially Sau3A digested L . micdadei DNA fragments (15-25 kilobase pairs (kb} were cloned into the tetracycline resistance gene of the cosmid vector pHC79 . Four thousand ampicillin resistant recombinants were obtained; seven hundred were screened for expression of Legionella antigens in Western blot analysis with a polyspecific E . coli-absorbed anti-L . micdadei rabbit antibody . One of the positive clones expressed a 60 kilodalton (K) antigen, which reacted strongly with a monospecific rabbit antiserum raised against L . micdadei "common antigen" (CA), and an additional 13 K L . micdadei protein . The region encoding these two proteins from the 17 kb recombinant plasmid (pBA 2) was subcloned in pBGS18+ . The DNA sequence of the CA encoding region in the 2.7 kb subcloned fragment will provide important information with respect to genetic vs . antigenic relatedness among Legionellae and other Gram-negative species, as well as to CA structure and possible function.

Mayo Clin Proc, 1989 Jan, 64(1), 84 - 94
The first 100 liver transplantations at the Mayo Clinic; Krom RA et al.; Between March 1985 and June 1987, the first 100 liver transplantations at the Mayo Clinic were performed in 83 patients (primarily adults) . The most frequent diagnoses were chronic active hepatitis (in 24 patients), primary sclerosing cholangitis (in 22), and primary biliary cirrhosis (in 20) . The median operating time was 406 minutes, and the median usage of erythrocytes was 13.2 units . A venovenous bypass was used in all patients older than 10 years of age . Hepatic artery thrombosis occurred in 10% of the 100 transplants . A choledochocholedochostomy was done in 58 patients and a choledochojejunostomy in 25 patients . Revision of the biliary anastomosis was necessary in 9 of the 83 patients (11%) . Rejection, diagnosed by clinical and histologic criteria, occurred in 50 patients (60%) and was treated with a corticosteroid bolus, followed by OKT3 (monoclonal antibody) treatment if necessary . Selective bowel decontamination helped prevent infections; only 16 bacteremias occurred, 1 of which was caused by a gram-negative organism . Fungal infections were rare . Cytomegalovirus infection occurred in 47 patients (57%) . Of the 83 patients, 16 required retransplantation, in 11 of whom graft rejection had occurred . One- and 2-year patient survival was 83% and 70%, respectively . Although problems still remain, liver transplantation is a reasonable option for patients with end-stage liver disease.

Metab Pediatr Syst Ophthalmol, 1989, 12(4), 110 - 2
Serum secretory IgA levels in patients with Behçet disease; Sunakawa M et al.; Serum IgA, IgC, IgM and secretory IgA levels in patients with Behcet disease were examined . Among them, serum IgA and secretory IgA levels, which increase in mucosal inflammation, were significantly higher than controls (p less than 0.001, p greater than 0.01) . These results indicate that mucosal inflammation, oral and gastrointestinal inflammation, may lead to gram-negative bacterial infection and endotoxin-induced uveitis in patients with Behcet disease.

Intensive Care Med, 1989, 15(7), 471 - 4
Calcium free hemodialysis: an effective therapy in hypercalcemic crisis--report of 4 cases; Kaiser W et al.; Hypercalcemic crisis represents a medical emergency . If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives . We report 4 patients treated with calcium free acetate hemodialysis because of hypercalcemic crisis due to breast cancer, hepatocellular carcinoma, cirrhosis of the liver and immobilisation with hydrochlorothiazids' medication . Following 3 h of hemodialysis, serum calcium concentrations fell from a mean value of 3.96 (range 3.53-4.46) mmol/l to 2.71 (2.28-3.12) mmol/l . In 2 patients rapid clinical improvement was achieved and in one oliguric patient diuresis started spontaneously during hemodialysis . One patient died from gram-negative sepsis . In 3 cases the subsequent conservative treatment was sufficient to maintain serum calcium levels within the normal range . Together with the previously reported cases (5 patients treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate) our experience indicates that hemodialysis is an effective and safe therapy for hypercalcemic crisis.

Microbiol Immunol, 1989, 33(11), 941 - 9
Studies on B-cell memory . IV . Effects of lipopolysaccharide on primary and secondary antibody responses to T-independent type-2 (TI-2) antigen in mice; Hosokawa T et al.; Effects of LPS on primary and secondary antibody responses to typical TI-2 antigens were investigated in mice . Simultaneous injection of LPS with a TI-2 antigen showed only little adjuvant effect on the following primary antibody response to the antigen . In contrast, either a single or multiple injections of LPS, prior to the immunization with a TI-2 antigen, significantly augmented the following primary antibody response to the antigen . LPS, however, inhibited the development of B-cell memory to a TI-2 antigen when administered together with the antigen . Moreover, an injection of LPS in mice, which had strong IgM and IgG B-cell memories to a TI-2 antigen, caused disappearance or profound reduction of the memories . The results suggest that LPS produced by gram-negative bacteria exerts inhibitory effects on the development and continuation of B-cell memory to bacterial infections.

Arch Microbiol, 1989, 152(6), 556 - 63
Anaerobic degradation of aniline and dihydroxybenzenes by newly isolated sulfate-reducing bacteria and description of Desulfobacterium anilini; Schnell S et al.; A new, rod-shaped, Gram-negative, non-sporing sulfate reducer (strain Ani1) was enriched and isolated from marine sediment with aniline as sole electron donor and carbon source . The strain degraded aniline completely to CO2 and NH3 with stoichiometric reduction of sulfate to sulfide . Strain Ani1 also degraded aminobenzoates and further aromatic and aliphatic compounds . The strain grew in sulfide-reduced mineral medium supplemented only with vitamin B12 and thiamine . Cells contained cytochromes, carbon monoxide dehydrogenase, and sulfite reductase P582, but no desulfoviridin . Strain Ani1 is described as a new species of the genus Desulfobacterium D . anilini . Marine enrichments with the three dihydroxybenzene isomers led to three different strains of sulfate-reducing bacteria; each of them could grow only with the isomer used for enrichment . Two strains isolated with catechol (strain Cat2) or resorcinol (strain Re10) were studied in detail . Both strains oxidized their substrates completely to CO2, and contained cytochromes, carbon monoxide dehydrogenase, and sulfite reductase P 582 . Desulfoviridin was not present . Whereas the rod-shaped catechol oxidizer (strain Cat2) was able to grow on 18 aromatic compounds and several aliphatic substrates, the coccoid resorcinol-degrading bacterium (strain Re10) utilized only resorcinol, 2,4-dihydroxybenzoate and 1,3-cyclohexanedion . These strains could not be affiliated with existing species of sulfate-reducing bacteria . A further coccoid sulfate-reducing bacterium (strain Hy5) was isolated with hydroquinone and identified as a subspecies of Desulfococcus multivorans . Most-probable-number enumerations with catechol, phenol, and resorcinol showed relatively large numbers (10(4)-10(6) per ml) of aryl compound-degrading sulfate reducers in marine sediment samples.

Arch Microbiol, 1989, 152(2), 132 - 7
Characterization and localization of phosphatidylglycerophosphate and phosphatidylserine synthases in Rhodobacter sphaeroides; Radcliffe CW et al.; Catalytic properties and membrane associations of the phosphatidylglycerophosphate (PGP) and phosphatidylserine (PS) synthases of Rhodobacter sphaeroides were examined to further characterize sites of phospholipid biosynthesis . In preparations of cytoplasmic membrane (CM) enriched in these activities, apparent Km values of PGP synthase were 90 microM for sn-glycerol-3-phosphate and 60 microM for CDP-diacylglycerol; the apparent Km of PS synthase for L-serine was near 165 microM . Both enzymes required Triton X-100 with optimal PS synthase activity at a detergent/CDP-diacylglycerol (mol/mol) ratio of 7.5:1.0, while for optimal PGP synthase, a range of 10-50:1.0 was observed . Unlike the enzyme in Escherichia coli and several other Gram-negative bacteria, the PS synthase activity had a specific requirement for magnesium and was tightly associated with membranes rather than ribosomes in crude cell extracts . Sedimentation studies suggested that the PGP synthase was distributed uniformly over the CM in both chemoheterotrophically and photoheterotrophically grown cells, while the PS synthase was confined mainly to a vesicular CM fraction . Solubilized PGP synthase activity migrated as a single band with a pI value near 5.5 in a chromato-focusing column and 5.8 on isoelectric focusing; in the latter procedure, the pI was shifted to 5.3 in the presence of CDP-diacylglycerol . The PGP synthase activity gave rise to a single polypeptide band in lithium dodecyl sulfate-polyacrylamide gel electrophoresis at 4 degrees C.

Pediatr Pulmonol, 1989, 7(3), 128 - 32
Branhamella catarrhalis bronchopulmonary isolates in PICU patients; Kasian GF et al.; Branhamella catarrhalis is commonly considered a respiratory commensal but has recently been implicated as a pathogen, particularly in adults . Over a 28 month period, B . catarrhalis was isolated from bronchopulmonary secretions of 14 PICU patients with acute respiratory infections . Twelve patients had pneumonia and two had tracheitis . The mean age was 3.5 years . Seven patients had chronic cardiopulmonary disease including two who were immunosuppressed . Three had an acute underlying condition and four had no complicating medical problem . Polymorphs and Gram-negative diplococci on Gram stain were found in respiratory secretions of all patients . Twelve of 14 isolates produced beta-lactamase, and six patients had a second potentially pathogenic bronchopulmonary isolate . All patients were treated for B . catarrhalis infection and none died . When isolated in pure culture from bronchopulmonary secretions in symptomatic patients, B . catarrhalis should be considered a pathogen . When isolated in mixed culture, its pathogenic role is uncertain . We conclude that B . catarrhalis can be a bronchopulmonary pathogen in critically ill children with otherwise normal cardiopulmonary function as well as in those with chronic cardiopulmonary dysfunction . When administering antibiotics the high frequency of beta-lactamase-producing strains must be taken into consideration.

DICP, 1989 Jan, 23(1), 33 - 8
Impact of a clinical pharmacokinetic service on patients treated with aminoglycosides for gram-negative infections; Destache CJ et al.; The present study was a retrospective, case-control design aimed at evaluating whether the clinical pharmacokinetic service (CPS) is cost-effective, as assessed by lengths of hospital stay and aminoglycoside therapy, incidence of a decrease in renal function, and time for resolution of infection as determined by vital signs . Forty-six patients were entered into this study, and were matched by defined criteria . The results of the study demonstrated a six-day difference in hospital stay for the CPS group (p less than 0.05) . Length of aminoglycoside therapy was 33 hours shorter for the CPS group . Additionally, the time necessary for resolution of the infection was significantly shorter for this group, as assessed by vital signs returning to normal or baseline . Three patients in each group expired . Two patients in the CPS group and five in the control group developed aminoglycoside-associated increases in serum creatinine . No significant difference was found between the two groups in age, weight, or APACHE II score . Additionally, the two groups were similar with respect to concomitant diseases and concomitant antibiotics used . The approximate cost of the CPS was calculated as $56 per patient . Use of the CPS decreasing hospital stay by six days (mean $1875/patient) would translate to an annual savings of $654,375 in hospital charges, assuming 365 patients received aminoglycoside therapy per year.

Ophthal Plast Reconstr Surg, 1989, 5(4), 277 - 80
The anophthalmic socket and the prosthetic eye . A clinical and bacteriologic study; Vasquez RJ et al.; Culture samples were obtained from the anophthalmic sockets of 40 consecutive patients using a prosthetic eye . We found an increased prevalence of bacteria in the conjunctivae of anophthalmic sockets . No significant differences in bacterial flora were observed between symptomatic and asymptomatic patients, suggesting that symptoms of irritation are not usually related to abnormal bacterial flora . Patients who frequently manipulated their prosthesis had a significantly higher proportion of gram-negative bacteria, suggesting that manipulation of the prosthesis should be avoided.

Tr Inst Im Pastera, 1989, 66, 104 - 9, 172
{Methods of isolating phospholipids from Coxiella burnetii}; Lukacheva M et al.; Phospholipids are a part of the outside membrane of Coxiella burnetii (or other gram negative bacteria) . It is possible to extract them with a mixture of chloroform-methanol (CM) . For extraction of phospholipids from C . burnetii it is important to take account of temperature, proportion of CM, and reaction time . The best results are obtained at CM 2:1, at boiling point of this mixture and reaction time of 2 hours . Longer reaction time does not influence the reaction, the additional amounts of phospholipids can be extracted only with fresh solvent mixture.

Nauchnye Doki Vyss Shkoly Biol Nauki, 1989, (7), 13 - 24
{Proteins--channel formers . II . Porins and proteins of the external mitochondrial membranes}; Krasil'nikov OV; The physical and chemical properties in protein external membranes of gram-negative bacteria and mitochondria are considered . A possible evolutional affinity between these proteins is discussed . The data on peculiarities of their polypeptide chain structure depending on environmental parameters and chemical modification of ionogeneous groups of protein-channel formers as well on a possible structure of water pore in ion channels are presented.

Complement Inflamm, 1989, 6(3), 175 - 204
Ba and Bb fragments of factor B activation: fragment production, biological activities, neoepitope expression and quantitation in clinical samples; Kolb WP et al.; Factor B is a centrally important component of the alternative complement pathway . Alternative pathway activation results in factor B cleavage and production of the amino-terminal Ba and the carboxyl-terminal Bb fragments which have molecular weights of approximately 30,000 and 63,000 daltons, respectively . Both Ba and Bb fragments have been reported to express a variety of biological activities in vitro . Thus, binding of Ba and Bb fragments to specific B lymphocyte surface receptors modulates proliferation of prestimulated B cells . In addition, the enzymatically active Bb fragment induces activation and spreading of human and murine macrophages and monocytes as well as regulates C5a des Arg chemotactic activity . The fractional catabolic rate and metabolism of factor B in vivo is similar to that of C3, C4 and C5 complement proteins, which are among the most metabolically active plasma proteins in the circulatory system . Factor B hyperconsumption and increased catabolism, concomitant with factor B fragment production, occurs in a wide variety of diseases, including gram-negative sepsis, autoimmune diseases and burns . Measurement of alternative pathway activation in vivo has been attempted utilized a number of different techniques to quantitate factor B fragments in biological fluids . However, the recent development of enzyme immunoassays (EIA) employing monoclonal antibodies (MoAbs) reactive with factor B fragment neoepitopes provides the best approach currently available for the quantitation of factor B activation fragments . Results obtained using these new MoAb-based EIAs have indicated that factor B fragment concentrations were elevated, as compared with normal donor levels, in EDTA plasma samples obtained from patients with rheumatoid arthritis and systemic lupus erythematosus (SLE) . Plasma concentrations of factor B fragments, especially Ba fragment levels, in these patients showed a positive correlation with disease activity scores . One of the highest disease activity correlations was obtained with Ba fragment measurements in SLE plasma samples . In fact, the results strongly suggested that quantitation of Ba fragment levels in SLE plasma samples more accurately reflected disease activity and was a more sensitive predictor of impending flare in these patients than any other test(s) currently available.

An Esp Pediatr, 1988 Dec, 29(6), 435 - 9
{Antibiotic therapy of infected cerebrospinal fluid in hydrocephalus treated by a shunt}; Isla Guerrero A et al.; Nine hydrocephalic shunted children with infected cerebrospinal fluid (CSF) were treated . Ages ranged from 0 to 10 years . Diagnosis was made through clinical symptoms, CSF examination, echographic and computed tomography (CT) . The microorganism which was seen more frequently, was S . epidermidis . This germ was more often found in young children . Treatment of these patients consisted of a systematic change of the shunt which was externally diverted, implantation of a CSF Ommaya reservoir in the lateral ventricle, and intraventricular and systemic administration of antibiotic, were made . Using this protocol CSF sterilization was obtained in all cases, after 5 to 12 days of treatment . CSF shunt infected with S . epidermidis can be effectively cleaned with daily intra-shunt vancomycin, and shunt infected with gram-negative are also cleaned with daily intra-shunt gentamycin.

Clin Chest Med, 1988 Dec, 9(4), 623 - 33
Bacterial colonization of the tracheobronchial tree; Salata RA et al.; Bacterial colonization of the tracheobronchial tree is a significant problem in hospitalized and chronically ill individuals . Colonization occurs because of both microbial and host factors, with the foremost mechanism being adherence of pathogenic gram-negative bacteria to mucosal epithelial cells . In the pathogenesis of nosocomial pneumonia, colonization appears to be an essential first step . In the diagnostic approach to hospital-acquired pneumonia, a distinction must be made between colonization and true lower respiratory tract infection . Future approaches to the major problem of colonization with gram-negative bacteria will require a better understanding of pathogenesis and employ strategies that not only focus upon limiting the bacterial pathogens but also attempt to improve upon pulmonary defense mechanisms.

Am J Pathol, 1988 Dec, 133(3), 472 - 84
Activation of glomerular mesangial cells by gram-negative bacterial cell wall components; Lovett DH et al.; The cell walls of gram-negative bacteria contain several biologically active components, including lipopolysaccharide (LPS), lipoprotein, and protein 1 . The effects of these individual components and a synthetic analog of lipoprotein, TPP, on several activation parameters of glomerular mesangial cells (MC) were examined . Prostaglandin secretion, synthesis of the autogrowth factor, mesangial interleukin-1 (IL-1), and new synthesis of cellular proteins were assessed as markers of MC activation . All bacterial cell wall components evaluated were active in varying degrees as stimulants of prostaglandin secretion . In general, PGE was the predominant product . TPP and protein 1 also induced substantial secretion of thromboxane . Each cell-wall component was effective in stimulating mesangial IL-1 secretion . The activation of MC was associated with the enhanced synthesis of many cellular proteins in addition to IL-1 . Stimulation by these bacterial components was dependent on the state of the mesangial cell cycle, because nonproliferating cells did not respond to these factors . Activation of MC by gram-negative bacterial cell wall components, with release of vasoactive prostaglandins and peptide mitogens, may be responsible for some of the glomerular hemodynamic alterations and cellular proliferative events associated with sepsis or chronic bacterial infection.

Infect Immun, 1988 Dec, 56(12), 3184 - 8
Comparison of type 2 and type 6 fimbriae of Bordetella pertussis by using agglutinating monoclonal antibodies; Li ZM et al.; Two types of fimbriae have been identified on the pathogenic gram-negative organism Bordetella pertussis . Monoclonal antibodies to these fimbriae were produced to better understand the role of fimbriae as serotype-specific agglutinogens and to investigate the antigenic relationship between these fimbriae . Three monoclonal antibodies were identified that specifically agglutinated B . pertussis cells containing the U.S . Reference Factor 2 agglutinogen, and six monoclonal antibodies were produced that agglutinated only those strains containing the U.S . Reference Factor 6 agglutinogen . Indirect immunofluorescence studies and immunogold electron microscopy demonstrated that these monoclonal antibodies bind to an outer membrane component on serotype-specific strains of B . pertussis . All of the monoclonal antibodies reacted with native or partially assembled type-specific fimbriae but not with monomeric fimbrial subunits as indicated by Western blot (immunoblot) analysis . The fimbrial agglutinogens recognized by the monoclonal antibodies were also uniquely reactive with either U.S . Reference Factor 2 or 6 antiserum (Eldering agglutinogen 2 or 6 polyclonal antiserum) in an indirect ELISA . No cross-reactivity of the monoclonal antibodies with the unrelated fimbriae was observed in any of the comparative immunological studies . Some of the monoclonal antibodies agglutinated certain strains of B . bronchiseptica, suggesting that this closely related species can contain antigenically similar fimbriae . These monoclonal antibodies should prove useful for further structural and functional analysis of Bordetella fimbriae and for studies on the role that these antigens play in prevention of infection and disease.

J Biol Chem, 1988 Nov 15, 263(32), 16586 - 90
The alpha-lytic protease gene of Lysobacter enzymogenes . The nucleotide sequence predicts a large prepro-peptide with homology to pro-peptides of other chymotrypsin-like enzymes; Epstein DM et al.; alpha-Lytic protease is a 19.8-kDa protein secreted from the Gram-negative bacterium Lysobacter enzymogenes . We have cloned and sequenced the gene for this serine protease . The nucleotide sequence contains an open reading frame which codes for the 198-residue mature enzyme and a potential prepro-peptide, also of 198 residues . The COOH-terminal 49 residues of the pro-peptide are significantly homologous to the propeptides of Streptomyces griseus proteases A and B . We suggest that this pro-peptide region facilitates formation of the active enzyme . A region bridging the NH2-terminal pre- and pro-peptides is homologous to a maize inhibitor of serine proteases . We speculate that this region inhibits enzymatic activity of the prepro-enzyme.

Gene, 1988 Nov 15, 71(1), 75 - 84
A broad-host-range shuttle system for gene insertion into the chromosomes of gram-negative bacteria; Barry GF; A deletion derivative of transposon Tn7 containing the Escherichia coli lacZY genes as a selectable marker for insertion of foreign DNA into the chromosomes of soil bacteria was improved to facilitate the cloning of additional genes and their insertion by this element . This report describes a series of plasmid vectors that enable this cloning to be carried out in small, high-copy, narrow host-range plasmids . The final Tn element can then be easily moved (by transposition) without further use of restriction enzymes, to plasmids suitable for delivering it to the bacterial chromosome . The very high specificity for insertion of Tn7 into single locations in bacterial chromosomes has been exploited in the construction of a shuttle system for delivering these Tn7 elements.

Anaesth Intensive Care, 1988 Nov, 16(4), 418 - 22
Altered aminoglycoside pharmacokinetics in the critically ill; Beckhouse MJ et al.; We studied prospectively 49 patients being treated in an intensive care unit with aminoglycosides for gram-negative sepsis . Pharmacokinetic data were calculated from three post-dose serum levels using a one-compartment model . Doses required to achieve peak levels between 5 and 10 mg/l with trough levels approximately 1.0 mg/l ranged between 2 and 12 mg/kg per day (mean dose 7 mg/kg per day) . During therapy 60% of the patients had a change in their apparent volume of distribution (Vd) of greater than 20% . These patients were likely to have confirmed infection and to be febrile at the start of treatment . Two to three weeks after discharge ten patients were restudied after a single dose of aminoglycoside . There was a reduction in mean Vd from 0.24 to 0.18 l/kg (P less than 0.02) . Critically ill patients have significantly larger volumes of distribution and may require larger doses per kilogram of body weight of aminoglycoside to achieve therapeutic concentrations . Due to considerable variation in kinetic parameters, the use of standard doses or dosing nomograms is not recommended.

J Clin Invest, 1988 Nov, 82(5), 1714 - 21
Bacterial lipopolysaccharide-induced intestinal microvascular lesions leading to acute diarrhea; Mathan VI et al.; Subcutaneous challenge of mice with lipopolysaccharide (LPS) from gram negative bacteria, produced an intestinal microvascular lesion causing fluid exudation into the lumen of the intestine and diarrhea . The microvascular lesion was characterized by endothelial cell damage and microthrombi in the venules and capillaries of the intestinal lamina propria . Marker organisms, given orally to challenged mice, grew in the exuded fluid and could invade the mucosa . Intravenous transfer of postchallenge plasma produced the lesion in normal mice and absorption of such plasma by Sepharose coupled to LPS-antibody abolished this effect . Instillation of large quantities of LPS into the lumen of the intestine produced scattered microvascular lesions, although none of these animals developed diarrhea . Since a similar microvascular lesion has been described in the rectal mucosal lamina propria of adults with acute diarrhea, it is suggested that LPS-induced vascular damage may be a novel mechanism in the pathogenesis of acute diarrhea.

Arch Surg, 1988 Nov, 123(11), 1367 - 70
Effect of bacteremia on mortality after thermal injury; Sittig K et al.; Infection is a common cause of death after thermal injury . Therefore, we reviewed the records of 1108 patients who had sustained burns to determine the effect of bacteremia on mortality . Overall, 32 patients died due to sepsis, 26 of whom had positive blood cultures . During this period, 93 patients had 133 bacteremic episodes . The 26 bacteremic patients (28%) who died had larger burns (71% +/- 24%) than the 67 patients who survived (39% +/- 24%), as well as a higher incidence of inhalation injuries . The patients dying of sepsis also were more likely to have polymicrobial bacteremias than the survivors . The distribution of microorganisms causing bacteremia was different between the surviving and nonsurviving patients, with patients sustaining fatal bacteremias having a higher incidence of infections with gram-negative enteric organisms or Pseudomonas . Thus, increased burn size and the presence of an inhalation injury, polymicrobial bacteremia, or gram-negative bacteremia were associated with an increased mortality rate in bacteremic patients with burns.

Antimicrob Agents Chemother, 1988 Nov, 32(11), 1684 - 92
RSF1010 and a conjugative plasmid contain sulII, one of two known genes for plasmid-borne sulfonamide resistance dihydropteroate synthase; Radstrom P et al.; The nucleotide sequence of the type II sulfonamide resistance dihydropteroate synthase (sulII) gene was determined . The molecular weight determined by maxicells was 30,000, and the predicted molecular weight for the polypeptide was 28,469 . Comparison with the sulI gene encoded by Tn21 showed 57% DNA similarity . The sulII-encoded polypeptide has 138 of 271 amino acids in common with the polypeptide encoded by sulI . The sulII gene is located on various IncQ (broad-host-range) plasmids and other small nonconjugative resistance plasmids . Detailed restriction maps were constructed to compare the different plasmids in which sulII is found . The large conjugative plasmid pGS05 and the IncQ plasmid RSF1010 contained identical nucleotide sequences for the sulII gene . This type of sulfonamide resistance is very frequently found among gram-negative bacteria because of its efficient spread to various plasmids.

Am J Vet Res, 1988 Nov, 49(11), 1950 - 4
Relationship between serologic recognition of Escherichia coli 0111:B4 (J5) and clinical coliform mastitis in cattle; Tyler JW et al.; Serum IgG1 ELISA titers recognizing gram-negative core antigens (Escherichia coli {J5}) were studied at a large dairy in central California . Population mean log10 titer was 2.7357 (equivalent to 1:544) with a SE of 0.03843 . Titers increased with increased lactation number (unstandardized regression coefficient = 0.06733) . Changes in lactation number accounted for only 6.77% of titer variation . Titers less than 1:240 were associated with 5.33 times the risk of clinical coliform mastitis . Also, older cattle were at greater risk to develop clinical coliform mastitis . These factors apparently affect incidence in a nonlinear fashion, with greatly increased risk associated with titers less than 1:240 and with fourth or greater lactations.

Mol Gen Mikrobiol Virusol, 1988 Nov, (11), 3 - 12
{Genetic determinants of antibiotic resistance in gram negative bacteria}; Anisimova LA et al.; Modern data on spreading, structural and functional organization and evolution of the genetic determinants of antibiotic resistance in the gram-negative bacteria are reviewed . Some mechanisms for resistance to trimethoprime, sulphonamides, tetracyclines, chloramphenicol aminoglycosides, beta-lactam antibiotics controlled by the plasmid and chromosomal genes are presented . The problem of using the molecular DNA-probes containing the genetical determinants for antibiotic resistance in the practical work of clinical laboratories is discussed.

JPEN J Parenter Enteral Nutr, 1988 Nov-Dec, 12(6 Suppl), 43S - 52S
Invited comment: lipids and the development of immune dysfunction and infection; Wan JM et al.; Excessive W-6 PUFA metabolism due to high levels of dietary fat intake can encourage infection via prolonged inflammation, enhanced Gram negative survival, reticuloendothelial blockage, immunosuppression, and monokine depression . Lipids can influence host immunity by altering eicosanoid metabolism and membrane structure and function . Further investigations are essential to answer questions regarding the levels and properties of various essential fatty acids in TPN lipid emulsions . Combining the features of LCT in the form of W-3 PUFA (fish oil) and MCT in the form of medium-chain triglyceride in a "structured lipid" may decrease infection and may improve survival rates by producing fewer inflammatory eicosanoids of the two- and four-series, and serving as a more "efficient fuel." The introduction of W-3 polyunsaturated fatty acids into the TPN emulsions as well as into normal diets may provide an important therapeutic advance in the pathogenesis of disease . Such unique antiinflammatory properties of W-3 PUFA require intensive research.

Anaesthesist, 1988 Nov, 37(11), 704 - 10
{Prevention of stress hemorrhage in an internal medicine intensive care station: sucralfate versus ranitidine}; Laggner AN et al.; Stress ulcer bleeding is a serious complication of critical illness and is associated with increased morbidity and mortality . For the prophylaxis of stress ulcers, antacids, H2-blockers, or sucralfate are prescribed . While H2-blockers inhibit the secretion of gastric acid, sucralfate appears to provide protection without reducing levels of gastric acid . Inhibition of acid secretion increases gastric pH, allowing bacterial overgrowth of the stomach by Gram negative bacteria, which colonize the pharynx and trachea and increase the risk of nosocomial pneumonia . For this reason, H2 blockers appear disadvantageous, though they offer adequate prophylaxis for stress ulcer bleeding . As it does not increase gastric pH, sucralfate provides adequate protection against Gram negative gastric overgrowth, however its prophylactic efficacy is not generally accepted . Therefore, we compared the H2-blocker ranitidine to sucralfate in the prophylactic treatment of stress ulcer bleeding and studied the incidence of positive bacteriological findings in the blood and bronchial secretions of the two groups . In a randomized study, 84 patients undergoing general intensive care received either ranitidine (6 x 50 to 6 x 100 mg daily i.v.) or sucralfate (6 x 1 g via gastric tube or per os) . Both groups were comparable with respect to age, underlying disorders, and factors predisposing to the development of stress ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Circ Shock, 1988 Nov, 26(3), 287 - 95
Effects of plasma administration on gram negative shock in granulocytopenic dogs; Crowley JP et al.; We studied the effect of an infusion of citrated plasma on the hemodynamic response and bacterial clearance of acutely septic dogs rendered severely neutropenic with cyclophosphamide . Two hours after a 5 X 10(9)/kg intravenous injection of E . coli, neutropenic control dogs infused with 20 ml/kg of normal saline became hypotensive and remained so for the next 2 hr . In contrast, the infusion of 20 ml/kg of citrated plasma after the initiation of bacteremia was followed by a significant (P less than .01) improvement in the mean arterial pressure (MAP), compared to saline-treated animals . The effect of citrated plasma administration on MAP was unrelated to bacterial clearance or to improvement in cardiac output but was associated with an increase in total peripheral resistance that was sustained for 2 hr after plasma infusion . The infusion of hyperimmune plasma from dogs previously immunized to core glycolipid antigen appeared to have no important advantage over normal plasma . At the doses of plasma that were given, a relatively higher arterial pH was the only observed significant difference (P less than .05) when immune plasma was compared to normal plasma . Resuscitation of septic neutropenic dogs with large volumes of plasma deserves further study with respect to the specific mechanisms responsible for its beneficial effect.

Circ Shock, 1988 Nov, 26(3), 227 - 35
Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons; Taylor FB Jr et al.; Infusion of Escherichia coli (LD100) was followed by coagulopathic and cell injury responses, cardiovascular collapse, and death in 18 to 32 hr in four out of four baboons . Infusion of AT-III in sufficient amounts to achieve AT-III levels of more than 4 units/ml of plasma before and during the infusion of E . coli reduced the intensity of the coagulopathic and cell injury response and prevented vascular collapse and death in four out of four baboons . Failure to achieve AT-III levels of more than six units/ml at T +60 min during the infusion of E . coli resulted in failure to prevent its lethal effects in three out of three baboons even though levels as high as 10 units/ml were achieved later in the course of the experiment . These studies suggest that thrombin and/or its products can contribute to the inflammatory response to E . coli and that AT-III is of potential value as a prophylactic but not as a therapeutic agent in the treatment of patients at high risk of developing gram negative sepsis.

J Surg Res, 1988 Nov, 45(5), 467 - 71
Antiserum to endotoxin in hemorrhagic shock; Pohlson EC et al.; Antiserum to Escherichia coli J5, a mutant endotoxin (LPS) which contains only core determinants, has proven effective in reducing mortality from endotoxic shock due to a wide variety of gram-negative bacteria . Twenty New Zealand white rabbits with coliforms in the gut were subjected to hemorrhagic shock of 36 mm Hg for 3 hr . Treated rabbits were resuscitated with 15 cc of rabbit J5 antiserum (hemagglutinating antibody titer against J5 lipopolysaccharide of 1:1024), remaining shed blood, and lactated Ringer's to achieve a mean arterial blood pressure (MABP) within 20% of baseline . The control group was similarly resuscitated but received 15 cc normal rabbit serum (titer 1:2) . Catheters were removed and rabbits were returned to their cages until death or 5 days of survival . Hemodynamic parameters (heart rate, MABP, cardiac output, and total peripheral resistance) did not differ significantly between groups . However, six treated rabbits survived 5 days (60%) and no control rabbit lived past the third postexperimental day (P less than 0.019) . Our data suggest that systemic endotoxemia may contribute to morbidity and mortality in severe hemorrhagic shock.

Presse Med, 1988 Oct 26, 17(37), 1968 - 70
{Antibiotic therapy protocol using ceftazidime 3g/day alone or in combination with vancomycin or amikacin . In febrile episodes in neutropenic patients}; Marie JP et al.; In a preliminary study of 21 febrile episodes in neutropenic patients ceftazidime used as empirical treatment in doses of 3 grams per day succeeded in controlling fever in 74 per cent of the cases . Laboratory studies performed in patients with Gram-negative septicaemia showed clinically effective plasma concentrations of the antibiotic . A trial of ceftazidime (3 g/day) administered alone or combined with amikacin or vancomycin is currently in progress in two medical centres . No statistically significant conclusions could be reached from an intermediate study.

J Biol Chem, 1988 Oct 15, 263(29), 14802 - 7
Lipid A binding sites in membranes of macrophage tumor cells; Hampton RY et al.; Lipopolysaccharide affects a variety of eukaryotic cells and mammalian organisms . These actions are involved in the pathogenesis of Gram-negative septicemia . Many of the actions of lipopolysaccharide are believed to be caused by its active moiety, lipid A . Our laboratory has previously identified a bioactive lipid A precursor, termed lipid IVA (Raetz, C . R . H., Purcell, S., Meyer, M . V., Qureshi, N., and Takayama, K . (1985) J . Biol . Chem . 260, 16080-16888), which can be labeled with 32P of high specific activity and purified . In this work we have used the labeled probe, 4'-32P-lipid IVA, to develop a novel assay for the specific binding of lipid IVA to whole cells . We have also demonstrated its use in a ligand blotting assay of immobilized cellular proteins . Using the whole cell assay, we show that 4'-32P-lipid IVA specifically binds to RAW 264.7 macrophage-like cultured cells . The binding is saturable, is inhibited with excess unlabeled lipid IVA, and is proteinase K-sensitive . It displays cellular and pharmacological specificity . Using the ligand blotting assay, we show that several RAW 264.7 cell proteins can bind 4'-32P-lipid IVA . The two principal binding proteins have Mr values of 31 and 95 kDa, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Fractionation studies indicate that the 31-kDa protein is enriched in the nuclear fraction and may be a histone, whereas the 95-kDa protein is enriched in the membrane fraction . The binding assays that we have developed should lead to a clearer understanding of lipid A/animal cell interactions.

Cancer Res, 1988 Oct 15, 48(20), 5766 - 9
Production of tumor necrosis factor in nude mice by muramyl peptides associated with bacterial vaccines; Noso Y et al.; Gram-negative vaccines can elicit the production of tumor necrosis factor (TNF) in mice primed by muramyl dipeptide (MDP) or by its lipophilic derivative MDP-dipalmitoyl glycerol (MDP-GDP) . In mice pretreated with MDP and particularly with MDP-GDP, Bordetella pertussis vaccine was shown to be more effective than typhoid vaccine . The time course of TNF production in the blood did not indicate any difference between the effect of MDP or of MDP-GDP . In both cases the cytotoxic activity reached maximal levels by 2 h after injection of the bacterial preparations and returned to normal values between 3 and 5 h after the challenge . In nude mice, high titers of circulating TNF were also produced by combined treatment with MDP-GDP and bacterial vaccine . Moreover, in tumor-bearing mice the association of MDP or of MDP-GDP to a bacterial vaccine induced a strong hemorrhagic necrosis, whereas each treatment alone was inactive . It was also found that mice were less sick when they were primed with MDP-GDP than with MDP, and when TNF was elicited by B . pertussis instead of lipopolysaccharide . Moreover, nude mice appeared more resistant to shock and to hemoconcentration than normal mice.

J Biol Chem, 1988 Oct 15, 263(29), 14684 - 9
Properties of Escherichia coli mutants lacking membrane-derived oligosaccharides; Fiedler W et al.; Membrane-derived oligosaccharides (MDO) consist of branched substituted beta-glucan chains and are present in the periplasmic space of Escherichia coli and other gram-negative bacteria . A procedure for the isolation of mutants defective in MDO synthesis is described . Their phenotype was compared with a mdoA mutant previously identified, and they are mapped in the mdoA region . Mutants lacking MDO showed imparied chemotaxis on tryptone swarm plates, a reduced number of flagella, and an enhanced expression of the OmpC porin . Revertants able to form swarm rings again had regained the ability to synthesize MDO and showed the wild-type porin pattern . A second group of chemotactic revertants were mutated in the ompB gene region involved in osmoregulation, and they were still devoid of MDO . These findings provide evidence for a link between MDO biosynthesis and other functions of E . coli related to its adaptation to the environment.

Gene, 1988 Oct 15, 70(1), 191 - 7
Improved broad-host-range plasmids for DNA cloning in gram-negative bacteria; Keen NT et al.; Improved broad-host-range plasmid vectors were constructed based on existing plasmids RSF1010 and RK404 . The new plasmids pDSK509, pDSK519, and pRK415, have several additional cloning sites and improved antibiotic-resistance genes which facilitate subcloning and mobilization into various Gram-negative bacteria . Several new polylinker sites were added to the Escherichia coli plasmids pUC118 and pUC119, resulting in the new plasmids, pUC128 and pUC129 . These plasmids facilitate the transfer of cloned DNA fragments to the broad-host-range vectors . Finally, the broad-host-range cosmid cloning vector pLAFR3 was improved by the addition of a double cos casette to generate the new plasmid, pLAFR5 . This latter cosmid simplifies vector preparation and has permitted the rapid cloning of genomic DNA fragments generated with Sau3A . The resulting clones may be introduced into other Gram-negative bacteria by conjugation.

Gene, 1988 Oct 15, 70(1), 181 - 9
Versatility of a vector for expressing foreign polypeptides at the surface of gram-negative bacteria; Charbit A et al.; A wide variety of peptides in terms of length and sequence can be expressed at the surface of the bacterium Escherichia coli by genetic insertion into a 'permissive' site of the outer membrane protein LamB, used as a carrier . The resulting hybrid proteins essentially keep their biological activities with inserts of up to about 60 amino acid residues, and of a large range of predicted structures or hydrophobicities . This reflects a remarkable flexibility in the organization of the protein, but also in the export machinery . The method used to select such a permissive site is quite general and its potential to generate applications, including a versatile type of live bacterial vaccine, are discussed.

Biochemistry, 1988 Oct 4, 27(20), 7919 - 24
Fluorescence measurement of the kinetics of DNA injection by bacteriophage lambda into liposomes; Novick SL et al.; Bacteriophage lambda attaches to Gram-negative bacteria using the outer membrane protein LamB as its receptor . Subsequently, DNA is injected by the bacteriophage into the host cell for replication and expression . The mechanism of DNA injection, however, is poorly understood . In order to begin to characterize DNA injection, a quantitative kinetic assay to detect injection into reconstituted LamB liposomes is described . The technique involves monitoring the increase in fluorescence of liposome-encapsulated ethidium bromide, which occurs as DNA enters the aqueous compartment of the vesicles . The data indicate that injection is several times faster than indicated by earlier studies and is complete within 1 min . Such assays which allow direct observation of this process are necessary first steps toward a mechanistic understanding.

Infect Immun, 1988 Oct, 56(10), 2552 - 7
Killing of Actinobacillus actinomycetemcomitans by human lactoferrin; Kalmar JR et al.; Actinobacillus actinomycetemcomitans is a fastidious, facultative gram-negative rod associated with endocarditis, certain forms of periodontal disease, and other focal infections . Human neutrophils have demonstrated bactericidal activity against A . actinomycetemcomitans, and much of the oxygen-dependent killing has been attributed to the myeloperoxidase-H2O2-halide system . However, the contribution of other neutrophil components to killing activity is obscure . Lactoferrin, an iron-binding glycoprotein, is a major constituent of neutrophil-specific granules and is also found in mucosal secretions . In this report, we show that human lactoferrin is bactericidal for A . actinomycetemcomitans . Killing activity required an unsaturated (iron- and anion-free) molecule that produced a 2-log decrease in viability within 120 min at 37 degrees C at a concentration of 1.9 microM . Besides exhibiting concentration dependence, killing kinetics were affected by minor variations in temperature and pH . Magnesium, a divalent cation thought to stabilize lipopolysaccharide interactions on the surface of gram-negative organisms, enhanced lactoferrin killing of A . actinomycetemcomitans, while other cations, such as potassium and calcium, had no effect . Our data suggest that lactoferrin contributes to killing of A . actinomycetemcomitans by human neutrophils and that it may also play a significant role in innate secretory defense against this potential periodontopathogen.

Infect Immun, 1988 Oct, 56(10), 2650 - 7
Recombinant interleukin-1 alpha and recombinant tumor necrosis factor alpha synergize in vivo to induce early endotoxin tolerance and associated hematopoietic changes; Vogel SN et al.; Endotoxin, the lipopolysaccharide (LPS) derived from gram-negative bacteria, invokes a wide range of responses in susceptible hosts . It is known that virtually all responses to LPS are mediated by the action of macrophage-derived cytokines (such as interleukin-1 {IL-1}, tumor necrosis factor {TNF}, and others) which are produced principally by macrophages and maximally within several hours of LPS administration . One manifestation of LPS administration which is not well understood is the phenomenon of "early endotoxin tolerance." In response to a single sublethal injection of LPS, experimental animals become refractory to challenge with a homologous or heterologous LPS preparation 3 to 4 days later . Animals rendered tolerant exhibit mitigated toxicity and a reduced capacity to produce circulating cytokines (i.e., colony-stimulating factor or interferon) in response to the challenge LPS injection . Previous studies have also shown that this state of transient, acquired hyporesponsiveness to LPS is accompanied by a marked increase in the size of cells in the bone marrow which are enriched in numbers of macrophage progenitors . In this study, we examined the capacity of recombinant IL-1 or recombinant TNF or both to induce early endotoxin tolerance and its associated hematopoietic changes . Neither cytokine alone was able to mimic LPS for induction of tolerance . Combined administration of recombinant IL-1 and recombinant TNF doses which were not toxic when administered individually led to synergistic toxicity (as assessed by death or weight loss) . However, within a nontoxic range, the two cytokines synergized to induce a significant reduction in the capacity to produce colony-stimulating factor in response to LPS, as well as the characteristic increase in bone marrow cell size and macrophage progenitors shown previously to be associated with LPS-induced tolerance.

Ann Ophthalmol, 1988 Oct, 20(10), 383 - 4
Lupus optic neuritis with negative serology; Deutsch TA et al.; A 56-year-old woman with a 12-year history of systemic lupus erythematosus presented with severe optic-disc swelling and blepharitis . At the same time, she developed acute pancreatitis and ultimately died of gram-negative sepsis . Although it appeared that the ocular and systemic disorders were manifestations of lupus, her serum antinuclear antibody and complement levels remained normal throughout her hospital course . Optic neuritis may be secondary to lupus, but the diagnosis is difficult to make when the serology is negative.

J Clin Microbiol, 1988 Oct, 26(10), 2206 - 8
Antithrombin III in the diagnosis of infection in febrile neutropenic patients; Kibbler CC et al.; Antithrombin III levels in plasma were measured in 29 febrile neutropenic patients (31 episodes) . They were lowest on day 2 in 62.5% of febrile patients and then increased or were normal in 81.3% . Low levels were present on day 2 in only 28.6% of patients with gram-negative infections, as compared with 33% of patients with doubtful infections.

J Clin Microbiol, 1988 Oct, 26(10), 2096 - 100
Comparative evaluation of selective media for isolation of Pseudomonas cepacia from cystic fibrosis patients and environmental sources; Carson LA et al.; Pseudomonas cepacia has recently emerged as an important pathogen affecting cystic fibrosis (CF) patients . We evaluated three selective media to assess their comparative potential for identification of patients colonized with P . cepacia and for efficacy of detection of P . cepacia in environmental fluids . Test organisms included P . cepacia isolates from CF patients (10 each from two CF centers), non-CF patients (10 isolates), and environmental sources (10 isolates) . Microbiologic assays were done by the membrane filter procedure; filters were placed on P . cepacia medium (PCM), OFPBL, TB-T, MacConkey agar (MAC), and blood agar (BA) or Standard Methods (SM) sugar, and colonies were counted after incubation at 30 or 35 degrees C for 72 h . Mean recovery efficiencies (MREs) (mean CFU/ml on selective media compared with CFU/ml on BA controls) for environmental and non-CF P . cepacia and patient isolates from one CF center showed a rank order of PCM greater than OFPBL greater than TB-T; for isolates from a second CF center, a rank order of PCM greater than TB-T greater than OFPBL was obtained . MREs for CF center isolates were generally lower than for non-CF patients or environmental isolates on P . cepacia-selective media . With MAC, the MREs for each group of CF isolates were extremely low (14 and 2%) compared with those for non-CF patient (47%) or environmental (84%) isolates . In laboratory and field studies, PCM and OFPBL showed good selectivity against bacteria commonly associated with CF patient respiratory secretions . These findings show that selective media should be used in clinical settings where P . cepacia is sought . With environmental fluids from CF centers, P . cepacia-selective media showed low selectivity against a variety of gram-negative water bacteria and appeared to afford little advantage over SM agar for isolating P . cepacia from environmental samples.

Chemioterapia, 1988 Oct, 7(5), 309 - 12
Antibiotic susceptibility of bacteria isolated from active, therapy-resistant periodontal sites; De Luca M; Periodontally affected sites may show resistance to mechanical therapy associated with conventional treatment . This periodontal situation is the result of the cooperation of bacteria, and in some cases the development of superinfections due to opportunistic bacteria is possible . These situations need particular attention in the choice of antibiotics . From some sites, bacteria not commonly found as periodontal pathogens may be isolated; they are generally resistant to antibiotics administered in periodontal therapy . Attention should be used particularly in cases where lesions most resemble those characteristic of the action of gram-negative bacteria . According to results of the present research these cases should be managed with antibiotic combinations and conventional mechanical therapy.

J Infect Dis, 1988 Oct, 158(4), 761 - 5
Comparison of the outer membrane proteins of 50 strains of Branhamella catarrhalis; Bartos LC et al.; Branhamella catarrhalis colonizes the respiratory tract of humans and commonly causes otitis media in children and respiratory infections in adults with chronic lung disease . In view of the emergence of this organism as an important human pathogen, we used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to examine the outer membrane proteins (OMPs) of 50 strains of B . catarrhalis . OMPs were isolated from broth culture supernatants . Typical of other gram-negative bacteria, eight proteins ranging in molecular weight (MW) from approximately 98,000 to 21,000 daltons were revealed by SDS-PAGE; these proteins were designated OMP A-OMP H . Of the OMPs identified, four were heat modifiable (C, D, E, and H) . The 50 strains were obtained from diverse geographic and clinical sources . The OMP patterns were strikingly homogeneous; there was minimal variability in the MW of OMPs between strains . Future studies should establish whether the similarity in MWs of OMPs is paralleled by their antigenic characteristics.

J Bacteriol, 1988 Oct, 170(10), 4493 - 500
Expression of the gene encoding the 17-kilodalton antigen from Rickettsia rickettsii: transcription and posttranslational modification; Anderson BE et al.; Recently, we reported the molecular cloning and nucleotide sequence analysis of a gene from Rickettsia rickettsii that codes for a 17-kilodalton antigen (17K antigen) and is preceded by sequences closely resembling the -10 and -35 consensus sequences for recognition by Escherichia coli RNA polymerase (Anderson et al., J . Bacteriol . 169:2385-2390, 1987) . Experiments described in this report indicate that the start sites for initiating transcription of the 17K antigen gene are identical in the E . coli clone and in intact R . rickettsii . In each case, initiation was shown to begin 9 bases downstream of the presumed Pribnow box sequence (TATACT) . A 169-base-pair fragment containing the promoter sequence initiated transcription in both directions when cloned into an E . coli promoter probe vector . The rickettsial fragment was found to contain sequences identical to the -10 region (but not the -35 region) of the E . coli promoter consensus sequence directed away from the 17K antigen gene . The amino-terminal portion (residues 17 to 20) of the deduced amino acid sequence for the 17K antigen contained the tetrapeptide Leu-Gln-Ala-Cys, a sequence that conforms favorably to those described for lipid modification and cleavage by lipoprotein signal peptidase II . The 17K antigen produced by the E . coli clone was shown to be labeled with {3H}palmitate and {3H}glycerol, indicative of lipid modification . In vitro mutagenesis designed to alter the cysteine at residue 20 to a glycine abolished incorporation of {3H}palmitate, suggesting that posttranslational modification occurs via a mechanism similar to that described for other gram-negative bacterial lipoproteins.

Chemioterapia, 1988 Oct, 7(5), 327 - 9
Chemoprophylaxis of bacterial infections in granulocytopenic cancer patients using norfloxacin; Casali A et al.; Sixty-five cancer patients pretreated with chemo or radiotherapy, with granulocytopenia less than 1000/mm3 and without fever, were entered into this study: 30 of them were submitted to prophylaxis with norfloxacin while the remaining 35 patients were used as a control group . 20% of the treated subjects versus 68.6% of the controls presented a subsequent infection (P less than 0.001), the lung representing the most frequent site of the infectious disease in both groups (3/6 and 14/24 respectively) . These data strongly suggest the use of norfloxacin as an effective prophylactic drug in nonfebrile, granulocytopenic cancer patients, especially as far as gram-negative infections are concerned . Because of the high prevalence of lung cancer in the patients of our study, and a related prevalence of lung infections, at the present time, a wider use of this antibiotic in every kind of solid tumor cannot be generalized.

Ann Surg, 1988 Oct, 208(4), 532 - 40
Intestinal gram-negative bacterial overgrowth in vivo augments the in vitro response of Kupffer cells to endotoxin; Billiar TR et al.; A number of disease states and therapeutic maneuvers common to surgical patients can result in changes in the intestinal flora, permitting bacterial overgrowth and translocation of bacteria to gut lymphoid tissue . It is possible that these changes in gut flora increase portal levels of several factors that are capable of altering macrophage activation state, including endotoxin, lymphokines, and eicosanoids . Since Kupffer cells are directly exposed to gut factors via the portal circulation, changes in intestinal flora may influence Kupffer cell responses . Using germfree rats, it has previously been shown that the presence of gut bacterial flora is important in inducing Kupffer cells to respond to endotoxin, and that an overgrowth of gram-negative bacteria can further augment Kupffer cell responses, supporting the above-mentioned hypothesis . The current set of experiments examines how intestinal gram-negative bacterial overgrowth in normal adult rats effects the response of Kupffer cells to septic stimuli . Kupffer cells were obtained from conventional rats with induced intestinal overgrowth with Escherichia coli C25 for 2 or 7 days . After 2 days of overgrowth, Kupffer cells were only slightly less responsive to lipopolysaccharide (LPS) than control Kupffer cells . However, after 7 days of overgrowth, when placed in coculture with normal hepatocytes, Kupffer cells were significantly more responsive to LPS (p less than 0.001), inducing a greater degree of suppression in hepatocyte protein synthesis at lower LPS concentrations . When cultured alone, Kupffer cells from these animals also produced more interleukin-1 (p less than 0.002) and prostaglandin E2 (PGE2) (p less than 0.009) in response to LPS . These results show that intestinal gram-negative bacterial overgrowth in conventional rats can have direct influences on the response of hepatic macrophages to septic stimuli, and provides further support to the hypothesis that imbalances in the intestinal flora can effect the responses of immune cells in other sites of the body.

Gene, 1988 Sep 30, 69(2), 237 - 44
Molecular analysis of the gene encoding alpha-lytic protease: evidence for a preproenzyme; Silen JL et al.; A 1.7-kb EcoRI fragment containing the structural gene for alpha-lytic protease has been cloned from Lysobacter enzymogenes 495 chromosomal DNA: the first example of a gene cloned from this organism . The protein sequence deduced from the nucleotide sequence encoding this serine protease matches the published amino acid sequence {Olson et al., Nature 228 (1970) 438-442} precisely . Sequence analysis and S1 mapping indicate that, like subtilisin {e.g., Wells et al., Nucleic Acids Res . 11 (1983) 7911-7925} alpha-lytic protease is synthesized as a pre-pro protein (41 kDa) that is subsequently processed to its mature extracellular form (20 kDa) . This first finding of a large N-terminal protease precursor in a Gram-negative bacterial protease strengthens the hypothesis that large precursors may be a general property of extracellular bacterial proteases, and suggests that the N- or C-terminal location of the precursor segment may be significant.

J Biol Chem, 1988 Sep 25, 263(27), 13479 - 81
A family of lipopolysaccharide binding proteins involved in responses to gram-negative sepsis; Tobias PS et al.; The lipopolysaccharides (LPS) of Gram-negative bacteria initiate potentially fatal processes in many host organisms . Recently published amino acid sequence data suggest that there is a family of LPS binding proteins that may participate in the host response to Gram-negative bacteremia . The first two members of the family to be identified are an LPS binding protein present in serum after an acute phase response in humans, mice, rabbits, and rats and a bactericidal/permeability increasing protein present in the primary granules of human and rabbit neutrophils . LPS binding protein and bactericidal/permeability increasing protein share an ability to bind to LPS, have homologous NH2-terminal amino acid sequences, and are immunologically cross-reactive . Nevertheless, these two molecules differ in their effects on LPS and Gram-negative bacteria, in their sites of biosynthesis, and localization in vivo.

J Mol Biol, 1988 Sep 5, 203(1), 275 - 8
Naturally crystalline porin in the outer membrane of Bordetella pertussis; Kessel M et al.; The Gram-negative bacterium Bordetella pertussis is the agent responsible for whooping-cough, and much interest has focused on the functions, structures and immunological properties of the molecules exposed at its outer surface . We have found by electron microscopy that cells of two strains of B . pertussis are covered with a crystalline surface lattice . This lattice is not an extrinsic layer of high molecular weight glycoproteins, such as occur on many other bacteria, but is a natural crystal of an intrinsic membrane protein of 40,000 Mr . This molecule has been shown to be an anion-selective member of an extensive family of proteins ("porins") that render Gram-negative outer membranes permeable to solutes of up to approximately 650 Mr . Computer image processing reveals a trimeric channel-like structure that closely resembles other porins visualized in artificial arrays after treatment with detergents, but in a novel (p2) crystal form . This correlation provides a "missing link" between earlier structural studies based on artificial arrays of porins (of undefined physiological status), and membrane-permeabilization experiments with solubilized porins (in undefined structural states) . For the strains characterized so far, crystallinity of the porin surface lattice shows an intriguing correlation with nonpathogenicity.

Biotechniques, 1988 Sep, 6(8), 752 - 60
A plasmid-based method to quantitate homologous recombination frequencies in gram-negative bacteria; Xu BW et al.; A method is described which enables quantitative evaluation of the ability of gram-negative bacterial cells to perform homologous recombination between DNA molecules . This method is particularly useful in cases where the stringency of rec mutations is to be determined . The procedure is based on a wide-host-range vector (pRK404) in which two unequally truncated and overlapping fragments of the neo gene were cloned . When introduced into gram-negative bacteria either by transformation or by conjugation, molecules of this plasmid, pBX404-7, undergo unequal crossing-over leading to the restoration of a functional neo gene . The stringency of putative rec mutations can thus be determined by measuring the frequency at which kanamycin-resistant colonies appear in bacterial strains harboring pBX404-7.

Int J Clin Pharmacol Ther Toxicol, 1988 Sep, 26(9), 432 - 5
Some questions of aminoglycoside therapy in the intensive care unit; Csapo K et al.; The pharmacokinetics of tobramycin and gentamycin was studied in patients of the intensive care unit . The "blood-bronchus barrier" was studied by determining the serum and sputum concentrations of the two drugs . At systemic administration, both aminoglycosides passed into the bronchial secretion and when they were inhaled, they appeared in the serum . By culturing the sputum samples of the patients of the intensive care unit, a high ratio of gram-negative pathogens was found . Bacteria were detected in some cases on the objects surrounding the patients, too.

Vet Microbiol, 1988 Sep, 18(1), 27 - 39
Development and evaluation of an enzyme-linked immunosorbent assay for endotoxin in milk; Mohammed AH et al.; A double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was developed for the detection of endotoxin in milk samples . Bovine and rabbit antisera raised in response to vaccination with the J5 mutant of Escherichia coli 0111:B4 were used . Antiserum to this mutant has been shown to be cross-reactive with endotoxin from other gram-negative organisms . Known quantities of endotoxin were added to milk samples to generate a standard curve . Acid treatment of whole milk enhanced the detection of endotoxin as compared to untreated whole milk, skim milk and chloroform-treated milk . Milk samples from experimentally induced mastitic cows were then assayed for endotoxin content . Recovery of endotoxin, as measured by ELISA, positively correlated with the amount of endotoxin infused and the time post-infusion of sampling . However, when endotoxin from these samples was quantitated using the Limulus Amebocyte Lysate (LAL) assay, readings tended to increase, suggesting false-positive reactions with the LAL assay . Milk samples from cases of clinical mastitis were assayed by ELISA with 64% of these showing measurable levels of endotoxin . While further studies of this assay are needed, refinements may produce an assay important for clinical applications.

Oral Surg Oral Med Oral Pathol, 1988 Sep, 66(3), 287 - 9
Metronidazole in the management of anaerobic neck infection in acute leukemia; Barrett AP; A case involving a rapidly progressive neck infection in a severely neutropenic patient with acute leukemia is reported . Resolution followed the addition of metronidazole to an existing standard piperacillin/gentamicin combination, which was used primarily to cover potential gram-negative bacillary pathogens . This indicated the importance of considering extension of anaerobic cover in such infections.

Circ Shock, 1988 Sep, 26(1), 15 - 26
Synergistic protection from lung damage by combining antithrombin-III and alpha 1-proteinase inhibitor in the E . coli endotoxemic sheep pulmonary dysfunction model; Redens TB et al.; Septicemic/endotoxic-induced adult respiratory distress syndrome (ARDS) remains a major clinical problem . The present study was to determine in the E . coli endotoxemic sheep ARDS model the efficacy of combination prophylaxis with antithrombin-III (AT-III) and alpha 1-proteinase inhibitor (alpha 1-PI) . We reasoned that 1) AT-III supplementation would ameliorate the endotoxin-induced coagulopathy, 2) alpha 1-PI supplementation would attenuate pulmonary damage caused by neutrophil elastase and inactivation of AT-III by neutrophil elastase, and 3) the therapeutic effects of this combination would be additive or synergistic . The typical increases in lung lymph flow microvascular permeability to protein, transvascular protein flow and transvascular protein clearance, and decrease in systemic arterial PO2 were prevented or significantly attenuated during 5 hours of endotoxemia by the AT-III/alpha 1-PI combination pretreatment . Limited efficacy was observed with AT-III pretreatment, and none was seen with alpha 1-PI alone . Results of this study demonstrate that combining AT-III and alpha 1-PI prophylaxis prevents or attenuates indices of ARDS during gram-negative endotoxemia and that this efficacy is due to a statistically significant synergism between AT-III and alpha 1-PI.

Appl Environ Microbiol, 1988 Sep, 54(9), 2203 - 7
Degradation of bromacil by a Pseudomonas sp; Chaudhry GR et al.; A gram-negative rod, identified as a Pseudomonas sp., was isolated from soil by using bromacil as the sole source of carbon and energy . During growth on bromacil or 5-bromouracil, almost stoichiometric amounts of bromide were released . The bacterium was shown to harbor two plasmids approximately 60 and 100 kilobases in size . They appeared to be associated with the ability to utilize bromacil as a sole source of carbon and also with resistance to ampicillin . This microorganism also showed the potential to decontaminate soil samples fortified with bromacil under laboratory conditions.

Rev Infect Dis, 1988 Sep-Oct, 10(5), 998 - 1004
Bone and joint infections caused by Kingella kingae: six cases and review of the literature; de Groot R et al.; Six cases of Kingella kingae arthritis, osteomyelitis, and diskitis were studied, and data were reviewed from an additional 23 cases in the English-language literature . K . kingae is a slow-growing, fastidious, gram-negative microorganism that colonizes mucous membranes of the upper respiratory tract . Infections were predominantly seen in infants and young children (86% of cases) and were preceded by an upper respiratory tract infection in 31% of patients . Low-grade fever (38 degrees C-39 degrees C) and pain or swelling involving the affected limb developed insidiously . However, 76% of the infections were diagnosed within 1 week after the onset of symptoms . The knee was involved in 47% and the hip in 33% of cases of arthritis . Osteomyelitis mainly involved the femur (36%); four cases of osteomyelitis (29%) were diagnosed as diskitis . The erythrocyte sedimentation rate was greater than 20 mm/h in all patients . Gram stains of aspiration fluid were positive in 19% of cases, whereas blood cultures yielded growth in only 5% . Radiographic signs indicating the presence of osteomyelitis were observed in 93% of patients . All patients recovered completely . K . kingae is an important causative agent in indolent bone, joint, and intervertebral disk infections.

J Clin Invest, 1988 Sep, 82(3), 964 - 71
Modulation of human platelet protein kinase C by endotoxic lipid A; Grabarek J et al.; Lipid A is the toxic principle of lipopolysaccharide of gram-negative bacteria, which causes a spectrum of changes in blood cells and vascular cells . We now report that human platelets are directly stimulated by endotoxic lipid A that activates protein kinase C . Rapid phosphorylation of a human platelet protein of Mr 47,000, a marker of protein kinase C activation, accompanies secretion of {14C}serotonin and aggregation triggered by endotoxic lipid A . These events are time and concentration dependent, with phosphorylation reaching maximum in 2 min and the concentration of lipid A causing a 50% effect (EC50) between 12 and 15 microM . Phospholipase C activation in lipid A-stimulated platelets was not observed as judged by a lack of generation of {3H}diacylglycerol in {3H}arachidonic acid-labeled platelets and a lack of generation of {32P}-phosphatidic acid in 32PO4-labeled platelets . Lipid A did not induce formation of TXA2 as measured by radioimmunoassay for TXB2 . The stimulation of human platelets and activation of protein kinase C by endotoxic lipid A was blocked by lipid X, a structural precursor of lipid A . Lipid X also blocked the stimulation of human platelets by phorbol 12-myristate 13-acetate, suggesting that lipid A, lipid X and phorbol ester share reactive site(s) on the human platelet membrane . Although lipid X inhibited thrombin-induced phosphorylation of P47 it did not suppress secretion of {14C}serotonin, indicating the role of protein kinase C-independent pathways in platelet stimulation by thrombin . The inhibitory effect of lipid X did not involve generation of cyclic AMP in human platelet membrane preparations . These results indicate that human platelets are stimulated by endotoxic lipid A, a naturally occurring biologic modifier of protein kinase C . Due to the widespread presence of this enzyme in blood cells, vascular cells, and neurons, its modulation by lipid A may represent a significant mechanism underlying hematologic and circulatory derangements observed in endotoxic shock in humans.

Clin Chest Med, 1988 Sep, 9(3), 449 - 57
Bacterial and fungal pneumonias; Fels AO; Bacterial pneumonias occur with increased frequency and can be associated with increased morbidity in the HIV-infected population compared with normals . The pathogens that most frequently cause community-acquired pneumonias are S . pneumoniae, H . influenzae, and occasionally S . aureus . These pneumonias usually respond to appropriate antibiotic therapy; however, patients diagnosed with bacterial pneumonias are at increased risk for subsequent episodes . Nosocomial pneumonias, by contrast, are usually caused by gram-negative organisms and have a high mortality . Fungal pneumonias also have an increased incidence in AIDS patients, and usually occur in the setting of disseminated disease . Infections caused by C . neoformans, H . capsulatum, and C . immitis often recur despite a good initial response to amphotericin B . Maintenance therapy with an antifungal agent is therefore recommended.

Crit Care Med, 1988 Sep, 16(9), 848 - 51
Effect of scavengers of oxygen-derived free radicals on mortality in endotoxin-challenged mice; Broner CW et al.; Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems . Recently, a role for free radicals has been proposed in the mortality associated with Gram-negative bacterial sepsis . To determine if pretreatment with free radical scavengers can prevent endotoxin-induced mortality, mice rendered sensitive to endotoxin with actinomycin D were treated with either superoxide dismutase (SOD), N-acetylcysteine (NAC) or saline and were then challenged with a dose of endotoxin calculated to cause a mortality of greater than 80% . Mortality was assessed at 12-h intervals after challenge . Increased survival was seen in the SOD-treated group compared to the control group (p less than or equal to .05) . In contrast, survival in mice treated with NAC, another potential scavenger, was not significantly different from the control group . These results support the hypothesis that superoxide and hydroxyl radicals contribute to mortality in Gram-negative bacterial sepsis.

Am Ind Hyg Assoc J, 1988 Aug, 49(8), 420 - 1
Airborne endotoxin associated with industrial-scale production of protein products in gram-negative bacteria; Palchak RB et al.; Human and animal proteins of therapeutic value can be produced in E . coli, a gram-negative bacteria . Endotoxin, a cellular component, is reported to have clinically significant health effects . Operations--including culturing the microbe, separating solids by centrifugation, and mixing/homogenizing--had associated endotoxin levels ranging from 0.07 ng/m3 to 12.8 ng/m3 . Utilizing a 10-fold safety factor under the threshold where clinically significant changes can be detected, an action level of 30 mg/m3 for large scale operations involving the use of E . coli was established . Operations conducted without engineering controls had maximum airborne endotoxin levels of 1812 ng/m3.

Vestn Khir Im I I Grek, 1988 Aug, 141(8), 14 - 7
{Treatment of acute complicated abscess of the lungs}; Grigor'ev EG et al.; Results of examination and treatment of 194 patients with acute complicated abscesses of the lungs were analyzed . The main pathogenic agent of this pathology is gram-negative microorganisms and anaerobic neclostridial flora . Methods of bacterioscopy and gas-liquid chromatography were used for its verification . It was noted that the basis of medical tactics in complicated abscesses of the lungs is the rational antibiotic therapy in combination with parasurgical methods of treatment . Surgical methods are indicated in gangrening abscess, pulmonary hemorrhage, non-effective complex therapy.

J Infect Dis, 1988 Aug, 158(2), 312 - 9
Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5: a prospective, double-blind, randomized trial; Calandra T et al.; In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli J5 (J5-IVIG) with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock . At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either J5-IVIG or IVIG . Of the 100 patients randomized, 71 (30 receiving J5-IVIG and 41 receiving IVIG) had a documented gram-negative infection . Mortality from gram-negative septic shock was 50% (15 of 30) in J5-IVIG recipients and 49% (20 of 41) in IVIG recipients . In addition, treatment with J5-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock . Thus we conclude that J5-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shock.

Jpn J Med Sci Biol, 1988 Aug, 41(4), 123 - 57
Pseudomonas pseudomallei and melioidosis, with special reference to the status in Thailand; Kanai K et al.; Melioidosis is a long-known disease since 1912, but only quite recently we have obtained the knowledges about its actual clinical and epidemiological features . The disease is so unique in having a wide spectrum of disease course and clinical manifestation . The causative agent, P . pseudomallei, is free-living bacterium in the natural environments (soil and surface water) of tropical and subtropical areas . Just like legionnaires' disease, melioidosis is a good example of infectious disease in which pneumonia is produced by inhalation of contaminated soil dusts or water droplets . The infection becomes dormant for years, but with a chance of recrudescence under a variety of insults to the host resistance . The disease, may it be acute or chronic, will be symptomatically confused with malaria, typhoid fever, leptospirosis, septicemia caused by other gram-negative bacteria, tuberculosis and mycotic infections . Isolation of the causative agent from clinical specimens is the only reliable method for diagnosis . Because of the increasing clinical awareness and the development of diagnostic methods, the reported cases of melioidosis have numbered almost one thousand in Thailand during the past 20 years . This country has now the most ample clinical experiences on melioidosis . We have reviewed the history of melioidosis research from bacteriological, immunological, clinical and epidemiological viewpoints, especially including the recent reports in Thailand.

J Biochem Biophys Methods, 1988 Aug, 16(4), 301 - 9
A sulfone group-labeled TEM-DNA probe: comparison with a 32P-labeled probe in dot-hybridization; Jouvenot M et al.; A non-radioactive DNA probe for the TEM-type beta-lactamase gene was obtained by using the 'Chemiprobe' system . It was used along with a 32P-labeled TEM probe to screen for TEM beta-lactamase gene in 107 bacterial isolates representing 7 Gram-negative genera and previously classified as TEM-positive or negative . The DNA to be tested was extracted from these bacterial isolates by the Birnboim-Doly method and, after blotting into charged nylon membranes, it was submitted to hybridization with either the TEM 'Chemiprobe' or the 32P-TEM probe . The TEM 'Chemiprobe' could detect as few as 25 pg specific DNA if it was used at a concentration of 5 ng per cm2 of membrane . The results obtained by both probes were concordant in 93.5% of the entire sample . The TEM 'Chemiprobe' was specific since only one false positive was observed . Furthermore, it appeared at least as sensitive as the 32P-labeled TEM probe . As the dot-hybridization with the sulfone-labeled probe was sensitive, simple and easy to perform, it will be useful for large-scale screening in clinical laboratory.

Br J Exp Pathol, 1988 Aug, 69(4), 537 - 49
Morphological damage induced by Escherichia coli lipopolysaccharide in cultured hepatocytes: localization and binding properties; Pagani R et al.; Lipopolysaccharides (LPS) from Gram-negative bacteria are considered to be the responsible agents for the induction of endotoxic shock, affecting the liver as a target organ . In this study, the cell morphology and some biochemical properties of 24 h-culture-hepatocyte monolayers treated with Escherichia coli 0111:B4 lipopolysaccharide, were observed . Cell morphology was observed by scanning electron microscopy and immunofluorescence methods . LPS interaction induced an increase in rounded cells with diminished adhesion capacity . As biochemical parameters, albumin synthesis and 2-deoxyglucose uptake were measured . LPS decreased the hexose uptake in a dose-dependent manner . Binding of (14C)LPS to cultured hepatocytes showed that LPS binds to non-specific constituents of the membrane bilayer.

J Bacteriol, 1988 Aug, 170(8), 3750 - 1
Penicillin-binding proteins of bdellovibrios; Park JT et al.; We examined the predacious gram-negative bacterium Bdellovibrio bacteriovorous 109J and free-living strains 109J-A1 and 109J-KA1 derived therefrom for penicillin-binding proteins (PBPs) . We compared their PBPs with those of the host bacterium, Escherichia coli, and with those of a facultatively predacious bdellovibrio, B . stolpii UKi2, grown axenically . The multiple PBPs of the 109J strains and of UKi2 differed from each other and from those of E . coli, which suggests that screening for PBPs may be a convenient way to determine to what extent the bdellovibrios may represent a diverse group of organisms . A method for labeling furazlocillin and cefaperizone with iodine-125 is also described.

Antibiot Khimioter, 1988 Aug, 33(8), 591 - 4
{The action of combinations of the nonapeptide polymyxin B with antibiotics on gram-negative bacteria}; Bairamashvili DI et al.; Activity of polymyxin B nonapeptide alone and in combination with other antibiotics against clinical strains of Pseudomonas and enteric bacteria was studied . It was shown that nonapeptide was highly active against Pseudomonas and moderately active against enteric bacteria . In combination with rifampicin, fusidic acid or erythromycin the nonapeptide had a potentiating effect on the tested strains.

Gene, 1988 Jul 30, 67(2), 301 - 5
Insertion sequence IS2 in the cyanobacterium Chlorogloeopsis fritschii; Machray GC et al.; A cloned DNA fragment, previously demonstrated to encode ribulose bisphosphate carboxylase/oxygenase (RuBisCO) of Chlorogloeopsis fritschii strain CCAP1411/1b, is shown also to include the entire transposable element, IS2, normally a resident in the Escherichia coli genome . Southern-blot hybridisation experiments confirm the presence of IS2 in the C . fritschii genome . This finding adds a new and unrelated species to the known host range of this element and provides evidence of genetic transfer between the Gram-negative E . coli and cyanobacteria . This may also have significance in relation to the nucleotide sequence rearrangements known to occur adjacent to RuBisCO and nif genes in other nitrogen-fixing cyanobacteria.

Biochem J, 1988 Jul 15, 253(2), 371 - 6
A novel aspect of the inhibition by arsenicals of binding-protein-dependent galactose transport in gram-negative bacteria; Richarme G; The inhibitory effects of arsenate and arsenite on binding-protein-dependent transport systems are reconsidered . It is shown that arsenate inhibits binding-protein-dependent galactose transport in proteoliposomes energized either by dihydrolipoamide and NAD+ or by a membrane potential (under conditions where ATP metabolism is not implicated); this result is in contradiction with the current interpretation of arsenate inhibition of binding-protein-dependent transport systems (which is based on ATP depletion) and can be explained by reference to the recently discovered ATP inhibition of the binding-protein-dependent galactose transport . In whole cells, the greater inhibition by arsenate of lipoamide-dependent transport than of protonmotive-force-dependent transport may be explained by a modification by arsenate of the pools of several compounds metabolized by 2-oxo-acid dehydrogenases (which have been implicated in binding-protein-dependent transport) . The inhibition of binding-protein-dependent galactose transport by arsenite is probably linked to the inhibition by arsenite of the galactose-stimulated lipoamide dehydrogenase activity implicated in this transport and is reminiscent of the known arsenite inhibition of lipoamide dehydrogenases.

Nature, 1988 Jul 14, 334(6178), 173 - 5
Phosphatidylglycerol is involved in protein translocation across Escherichia coli inner membranes; de Vrije T et al.; Newly synthesized proteins to be exported out of the cytoplasm of bacterial cells have to pass across the inner membrane . In Gram-negative bacteria ATP, a membrane potential, the products of the sec genes and leader peptidases (enzymes which cleave the N-terminal signal peptides of the precursor proteins) are required . The mechanism of translocation, however, remains elusive . Important additional roles for membrane lipids have been repeatedly suggested both on theoretical grounds and on the basis of experiments with model systems but no direct evidence had been obtained . We demonstrate here, using mutants of Escherichia coli defective in the synthesis of the major anionic membrane phospholipids, that phosphatidylglycerol is involved in the translocation of newly synthesized outer-membrane proteins across the inner membrane.

Drug Intell Clin Pharm, 1988 Jul-Aug, 22(7-8), 577 - 81
Endotracheal tobramycin in gram-negative pneumonitis; Stillwell PC et al.; This report describes the treatment of resistant gram-negative pneumonitis in a compromised host by the combined use of intravenous and endotracheal tobramycin . The endotracheal administration appeared to have an effect on the serum concentration and elimination rate, necessitating a reduction in the amount of drug given intravenously . The only apparent clinical complication of endotracheal drug administration was transient coughing . The addition of endotracheal aminoglycosides to intravenous antibiotics may be useful in pediatric patients with unresponsive (or other difficult-to-treat) pneumonitis caused by resistant microorganisms . The potential contribution of endotracheal aminoglycosides to the serum level and/or disposition profile must be recognized, and therapeutic drug monitoring guided accordingly when this route of administration is used.

Appl Environ Microbiol, 1988 Jul, 54(7), 1756 - 60
Efficacy of chemical dosing methods for isolating nontuberculous mycobacteria from water supplies of dialysis centers; Carson LA et al.; Investigations of nontuberculous mycobacterium (NTM) infections associated with various environmental sources have been hampered by the lack of adequate techniques for selective isolation of these organisms from environmental fluids . This study compared chemical dosing techniques for recovery of NTM from water samples collected from 115 randomly selected dialysis centers . Cell suspensions of NTM group II and IV isolates and gram-negative bacteria were exposed to solutions containing sodium hypochlorite (0.2 micrograms/ml of free available chlorine), formaldehyde (1, 0.75, or 0.5%), oxalic acid (1.25%), cetylpyridinium chloride (25 micrograms/ml), or cetyltrimethylammonium bromide (100 micrograms/ml) . Results of standard membrane filtration assays with laboratory test strains and water samples from dialysis centers showed that 5 min of exposure to 1% formaldehyde effectively reduced gram-negative bacterial populations and allowed increased recovery of NTM in environmental fluids containing mixed microbial populations.

J Pediatr Orthop, 1988 Jul-Aug, 8(4), 445 - 9
Kingella kingae infection in healthy children; Gamble JG et al.; Kingella kingae is a gram-negative occasional, but normal, inhabitant of the nasopharynx . We present two new cases of this infection that occurred in previously healthy children, and compare and contrast them to other cases reported in the literature . K . kingae osteomyelitis generally has an insidious, subacute onset, whereas septic arthritis has an acute presentation . To date, all strains of K . kingae have been sensitive to penicillin, and no residual damage has been reported following osteomyelitis or septic arthritis, except that residual disk space narrowing did occur after K . kingae discitis.

Vet Q, 1988 Jul, 10(3), 211 - 6
Pharmacokinetics of ciprofloxacin in carp, African catfish and rainbow trout; Nouws JF et al.; The plasma disposition of ciprofloxacin was studied in carp, African catfish and trout after intravenous (IV) and intramuscular (IM) administration at a dose rate of 15 mg/kg . Pharmacokinetic analysis of IV data showed that ciprofloxacin was well distributed (distribution volume Vd(area): 3.08-5.59 litre/kg) and exhibited a similar elimination half-life of about 14 h in these 3 fish species . After IM administration to carp and trout a rapid absorption was noticed; the maximum ciprofloxacin plasma concentrations (mean: 3.49 and 2.37 micrograms/ml, respectively), were achieved within 1 h after injection . At the dose level applied, ciprofloxacin has potential therapeutic value for 2-5 days especially against gram-negative bacterial fish pathogens.

J Reprod Med, 1988 Jul, 33(7), 657 - 60
Peripartum infections with Capnocytophaga . A case report; Hager H et al.; Capnocytophaga is an increasingly recognized genus of pathogens . Originally associated with periodontal disease, this fastidious, gram-negative organism is now established as the cause of a wide variety of infections in both the immunocompetent and immunocompromised . We treated a woman for amnionitis and subsequent neonatal colonization . Capnocytophaga should be considered one of the various organisms that can complicate the peripartum period.

J Clin Periodontol, 1988 Jul, 15(6), 390 - 8
Clinical, microbiological and immunological features of subjects with refractory periodontal diseases; Haffajee AD et al.; 27 subjects with active destructive periodontal diseases were treated by modified Widman flap surgery and systemic tetracycline and divided into 4 groups based on pre- and post-therapy hazard rates (% of sites losing greater than 3 mm of attachment in 1 year) . Pre- and post-therapy hazard rates were respectively: group I (3 subjects) less than 4 and less than 4; group II (8 subjects) greater than 4 and less than 4; group III (3 subjects) less than 4 and greater than 4; group IV (refractory group of 13 subjects) greater than 4 and greater than 4 . Baseline mean pocket depths and attachment loss of groups I and II subjects were less than groups III and IV subjects and exhibited less suppuration . 6 group IV subjects lost a total of 38 teeth after therapy, in contrast to no tooth loss in subjects in the other 3 groups . Redness, bleeding on probing, plaque levels and age did not differ among groups . Subjects in the 4 groups differed in the subgingival species to which they showed elevated serum antibody responses . Group IV subjects showed elevated responses to a select range of gram-negative species, including A . actinomycetemcomitans strains Y4 or ATCC 29523, F . nucleatum and B . intermedius . No subject in any of the other groups exhibited an elevated response to B . intermedius . The mean % of each species in all sampled sites, both before and after therapy, was computed for each subject . Subjects in groups III and IV (high post-therapy hazard rates) exhibited elevated mean levels of B . forsythus, F . nucleatum, S . intermedius, E . corrodens, and B . gingivalis.(ABSTRACT TRUNCATED AT 250 WORDS)

J Antimicrob Chemother, 1988 Jul, 22 Suppl A, 17 - 22
Bacterial resistance to antibiotics as a function of outer membrane permeability; Nikaido H; The outer membrane of Gram-negative bacteria serves as barrier to permeation . Transport across this barrier often occurs through channels created by porins . Changes in these porins can account for antibiotic resistance . The combination of a permeability barrier and beta-lactamases in the periplasmic space leads to a situation in which concentrations, at the target, of even third-generation cephalosporins, can be significantly decreased.

Rev Infect Dis, 1988 Jul-Aug, 10(4), 681 - 90
Recent developments in beta-lactamase research and their implications for the future; Bush K; beta-Lactamases, major determinants of bacterial resistance to beta-lactam antibiotics, can be classified into specific molecular classes following identification of active-site amino acid or nucleotide sequences . The use of gene probes for epidemiologic purposes is becoming commoner . A semiempirical classification scheme has been proposed using substrate profiles and inhibition by clavulanic acid and aztreonam as criteria . Class 1 cephalosporinases are potently inhibited by aztreonam but poorly inhibited by clavulanate, whereas class 2 penicillinases and broad-spectrum beta-lactamases have very poor affinities for aztreonam but are inhibited by clavulanic acid . Class 3 beta-lactamases include the metalloenzymes . Resistance to beta-lactam antibiotics can be related to many beta-lactamase-mediated phenomena, including increased frequency of beta-lactamase production in clinical isolates, wider distribution of beta-lactamase-mediating plasmids, production of multiple beta-lactamases, induction of chromosomal class 1 cephalosporinases, selection of depressed mutants for production of class 1 enzymes, leakage of beta-lactamase from gram-negative organisms, functions of penicillin-binding proteins as beta-lactamases, and identification of novel beta-lactamases.

Ontogenez, 1988 Jul-Aug, 19(4), 366 - 70
{Reversible suppression and activation of immunoglobulin genes in differentiated IgG+ sublines of human RPMI-6410t B-cells}; Seregina TM et al.; Differentiated human B-cells of the IgG+ sublines obtained as a result of switching from IgM to IgG synthesis in the 6410t line and its IgM+ lines gradually reduce the level of IgM secretion after the inductor removal . IgG synthesis can be partially or fully recovered by treating the IgG+ sublines with a polyclonal activator of B-lymphocytes, lipopolysaccharide W from Gram negative bacteria . In the conditions of certain regulatory effects, differentiated IgG+ cells are capable to pass reversibly in the state of functional rest and synthesis initiation.

Rev Infect Dis, 1988 Jul-Aug, 10 Suppl 2, S296 - 9
Understanding the structure and antigenicity of gonococcal pili; Getzoff ED et al.; Pili--filamentous protein structures found on the cell surface of many infectious gram-negative bacteria--often are virulence factors that mediate adherence to host epithelial cells . The pilus, a major surface antigen of the gonococcus, is formed by the specific association of thousands of repeating identical protein subunits (pilin) . Structural studies of the pilin protein and the pilus fiber may aid the rational design of a peptide-based vaccine by providing information on the antigenic surface of pili that includes the identification of sequence-distant antigenic regions that are localized to single areas of the three-dimensional structure . Preliminary results suggest that the pilin subunit has structural similarity to the 4-alpha-helix bundle fold in proteins such as the coat protein subunit of tobacco mosaic virus and myohemerythrin . Therefore, the monomeric protein myohemeythrin was used to identify structural correlations for antigenic determinants on 4-alpha-helix bundle proteins such as pilin.

Circ Shock, 1988 Jul, 25(3), 173 - 85
Coronary blood flow and cardiac adenine nucleotides in E . coli endotoxemia in dogs: effects of oxygen radical scavengers; Laughlin MH et al.; The purposes of this study were to determine the effects of E . coli endotoxin shock on coronary blood flow (CBF) and myocardial adenine nucleotides and to determine if reactive oxygen species are major causal factors in these effects of endotoxin . Twenty-three pentobarbital-anesthetized Beagle dogs were instrumented for recording cardiorespiratory parameters, injected i.v . with saline (time-matched controls; n = 6) or endotoxin (1.5 mg/kg; n = 17), and studied for 4 h . Endotoxin dogs also received either i.v . saline (shock controls; n = 6) or i.v . treatment with either deferoxamine (30 mg/kg; n = 5) or triple therapy (n = 6) with a combination of allopurinol (150 mg/kg), superoxide dismutase (SOD) (5 mg/kg), and catalase (CAT) (5 mg/kg) . Cardiorespiratory and tissue blood flow variables were constant in sham-shock controls during the study, whereas endotoxin dogs developed typical canine endotoxemia with decreased left ventricular (LV) function . CBF was decreased by approximately 40% (P less than or equal to 0.5) in all endotoxin groups throughout the 4 h study period . However, based on hemodynamic estimates of myocardial O2 demand and endocardial/epicardial blood flow ratios, it seemed that coronary flow was matched to metabolic rate in all endotoxin groups . Endotoxin significantly lowered LV myocardial concentrations of ADP, AMP, NADH, and NADPH (range = 37 to 54%, P less than or equal to 0.05), but ATP, NAD, and NADP concentrations were not changed . The adenylate charge of the myocardium was between 0.91 and 0.95 in all endotoxin groups, suggesting that adequate energy was available in the myocardium during endotoxin shock . The lack of influence of deferoxamine, allopurinol, SOD, and CAT is indirect evidence that oxygen radicals are not primary pathophysiologic mediators in the cardiac response to gram-negative endotoxemia in this endotoxin model.

Rev Infect Dis, 1988 Jul-Aug, 10 Suppl 2, S279 - 81
Structure and functions of the cell envelope of gram-negative bacteria; Nikaido H; The surface of gram-negative bacteria contains structures that prevent the entry of noxious compounds into the cell and that help the cell evade recognition by host elements such as antibodies and complement while allowing the bacteria to obtain nutrients from the environment and to attach to structures of the host cell . This review discusses the role of outer-membrane components such as lipopolysaccharides and porin, as well as appendages such as capsules and fimbriae in such functions.

Acta Cytol, 1988 Jul-Aug, 32(4), 465 - 70
Cytologic manifestation of an unusual bacterial form, Simonsiella species; Greenebaum E et al.; Puzzling rodlike structures overlying benign squamous cells in exfoliative cytologic specimens from the upper gastrointestinal and respiratory tracts were initially considered to be fungi, protozoa, bronchodilator crystals, hemoglobin tactoids or plastic fragments . Their morphologic similarity to Simonsiella, a gram-negative bacteria frequently found in the oral cavity, was ultimately recognized . Further studies of smears and cultures obtained from the oral cavities of the authors and from the American Type Culture Collection confirmed the nature of the original findings . These giant bacterial forms were usually found in caterpillarlike side-by-side arrangements of 10 to 12 organisms . Cytologists should be aware of their appearance to avoid possible confusion with pathogenic organisms.

Thromb Haemost, 1988 Jun 16, 59(3), 451 - 4
Plasminogen activator inhibitor activity in bacterial infection; Paramo JA et al.; It has been experimentally shown that endotoxin induces a marked increase in the levels of a fast-acting inhibitor of plasminogen activator (PAI) . The plasma PAI activity and tissue-type plasminogen activator (t-PA) concentrations were measured in 61 patients with human septicaemia and results were compared with those observed in healthy controls . There was a markedly significant increase of PAI in plasma and platelet extracts of patients with septicaemia as compared to controls (p less than 0.0001) . No correlation between PAI and endotoxin concentration was observed . Fibrin autography of plasma samples confirmed that activator inhibition was associated with the formation of an enzyme-inhibitor complex . t-PA activity was similar in patients and controls, whereas t-PA Ag showed a significant increase in patients (p less than 0.0001) . A significant inverse correlation between t-PA activity and PAI was observed (p less than 0.05) . PAI activity was higher in patients with positive blood cultures (p less than 0.0001) and gram-negative septicaemia (p less than 0.0001) . There was also a significant increase of PAI levels in patients with disseminated intravascular coagulation (DIC) as compared with patients without DIC (p less than 0.001) . We conclude that there is a marked increase of PAI in patients with sepsis . Increased PAI activity may contribute to the pathogenesis of DIC associated with septicaemia.

Appl Environ Microbiol, 1988 Jun, 54(6), 1462 - 5
A method to assess the bacterial content of refrigerated meat; Perez de Castro B et al.; A new method has been developed to estimate the levels of gram-negative bacteria on refrigerated meat . The method is based on the aminopeptidase activity of these bacteria, which cleaves L-alanine-p-nitroanilide to yield p-nitroaniline, which is easily determined spectrophotometrically . This method allows the determination of levels around 10(6) to 10(7) CFU cm-2 in about 3 h . Because of the yellow color of p-nitroaniline, bacterial loads around 10(7) CFU cm-2 develop a color intense enough to be detected with the naked eye.

Am J Infect Control, 1988 Jun, 16(3), 95 - 100
Restriction of bacterial growth under commercial catheter dressings; Aly R et al.; The effect on the normal cutaneous flora after iodine and alcohol disinfection of the skin of three commercially available moisture-permeable polyurethane dressings was compared with that of a gauze-and-tape dressing . Dressings also were evaluated clinically for membrane adhesion and skin erythema, pruritis, hyperpigmentation, vesiculitis, and tenderness . Each of 50 healthy volunteers and 49 long-term inpatients, 25 of whom were receiving antibiotic therapy, received simultaneously on their volar forearm patches of Op-Site, Tegaderm, Uniflex, and gauze dressings . Controls consisted of one exposed skin site and one covered with moisture-retaining vinylidene film (Saran Wrap) . Although after 3 days of adhesion, commercial dressings prevented indigenous flora from returning to normal population densities, no significant quantitative differences were found between them and the gauze-and-tape dressing . Generally, all clinical dressings maintained normal flora at one tenth the population of the uncovered site; the Saran Wrap control supported 100-fold more bacteria than the exposed site . No differences were discovered in the levels of gram-negative bacteria, or among patient groups and between patients and healthy subjects, except for the lower incidence of erythema and itching among patients compared with healthy subjects.

J Trauma, 1988 Jun, 28(6), 823 - 7
Factors increasing the risk of infection in patients with open fractures; Merritt K; A study was undertaken to determine what factors are important in determining whether or not a patient with an open fracture will develop an infection . Debrided tissue was cultured to determine quantitative bacterial counts . The patients' subsequent records were evaluated and the infection rate correlated with culture data and other factors that might be associated with development of infection . Of the 70 patients evaluated, 13 (19%) became infected . When the infection rate was correlated with the use of fixation devices, it was found that 1/19 (5%) of the patients with no implants, 3/16 (19%) of the patients with external fixation devices, and 9/35 (26%) of the patients with internal fixation became infected . Most of the infections were caused by Gram-negative bacteria . There was little correlation between the bacterial counts in the first piece of tissue taken at debridement and the development of infection . There was significant correlation between the bacterial count in the last piece of tissue taken at debridement and the development of infection . Thus the infection was correlated with what was in the tissue when the patient left the operating room and not with what was in the tissue when the patient entered the operating room.

Laryngoscope, 1988 Jun, 98(6 Pt 1), 589 - 92
Retropharyngeal abscess in children: a retrospective and historical analysis; Thompson JW et al.; The charts of 65 pediatric patients with the diagnosis of retropharyngeal abscess were reviewed . These represented a 36-year experience with the disease . The findings were compared with those documented at the turn of the century and were also compared with findings over the last four decades . The data suggests that retropharyngeal abscess may be occurring later in childhood and may not always be preceded by a major detectable infection . Classic diagnostic findings of retropharyngeal bulge and neck stiffness were present in less than half of the patients . Gram-negative and anaerobic organisms are being documented on culture more frequently than in the past . We theorize that liberal use of oral antibiotics prior to admission may have brought about these changes.

Urology, 1988 Jun, 31(6 Suppl), 33 - 6
Role of aztreonam in lower respiratory tract infections; Cook JL; Pneumonia caused by Gram-negative bacteria is a major cause of morbidity and mortality among hospitalized and immunocompromised patients . Most antibiotic regimens used to treat these pulmonary infections include aminoglycoside antibiotics . Since achievable serum and tissue levels of aminoglycosides are limited by dose-related nephrotoxicity and ototoxicity, alternative forms of antibiotic therapy would be desirable . Aztreonam, the first clinically available monobactam antibiotic, achieves high serum levels and adequate levels in bronchial secretions and lung parenchyma for efficacy against most Gram-negative pathogens implicated in nosocomial pneumonias . The results of early clinical trials comparing aztreonam with aminoglycosides for treatment of Gram-negative bacterial pneumonias indicate that this monobactam antibiotic is a safe, effective alternative to aminoglycoside therapy.

Infect Immun, 1988 Jun, 56(6), 1593 - 601
Endotoxin-associated protein: interleukin-1-like activity on serum amyloid A synthesis and T-lymphocyte activation; Johns MA et al.; Bacterial endotoxins or lipopolysaccharides (LPS) elicit a variety of biologic activities in intact animals and various in vitro systems . LPS from most gram-negative bacteria have appeared to have similar biologic activities regardless of the species of origin or method of preparation of the LPS . More recent studies have suggested differences in the effects of protein-rich as opposed to protein-free LPS in inducing mitogenesis of lymphocytes from endotoxin-resistant C3H/HeJ mice . These studies examine other activities of endotoxin-associated protein (EAP), purified to less than 0.007% contamination with LPS, and demonstrate that this material has activity mimicking some of the effects of interleukin-1 (IL-1) . EAP proved to be as potent as LPS in eliciting rises in concentrations of serum amyloid A (SAA) and was active in both endotoxin-sensitive (CF1) and endotoxin-resistant (C3H/HeJ) mice . In contrast to LPS, which mediates its SAA-inducing activity by release of an inducer (IL-1) from LPS-stimulated macrophages, EAP appeared to act directly to induce SAA production, in that incubation with macrophages failed to increase its activity . EAP also exhibited IL-1-like activity in the lymphocyte-activating factor assay when both CF1 and C3H/HeJ thymocytes and macrophages were tested . The lymphocyte-activating factor activity of EAP was not blocked by addition of polymyxin B . In addition, EAP exerted stimulatory activity on resting human T lymphocytes, costimulated with Sepharose-bound anti-CD3 monoclonal antibody 64.1, comparable to that observed with purified human monocyte IL-1 . These studies indicate that proteins from procaryotic cells may act as cytokines for some eucaryotic cells.

Crit Care Med, 1988 Jun, 16(6), 601 - 5
Plasma endotoxin concentration in healthy primates and during E . coli-induced shock; Wessels BC et al.; The normal range for circulating plasma endotoxin concentration was determined in 62 healthy primates (vervet monkeys, Cerecopithecus aethiops) by the chromogenic substrate modification of the Limulus amoebocyte lysate test, and found to have a mean of 0.076 +/- 0.004 ng/ml (range 0.000 to 0.0127) . Four anesthetized primates received an LD100 iv infusion of Escherichia coli over one hour . Plasma concentrations of endotoxin (lipopolysaccharide, LPS) and anti-LPS IgG, and viable E . coli colonies in circulating whole blood samples were determined at specified intervals . Plasma antiendotoxin IgG concentration was determined by an enzyme-linked immuno-absorbent assay, and viable bacterial counts were assayed by standard plate count techniques . LPS concentration increased during E . coli infusion to a mean of 1.13 +/- 0.068 ng/ml (p less than .001) with a concomitant decrease in the concentration of anti-LPS IgG to 59 +/- 5% of control values (p less than .005) . Viable circulating E . coli colonies increased during the infusion to a maximum of 425 X 10(6) cfu/ml 10 min after the completion of the infusion, but fell precipitously 20 min later to 10.1 X 10(6) cfu/ml . When each animal succumbed, their respective plasma LPS concentrations were still raised, whereas no viable circulating E . coli colonies were present at a dilution of 10(2) . Elevated plasma LPS could prove to be a significant circulating pathogen during Gram-negative bacterial shock and supports the possible association between plasma LPS and morbidity, and mortality in septic shock.

Biomed Environ Sci, 1988 Jun, 1(1), 115 - 24
Inflammatory potential of grain dust; Ye TT et al.; A comparative analysis of toxicity and inflammatory potential of spring wheat, oat, corn, and flax seed was performed . The extracts were examined by quantification of gram-negative bacterial endotoxin and protein contents, chemotaxis for purified human polymorphonuclear leukocytes, and several alveolar macrophage functions including phagocytosis, release of lactate dehydrogenase, macromolecular synthesis (protein and RNA), and interleukin-1 production . The results suggested that the extracts of all four grain dusts inhibited protein synthesis and decreased phagocytosis of alveolar macrophages at 7.5-25 mg/ml . Protein synthesis was inhibited to 40.2% of control and phagocytosis to 47.9% of control . Interleukin-1 production was stimulated, as indicated by a stimulation index range from 3.8-fold to 14.3-fold over controls . The activity of these grain dust extracts did not correlate with the endotoxin content of the samples . The data demonstrate that the extracts of all four dusts produced ill effects in rat alveolar macrophages in vitro and suggested a potential hazard to agricultural workers exposed to grain dust.

J Interferon Res, 1988 Jun, 8(3), 283 - 93
Interferon-gamma and antibiotics fail to act synergistically to kill Legionella pneumophila in human monocytes; Bhardwaj N et al.; Legionella pneumophila, the agent of Legionnaires' disease, is a gram-negative facultative intracellular bacterial pathogen that multiplies in human blood monocytes and alveolar macrophages . Interferon-gamma (IFN-gamma)-activated human monocytes inhibit the intracellular multiplication of L . pneumophila but fail to kill the organism . Similarly, erythromycin and rifampin, the drugs of choice in the treatment of Legionnaires' disease, inhibit the growth of L . pneumophila within monocytes without exerting a cidal effect . In this study, we examined the combined effects of IFN-gamma and antibiotics (erythromycin, rifampin, and clindamycin) to determine whether these independently acting agents would synergistically mediate the killing of intracellular L . pneumophila . Each agent alone or in combination was effective in inhibiting the intracellular multiplication of L . pneumophila . However, IFN-gamma and antibiotics together were unable to kill intracellular L . pneumophila, regardless of the sequence in which they were administered to monocytes . Like erythromycin and rifampin, clindamycin, which is highly concentrated in human alveolar macrophages, was capable of inhibiting the intracellular multiplication of L . pneumophila but failed to kill the bacteria in nonactivated or IFN-gamma-activated monocytes . These results demonstrate that intracellular L . pneumophila are highly resistant to the bactericidal effects of both activated monocytes and antibiotics, alone or in combination.

Gastroenterology, 1988 Jun, 94(6), 1308 - 14
Decreased gastric acid secretion and bacterial colonization of the stomach in severely malnourished Bangladeshi children; Gilman RH et al.; To assess the effect of malnutrition on gastric acidity and gastric bacterial colonization, we studied 35 severely malnourished Bangladeshi children before (0 wk) and after (3 wk) they received nutritional rehabilitation for 3 wk . These results were compared with those obtained from a similarly examined group of 20 better-nourished Bangladeshi children . Gastric acid output, both basal and after betazole stimulation, was significantly lower in the malnourished group at 0 wk compared with the better-nourished children (p less than 0.01): basal 0.22 vs . 0.52 mEq HCl/h and stimulated 0.90 vs . 2.5 mEq HCl/h . Both the concentration of acid and the rate at which gastric juice was secreted were decreased in the malnourished group but serum gastrin levels were not significantly different . After 3 wk, the malnourished children had improved from 61% (+/- 9.0%; SD) to 81% (+/- 8.1%) of expected weight-for-height and were not significantly different than the better-nourished group (86% +/- 11%) . Nevertheless, gastric acid concentration remained depressed in the 3-wk group, although the rate of gastric juice secretion equaled levels observed in the better-nourished group . None of the better-nourished children had detectable gram-negative bacterial colonization of their gastric juice . In contrast, 26 of 32 (81%) malnourished children at 0 wk were colonized--even after betazole stimulation, 11 of 33 (33%) gastric juice samples yielded viable organisms--suggesting that the decrease in gastric acid output greatly reduced the gastric acid barrier . Interestingly, only 9 of 20 (45%) better-nourished children had gastric juice with basal pH values below 4.0, suggesting that the gastric acid barrier may be an intermittent defense factor in Bangladeshi children.

Am Rev Respir Dis, 1988 Jun, 137(6), 1364 - 70
Tumor necrosis factor causes increased pulmonary permeability and edema . Comparison to septic acute lung injury; Stephens KE et al.; Tumor necrosis factor alpha (TNF), a monokine produced by mononuclear cells in response to bacterial endotoxin (LPS), creates a syndrome similar to septic shock in animal models . To study whether TNF could induce acute lung injury similar to that seen in gram-negative sepsis, we injected recombinant human TNF (rHuTNF alpha) into guinea pigs and monitored arterial blood gases, leukocyte counts, and left atrial (Pla), pulmonary artery (Ppa), and mean arterial pressures (MAP) serially for 8 h . Pulmonary histopathology was assessed microscopically, and cell counts and 125I-labeled albumin (125I-albumin) in bronchoalveolar lavage (BAL) fluid and lung wet/dry weight ratios were determined . Five groups of animals were studied; the 2 TNF groups received high (1.4 X 10(6) U/kg) or low (1.0 X 10(6) U/kg) doses of rHuTNF alpha, the sepsis group received 2 X 10(9) Escherichia coli/kg intravenously, and the control group received saline . An LPS control group receiving 40 ng/kg E . coli LPS was also included because the rHuTNF alpha contained a small amount of LPS as a contaminant . Pulmonary permeability was assessed by studying the Pla and the BAL fluid/plasma 125I-albumin ratio (permeability index) . The permeability index was significantly increased in the high-dose TNF (0.0408 +/- 0.0041, p less than 0.05) and sepsis groups (0.0466 +/- 0.0068, p less than 0.01) relative to controls (0.0215 +/- 0.0028) . The wet/dry lung weight ratios were also significantly increased in the high-dose TNF (6.07 +/- 0.29, p less than 0.05) and sepsis groups (6.22 +/- 0.30, p less than 0.05) relative to the control group (5.18 +/- 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunol Lett, 1988 Jun, 18(2), 93 - 7
Human--human hybridomas secreting lipid A reactive monoclonal antibodies; Ramachandra RN et al.; Five human-human hybridoma cell lines secreting monoclonal antibodies (mAbs) against lipid A (LA) were produced by cell fusion of Epstein-Barr virus (EBV) transformed human peripheral blood lymphocytes and a human lymphoblastoid cell line KR-4 . All these mAbs were isotyped as IgM(kappa) and reacted with lipopolysaccharides (LPS) and LA of various gram-negative bacteria . Whereas the binding of only four of the five mAbs to solid-phase LA was blocked by polymyxin-B sulphate, the mitogenic effect of LPS and LA on murine B lymphocytes was inhibited by all five mAbs . These results demonstrate that the human immune system recognizes at least two common epitopes in lipid A of various gram-negative bacteria.

J Leukoc Biol, 1988 Jun, 43(6), 547 - 56
Bacterial lipopolysaccharide enhances chemoattractant-induced elastase secretion by human neutrophils; Fittschen C et al.; Bacterial lipopolysaccharide (LPS) has previously been shown to enhance a number of chemoattractant-induced responses by human neutrophils . The possible role of elastase, a neutral protease with broad substrate specificity, in neutrophil-mediated vascular injury of a variety of diseases prompted us to examine a) whether or not LPS enhances the direct chemoattractant-induced secretion of elastase, b) the quantitative requirements of LPS and chemotactic factors, and c) some structural requirements of LPS for this effect . Our results show that LPS at 10 ng/ml and above, enhanced formyl-methionyl-leucyl-phenylalanine-induced neutrophil secretion of elastase, as well as secretion of myeloperoxidase and vitamin B12-binding protein . This effect was independent of cytochalasins or surface stimulation, and thus may occur during chemotactic factor stimulation in vivo . LPS also enhanced neutrophil secretory responses to the complement fragments C5a, C5a des arg, and, to a lesser degree, to leukotriene B4 and platelet-activating factor . This enhancement effect appeared to require the presence of the lipid A moiety and/or parts of the core polysaccharide but not the O-antigen portion of the LPS molecule . Our findings identify a possible LPS-dependent mechanism of neutrophil elastase-mediated tissue injury in Gram-negative infections.

Biochemistry, 1988 May 17, 27(10), 3826 - 33
Alternative substrate and inhibition kinetics of aminoglycoside nucleotidyltransferase 2''-I in support of a Theorell-Chance kinetic mechanism; Gates CA et al.; Aminoglycoside nucleotidyltransferase 2''-I conveys multiple antibiotic resistance to Gram-negative bacteria because the enzyme adenylylates a broad range of aminoglycoside antibiotics as substrates {Gates, C . A., & Northrop, D . B . (1988) Biochemistry (preceding paper in this issue)} . The enzyme also catalyzes the transfer of a variety of nucleotides {Van Pelt, J . E., & Northrop, D . B . (1984) Arch . Biochem . Biophys . 230, 250-263} . This doubly broad substrate specificity makes it an excellent candidate for application of the alternative substrate diagnostic {Radika, K., & Northrop, D . B . (1984) Anal . Biochem . 141, 413-417} as a means to determine its kinetic mechanism . The kinetic patterns presented here are composed of one set of intersecting lines and one coincident line and are consistent with a Theorell-Chance kinetic mechanism in which nucleotide binding precedes aminoglycosides, pyrophosphate is released prior to the nucleotidylated aminoglycoside (Q), and turnover is controlled by the rate-limiting release of the final product . Substrate inhibition by tobramycin (B) is partial and uncompetitive versus Mg-ATP, indicating that B binds to the EQ complex, but not in the usual dead-end fashion common to an ordered sequential release of products; instead, Q may escape from the abortive EQB complex at a finite rate . Dead-end inhibition by neomycin C (I) is also partial and uncompetitive versus Mg-ATP but is slope-linear, intercept-hyperbolic, partial noncompetitive versus gentamicin A; both kinetic patterns signify the formation of a partial abortive EQI complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1988 May 17, 27(10), 3820 - 5
Substrate specificities and structure-activity relationships for the nucleotidylation of antibiotics catalyzed by aminoglycoside nucleotidyltransferase 2''-I; Gates CA et al.; Aminoglycoside nucleotidyltransferase 2''-I (formerly gentamicin adenylyltransferase) conveys antibiotic resistance to Gram-negative bacteria by transfer of AMP to the 2''-hydroxyl group of 4,6-substituted deoxystreptamine-containing aminoglycosides . The kinetics constants of thirteen aminoglycoside antibiotics and the magnesium chelates of eight nucleotide triphosphates were determined with purified enzyme . Eleven of the antibiotics exhibit substrate inhibition attributed to secondary binding of the aminoglycoside to an enzyme-AMP-aminoglycoside complex . Maximal velocities vary by only 4-fold, versus variation of values of Vmax/Km for the aminoglycosides of nearly 4000-fold, consistent with a Theorell-Chance kinetic mechanism as proposed for this enzyme {Gates, C . A., & Northrop, D . B . (1988) Biochemistry (second of three papers in this issue)} with the added specification that the binding of aminoglycosides is in rapid equilibrium . Under these conditions, Vmax/Km becomes kcat/Kd, where kcat is the net rate constant for catalysis (but not turnover) and Kd is the dissociation constant of aminoglycosides from a complex with enzyme and nucleotide . Values of kcat fall closely together into three distinct sets, with the 3',4'-dideoxygentamicins greater than gentamicins greater than kanamycins . These sets reflect unusual structure-activity correlations which are specific for catalysis but have nothing to do with the maximal velocity of this enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell, 1988 May 6, 53(3), 347 - 56
Capsule loss in H . influenzae type b occurs by recombination-mediated disruption of a gene essential for polysaccharide export; Kroll JS et al.; The capsulation locus cap in H . influenzae type b contains directly repeated segments of DNA flanking a bridge region . Here we show that this bridge region contains a gene, bexA, encoding a 24.7 kd protein essential for export of capsular polysaccharide . bexA is disrupted, with loss of part of its coding sequence, in the spontaneous reduction of the duplicated cap locus to single-copy that accompanies loss of capsule expression . The predicted amino acid sequence of BexA aligns significantly with that of MalK from E . coli and with HisP and OppD of S . typhimurium . Thus, polysaccharide export might occur via an energy-dependent transporter with similarities to those identified for the import of various substrates into Gram-negative bacteria, BexA being the "energizer" of the transporter.

Antimicrob Agents Chemother, 1988 May, 32(5), 710 - 6
Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonbacteremic patients; Harkonen S et al.; Nine patients with suspected gram-negative bacterial sepsis were studied to determine the safety, pharmacokinetics, and immunogenicity of XMMEN-0E5, a murine immunoglobulin M monoclonal antibody directed against the core lipid A region of bacterial endotoxin . Antibody was administered by single intravenous infusion of 1 to 4 h duration at doses ranging from 0.1 to 15 mg/kg . Five patients had positive blood cultures for gram-negative bacteria, one patient had Torulopsis septicemia, one patient had gram-negative bacterial meningitis, and two patients were culture negative . No evidence of antibody-mediated toxicity was observed at any dose level . The serum half-life of the antibody was approximately 10 h at doses of 0.1 to 7.5 mg/kg and approximately 18 h at a dose of 15 mg/kg . No apparent difference in clearance of antibody was observed between bacteremic and nonbacteremic patients . Human anti-mouse antibodies were detected in the sera of three evaluable patients that received doses equal to or greater than 2.0 mg/kg but not in patients that received lower doses of antibody . This study demonstrates that XMMEN-0E5 is well tolerated at doses from 0.1 to 15 mg/kg and may be immunogenic at doses of 2.0 mg/kg and above . Controlled trials to establish the efficacy of this antibody in the treatment of gram-negative bacteremia are indicated.

Arch Dis Child, 1988 May, 63(5), 533 - 5
Factors influencing colonisation with gentamicin resistant gram negative organisms in the neonatal unit; Isaacs D et al.; The proportion of babies colonised with gentamicin resistant Gram negative organisms in a nursery over a 30 month period did not correlate with the quantity or duration of aminoglycosides used, but it did correlate with two indicators of workload: the number of baby days and a score based on the level of nursing care required . Spread of resistant organisms may be more likely as workload increases.

J Clin Microbiol, 1988 May, 26(5), 1072 - 3
Isolation of an unidentified pink-pigmented bacterium in a clinical specimen; Odugbemi T et al.; An unidentified pink-pigmented bacterium isolated from a clinical specimen is reported . The organism was oxidase, urease, and catalase positive; it grew on Thayer-Martin and MacConkey media . The isolate is possibly similar to an unnamed taxon (G.L . Gilardi and Y.C . Faur, J . Clin . Microbiol . 20:626-629, 1984); however, it had unique characteristics of nonmotility with no flagellum detectable and was a gram-negative coccoid with a few rods in pairs and negative for starch hydrolysis.

Br J Ind Med, 1988 May, 45(5), 325 - 8
Low prevalence of byssinotic symptoms in 12 flax scutching mills in Normandy, France; Cinkotai FF et al.; The concentrations of airborne dust and bacteria were determined in 12 flax scutching mills and in two milk processing plants in Normandy, France . A total of 308 of 340 flax workers and 111 of 113 milk processors volunteered to answer a respiratory questionnaire . Personal exposure to airborne dust in the scutching mills varied from 22.2 mg/m3 to 144 mg/m3 and areal concentrations from 8.92 mg/m3 to 47.1 mg/m3 . The concentration of Gram negative bacteria ranged from 3970 (colony forming units) cfu/m3 to 67,900 cfu/m3 and that of total bacteria from 12,900 cfu/m3 to more than 600,000 cfu/m3 . In all, 20% of the flax scutchers were found, on the basis of the questionnaire, to suffer from persistent cough and 25% from chronic phlegm production . The corresponding figures among milk processors were 3.6% and 4.5% . Unexpectedly, only 12.5% of the scutchers appeared to suffer from byssinotic symptoms even though they were heavily exposed to airborne dust and bacteria . The low prevalence of byssinosis might be due to self selection of the workforce or a relatively low concentration of the causative agent despite high airborne contamination.

Am J Obstet Gynecol, 1988 May, 158(5), 1044 - 9
Labor and infection . II . Bacterial endotoxin in amniotic fluid and its relationship to the onset of preterm labor; Romero R et al.; We have previously reported the detection of endotoxin in the amniotic fluid of patients with gram-negative intraamniotic infection . Endotoxin or lipopolysaccharide is a potent biologic product capable of inducing prostaglandin release from several cell types and, therefore, may be involved in the onset of human parturition in the presence of intraamniotic infection . This article describes a technique for the quantification of endotoxin in amniotic fluid . The method uses a computer-assisted quantification of the turbidimetric reaction between the Limulus amebocyte lysate and endotoxin . Serial dilutions of Escherichia coli endotoxin in culture-negative amniotic fluid were prepared, and the samples were run in the assay . Amniotic fluid was found to enhance the reaction, and a dilution of 1:20 was required for this biologic fluid to behave similarly to pyrogen-free water . The sensitivity of this kinetic turbidimetric technique in the detection of endotoxin in amniotic fluid was 40 pg/ml . This method was applied to the quantification of endotoxin concentration in amniotic fluid in 26 patients with intraamniotic infection and premature rupture of membranes . Patients in active labor had higher concentrations of endotoxin (median = 47,514 pg/ml) than nonlaboring patients (median = 635 pg/ml) (p less than 0.025) . Therefore, women with preterm labor had a higher median concentration of endotoxin in amniotic fluid than patients who were not in labor.

J Trauma, 1988 May, 28(5), 632 - 7
Identification of novel prognostic indicators in burned patients; Peterson VM et al.; The size and depth of burn and patient age are useful early prognostic indicators in burned patients, but have limited value in predicting which patients in a given cohort are likely to die . The objective of this study was to identify additional variables in the first 10 days of burn injury which could better predict patient outcome . Variables consisting of demographic information, routine laboratory data, and clinical observations on 89 burned patients (63 survivors and 26 nonsurvivors) were analyzed . Compared to survivors, nonsurvivors had significantly larger burns (58 +/- 23% vs . 37 +/- 17%; p less than 0.0002) and a higher incidence of Gram-negative septicemia (20 of 26 {77%} vs . 24 of 63 {38%}; p less than 0.001) . Potential prognostic variables were subjected to multivariate logistic regression analysis for each of the first 10 days following burn injury in order to identify a combination of parameters which predicted patient outcome . The regression analyses revealed that, as previously demonstrated, patient age and burn size were significant predictors of mortality on admission and throughout the first 10 days postburn . In addition, absolute monocyte count (AMC), absolute lymphocyte count (ALC), maximum daily temperature (Tmax), and BUN were also significant predictors (p less than 0.05) . These data indicate that logistic regression models can identify simple prognostic variables in burned patients which may improve clinicians' ability to identify high-risk patients early in the course of their burn injuries.

Infect Immun, 1988 May, 56(5), 1394 - 8
Monoclonal antibodies to Actinobacillus actinomycetemcomitans; Place DA et al.; Murine hybridoma cell lines were developed which synthesized monoclonal antibodies against Actinobacillus actinomycetemcomitans-associated antigens . Monoclonal antibodies specific for an antigen(s) common to all A . actinomycetemcomitans isolates tested but not detected on other gram-negative oral plaque microorganisms or other Actinobacillus species were identified . Monoclonal antibodies specific for each serotype group of A . actinomycetemcomitans which did not bind to other Actinobacillus species or oral plaque microorganisms were also identified.

Am J Physiol, 1988 May, 254(5 Pt 2), H954 - 62
Evidence for lack of importance of oxygen free radicals in Escherichia coli endotoxemia in dogs; Novotny MJ et al.; Reactive oxygen species have been proposed as pathophysiological factors responsible for the hypodynamic circulatory response to gram-negative endotoxin . To test this hypothesis, we examined the cardiorespiratory effects of mechanistically different oxygen free radical scavenging agents during Escherichia coli endotoxemia in beagle dogs . Pentobarbital-anesthetized dogs were instrumented for repeated sampling of cardiorespiratory, hematologic, and tissue blood flow (radiolabeled 15-micron microspheres) indexes . Four groups were studied: 1) time-matched control dogs (n = 6); 2) dogs receiving only endotoxin (1.5 mg/kg; n = 6); 3) dogs receiving endotoxin and combination therapy with allopurinol (150 mg/kg) plus superoxide dismutase (5 mg/kg) and catalase (5 mg/kg; n = 6); and 4) dogs receiving endotoxin and deferoxamine (30 mg/kg; n = 5) . Measured variables in control dogs were constant during the 4-h study, whereas endotoxin-injected dogs consistently demonstrated the following: 1) maintained reductions in blood pressure (greater than 45%), left ventricular systolic pressure (greater than 43%), left ventricular maximum rate of pressure development (+/- dP/dtmax) (greater than 41%), cardiac index (greater than 33%), and blood flow in all sampled tissues except liver and skeletal muscle; 2) transient tachypnea, bradycardia, and arterial acidosis; and 3) persistent neutropenia and hemoconcentration . Neither of the free radical scavenging protocols significantly improved measured variables during endotoxemia (P greater than 0.05) . This lack of efficacy suggests that superoxide anion, hydrogen peroxide, and hydroxyl radical may lack primary pathophysiological importance during the development of E . coli endotoxicosis in intact dogs.

Med Clin North Am, 1988 May, 72(3), 581 - 612
Aminoglycoside antibiotics in clinical use; Pancoast SJ; Aminoglycosides are among the most used antibiotics despite competitive pressure from newer beta-lactam agents . The activity profile, pharmacology, toxicity potential, and methods of toxicity prevention of aminoglycosides are well appreciated after three decades . Nephrotoxicity, ototoxicity, and the added costs of drug level monitoring limit wider usage, but great activity against highly antibiotic resistant gram negative bacteria often outweigh these disadvantages and will likely keep aminoglycosides available for the foreseeable future.

J Ultrastruct Mol Struct Res, 1988 May, 99(2), 150 - 5
Ultrastructure of the flagellar basal body complex of Centipeda periodontii; Berthold P et al.; The morphology and insertion of the flagellar basal body complex into the cell wall of Centipeda periodontii was studied by electron microscopy of both negatively and positively stained specimens . Freshly harvested cells were examined either after treatment with 0.2% sodium dodecyl sulfate (SDS) for 2 min and negatively stained with phosphotungstic acid, or after treatment according to standard electron microscopy procedures that included positive staining . Small numbers of flagella were dislocated from the cell body after treatment with SDS . The flagella demonstrated an unusual basal body structure: five rings were attached to a rod in a three-ringed (distal) and two-ringed (proximal) patterns; ring diameters produced a distinctive hourglass shape . The cell envelope was typical for gram-negative bacteria with a cytoplasmic membrane and an outer membrane separated by a peptidoglycan layer . Basal body length and cell wall width were in general agreement, approximately 29 nm . Cell wall width exceeded dimensions previously reported for Escherichia coli; this was attributed to an unusually thick peptidoglycan layer.

J Trauma, 1988 May, 28(5), 571 - 81
Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis; Holman JM Jr et al.; Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion . Plasma fibronectin deficiency exists in such septic patients . We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin . Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin . Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV) . Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr . Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography . Bacterial challenge rapidly resulted in severe systemic hypotension . Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg . Its rate of infusion was periodically adjusted to maintain this hemodynamic status . Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups . Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate . Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.

J Bacteriol, 1988 May, 170(5), 2063 - 9
Identification of putative methanol dehydrogenase (moxF) structural genes in methylotrophs and cloning of moxF genes from Methylococcus capsulatus bath and Methylomonas albus BG8; Stephens RL et al.; An open-reading-frame fragment of a Methylobacterium sp . strain AM1 gene (moxF) encoding a portion of the methanol dehydrogenase structural protein has been used as a hybridization probe to detect similar sequences in a variety of methylotrophic bacteria . This hybridization was used to isolate clones containing putative moxF genes from two obligate methanotrophic bacteria, Methylococcus capsulatus Bath and Methylomonas albus BG8 . The identity of these genes was confirmed in two ways . A T7 expression vector was used to produce methanol dehydrogenase protein in Escherichia coli from the cloned genes, and in each case the protein was identified by immunoblotting with antiserum against the Methylomonas albus methanol dehydrogenase . In addition, a moxF mutant of Methylobacterium strain AM1 was complemented to a methanol-positive phenotype that partially restored methanol dehydrogenase activity, using broad-host-range plasmids containing the moxF genes from each methanotroph . The partial complementation of a moxF mutant in a facultative serine pathway methanol utilizer by moxF genes from type I and type X obligate methane utilizers suggests broad functional conservation of the methanol oxidation system among gram-negative methylotrophs.

Circ Shock, 1988 May, 25(1), 53 - 60
The role of complement in glucan-induced protection against septic shock; Williams DL et al.; Previous studies from our laboratory have shown that glucan will significantly enhance survival, decrease bacteremia, maintain reticuloendothelial function, and reduce histopathology in a murine model of gram-negative septic shock {1} . The present study was undertaken to evaluate the role of complement in glucan-enhanced protection against septic shock . AKR/J mice, which are congenitally C5-deficient, and ICR/HSD mice that were complement-depleted by treatment with purified cobra venom factor (CVF), were injected IP with glucan (50 mg/kg) on days 5 and 3 prior to IP challenge with 1 X 10(8) E . coli . Survival data indicated that glucan (p less than 0.05) increased survival in both C5-deficient and complement-depleted mice . Glucan prophylaxis resulted in a neutrophilic leukocytosis 8 h following E . coli challenge . However, glucan did not alter bone marrow proliferation . We conclude that, 1) glucan's protective effect on survival is not dependent on complement, 2) complement is not required for glucan-induced neutrophilic leukocytosis in this model, and 3) glucan does not enhance bone marrow proliferation in complement-deficient mice.

Infect Immun, 1988 May, 56(5), 1301 - 8
Bacterial activation of human natural killer cells: role of cell surface lipopolysaccharide; Lindemann RA; Culture of human peripheral blood lymphocytes with gram-negative bacteria associated with periodontal disease caused a rapid increase in the cytotoxic potential of natural killer (NK) cells . The NK cells were activated to kill NK-resistant targets, the peak cytotoxicity occurring on day 1 of culture . The addition of anti-Tac, anti-CD3, or anti-OKT-11 antibodies to block activation via the interleukin-2 (IL-2), T-cell, or E rosette receptors had a minimal effect on this inductive process . Anti-IL-2 antiserum was effective in blocking a significant amount, but not all, of the cytotoxicity in bacterium-activated cultures . Modest IL-2 production (5 to 6 National Institutes of Health units) was measured in lymphocyte cultures activated by bacteria, but proliferation was not induced during a 1-week period . When polymixin B sulfate was added to bind and block lipopolysaccharides, bacterium-induced cytotoxicity was completely abrogated for all activating bacteria . In addition, when culture supernatants from Actinobacillus actinomycetemcomitans were tested, activation still occurred . However, again, this activation was totally inhibited by polymixin B sulfate . Monocytes were also activated by bacteria to produce tumor necrosis factor (TNF) . To exclude the possibility that TNF was responsible for cytotoxicity, an antiserum to TNF was added to cocultures of bacteria and lymphocytes with adherent cells removed . The antiserum had no effect on the inductive process . In addition, exogenous TNF did not kill M14 targets . These results suggest that bacterial cell surface lipopolysaccharides provide a major activation signal for NK cells to enhance cytotoxicity.

J Lab Clin Med, 1988 May, 111(5), 584 - 90
Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study; Vadas P et al.; Lipocortins, a group of corticosteroid-induced phospholipase-inhibitory proteins, are thought to play a prominent role in the mediation of the anti-inflammatory effects of steroids . The synthesis and release of these proteins may represent a major endogenous mechanism of regulation of extracellular phospholipase A2 (PLA2) activity . Because soluble PLA2 activity has been associated with circulatory collapse in hyperphospholipasemic conditions, such as septic shock and pancreatitis, we examined the relationship between circulating PLA2 activity and adrenocortical function . In a prospective study of 10 episodes of septic shock, serum PLA2 and cortisol levels correlated significantly in all survivors (p less than 0.0001), whereas such a correlation was absent in all nonsurvivors (p less than 0.07) . No significant correlation of cortisol and adrenocorticotropic hormone (ACTH), or PLA2 and ACTH, was found in any patient, suggesting that the stimulus for cortisol release arises from outside the hypothalamic-pituitary axis . These data suggest that, in human beings, the regulation of soluble PLA2 activity may be mediated by adrenocortical hormones, perhaps through the intermediary action of lipocortins.

J Immunol Methods, 1988 Apr 6, 108(1-2), 153 - 8
Concurrent assessment of inner and outer membrane permeabilization and bacteriolysis in E . coli by multiple-wavelength spectrophotometry; Lehrer RI et al.; We developed a dual wavelength spectrophotometric assay that permitted beta-lactamase and beta-galactosidase activities to be measured concurrently in a single sample . We also constructed a target cell, E . coli ML-35p, that was substantially cryptic for its periplasmic beta-lactamase and cytoplasmic beta-galactosidase unless outer membrane (beta-lactamase) or inner membrane (beta-galactosidase) permeabilization occurred . By applying the spectrophotometric assay to whole target cells, we could ascertain the kinetics of inner and outer membrane permeabilization by biological agents, including serum, polymyxin B and mellitin . By monitoring the reactions at an additional wavelength, we could also follow the kinetics of serum-mediated bacteriolysis . These experiments illustrate the principle of multiple wavelength spectrophotometry and provide examples of its use to monitor and dissect the action of biological agents on a gram-negative bacterium.

J Clin Gastroenterol, 1988 Apr, 10(2), 197 - 200
Acute cholangitis: a histopathologic study; Shimada H et al.; We studied the histology of the liver in acute cholangitis to determine whether microscopic changes corresponded to the patients' clinical status . Thirty-four cases of acute cholangitis were divided clinically into mild and severe cases . The incidence of endotoxemia, gram-negative bacteremia, disseminated intravascular coagulation (DIC), and hepatic failure were significantly higher in the severe cases than in the mild ones . In the severe cases, the incidence of neutrophile infiltration into the sinusoids (12 of 16) and microabscesses in the lobules (11 of 16) was also significantly higher than in the mild cases . Finally, the incidence of portal thrombosis (10 of 16) and massive necrosis of the hepatic cells (5 of 16) was significantly higher in the severe than in the mild cases, especially in the patients who later died . The results suggest that neutrophilic infiltration into the sinusoid and microabscesses in the lobules is a characteristic finding in severe cholangitis.

J Am Vet Med Assoc, 1988 Apr 1, 192(7), 923 - 5
Gentamicin-induced nephrotoxicosis in a cow; Hinchcliff KW et al.; Gentamicin-induced nephrotoxicosis developed in a mature Holstein cow without evidence of preexisting renal disease . Factors possibly predisposing to the nephrotoxicosis included coadministration of a nonsteroidal anti-inflammatory drug and severe gram-negative bacterial sepsis . The cow recovered after prolonged hospitalization.

Minerva Med, 1988 Apr, 79(4), 261 - 2
{Infections in acute leukemia}; Garavelli PL; Opportunistic infections are a major cause of mortality in leucosis patients . Most such infections are caused by gram negative schizomycetes and fungi and granulocytopenia is the main risk factor . The onset of such infections in 36 patients with acute leukemia is examined.

J Gen Microbiol, 1988 Apr, 134 ( Pt 4), 943 - 52
Plasmid analysis and cloning of the dichloromethane-utilization genes of Methylobacterium sp . DM4; Galli R et al.; The dichloromethane (DCM)-utilizing facultative methylotroph Methylobacterium sp . DM4 was shown to contain three plasmids with approximate size of 120 kb, 40 kb and 8 kb . Curing experiments suggested that the DCM-utilization character was correlated with the possession of an intact 120 kb plasmid . The DCM-utilization genes were cloned on the broad-host-range vector pVK100 . Plasmid pME1510, a recombinant plasmid carrying a 21 kb HindIII fragment complemented DCM-utilization-negative derivatives of Methylobacterium sp . DM4 and conferred the DCM-utilization-positive phenotype to a number of Gram-negative methylotrophic bacteria . In Southern hybridization experiments with pMe1510 as a probe, chromosomal DNA from Methylobacterium sp . DM4 gave definite signals while purified plasmid DNA did not . Plasmid pME1510 did not hybridize with total DNA from a cured DCM-non-utilizing derivative of Methylobacterium sp . DM4 . It is concluded that the DCM-utilization genes are located on the chromosome or on a megaplasmid . Curing procedures thus led to the formation of a chromosomal or megaplasmid deletion larger than 21 kb and covering the DCM-utilization genes or to the loss of an undetected megaplasmid.

Bioorg Khim, 1988 Apr, 14(4), 437 - 52
{Synthesis of lipid A analogs: achievements and perspective}; Gorbach VI et al.; Data on the synthesis of analogues of lipid A, a biologically active fragment of gram-negative bacteria's lipopolysaccharides, are summarized . Main types of the compounds obtained are systematized, and problems of the synthesis of various parts of the molecule considered . The results of studying biological activity of lipid A analogues are discussed, which led to some conclusions on the structure-function relation . Perspectives of further studies are briefly outlived.

Int J Clin Pharmacol Ther Toxicol, 1988 Apr, 26(4), 176 - 84
Folklore therapeutic indigenous plants in periodontal disorders in India (review, experimental and clinical approach); Patel VK et al.; Though a number of plants and their parts are used for dental ailments among population in rural and urban areas of developing countries, in India however, the most common house-hold, road-side plants are mango (Mangifera indica), neem (Azadirachta indica; Melia azadirachta), ocimum (Ocimum basilicum), tea-dust (Camellia sinensis) and uncommonly murayya, i.e., currey leaf (Murayya koenigi) {Chopra et al . 1958, Kirtikar and Basu 1935, Nadakarni 1954, Satyavati 1984} . The leaves of these plants are folded and brushed (massage with teadust) against the teeth . Therefore, the present study is restricted only to the fleshy leaf extracts {Jindal et al . 1975} (except tea) of these plants inspite of certain limitations in the methodology and arbitrations in the microbial identification and isolation in the light of recent advances in folk dentistry . The investigation was carried out in two parts: 1) Experimental study: The efficacy of various dentifrices (commonly available in the market) and the potentiating effect of the leaf extract (LE) of the aforesaid indigenous plants when amalgamated with the tooth-paste against pathogens, were investigated . Further, the protection afforded by the said plant extracts (PE) over the conventional allopathic medicines on the human plaque cultures and gram negative bacteria from patients were studied . 2) Clinical study: The therapeutic effects of the said PE (individually) on clinical application among severely infected patients were examined.

Microbiol Sci, 1988 Apr, 5(4), 100 - 3
Bdellovibrios: recycling, remodelling and relocalizing components from their prey; Diedrich DL; The predatory bdellovibrios acquire all their growth requirements by preying upon other Gram-negative bacteria . They reutilize biosynthetic monomers, remanufacture the prey's lipopolysaccharide, and relocalize specific outer membrane proteins from the prey to their own outer membranes . This lifestyle occurs without loss of the biosynthetic potential for axenic growth.

Xenobiotica, 1988 Apr, 18(4), 407 - 16
Biotransformation of chlordecone by Pseudomonas species; George SE et al.; 1 . Six-month chlordecone enrichment cultures with added chlordecone yielded several Gram-negative micro-organisms that were resistant to and/or degraded chlordecone . 2 . Three Pseudomonas spp . were further characterized for their chlordecone degrading ability . 3 . Chlordecone and two derivatives, Mirex and Kelevan, supported growth of these strains . 4 . All three Pseudomonas spp . decreased the concentration of chlordecone in the medium after 14 days incubation, as determined by h.p.l.c . analysis when it was added either as sole carbon source or in the presence of medium supplements.

Nature, 1988 Mar 24, 332(6162), 362 - 4
Stimulus-dependent myristoylation of a major substrate for protein kinase C; Aderem AA et al.; Bacterial lipopolysaccharide (LPS), the major surface component of gram-negative bacteria, exerts a profound effect on the immune system by enhancing the release of proteins and arachidonic acid metabolites from macrophages (for review see ref . 1) . The molecular mechanism(s) by which LPS induces these various secretory responses is unknown . We previously reported that LPS promotes the myristoylation of several macrophage proteins including one with a relative molecular mass (Mr) of 68K2 . We have now found that by several criteria the 68K myristoylated protein is similar or identical to the 80/87K protein, a major specific substrate for protein kinase C (PKC) found in brain and fibroblasts (for review see refs 7,8) . We have also found that the myristoylated PKC substrate is quantitatively associated with the membrane fraction . Myristoylation of the PKC substrate may target it to the membrane and constitute a transduction pathway for stimulus-response coupling.

Rev Infect Dis, 1988 Mar-Apr, 10(2), 424 - 7
Septic anaerobic jugular phlebitis with pulmonary embolism: problems in management; Bach MC et al.; Anaerobic gram-negative bacillary bacteremia and multiple septic pulmonary emboli developed rapidly in two previously healthy young men after an episode of pharyngitis . One patient developed proptosis and subsequent uniocular blindness . In both cases facial swelling was an early sign of jugular vein involvement . In patients not responding to antibiotic therapy, systemic anticoagulation or surgical venous ligation may be potentially useful as an additional therapeutic measure . Septic jugular vein phlebitis is a serious condition that requires early recognition and rapid institution of appropriate therapy.

J Bacteriol, 1988 Mar, 170(3), 1129 - 36
Turgor pressure responses of a gram-negative bacterium to antibiotic treatment, measured by collapse of gas vesicles; Pinette MF et al.; The internal hydrostatic pressure of Ancylobacter aquaticus was measured by collapsing the gas vesicles with an externally applied pressure . Turgor pressure was measured in conjunction with various antibiotic treatments to elucidate some aspects of the biophysics of gram-negative cell wall function . Differences in the effects of these drugs either alone or in combination with other treatments were related to known biochemical activities of these drugs . Our previous work, demonstrating a heterogeneous cellular response to beta-lactam antibodies, was confirmed and extended . Most of the cell wall growth-inhibiting antibiotics resulted in some cells (those in component I) developing a higher pressure, while the remainder (those in component II) lost turgor . Although the fraction of the cells in each component varied a little from subculture to subculture, it did not vary with time or choice of antibiotic treatment . Mecillinam gave a nearly monophasic response . All antibiotics blocking macromolecular synthesis gave monophasic curves . The 50% collapse pressure in some cases, however, was lower higher, or the same as the control.

Pathol Biol (Paris), 1988 Mar, 36(3), 250 - 4
{Electrophoretic behavior of beta-lactamases in gram-negative bacteria}; Vedel G et al.; The ongoing discoveries of new beta-lactamases, mainly penicillinases, in Gram-negative bacteria has emphasized the problem of their precise identification, and thus their phylogeny . Crude extracts, prepared by sonication, of 14 plasmid beta-lactamases, types TEM, carbenicillinases (CARB or PSE) and oxacillinases (OXA) were analysed by a simple, rapid (3.5 to 4 hours) method of electrophoresis on polyacrylamide (7%) agarose (1.4%) gels, using Tris-glycine buffer at pH 8.7 . Preliminary serial dilutions were made to determine enzymic activity levels . Enzymes were then characterized by their relative electrophoretic mobilities . These mobilities had coefficients of variability between 2% and 10%, ranged from 5 to 61, and were correlated with their isoelectric points (pI) . Thus, the lower the pI is, the greater the mobility is . Despite the high resolving power of the polyacrylamide-agarose gel system, enzymes with similar pI's and of similar types (PSE-1 and CARB-3, or OXA-1 and OXA-4) or different types (SHV-1 and OXA-6) could not be distinguished on the basis of their mobilities . However, this technique provides for rapid and easy identification of the major penicillinases in Gram-negative bacteria . A combination of polyacrylamide-agarose gel electrophoresis and pH gradient electrophoresis (titration curve) could provide a powerful approach to the study of the molecular structure of these enzymes.

Am J Med, 1988 Mar, 84(3 Pt 2), 581 - 9
Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients; Anaissie EJ et al.; A three-arm prospective randomized trial was designed to compare the efficacies of piperacillin plus vancomycin, ceftazidime plus vancomycin, or all three drugs as initial therapy for fever in neutropenic cancer patients . The objectives were to determine whether a broad-spectrum penicillin was as effective as a broad-spectrum cephalosporin and whether two beta-lactam antibiotics were more effective than one . Four hundred and seventy of the 519 febrile episodes entered in the study could be evaluated for response . Ceftazidime plus vancomycin was significantly more effective than piperacillin plus vancomycin, considering all febrile episodes (79 percent versus 61 percent, p = 0.001), documented infections (79 percent versus 57 percent, p = 0.004), gram-negative infections (88 percent versus 47 percent, p = 0.001), and bacteremias (81 percent versus 51 percent, p = 0.01) . The addition of piperacillin to ceftazidime (piperacillin plus ceftazidime and vancomycin versus ceftazidime plus vancomycin) did not improve the response rate and was associated with a significantly higher incidence of skin rash . Vancomycin plus ceftazidime provides adequate antibiotic coverage for initial treatment of fever in neutropenic patients . This combination was equally effective, less expensive, and less toxic than the double beta-lactam combination used in this study.

Transplantation, 1988 Mar, 45(3), 570 - 4
Selective bowel decontamination to decrease gram-negative aerobic bacterial and Candida colonization and prevent infection after orthotopic liver transplantation; Wiesner RH et al.; Gram-negative bacterial and fungal infections are a major cause of morbidity and mortality following liver transplantation . We therefore used selective bowel decontamination (SBD) to eliminate the endogenous source of gram-negative aerobic bacteria and Candida pathogens in an attempt to reduce the high incidence of infection related to these organisms . Thirty consecutive patients undergoing liver transplantation were treated with SBD starting 3 days prior to donor search and continuing for 21 days postliver transplantation . Selective bowel decontamination consisted of administering nonabsorbable antibiotics (Polymixin E, gentamicin, Nystatin) and a low bacterial diet . Surveillance cultures of the throat and rectum were obtained to monitor efficacy of selective bowel decontamination . In addition, in the posttransplant period, tracheal, wound, blood, and bile cultures were obtained to screen for gram-negative bacterial and Candida colonization and infection . Our baseline surveillance culture revealed that 29/30 (97%) of recipients were colonized with gram-negative aerobic bacteria and 16/30 (53%) with Candida . Three days after selective bowel decontamination was started, 26/30 (87%) were free of gram-negative bacteria, and 100% were free of Candida colonization of the gastrointestinal tract . There was a similar reduction in the oropharyngeal gram-negative aerobic bacteria and Candida colonization . In the first 30 days following liver transplantation, gram-negative infections were not diagnosed in any of our patients . Following discontinuation of SBD, recolonization of the gastrointestinal tract with gram-negative aerobic bacteria and Candida occurred within 5 days in 26/28 (90%) and 11/28 (35%), respectively . Our study suggests that prophylactive administration of nonabsorbable antibiotics will markedly reduce gram-negative aerobic bacterial and Candida colonization and appears to reduce the high incidence of infection related to these organisms in the early posttransplant period.

Hematol Oncol Clin North Am, 1988 Mar, 2(1), 81 - 100
Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome; Leung DY et al.; The HIE syndrome is a rare disorder characterized by extremely high serum IgE levels; recurrent serious infections, primarily involving the skin and sinopulmonary tract; and chronic eczematoid dermatitis dating from early infancy . The most common organisms that infect these patients are S . aureus and C . albicans . In addition, they have increased susceptibility to infection with H . influenzae, S . pneumoniae, enteric gram-negative rods, herpesviruses, and a variety of fungal organisms . The infections are frequently deep-seated, with abscess formation in the case of skin infection and pneumatocele formation in the case of pneumonias . Osteomyelitis, septic arthritis, and visceral abscesses are also seen but less frequently . Associated features of this syndrome are coarse facies, growth retardation, osteoporosis, keratoconjunctivitis, and eosinophilia . The immunologic basis of the HIE syndrome is still speculative . It is believed that the elevated IgE levels reflect a T-cell imbalance characterized by T-cell activation and a deficiency of suppressor T cells to inhibit IgE production . The propensity for recurrent infection may be related to a unique abnormality in the humoral immune system: excessive production of IgE directed to S . aureus and other infectious organisms with a concurrent deficit in their ability to synthesize protective IgG antibody against the same organisms . The fluctuating neutrophil chemotactic abnormality found in these patients may be secondary to the underlying T-cell defect with secretion of chemotactic inhibitor substances from mononuclear cells . Alternatively, the interaction of infectious agents with IgE on the surface of Fc epsilon R-bearing immune effector cells results in the release of inflammatory mediators that impair local host immune response . Activation of the immune system may also contribute to the associated features in this syndrome via the secretion of mediators that regulate connective tissue production and bone mineralization . Further studies will be needed before we completely understand the pathogenesis of HIE syndrome . Therapy primarily involves use of prophylactic anti-S . aureus antibiotics and the use of intravenous antibiotics, antifungal agents, or antiviral agents during acute infections . Surgical drainage or resection of deep-seated infections are frequently indicated . In patients who do not respond to conservative management, there may be a role for intravenous gammaglobulin and/or plasmapheresis.

Antimicrob Agents Chemother, 1988 Mar, 32(3), 397 - 9
Oligonucleotide probes (TEM-1, OXA-1) versus isoelectric focusing in beta-lactamase characterization of 114 resistant strains; Ouellette M et al.; Oligonucleotide probes specific for detection of the TEM-1 and OXA-1 beta-lactamase genes were compared with isoelectric focusing in 114 gram-negative beta-lactamase-producing strains representing at least 16 species . Correlations of 96 and 100% with isoelectric points were found for the TEM-1 and OXA-1 probes, respectively.

J Clin Microbiol, 1988 Mar, 26(3), 564 - 6
Evaluation of a rapid tube assay for presumptive identification of Escherichia coli from veterinary specimens; Iritani B et al.; Three hundred sixty-six isolates of gram-negative, oxidase-negative bacteria from veterinary specimens were tested by a tube test for identification as Escherichia coli by production within 60 min of indole, beta-galactosidase, and beta-glucuronidase . The test correctly identified 255 of 269 isolates of E . coli (95% sensitivity) and correctly indicated that 97 of 97 isolates were not E . coli (100% specificity) . We conclude that production of indole, beta-galactosidase, and beta-glucuronidase as measured by a rapid tube test is useful for identification of E . coli from veterinary specimens.

J Clin Microbiol, 1988 Mar, 26(3), 405 - 8
Selective medium with DNase test agar and a modified toluidine blue O technique for primary isolation of Branhamella catarrhalis in sputum; Soto-Hernandez JL et al.; A selective medium with DNase test agar and incorporating vancomycin (10 micrograms/ml), trimethoprim (8 micrograms/ml), and amphotericin B (2 micrograms/ml) supported the growth of 305 Branhamella catarrhalis isolates . A modified toluidine blue O technique was used after 48 h of incubation in CO2 to overlay suspected B . catarrhalis colonies . A metachromatic color change was observed in 15 min, indicating DNase production . In 200 unselected sputum samples of hospitalized patients, this method was compared with routine microbiologic procedures; 31 B . catarrhalis isolates were recovered with the method, compared with 22 isolated from the clinical laboratory . This medium will be particularly useful for culture of sputum, which shows inflammatory cells and gram-negative diplococci on Gram-stained smears.

Genetika, 1988 Mar, 24(3), 405 - 13
{Mapping of the regions participating in the replication, maintenance and mobilization of the R-plasmid pBS222 with a wide circle of bacterial hosts}; Polevoda BV et al.; The analysis of the deletion derivative of pBS359 obtained as a result of sodium bisulphite mutagenesis and of recombinant derivatives pBS361-pBS363 permitted to map genes of the broad-host-range pBS222 plasmid which participate in replication, maintenance and mobilization . These genes are localized within the coordinates 0.2 to 2.5 kb in the region including a unique HindIII restriction site on the pBS222 physical map . Possible participation of the in vitro synthesized polypeptides in providing functions of cosmopolitanism and mobilization is being considered . Putative molecular-genetic structure of pBS222 and the presence of active recombination points are discussed, as well as the merits of the employed method for obtaining derivatives . The derivatives obtained and recombinant plasmids belong to the smallest plasmids which may be inherited in various gram-negative bacteria.

J Bacteriol, 1988 Mar, 170(3), 1275 - 8
A clinical isolate of transposon Tn5 expressing streptomycin resistance in Escherichia coli; Genilloud O et al.; The central region of transposon Tn5 carries three antibiotic resistance markers: neo, ble, and str . The str gene codes for a phosphotransferase that inactivates streptomycin . This activity is phenotypically expressed in several gram-negative bacteria but not in Escherichia coli . We identified a Tn5 variant in E . coli clinical isolates that express streptomycin resistance . This transposon carries a 6-base-pair deletion within the str gene, near the 3' end . The same kind of mutation had been previously obtained experimentally from Tn5.

Ann Trop Paediatr, 1988 Mar, 8(1), 1 - 17
Human immunodeficiency virus infection in childhood; Blokzijl ML; Acquired immunodeficiency syndrome is associated with considerable morbidity in infants and children . It is caused by human immunodeficiency virus (HIV) which can be transmitted vertically from mother to infant early in pregnancy . Transmission might also occur via breast milk . Although the exact transmission rate of HIV from mother to infant is not known, HIV can become a major threat to child survival . This threat is already present in Africa where high seroprevalences have been reported among infants and young children . Transmission via blood products is decreasing due to reliable methods of screening donors for HIV antibody . Where these tests are not available, parenteral transmission will increase the incidence of HIV infection . The clinical picture of HIV infection in children presents with failure to thrive, pulmonary interstitial pneumonitis, hepatosplenomegaly and recurrent bacterial infections . These are common manifestations of diseases prevalent in children in Africa where malnutrition and recurrent parasitic infections already cause immunosuppression . Recognition of the syndrome is therefore difficult . There is no available cure for HIV infection . Supportive treatment and relief of pain and suffering are the only means of management at present . Prevention of spread of the illness to infants and young children is therefore of paramount importancePIP: This review describes the transmission, clinical picture and immunological abnormalities of HIV infection in children in general, and the special problems of AIDS in African children . The review begins with a thorough introduction to the epidemiology of AIDS . Transmission to children generally involves vertical transmission by placental transfer or transmission of HIV via transfusion of blood and blood products, or by contaminated needles . Casual transfer is unknown, and only a few cases of transmission via breast milk are known . The clinical picture of HIV infection in infants and children differs from that in adults in 3 important aspects: earlier onset, different clinical presentation and existence of AIDS embryopathy . The average onset was 5 months of age . The most common symptoms in young children are chronic interstitial pneumonitis without demonstrable etiology, hepatomegaly, failure to thrive, adenopathy, diarrhea, oral or perineal thrush, eczema and thrombocytopenia . The common opportunistic infections are pneumocystis carinii pneumonia, cytomegalovirus, Epstein-Barr virus, Cryptosporidium diarrhea, pyogenic infections of the middle ear and gram-negative septicemia . Several infections seen in adult AIDS cases are rare in children: mycobacterium avium-intracellulare, toxoplasma gondii, hepatitis B, as well as Kaposi's sarcoma, malignant lymphoma and cardiac abnormalities . The AIDS embryopathy or HIV dysmorphic syndrome is characterized by immunological abnormalities, growth failure, and craniofacial dysmorphism, particularly microcephaly, prominent box-like forehead, hypertelorism, flattened nasal bridge, obliquity of the eyes, blue sclerae and patulous lips . AIDS in African children is extremely difficult to diagnose because of similarities between the presenting symptoms and those commonly seen in sick children there, many of whom are also immune compromised . Where serotesting is available, the picture is complicated by cross reaction between the test agents and some factor found in sera from malaria patients . Seropositivity in some areas is high, increased by the prevalence of transfusion and injection treatments . Diagnosis is made more difficult by lack of laboratory facilities and difficulties in follow-up for pediatric patients . The CDC definitions of AIDS and ARC, and the WHO/CDC definitions of AIDS are appended .

Diagn Microbiol Infect Dis, 1988 Feb, 9(2), 87 - 96
In vitro activity of amdinocillin in combination with other beta-lactam antibiotics against aminoglycoside-susceptible and resistant gram-negative bacteria; Nachamkin I et al.; Amdinocillin alone and in combination with other beta-lactam antibiotics was tested for in vitro activity against aminoglycoside-susceptible and resistant gram-negative bacteria . Amdinocillin alone or in combination with ampicillin, ticarcillin, piperacillin, cefazolin, cefoxitin, and cefamandole had little to no activity against aminoglycoside-resistant E . coli, E . cloacae, K . pneumoniae, and S . marcescens . There was better activity with aminoglycoside-susceptible organisms, however, Overall, there was significantly more antagonism of amdinocillin combinations when tested with aminoglycoside-resistant organisms than with aminoglycoside-susceptible strains.

Antimicrob Agents Chemother, 1988 Feb, 32(2), 236 - 40
Amikacin pharmacokinetics during continuous ambulatory peritoneal dialysis; Smeltzer BD et al.; The pharmacokinetics of amikacin were investigated in five stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . Each patient was studied after the administration of 7.5 mg of amikacin per kg by both the intravenous (i.v.) and intraperitoneal (i.p.) route, allowing a 1-month washout period between doses . No differences in amikacin half-life, volume of distribution, total body clearance, or time-averaged peritoneal clearance were noted between the two routes of administration . After a 5-h dwell period, bioavailability as calculated by the area under the curve for i.p . amikacin was 53 +/- 14.0% . Amikacin pharmacokinetics parallel those of other aminoglycosides in CAPD patients when the drug is administered either i.v . or i.p . Single loading doses of amikacin administered i.v . to uninfected CAPD patients provided therapeutic serum and dialysate levels for many aerobic gram-negative organisms for up to 72 h . Because of the variability of absorption of i.p . administered amikacin, single i.p . doses are not recommended.

Am J Surg, 1988 Feb, 155(2), 343 - 7
Circulating immune complex, endotoxin, and biliary infection in patients with biliary obstruction; Ohshio G et al.; Immunoglobulin A-containing circulating immune complexes, immunoglobulin G-containing circulating immune complexes, and endotoxin were measured in the sera of patients with obstructive jaundice . The bile of patients with percutaneous transhepatic biliary drainage was also cultured for bacteriologic studies . There was a significantly positive correlation between the endotoxin levels and both immunoglobulin A-containing circulating immune complex and immunoglobulin G-containing circulating immune complex . The endotoxin levels of the patients with gram-negative infections were significantly increased compared with those of the patients with sterile cultures . The immunoglobulin G-containing circulating immune complex levels of the patients with bacteria in bile were significantly increased compared with those of the patients with sterile cultures . The immunoglobulin A-containing circulating immune complex levels of the patients with bacteria in bile were slightly increased, but the difference did not reach statistical significance . These results indicate that one of the causes of increased circulating immune complex levels may be endotoxemia in combination with biliary infection in patients with biliary obstruction.

Am J Surg, 1988 Feb, 155(2), 314 - 21
Endotoxemia in obstructive jaundice . Observations on cause and clinical significance; Thompson JN et al.; Perioperative endotoxemia was detected in 24 of 40 patients who underwent operation for obstructive jaundice (bilirubin level greater than 5.8 mg/dl) . Endotoxemia was associated with an increased admission serum bilirubin level (p less than 0.05) and white blood cell count (p less than 0.05) and a decreased hematocrit value (p less than 0.05), but there was no significant association with other established preoperative risk factors . Patients with preoperative endotoxemia had a decreased immunoglobulin M anti-J5 endotoxin titer (p less than 0.05) and a decreased serum bile acid concentration (p less than 0.05) . Preoperative endotoxemia was associated with reduced creatinine clearance before and after operation (p less than 0.05) . There was no association between endotoxemia and clinical sepsis, gram-negative infection, or small-bowel colonization . Patients who died had increased preoperative serum fibrin degradation products (p less than 0.05).

Br J Surg, 1988 Feb, 75(2), 177 - 80
Effect of splenectomy on gram-negative bacterial clearance in the presence and absence of sepsis; Cheslyn-Curtis S et al.; Severe sepsis leads to depression of the reticulo-endothelial system (RES) with delayed bloodstream clearance of particulate matter and bacteria . Splenectomy results in increased susceptibility to infection with encapsulated organisms but its effect on the resistance to postoperative Gram-negative infection has been little studied . We have investigated the effect of splenectomy on RES function by measurement of plasma fibronectin concentrations and bacterial clearance in the presence and absence of sepsis . In experiment 1, rabbits underwent splenectomy (n = 8) or laparotomy only (n = 8) 4 weeks before a second laparotomy . In experiment 2, animals had either splenectomy (n = 8) or laparotomy only (n = 8) followed 4 weeks later by devascularization of the appendix (sepsis) . Plasma fibronectin concentrations and the blood clearance and organ distribution of an intravenous injection of 75Se-labelled viable Escherichia coli (2-3 X 10(8) colony forming units (c.f.u.} were measured 24 h after the second operation . Splenectomy resulted in: (1) a persistent reduction in plasma fibronectin concentration in the presence and absence of sepsis, and (2) a delay in the bloodstream clearance with reduced hepatic (Kupffer cell) uptake of E . coli which was exaggerated in the septic splenectomized animal . It is concluded that the spleen may be important for Gram-negative bacterial clearance, possibly related to its influence on plasma fibronectin concentration and Kupffer cell function.

J Bioenerg Biomembr, 1988 Feb, 20(1), 1 - 18
Structure and mechanism of bacterial periplasmic transport systems; Ames GF; Bacterial periplasmic transport systems are complex, multicomponent permeases, present in Gram-negative bacteria . Many such permeases have been analyzed to various levels of detail . A generalized picture has emerged indicating that their overall structure consists of four proteins, one of which is a soluble periplasmic protein that binds the substrate and the other three are membrane bound . The liganded periplasmic protein interacts with the membrane components, which presumably form a complex, and which by a series of conformational changes allow the formation of an entry pathway for the substrate . The two extreme alternatives for such pathway involve either the formation of a nonspecific hydrophilic pore or the development of a ligand-binding site(s) on the membrane-bound complex . One of the membrane-bound components from each system constitutes a family of highly homologous proteins containing sequence domains characteristic of nucleotide-binding sites . Indeed, in several cases, they have been shown to bind ATP, which is thus postulated to be involved in the energy-coupling mechanism . Interestingly, eukaryotic proteins homologous to this family of proteins have been identified (mammalian mdr genes and Drosophila white locus), thus indicating that they perform a universal function, presumably related to energy coupling in membrane-related processes . The mechanism of energy coupling in periplasmic permeases is discussed.

Transplantation, 1988 Feb, 45(2), 424 - 9
Antibody immunotherapy of gram-negative bacterial sepsis in an immunosuppressed animal model; Dunn DL; Leukopenic, immunosuppressed recipients of solid organ allografts are at high risk for gram-negative bacterial sepsis, and mortality remains unacceptably high (greater than 30%) . The purpose of this study was to determine whether murine monoclonal antibody (MAb) directed against lipopolysaccharide (LPS, endotoxin) would reduce lethality caused by a septic insult in immunosuppressed mice, and to determine if a specific antibody class would prove more efficacious in this setting . Two MAbs (3-H9, IgG3; 7-B5, IgM) were selected that reacted by ELISA, immunodot blot, and Western blot analysis against the O antigen polysaccharide portion of Escherichia coli 0111:B4 LPS . The 3-H9 MAb, 7B-5 MAb, or sterile saline was administered i.v . to normal or neutropenic Swiss-Webster mice immediately prior to an E coli 0111:B4 bacterial (i.v . or i.p . plus hemoglobin) or LPS (i.v.) challenge . In normal mice, administration of 3-H9 MAb or 7-B5 MAb i.v . immediately prior to a bacterial or endotoxin challenge resulted in a significant increase in the LD50 . Neutropenia lowered the LD50 by nearly one log10 in both the bacteremia and peritonitis models . Both MAbs provided similar protection, raising the LD50 one log10 in neutropenic mice . Thus neutropenic animals receiving either MAb had a mortality nearly identical to that of normal animals receiving saline . No significant difference between the protective capacity of these MAbs was noted in any of the three models . These studies demonstrate that MAbs directed against LPS exert protection during gram-negative bacterial sepsis in either normal or neutropenic animals . In addition, the particular IgG and IgM MAbs examined provided similar protective capacity . Antibody directed against LPS may provide an additive form of therapy that may serve to decrease lethality during clinical gram-negative sepsis in immunosuppressed patients.

Am J Surg, 1988 Feb, 155(2), 187 - 92
The gut as source of sepsis after hemorrhagic shock; Sori AJ et al.; In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock . The organisms cultured were primarily gram-negative . To test the hypothesis that the gut was the source of the bacteria, E . coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock . Their plasma was then assayed for carbon-14 activity . Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock . The mortality rate was 100 percent 80 hours postshock, and all animals had E . coli on subsequent blood culture . The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock . Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels . These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.

J Bacteriol, 1988 Feb, 170(2), 646 - 52
Metabolism of periplasmic membrane-derived oligosaccharides by the predatory bacterium Bdellovibrio bacteriovorus 109J; Ruby EG et al.; Membrane-derived oligosaccharides (MDO), a class of osmotically active carbohydrates, are the major organic solutes present in the periplasm of Escherichia coli and many other gram-negative bacteria when cells are grown in a medium of low osmolarity . Analyses of growing cells of Bdellovibrio bacteriovorus, a gram-negative predator of other bacteria, have confirmed that they also synthesize a characteristic MDO-like class of oligosaccharides . The natural growth environment of bdellovibrios is the periplasm of other gram-negative bacteria . Because of this location, prey cell MDO constitute a potential source of organic nutrients for growing bdellovibrios . Using cells of E . coli whose MDO were 3H labeled, we examined the extent to which B . bacteriovorus 109J metabolizes these prey cell components . Interestingly, there was neither significant degradation nor incorporation of prey cell MDO by bdellovibrios during the course of their intracellular growth . In fact, bdellovibrios had little capability either to degrade extracellular MDO that was made available to them or to transport glucose, the major monomeric constituent of prey cell MDO . Instead, periplasmic MDO were irreversibly lost to the extracellular environment during the period of bdellovibrio attack and penetration . Thus, although prey cell periplasmic proteins are retained, other important periplasmic components are released early in the bdellovibrio growth cycle . The loss of these MDO may aid in the destabilization of the prey cell plasma membrane, increasing the availability of cytoplasmic constituents to the periplasmic bdellovibrio.

J Bacteriol, 1988 Feb, 170(2), 598 - 604
An N-terminal domain of the tetracycline resistance protein increases susceptibility to aminoglycosides and complements potassium uptake defects in Escherichia coli; Griffith JK et al.; Expression of extrachromosomal tet genes increased the susceptibility of gram-negative bacteria to specific aminoglycoside antibiotics . The magnitude of the increase in susceptibility was dependent on the amount and the class of the tet gene product (designated Tet) and the bacterial species in which the tet gene was expressed . Truncated Tet proteins that contained more than the first 33, but not more than the first 97, N-terminal amino acids of Tet also increased the susceptibility to aminoglycosides and complemented the potassium uptake defects in Escherichia coli . The primary structure of this N-terminal Tet fragment has the hydropathic characteristics of a multimeric, transmembrane structure and is highly conserved in three different classes of Tet proteins.

Postgrad Med J, 1988 Feb, 64(748), 155 - 6
Disseminated intravascular coagulation with Fusobacterium necrophorum septicaemia; Potter MN et al.; A 23 year old woman died within six hours of admission from acute disseminated intravascular coagulation . Fusobacterium necrophorum, a Gram negative anaerobic organism, was isolated as a single pathogen from the blood cultures . This association has not previously been reported.

Arthritis Rheum, 1988 Feb, 31(2), 238 - 47
Stimulation of rabbit synoviocyte prostaglandin E2 synthesis by lipopolysaccharides and their subunit structures; Rothenberg RJ et al.; Lipopolysaccharides (LPS) induce synoviocyte activation and may lead to destruction of synovial joint tissues . We assessed the production of prostaglandin E2 (PGE2) as a measure of synoviocyte activation by LPS and their subunit structures . Diphosphoryl lipid A was the smallest portion of lipid A tested that stimulated PGE2 production . The polysaccharide fraction of LPS, containing the O antigen, was also active . Intraarticular injections of the polysaccharide resulted in a synovitis very similar to that found in association with the intact LPS molecule . These observations suggest that both parts of LPS might be involved in gram-negative, organism-associated synovitis.

Circ Shock, 1988 Feb, 24(2), 143 - 8
Endotoxin-induced hypocalcemia results in defective calcium mobilization in rats; Zaloga GP et al.; Hypocalcemia is common in critically ill patients with sepsis; however, its etiology remains unclear . We have previously reported that hypocalcemia occurs in approximately 20% of patients with gram-negative septicemia . Based upon this finding, we evaluated the effect of endotoxin on calcium homeostasis in laboratory animals . We report here that endotoxin produces a dose-related decrease in circulating ionized calcium levels and impairs calcium mobilization during ethylenebis (oxyethylenenitrilo)-tetraacetic acid infusion . We conclude that endotoxin or its products can cause ionized hypocalcemia during sepsis by impairing calcium mobilization.

J Exp Med, 1988 Feb 1, 167(2), 623 - 31
Calcium ionophore synergizes with bacterial lipopolysaccharides in activating macrophage arachidonic acid metabolism; Aderem AA et al.; LPS, a major component of Gram-negative bacterial cell walls, prime macrophages for greatly enhanced arachidonic acid {20:4} metabolism when the cells are subsequently stimulated . The LPS-primed macrophage has been used as a model system in which to study the role of Ca2+ in the regulation of 20:4 metabolism . The Ca2+ ionophore A23187 (0.1 microM) triggered the rapid release of 20:4 metabolites from LPS-primed macrophages but not from cells not previously exposed to LPS . Macrophages required exposure to LPS for at least 40 min before A23187 became effective as a trigger . A23187 (0.1 microM) also synergized with PMA in activating macrophage 20:4 metabolism . The PMA effect could be distinguished from that of LPS since no preincubation with PMA was required . A23187 greatly increased the amount of lipoxygenase products secreted from LPS-primed macrophages, leukotriene C4 synthesis being increased 150-fold . LPS-primed macrophages, partially permeabilized to Ca2+ with A23187, were used to titrate the Ca2+ concentration dependence of the cyclooxygenase and lipoxygenase pathways . Cyclooxygenase metabolites were detected at an order of magnitude lower Ca2+ concentration than were lipoxygenase products . The data suggest that Ca2+ regulates macrophage 20:4 metabolism at two distinct steps: an increase in intracellular Ca2+ regulates the triggering signal and relatively higher Ca2+ concentrations are required for 5-lipoxygenase activity.

J Hosp Infect, 1988 Feb, 11(2), 161 - 8
Influence of disposable ('Conchapak') and reusable humidifying systems on the incidence of ventilation pneumonia; Daschner F et al.; The contamination of disposable ('Conchapak') and reusable humidifying systems and their influence on the incidence of pneumonia was studied in 116 patients requiring continuous mechanical ventilation therapy . The water reservoirs of 11 (15.9%) of the 69 disposable systems became colonized, but all reusable systems were found to be sterile . In four of the 11 samples, the organisms isolated corresponded with those cultured from tracheal secretions several days before . Ventilator-associated pneumonia occurred in 36 (31.0%) of the patients, but there was no statistically significant difference in the incidence of pneumonia between the patients treated with the disposable or the reusable humidifying systems . Gram-negative bacteria were the predominant organisms isolated from tracheal aspirates of patients who developed ventilator-associated pneumonia . These results suggest that disposable humidifying systems do not influence the rate of ventilator-associated pneumonia in mechanically ventilated patients.

J Biol Chem, 1988 Jan 25, 263(3), 1199 - 203
Characterization of calcium-binding sites in development-specific protein S of Myxococcus xanthus using site-specific mutagenesis; Teintze M et al.; Protein S, the most abundant protein synthesized during development of the Gram-negative bacterium Myxococcus xanthus, assembles on the surface of the spores . It can be dissociated from the spores using divalent metal chelators and will reassemble on the spores in the presence of calcium . The amino acid sequence of protein S contains regions which have homology to the calcium-binding sites of calmodulin . Protein S was found to bind 2 mol of calcium/mol of protein with Kd values of 27 and 76 microM . Using oligonucleotide-directed site-specific mutagenesis, the gene coding for protein S was changed in each of two regions of homology to calmodulin (Ser40----Arg,Ser129----Arg), and a double mutant was also constructed . Each mutant gene was then transduced into the genome of a M . xanthus strain from which the wild-type genes had been deleted . All three mutants produced protein S normally during development . One of the mutants (Ser129----Arg) had normal amounts of protein S on its spores, whereas the other (Ser40----Arg) bound much less and the double mutant had virtually none . Analysis of the calcium binding affinities of the purified proteins showed that {Arg40}protein S and {Arg40, Arg129}protein S did not bind detectable quantities of calcium, whereas {Arg129}protein S bound less calcium than the wild-type protein and with a reduced affinity.

FEBS Lett, 1988 Jan 4, 226(2), 241 - 6
Broad-host range expression vectors containing manipulated meta-cleavage pathway regulatory elements of the TOL plasmid; Ramos JL et al.; The construction of pERD20 and pERD21, two broad-host range expression vectors, is described . The vectors contain the Pm promoter of the meta-cleavage pathway operon of the TOL plasmid pWWO; this promoter is present within a polylinker which provides a number of downstream cloning sites close to the transcription initiation site . Transcription from the Pm promoter in these vectors is controlled not by the natural positive regulator of Pm, the Xy1S protein, but by an Xy1S mutant analogue, Xy1S2tr6, which inhibits an altered effector specificity and can mediate a 3-8-fold higher level of transcription than can Xy1S in a wide range of temperatures . Controlled expression of cloned genes can be achieved in a broad spectrum of Gram negative bacteria grown at a wide range of temperatures.

Prog Clin Biol Res, 1988, 272, 383 - 93
Generation of a protective human monoclonal for the treatment of gram-negative sepsis; Larrick JW et al.; Using a combination of Epstein-Barr virus transformation and cell fusion to a mouse/human heteromyeloma cell line, we have generated a human monoclonal antibody, D234, that recognizes cross-reactive determinants on the lipopoly-saccharides (LPS) of Gram-negative bacteria . Direct binding to a series of rough mutant LPSs and smooth LPSs demonstrates the broad cross-reactivity of this monoclonal . D234 inhibits Re LPS-induced chemiluminescence . In a murine model of Gram-negative sepsis, D234 given after infection significantly increases survival . This antibody may have therapeutic potential for the treatment of life-threatening Gram-negative infections in humans.

Prog Clin Biol Res, 1988, 272, 3 - 15
The horseshoe crab: a model for gram-negative sepsis in marine organisms and humans; Levin J; The roles of the amebocyte in providing hemostasis and controlling infection, and its reaction to endotoxin, suggest that the response of platelets and the blood coagulation system in various mammals to gram-negative infection or endotoxin is an evolutionary remnant of this ancient mechanism . In humans, this mechanism occasionally subverts its presumed protective function by overresponding in a manner that results in pathophysiologic thrombosis or hemorrhage . (In this regard, it is interesting that human platelets are much more resistant to the effects of bacterial endotoxins than are other species.) Similarly, the rudimentary ability of mammalian platelets to phagocytose particles and kill bacteria may be another remnant of functions that are more important in amebocytes (or the thrombocytes of other invertebrates) . Thus, these two cells, one from an ancient invertebrate and the other from mammals, have remarkably similar characteristics, although the relative importance of their various functions has changed as evolution has taken place . Nevertheless, after at least 400,000,000 years of evolution, coagulation and anti-bacterial mechanisms remain at least partially linked.

Prog Clin Biol Res, 1988, 272, 295 - 308
Hypersensitivity to endotoxin and mechanisms of host-response; Galanos C et al.; It was shown here that the lethal activity of endotoxin may be considerably enhanced in experimental animals treated with different agents . Some of these agents represent killed bacteria, bacterial products or hepatotoxic agents and their sensitizing effects may be relevant to the sensitization seen during gram-negative infections . This study provided direct evidence that macrophages are cells mediating the lethal activity of endotoxin and that the direct interaction of LPS with macrophages is the first step in its initiation . Further, TNF is a macrophage mediator responsible for the induction of lethality . In normal animals as well as in the various sensitization models investigated, TNF alone was sufficient to induce lethality . Therefore, the stimulation of macrophages by LPS to produce TNF is a mechanism common to diverse lethality models . It would seem therefore that the complexity of endotoxicity in gram-negative infections is related primarily to the complexicity of the factors altering the susceptibility of the host rather than to be actual mechanisms of the lethal action of endotoxin . The identification of the factors leading to sensitization and their underlying mechanisms would contribute to a better understanding of the complex phenomenon endotoxicity.

Antonie Van Leeuwenhoek, 1988, 54(1), 19 - 36
Oligotrophic bacteria from rendzina forest soil; Whang K et al.; Oligotrophic bacteria were shown to exist abundantly in all layers of a rendzina forest soil throughout the year . Two-hundred-three oligotrophic bacteria were isolated from forest soil (Aoba, Sendai) at different layers (L, F, H and A layers) throughout the year, and their morphological and physiological characteristics were examined . A high proportion (95%) of the isolated oligotrophs were Gram-negative, non-spore forming bacteria . Based on the cell shape, the isolates were divided into four groups: regular rods, curved/spiral bacteria, irregular rods, and buddin and/or prosthecate bacteria . Each group of bacteria is discussed in relation to the physiological characteristics . Notably oligotrophic bacteria of different cell types showed a marked zonal distribution in respect to profile depth.

Klin Padiatr, 1988 Jan-Feb, 200(1), 40 - 4
{Peritonitis and infection in children with idiopathic nephrotic syndrome}; Feldhoff C et al.; We analyzed episodes of peritonitis and/or sepsis associated with the idiopathic nephrotic syndrome (ns) in 23 children treated between 1975 and 1985 at our clinic . 37.5% of the children with infantile ns, 16% of those with steroidsensible ns, and 13.6% of those with steroidresistant ns developed peritonitis . Children with infantile ns and one girl with gram-negative secondary peritonitis presented with sepsis . 3 septic children died . Four patients developed peritonitis secondary to intestinal perforation . The most common bacterial pathogen in primary peritonitis was S . pneumoniae (7 patients) . 7 cases were culture-negative . All episodes of peritonitis coincided with an active nephrotic syndrome: in more than half of the patients therapy with corticosteroids had already been started . Eight patients underwent surgical exploration for presumed appendicitis, but none was confirmed by histological examination of the appendix . In 2 instances S . pneumoniae was cultured from ascitic fluid . Prophylactic polyvalent pneumococcal vaccination and early start of corticotherapy during the acute illness of ns is warranted.

Antimicrob Agents Chemother, 1988 Jan, 32(1), 37 - 41
Elimination and tissue distribution of the monosaccharide lipid A precursor, lipid X, in mice and sheep; Golenbock DT et al.; Lipid X (2,3-diacylglucosamine 1-phosphate) is a novel monosaccharide precursor of lipid A (the active moiety of gram-negative endotoxin) and has been found to be protective against endotoxin administered to mice and sheep and against life-threatening gram-negative infections in mice . Because of the need to design optimal dosing regimens in experimental models of ovine and murine septicemia, the pharmacokinetic profile of lipid X was investigated in sheep and in two strains of mice by using 32P-labeled lipid X . In sheep, peak whole blood lipid X levels after a bolus injection of 100 micrograms of lipid X per kg were 900 ng/ml . An initial rapid distribution phase of 7.98 +/- 0.1 min was observed, followed by a prolonged elimination phase of 3.0 +/- 0.5 h; the area under the curve from time zero to infinity was 428 +/- 27 ng.h/ml . The serum half-lives of lipid X were slightly shorter than whole blood half-lives, suggesting that lipid X associates with cellular elements . Metabolites of lipid X could not be detected in serum over a 4-h period . Lipid X appears to accumulate mainly in the liver, and the tissue distribution of lipid X resembles that of lipopolysaccharide . The elimination rate of lipid X in mice was approximately four times as rapid as that seen in sheep . Lipid X pharmacokinetics in lipopolysaccharide-sensitive DBA/2J mice were virtually identical with those seen in endotoxin-resistant C3H/HeJ mice . The pharmacokinetics described here should greatly aid in the design and interpretation of animal studies investigating the therapeutic applications of lipid X in gram-negative septicemia.

J Neurosci Res, 1988, 19(1), 140 - 8
Neuroimmune intercommunication, central opioids, and the immune response to bacterial endotoxin; Dougherty PM et al.; Muramyl dipeptide is the smallest biologically active fragment of the lipopolysaccharide (LPS) moiety of gram-negative bacteria cell walls . The present report demonstrates that this product, associated with the immune response to bacterial infection, can modify CNS activity . Specifically, it is demonstrated that 6-0-stearoyl-muramyl dipeptide (MDP) can attenuate opiate withdrawal severity in a dose-dependent fashion when injected directly into areas of the brain essential for this phenomenon . In addition, MDP alters both baseline and postnarcotic electrophysiologic responses of four brain areas essential for various opioid activities . Similar findings have been reported for interferon-alpha (IFN-alpha), a peptide associated with the immune response to virus . Yet, even though MDP and IFN are shown to exert similar effects on opioid activity, there are also some very distinct differences in the actions of both of these immune response products . These observations suggest that central opioid systems may provide targets for the perception as well as the differentiation of afferent immunologic sensory input to the brain.

Drugs, 1988, 35 Suppl 2, 185 - 9
Cefotaxime treatment of gram-negative enteric meningitis in infants and children; Jacobs RF; 18 infants and children (1 week to 3 months of age) were treated with cefotaxime 200 mg/kg/day for Gram-negative enteric bacillary meningitis . 17 of these patients (94.4%) survived, with a complication rate of 23.5% (4/17 patients) . The follow-up cerebrospinal fluid cultures at 24 hours were sterile in all patients . Cefotaxime was safe and effective in treating Gram-negative enteric bacillary meningitis in infants and children and should be considered as a potential drug of choice in Gram-negative neonatal meningitis due to susceptible organisms.

Drugs Exp Clin Res, 1988, 14(1), 1 - 8
Monobactam antibiotics in subinhibitory concentrations enhance opsonophagocytosis and serum bacteriolysis in certain Escherichia coli strains; Veringa E et al.; Capsular polysaccharides are known to protect Gram-negative bacteria from complement-mediated killing and opsonophagocytosis . Monobactam antibiotics selectively inhibit penicillin-binding protein 3 (PBP3), resulting in abnormally structured peptidoglycan, causing defective cell surface structures . The authors studied the influence of subinhibitory concentrations of the monobactam antibiotics aztreonam and carumonam on serum bacteriolysis and opsonophagocytosis of four K-encapsulated and five non-K-encapsulated Escherichia coli strains . It was observed that monobactam antibiotics in subinhibitory concentrations enhanced opsonophagocytosis of the four K-encapsulated and one non-K-encapsulated E . coli strains tested . Opsonophagocytosis of the other four non-K-encapsulated E . coli strains was not enhanced . Serum bacteriolysis studies revealed that of the four K-encapsulated strains tested only one strain showed a significant enhancement of bacteriolysis after treatment with subinhibitory concentrations of monobactam antibiotics . None of the unencapsulated strains showed a significant change in percentage lysis after treatment with either aztreonam or carumonam.

Ann Biol Clin (Paris), 1988, 46(4), 259 - 62
{Comparative study of various API galeries for the identification of gram negative bacteria}; Reynaud AE et al.; 116 strains of Gram negative bacteria were identified with the use of API ATB 32 GN and Rapid 20 E galeries, in order to evaluate their performance as compared with API 20 E or API NE galeries used as reference . The identification concur (bacterial genus and species) in approximately 80 per cent of the cases . There are only 2 major discrepancies with ABT 32 GN galleries and only one with Rapid 20 E . In other cases, the profile that is obtained only permits identification of the genus but without a sufficient differentiation, requiring a study of additional characteristics or repetition of the test . These galeries enable to solve most routine diagnosis problems due to Gram negative bacteria, with the advantage of Rapid (Rapid 20 E) or automatized reading (ATB 32 GN).

Rev Pneumol Clin, 1988, 44(1), 24 - 32
{Complications of tracheotomy}; Viau F et al.; The complications of tracheotomy are reviewed and divided into two categories: early and late complications depending on whether the cannula has been removed or remains in situ . In the acute period, severe haemorrhages (0.3 to 2%) and oesophagotracheal fistulae (0.5 to 2%) result from a conflict between cannula and trachea during prolonged intensive care . Cardiac arrhythmia is frequent during aspiration (35%) but rarely lethal . Various technical problems related to the tracheotomy material are common (4 to 6%) and often very serious . Air leakage is represented mainly by severe pneumothorax (1 to 5%) under artificial ventilation . Tracheotomy wound infections (0.5 to 3.5%) may facilitate pulmonary superinfections (15 to 30%) which have a 5 to 8.5% mortality rate . In the acute phase, the overall mortality rate due to the tracheotomy itself is 1.7% (40 deaths in the 2,692 tracheotomies reviewed) . The main post-decannulation complication is tracheal stenosis . The incidence of severe stenosis (more than two-thirds of the tracheal diameter) varies from 8 to 12% . Stenosis is difficult to diagnose unless endoscopic examination is routinely performed . The classical treatment is surgical, but laser is helpful in this as in granulomas . In patients with in-dwelling cannula, granulomas may be responsible for pain, obstruction and bleeding which can be avoided by using an adequate equipment . Chronic invasion of the bronchi by Gram-negative organisms is almost constant and results in episodes of superinfection . Finally, patients with a permanent cannula often have psychological and social problems influencing their quality of life.

Int Orthop, 1988, 12(1), 69 - 73
Two-day cefamandole versus five-day cephazolin prophylaxis in 965 total hip replacements . Report of a multicentre double blind randomised trial; Evrard J et al.; The aim of this trial was to compare a 5-day course of cephazolin with a regimen of 2 days of cefamandole in 965 total hip replacements (488 in the cefamandole group and 477 in the cephazolin group) . The effect of the prophylactic antibiotic on the bacterial colonization of drains (mean duration of drainage: 3.2 +/- 0.3 days) and on the susceptibility of colonizing organisms was assessed . No significant difference was observed in the percentage of infected drains between the two groups . The cefamandole group had a lower rate of Gram-negative organisms (23% versus 44%, p less than 0.01) . The rate of deep infections within one year after operation was 0.7% in the cefamandole group versus 0.5% in the cephazolin group, and the difference is not significant . Cefamandole given for two days appears to be an effective prophylaxis against sepsis in total hip replacements.

Biochem Pharmacol, 1988 Jan 1, 37(1), 125 - 32
Structure-activity relationships in the beta-lactam family: an impossible dream; Frere JM et al.; The difficulty of establishing structure-activity relationships in the beta-lactam family of antibiotics stems from the fact that: (1) The targets in various bacteria exhibit widely different sensitivities . (2) Some bacteria produce beta-lactamases, enzymes capable of destroying the antibiotics . The rates of the reactions with the beta-lactamases and the target enzymes are not necessarily related . (3) In Gram-negative bacteria, the diffusion rate through the outer membrane varies independently from the two other factors.

J Bacteriol, 1988 Jan, 170(1), 436 - 8
Leucine uptake and protein synthesis are exponential during the division cycle of Escherichia coli B/r; Cooper S; The rate of leucine uptake, which is a measure of protein synthesis, was measured during the division cycle of Escherichia coli B/r by the membrane elution technique . The rate of leucine uptake was exponential, indicating that protein synthesis is exponential, and not linear, during the division cycle . These results, coupled with the results of other work on the exponential rate of RNA synthesis during the division cycle, indicate that the accumulation of mass in E . coli and other gram-negative organisms is exponential during the division cycle.

Mikrobiyol Bul, 1988, 22(3), 193 - 8
{Resistance of gram negative bacteria to new generation cephalosporins and the role of beta-lactamases in this type of resistance}; Gur D et al.; In this study, by using the microbroth dilution method, in vitro susceptibilities of gram negative bacteria to new generation cephalosporins were examined, and among these, 40 bacteria which showed resistance against at least two antibiotics were tested for beta-lactamase production . Beta-lactamase production was positive in all of them . However, this type of resistance could not be transferred to susceptible recipients by conjugation experiments . Our results suggest that the resistance to beta-lactam antibiotics in these strains are related with chromosomally mediated beta-lactamases.

Br J Rheumatol, 1988, 27 Suppl 2, 29 - 31
Gram-negative bacteria, HLA-B27 and inflammatory bowel disease; Pease PE et al.; Lymphocytes from 48 IBD patients including nine with HLA-B27 were examined for their capacity to absorb Y.enterocolitica 0:9 antiserum . They possessed a range of absorption ability which was unconnected with HLA-B27 status . Samples of lymphocytes from 28 AS patients, 10 RA patients and 28 normal control subjects were included for comparison . The significance of the findings is discussed.

Ann Biol Clin (Paris), 1988, 46(2), 151 - 6
Beta-lactamases as the main resistance factor to penicillin-related antibiotics; Frere JM et al.; The interplay between the three factors involved in the resistance of bacteria to beta-lactam antibiotics (sensitivity of target, synthesis of beta-lactamase, permeability barrier) is analysed and discussed on the basis of a simple kinetic model . The three factors do not act independently . In Gram-negative bacteria, the permeability barrier is only significant when the bacterial cell also produces a beta-lactamase . Special attention is devoted to cases where large periplasmic beta-lactamase concentrations prevail, a situation which has been observed in some clinical isolates.

Mikrobiyol Bul, 1988, 22(4), 276 - 83
{The effect of netilmicin on gram negative rods isolated in the Konya region}; Sengil AZ et al.; Netilmicin, was tested for the effect against 276 isolates of gram negative bacteria, before had used in Konya region . 15.9% of the isolates were resistant and 84.1% were sensitive to netilmicin . The effects of Netilmicin and gentamicin for 50 Pseudomonas isolates were compared . The other aminoglycosides also were tested against isolates of the bacterium, amikacin was the most active one.

Vutr Boles, 1988, 27(4), 99 - 103
{Long-term myelodysplastic syndrome transformed into blastic leukemia}; Dimova R et al.; A very rare case of myelodysplastic syndrome of long duration transformed into acute leukemia is reported . The syndrome presented with refractory anemia with ring sideroblasts and after eight years of favourable course abruptly turned into acute myelomonoblastic leukemia with a rapid fatal outcome caused by gram-negative sepsis . The disappearance of the ring-sideroblasts from the bone marrow is pointed out as a bad prognostic sign . Treatment of the myelodysplastic syndrome with small doses of cytosine arabinoside is discussed as well as the nonobligatory passing through the stage of a gradual increase of the blast cells before the transformation into acute leukemia.

Chemotherapy, 1988, 34(5), 361 - 6
Influence of infusion systems on pharmacokinetic parameters of tobramycin in newborn infants; Nahata MC; The objective of this study was to assess the impact of intravenous infusion systems on the pharmacokinetic parameters of tobramycin in newborn infants . Thirty infants (gestational age 28-38 weeks; birth weight 0.8-3.5 kg; postnatal age 4-10 days) with presumed or proven gram-negative infection were studied . Tobramycin (2.5 mg/kg) was administered every 12 h over 0.5 h using two of four infusion systems at similar flow rates in a crossover fashion: syringe pump (auto syringe) versus either IVAC-y site, IVAC-flashball or IMED-y site . Blood samples were collected at 0.5 h after the end of infusion to determine the peak and prior to the dose to determine the trough serum concentration . Peak and time to achieve peak were different for IVAC-y versus auto syringe; the mean peak was 2 micrograms/ml higher and the time to achieve peak was 2 h shorter with auto syringe than IVAC (p less than 0.02) . The apparent distribution volume of tobramycin was 1.02 +/- 0.68 with IVAC-y and 0.65 +/- 0.22 l/kg with auto syringe (p less than 0.05) . The elimination half-life was 10.4 +/- 6.9 h with IVAC-y and 6.6 +/- 2.3 h with auto syringe (p less than 0.05); other systems and parameters were not different . These data demonstrate that the type of infusion system can markedly influence the estimation of certain pharmacokinetic parameters of tobramycin in newborn infants.

Electron Microsc Rev, 1988, 1(2), 261 - 78
The ultrastructural morphology of endotoxins and lipopolysaccharides; Brogden KA et al.; Endotoxins and LPS are constituents unique to the outer surface of gram-negative bacteria . Cell-associated endotoxins are now readily observable on the cell outer membrane with labelled monoclonal antibodies . These probes are not only more specific than those used in the past, but also easier to see . Interest in free endotoxin as a method to generate outer membrane proteins without contamination with other cell constituents is also increasing (Gamazo and Moriyon, 1987) . The morphologic identification and characterization of LPS by electron microscopy has been facilitated recently by advances in chemical extraction and purification techniques . LPS, originally thought to be heterogenous, exists in forms that are dependent upon (1) the method of its extraction, (2) its chemical composition, and (3) the physical or chemical conditions of its environment . New models were proposed on the arrangement of LPS molecules in molecular aggregates (i.e . discs, vesicles or ribbons) and a schematic was presented on the dissociation from one morphologic type to another . Morphologic studies on endotoxins and LPS will continue in the future . Using molecular biological techniques, carbohydrate epitopes of LPS from one bacterial species will be expressed with increasing frequency in other bacterial species (Manning et al., 1986; Stein et al., 1988) . Electron microscopy will help visualize the distribution of the 'new' LPS on the recipient cell surface . Labelled monoclonal antibodies will also differentiate host cell LPS from the recombinant LPS . As molecular model programming becomes more complex, new schematics will help visualize the arrangement of LPS in membranes to explain recombinant LPS structure as well as other characteristics (i.e . membrane permeability to various antibiotics).

Parasitol Res, 1988, 75(2), 88 - 97
Influence of Blastocrithidia triatomae (Trypanosomatidae) on the reduviid bug Triatoma infestans: alterations in the Malpighian tubules; Schaub GA et al.; To investigate the cellular basis of our recent observation that the trypanosome Blastocrithidia triatomae disturbs excretion in Triatoma infestans, we compared the morphology and ultrastructure of Malpighian tubules in infected and noninfected bugs . Tubules of bugs infected 3-4 months before dissection did not show any morphological alterations in either the upper or lower regions . In fifth instars with a long lasting infection (9-10 months) and a correspondingly retarded larval development, the tracheal system supplying the Malpighian tubules was reduced and alterations were conspicuous in the upper region, where the tubules were slightly widened, sometimes having parts with conspicuous swellings . The cells were filled with white concretions and a strong autofluorescence was evident by fluorescence microscopy . Transmission electron microscopy demonstrated an increase in the number of these concretions, even after short infection periods . In the extremely swollen parts of the tubules there was a reduction in basal cell interdigitations, mitochondria, and microvilli . B . triatomae (but also gram-negative bacteria) occurred only in these swollen parts.

Antonie Van Leeuwenhoek, 1988, 54(6), 521 - 34
Characteristics of a nitrogen-fixing methanotroph, Methylocystis T-1; Takeda K; A methane-oxidizing bacterium capable of nitrogen fixation was isolated from soil taken from an area which leaked methane gas . Strain T-1 was a catalase and oxidase-positive, gram-negative straight rod-shaped strictly aerobic bacterium which formed lipid cysts and type II intracytoplasmic membranes . The organism was a microaerophilic nitrogen-fixing methanotroph . Strain T-1 is considered to be classified into Methylocystis . The organism evolved hydrogen gas when grown in the nitrogen-free medium of atmospheric oxygen concentrations of 1.5% or more . Below this level, however, hydrogen gas was not evolved . In addition to methanol, formaldehyde and formate, ethanol, acetate and hydrogen gas served as oxidizable substrates for the acetylene reduction test . H2-stimulated nitrogenase activity was limited in a very narrow range of oxygen concentration and not detected at 2% O2 . With acetate as the substrate, however, about an 80% of the maximum acetylene reduction activity was detected at 2% O2 . These results suggest that strain T-1 is capable of recycling the hydrogen gas evolved during nitrogen fixation under low partial pressures of O2.

Eur J Cancer Clin Oncol, 1988, 24 Suppl 1, S5 - 13
Systemic infection and colonization with and without prophylactic norfloxacin use over time in the granulocytopenic, acute leukemia patient; Karp JE et al.; Patients undergoing intensive antileukemic chemotherapy and profound granulocytopenia are susceptible to overwhelming infections, particularly those arising from disease- and therapy-related gastrointestinal tract damage . We have previously demonstrated that the ability to suppress bacterial colonization of this site with oral norfloxacin prophylaxis (400 mg every 12 h) affects the incidence and distribution of aerobic gram-negative bacterial infections and the overall management of infectious complications in this patient population . We have now determined the broad impact of continuous, long-term use of oral norfloxacin on aerobic gram-negative bacterial infection and colonization, overall management of presumed and documented infections during marrow aplasia and emergence of clinically significant antibiotic resistant pathogens during intensive antileukemic chemotherapy . Oral norfloxacin prophylaxis administered throughout the course of induced granulocytopenia continues to afford effective protection by suppressing the development of aerobic gram-negative infections, particularly those arising from the gastrointestinal tract, and preventing the acquisition or emergence of multiply resistant pathogens . A long-range effect of norfloxacin on pathogens colonizing the respiratory tract is also detected, with inhibition of acquired drug resistance occurring at that site as well . For these reasons, norfloxacin continues to be an excellent agent for oral prophylactic use in this patient population.

Arch Intern Med, 1988 Jan, 148(1), 153 - 5
Severe hypophosphatemia in hospitalized patients; Halevy J et al.; Severe hypophosphatemia (serum phosphorus less than or equal to 0.48 mmol/L {less than or equal to 1.5 mg/dL}) was found in 120 patients admitted to a major university hospital, during a period of 16 months . Fifty-one patients (42.5%) developed hypophosphatemia postoperatively . Medications known to precipitate hypophosphatemia were a causative factor in 82% of the patients, with glucose administered intravenously, antacids, diuretics, and steroids being the most common agents associated with profound hypophosphatemia . Gram-negative septicemia was observed in 16 patients, and it was the second most common cause of severe hypophosphatemia . The mortality rate was 20% in patients with a serum phosphorus concentration between 0.36 and 0.48 mmol/L (1.1 and 1.5 mg/dL) (group A) and 30% in patients with a serum phosphorus concentration of less than or equal to 0.32 mmol/L (less than or equal to 1.0 mg/dL) (group B) . The cause of death and its temporal association with the lowest observed values of phosphorus concentration indicate that severe hypophosphatemia might be a contributory factor to mortality . Our data indicate that severe hypophosphatemia in hospitalized patients is the result of a combination of factors . Surgery, followed by a period of fasting with intravenous administration of glucose, and gram-negative septicemia are the most common causes.

J Clin Anesth, 1988, 1(1), 12 - 20
Prevention of stress bleeding with ranitidine or pirenzepine and the risk of pneumonia; Tryba M; In a prospective, controlled, randomized trial of stress bleeding prophylaxis, 400 patients in a surgical intensive care unit received 50 mg pirenzepine (n = 200) or 200 mg ranitidine (n = 200) daily . The drugs were administered continuously via an intravenous line . The mean duration of the treatment was 3.9 days . Patients were included in the study if no long-term ventilation was expected . In patients with a stomach tube in place, the intragastric pH was determined every eight hours . Bleeding was defined as macroscopically visible . Along with stress bleeding, the development of postoperative pneumonia was documented . The intragastric pH was less than 4 significantly more often in patients treated with pirenzepine . In patients treated with ranitidine, six stress bleedings were observed, while in the pirenzepine group three bleeding episodes occurred . Seven of the nine bleeding patients were found to have a very high bleeding risk . In mechanically ventilated patients, a significantly higher risk of pneumonia was observed compared with non-ventilated patients (18.0% vs 2.7%) . Fourteen of the 20 pneumonias occurred in patients treated with ranitidine . In ventilated patients treated with ranitidine, the pneumonia rate was 28.6%, while in the pirenzepine group the pneumonia rate reached only 9.1% (p less than 0.05) . The increased frequency of pneumonia in patients treated with ranitidine appears to be caused by overgrowth of gram-negative bacteria in the stomach . Pirenzepine provides adequate protection against stress bleeding while also minimizing the danger of pneumonia caused by infection via the gastropulmonary route.

Arkh Patol, 1988, 50(11), 84 - 9
{Acute respiratory distress syndrome in endotoxic shock}; Iakovlev MIu et al.; Large amounts of lipopolysaccharides released in blood after death of Gram-negative bacteria are responsible for endotoxinemia and endotoxic shock . Endotoxin is eliminated from the body via different routes including the lungs . One of the mechanisms of lipopolysaccharides transport to the lungs, which respond with acute distress syndrome, is their transfer by polymorphonuclear leukocytes.

J Orthop Trauma, 1988, 2(3), 175 - 80
Severe open tibial fractures: a study protocol; Johnson KD et al.; A prospective randomized study of severe open tibial fractures (Type II and III) was performed . Individual fractures were randomized to treatment groups according to initial antibiotic therapy: One consisted of a first-generation cephalosporin, and the other consisted of a third-generation cephalosporin . Initial antibiotic therapy was given in all patients for 48 h and then specific antibiotic treatment was used as indicated by culture . The purpose of this study was to determine whether or not additional gram-negative coverage had an effect on the overall infection rate or the type of infection in severe open tibial fractures . Additional factors, such as the timing of bone grafts and soft tissue coverage, were evaluated in this study as well . Although there was no statistical difference in the rate of infection with the use of a first- versus a third-generation cephalosporin, there was a trend toward a decreased infection rate as well as toward less morbid infections with the use of a third-generation cephalosporin . The study also confirms that early bone graft should not be performed prior to 6 weeks post injury or after successful soft tissue coverage has been achieved . On the other hand, soft tissue coverage procedures should be performed at the earliest possible date to decrease the overall infection rate.

Clin Ther, 1988, 10(5), 589 - 93
Ceftazidime versus a combination of amikacin and ticarcillin in the treatment of severe infections; Limson BM et al.; Hospital patients with severe gram-negative bacterial infections were randomly assigned to treatment with ceftazidime (2 gm every eight or 12 hours) or a combination of amikacin (500 mg every 12 hours) and ticarcillin (3 gm every six or eight hours) . The clinical and bacteriological responses to treatment were satisfactory in most of the patients in both treatment groups . Clinical cure was achieved in 18 of the 20 patients treated with ceftazidime and in 17 of the 20 treated with amikacin-ticarcillin . The bacterial eradication rate was 19 of 21 pathogens in the ceftazidime group and 17 of 20 pathogens in the amikacin-ticarcillin group.

Gene, 1988, 62(2), 209 - 17
Analysis of the nourseothricin-resistance gene (nat) of Streptomyces noursei; Krugel H et al.; A gene (nat) conferring resistance to the streptothricin antibiotic nourseothricin (Nc) was cloned from the producer Streptomyces noursei into Streptomyces lividans on the vector pIJ702 to form pNAT1 . The nat gene was localized on a 1-kb SalI-MboI fragment, which also carries the nat promoter . Divergent promoter activity from the nat promoter region was identified on the cloned fragment using promoter probe plasmids pIJ486 and pIJ487 . The nat gene is not expressed from its own promoter in Escherichia coli as shown by its failure to promote cat expression in promoter-less plasmid pBB100 and by the expression of NcR in only one orientation, when cloned in pUC19 . In S . lividans 7A, harbouring plasmid pNAT1, an Nc-acetylating activity (NAT) was associated with the cloned resistance gene . The substrate specificity of NAT correlated well with the substrate range of the acetyltransferase in S . noursei and Tn1825-determined streptothricin resistance in Gram-negative bacteria . Moreover, an extract of S . lividans carrying pNAT1 showed specific serological cross-reactivity with an extract of E . coli carrying Tn1825.

J Biochem (Tokyo), 1988 Jan, 103(1), 5 - 7
Production of eicosapentaenoic acid by marine bacteria; Yazawa K et al.; About 5,000 strains of marine microorganisms were screened for eicosapentaenoic acid (EPA)-producing ability, which was detected in 88 of them . All of the latter were found to be obligate aerobic, Gram-negative, motile, short rod-shaped bacteria . One strain, designated as SCRC-8132, showed a doubling time of 30 min at 25 degrees C and produced 20 mg/liter (4 mg/g dry cells) when cultured in a P-Y-M-Glucose medium for 18 h . The EPA to total fatty acids ratio was 24% . The strain produced 26 mg EPA/liter (15 mg/g dry cells) when cultured at 4 degrees C for 5 days, the EPA ratio being increased to 40%.

Gan To Kagaku Ryoho, 1987 Dec, 14(12), 3365 - 8
{Complications due to high-dose OK-432 administration into tumors and the peritoneal cavity in patients with advanced gastric cancer}; Fukasawa K et al.; It has been assumed that a high dose of OK-432 can be safely injected into tumor tissues or intraperitoneally under general anesthesia . Among 40 patients with advanced carcinoma of the stomach, high doses of OK-432 were injected into the tumor in six and intraperitoneally in 34 . Circulatory shock associated with subsequent disseminated intravascular coagulation (DIC) developed within 3 days in one of the former and in two of the latter group . Hypovolemic shock was initially considered to indicate that hypovolemia actually existed in these three patients . However, the shock state with DIC persisted even after the blood volume had been corrected . Gram-negative bacteremia was verified in two of the patients . The shock and DIC seen in these patients could have been attributed to septicemia through either the necrotic tumor or the intestinal wall showing increased permeability as a result of the drug . When and if a high dose of OK-432 is administered locally, the prophylaxis of infection seems to be of crucial importance in order to avoid such complications as those reported above.

J Pediatr, 1987 Dec, 111(6 Pt 1), 824 - 9
Bacterial cholangitis after surgery for biliary atresia; Ecoffey C et al.; We retrospectively studied the incidence of bacterial cholangitis in 129 infants operated on because of biliary atresia over 5 years . Forty-six of the 101 children who underwent hepatic portoenterostomy had a total of 105 episodes of cholangitis (range one to eight episodes per child) . Most episodes occurred within 3 months of the operation . Factors associated with cholangitis included good or partial restoration of bile flow, abnormal intrahepatic bile ducts or cavities at the porta hepatis, and routine postoperative use of antibiotics . External jejunostomy was not effective in preventing cholangitis . In addition to fever and decreased bile flow, increased erythrocyte sedimentation rate and signs of shock were frequently observed . The responsible organisms, most often gram-negative bacteria, were identified in 79 (75%) episodes by blood or liver cultures . Most were susceptible to trimethoprim-sulfamethoxazole and third-generation cephalosporins during the first episode, but only to cephalosporins during later episodes . The incidence of signs of portal hypertension in children with normal serum bilirubin values at age 5 years was not higher in those who had previously experienced one or more episodes of cholangitis.

Infect Dis Clin North Am, 1987 Dec, 1(4), 907 - 26
Renal and perirenal abscesses; Patterson JE et al.; Our knowledge of the spectrum of renal abscesses has increased as a result of more sensitive radiologic techniques . The classification of intrarenal abscess now includes acute focal bacterial nephritis and acute multifocal bacterial nephritis, as well as the previously recognized renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis . In general, the clinical presentation of these entities does not differentiate them; various radiographic studies can distinguish them, however . The intrarenal abscess is usually treated successfully with antibiotic therapy alone . Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities . The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat . Drainage of the abscess and sometimes partial or complete nephrectomy are required for resolution.

Eur J Epidemiol, 1987 Dec, 3(4), 336 - 42
The epidemiology of Pseudomonas cepacia in patients with cystic fibrosis; Tablan OC et al.; Pseudomonas cepacia has emerged as an important nosocomial pathogen colonizing and infecting the respiratory tract of patients with cystic fibrosis (CF) . Although assessment of outcomes associated with P . cepacia colonization has been difficult, controlled studies have shown that colonized patients experience more adverse outcomes compared with those not colonized . In the United States, an increasing trend in national incidence and prevalence of P . cepacia colonization has been shown, but cases have been unevenly distributed in a few centers . These estimates, however, may be biased by intercenter differences in laboratory methods for detecting P . cepacia in patient sputum . The source and mode of transmission of P . cepacia have not been adequately demonstrated, and may vary from center to center . Until further studies elucidate the epidemiology of P . cepacia in patients with CF, it may be prudent for CF centers to consider the use of selective media to isolate P . cepacia from sputa of patients with CF, to conduct investigations of clusters of P . cepacia-colonized patients, and to consider adopting infection control precautions recommended for control of multiply resistant gram negative organisms.

Ann Surg, 1987 Dec, 206(6), 699 - 705
Pyogenic liver abscess . Diagnostic and therapeutic strategies; Gyorffy EJ et al.; A retrospective review of 26 adult patients admitted to University of California, Davis, Medical Center (UCDMC) with pyogenic liver abscess (1980-1986) was performed to ascertain the impact of rapid diagnosis and percutaneous drainage . Ultrasonographic examinations and computed tomography (CT) scans were highly sensitive and noninvasive imaging modalities . Sixteen patients had solitary abscesses and seven had multiple microscopic abscesses . The median time interval from admission to diagnosis and therapy was 2 and 3 days, respectively . Origin of the abscess was determined in 22 patients, the biliary tree being the most common source . Medical therapy was successful in three patients with microabscesses but failed in two . Nine patients had percutaneous drainage; two required repetitive percutaneous catheter placement, and two proceeded to surgical drainage . Twelve patients had surgical drainage; one required repetitive surgical drainage . Postdrainage complications were minimal in all groups . Overall mortality role was 11.5% (two patients) . Deaths were related to delay in diagnosis, gram-negative sepsis at presentation, and biliary origin of the abscess.

J Immunol, 1987 Dec 1, 139(11), 3697 - 702
Lipid A-associated proteins provide an alternate "second signal" in the activation of recombinant interferon-gamma-primed, C3H/HeJ macrophages to a fully tumoricidal state; Hogan MM et al.; Previous studies have shown that the activation of murine macrophages to a fully tumoricidal state requires that specific environmental signals be delivered to the macrophage in a stepwise manner: a "priming" signal first renders the macrophage responsive to a second or "trigger" signal . One potent "priming" signal has been identified as the T cell-derived lymphokine, interferon-gamma (IFN-gamma) and one often used "trigger" signal is lipopolysaccharide (LPS), the endotoxin derived from Gram-negative bacteria . In these studies, endotoxin-responsive C3H/OuJ (Lps(n)) and endotoxin-hyporesponsive C3H/HeJ (Lps(d)) macrophages were exposed in vitro to recombinant IFN-gamma (rIFN-gamma) and various preparations of endotoxin or purified lipid A-associated proteins (LAP) . The resultant tumoricidal responses were evaluated to define the activation requirements of murine macrophages and to examine further the LPS defect exhibited by C3H/HeJ mice . The findings presented herein demonstrate that C3H/OuJ macrophages primed by rIFN-gamma respond to protein-free LPS (phenol-water extracted LPS), protein-rich LPS (butanol-extracted LPS), or purified LAP . In contrast, rIFN-gamma-primed C3H/HeJ macrophages failed to become cytolytic with phenol-water extracted LPS, but could be rendered fully tumoricidal if either butanol-extracted LPS or LAP were used as "second signals." These data indicate that C3H/HeJ macrophages are fully responsive to the priming effects of IFN-gamma, but remain restricted in their capacity to recognize protein-free LPS as a second signal . Alternate second signals, such as LAP, may provide a compensatory pathway by which these macrophages are rendered fully tumoricidal.

J Antibiot (Tokyo), 1987 Dec, 40(12), 1733 - 9
CGP 4832, a new semisynthetic rifamycin derivative highly active against some gram-negative bacteria; Wehrli W et al.; CGP 4832 (5) is a new derivative of rifamycin S, showing a very high degree of activity against certain Gram-negative bacteria, with MICs as much as 400 times lower than those of rifampicin . CGP 4832 and rifampicin inhibit DNA-dependent transcription in vitro to a similar extent, which excludes any difference in their effect on the target enzyme . The most plausible explanation for the potent activity of CGP 4832 is that it penetrates into bacterial cells by way of a specific mechanism . This hypothesis is corroborated by the high rate of mutations leading to bacterial strains resistant against CGP 4832.

J Clin Microbiol, 1987 Nov, 25(11), 2132 - 5
Isolation and antigenic reactivity of Brucella ovis outer membrane proteins; Afzal M et al.; Brucella ovis cell membranes were isolated from fractured and lysozyme-treated cells by ultracentrifugation . These preparations appeared to consist largely of outer membranes, as judged from the results of ultracentrifugation experiments in sucrose density gradients under conditions that are widely used to separate inner and outer membranes of gram-negative bacteria . The sequential detergent extraction of cell membranes yielded mainly lipopolysaccharide and three groups of outer membrane proteins . In immunoblotting, lipopolysaccharide had good antigenic reactivity with all sera from rams exposed to B . ovis (vaccination or natural infection), but some outer membrane proteins reacted strongly only with sera from immune (vaccinated) rams, not from infected rams, suggesting a possible diagnostic role for such proteins in predicting immunity or infection.

J Exp Med, 1987 Nov 1, 166(5), 1310 - 28
Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes; Horwitz MA; Legionella pneumophila, the causative agent of Legionnaires' disease, is a Gram-negative bacterium and a facultative intracellular parasite that multiplies in human monocytes and alveolar macrophages . In this paper, mutants of L . pneumophila avirulent for human monocytes were obtained and extensively characterized . The mutants were obtained by serial passage of wild-type L . pneumophila on suboptimal artificial medium . None of 44 such mutant clones were capable of multiplying in monocytes or exerting a cytopathic effect on monocyte monolayers . Under the same conditions, wild-type L . pneumophila multiplied 2.5-4.5 logs, and destroyed the monocyte monolayers . The basis for the avirulent phenotype was an inability of the mutants to multiply intracellularly . Both mutant and wild-type bacteria bound to and were ingested by monocytes, and both entered by coiling phagocytosis . Thereafter, their intracellular destinies diverged . The wild-type formed a distinctive ribosome-lined replicative phagosome, inhibited phagosome-lysosome fusion, and multiplied intracellularly . The mutant did not form the distinctive phagosome nor inhibit phagosome-lysosome fusion . The mutant survived intracellularly but did not replicate in the phagolysosome . In all other respects studied, the mutant and wild-type bacteria were similar . They had similar ultrastructure and colony morphology; both formed colonies of compact and diffuse type . They had similar structural and secretory protein profiles and LPS profile by PAGE . Both the mutant and wild-type bacteria were completely resistant to human complement in the presence or absence of high titer anti-L . pneumophila antibody . The mutant L . pneumophila have tremendous potential for enhancing our understanding of the intracellular biology of L . pneumophila and other parasites that follow a similar pathway through the mononuclear phagocyte . Such mutants also show promise for enhancing our understanding of immunity to L . pneumophila, and they may serve as prototypes in the development of safe and effective vaccines against intracellular pathogens.

Crit Care Med, 1987 Nov, 15(11), 1012 - 4
Active tuberculosis in the medical intensive care unit: a 15-year retrospective analysis; Frame RN et al.; Of approximately 6000 admissions to the Henry Ford Hospital medical ICU between October 1969 and September 1984, 61 (1%) had active tuberculosis (TB) . Forty-three (70%) of these 61 had acute respiratory failure (ARF) . TB was considered to be the sole cause of ARF in 12 and contributory in 31 . Eighteen patients with TB but without ARF were admitted for treatment of other critical illnesses . Alcoholism was present in 31 (51%) of the TB patients . Only one of 12 whose ARF was caused primarily by TB had a history of known TB at the time of admission . Important factors contributing to ARF in TB patients included Gram-negative pneumonia and/or sepsis, chronic obstructive pulmonary disease, prior TB with anti-TB medication noncompliance, and malignancy . Six patients were not suspected of having TB when admitted to the medical ICU; three patients who had not been treated for TB were found to have TB on autopsy . The inhospital mortality rate for all patients with TB requiring intensive care was 67%, but was 81% in those with ARF.

Am J Med, 1987 Nov, 83(5), 945 - 8
Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome; Maayan S et al.; Severe infections with Strongyloides stercoralis occur in immunocompromised patients . Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with the acquired immune deficiency syndrome (AIDS) is described . Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis . Multiple stool examinations should be performed routinely for such patients . Examination of sputum for the parasite is recommended if pneumonia is present . Prompt diagnosis and therapy are essential for prevention of fatal disseminationPIP: Severe infections with Strongyloides stercoralis occur in immunocompromised patients . Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with acquired immune deficiency syndrome (AIDS) is described . Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis . Multiple stool examinations should be performed routinely for such patients . Examination of sputum for the parasite is recommended if pneumonia is present . Prompt diagnosis and therapy is essential for prevention of fatal dissemination .

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1816 - 21
Influence of hydrocortisone succinate on intrarenal accumulation of gentamicin in endotoxemic rats; Bergeron MG et al.; Gentamicin is a commonly used antibiotic in the treatment of gram-negative infections including septicemia and pyelonephritis . Bacterial endotoxin is liberated during antibiotic therapy and may lead to endotoxemic shock . Steroids such as hydrocortisone are generally recommended in the treatment of endotoxemic shock . There are very limited data on the influence of endotoxin or corticosteroids on the pharmacology of antibiotics, especially aminoglycosides, which are nephrotoxic . We studied the influence of both Escherichia coli endotoxin and hydrocortisone succinate on the renal uptake of gentamicin in rats . Animals were injected intravenously with endotoxin (0.25 mg/kg) and/or hydrocortisone (25 mg/kg) plus gentamicin (10 mg/kg) . Gentamicin levels in the serum and renal parenchyma as well as renal function and histology were evaluated . Both endotoxin and hydrocortisone given alone increased the concentration of gentamicin in the renal cortex (P less than 0.05) . Normal values in serum were observed in all groups at most time intervals . When administered together, endotoxin and hydrocortisone did not potentiate each other . The combination of endotoxin and hydrocortisone gave significantly higher levels of gentamicin than endotoxin or hydrocortisone alone when endotoxin was injected 3 h before hydrocortisone (P less than 0.05) . Blood pressure and cardiac frequency were normal when gentamicin was given . Endotoxin alone slightly decreased the glomerular filtration rate, and hydrocortisone alone slightly modified renal plasma flow . The combination of both drugs did not significantly affect renal function . No histological lesion was noted on light microscopy in animals receiving endotoxin . Competitive or synergistic activity of endotoxin, gentamicin, and hydrocortisone at the cellular level, especially on membranes or lysosomes, might explain in part our observation on the renal uptake of gentamicin . By increasing the total amount of drug within the kidney, endotoxin and hydrocortisone might increase the risk of nephrotoxicity associated with aminoglycosides.

Med Clin North Am, 1987 Nov, 71(6), 1113 - 33
The cephalosporins; Goldberg DM; Structural modification of cephalosporin antibiotics has produced a broad array of new compounds, notable chiefly for greatly extended gram negative activity with minor toxicity . An understanding of basic principles will enable most clinicians to use these drugs appropriately and effectively.

J Infect Dis, 1987 Nov, 156(5), 713 - 9
Implications of endotoxin contamination in the evaluation of antibodies to lipopolysaccharides in a murine model of gram-negative sepsis; Chong KT et al.; The pharmacological factors involved in lipopolysaccharide (LPS)-induced host resistance against infection were investigated in relation to the problem of endotoxin contamination of preparations of monoclonal antibody to the common structure of endotoxin . When administered prophylactically, purified LPS (as low as 4 ng/kg of mouse body weight) or antibody preparations contaminated with endotoxin (assayed by Limulus amoebocyte lysate test) were protective against lethal challenge with a clinical isolate of Escherichia coli (P less than .01) . Antibodies that were nonreactive to LPS were similarly protective (P less than .001) when spiked with low doses of LPS (100 ng/mg of protein) but, as with LPS, were without effect when administered after infection . Endotoxin contamination of core-reactive antibody to LPS is mostly a problem associated with the large-scale production, purification, and concentration of the monoclonal antibody . The efficacy (as reported in studies in animal models of gram-negative bacterial sepsis) of antibody to LPS core is controversial . We suggest that endotoxin contamination is a likely factor in this controversy.

J Gen Microbiol, 1987 Nov, 133 ( Pt 11), 3121 - 7
Comparison of the phosphatases of Lysobacter enzymogenes with those of related bacteria; von Tigerstrom RG et al.; Lysobacter enzymogenes ATCC 29487 (UASM 495) produces an outer-membrane-associated phosphatase and an excreted phosphatase . The cell-associated enzyme was compared to phosphatases of nine other Gram-negative gliding bacteria and to that of Escherichia coli . The other three species of the genus Lysobacter also produce a particulate, cell-associated phosphatase . Antiserum prepared against the phosphatase from the outer membrane of L . enzymogenes effectively precipitated the phosphatases of two other L . enzymogenes strains and the enzymes of L . antibioticus, L . brunescens and L . gummosus . Some inhibition of the enzyme by the antiserum also was observed . No significant reaction could be detected between the antiserum and the cell-associated phosphatases of species of Cytophaga johnsonae, 'C . compacta', Myxococcus xanthus, E . coli and the excreted phosphatase of L . enzymogenes . The results indicate that the four species of the genus Lysobacter are closely related despite their physiological differences and that the outer-membrane-associated phosphatases of these organisms have different structural characteristics than the phosphatases of the other Gram-negative bacteria that were used . Furthermore, differences in the amino acid compositions of the cell-associated and the excreted phosphatase of L . enzymogenes confirm the immunological results and are in agreement with the physical and chemical differences noted between the two enzymes.

J Infect Dis, 1987 Nov, 156(5), 706 - 12
Polymyxin B moderates acidosis and hypotension in established, experimental gram-negative septicemia; Flynn PM et al.; Polymyxin B (PMB), an antibiotic, and sodium deoxycholate (NaD), a bile salt, are surface-active agents . Each protected mice against an otherwise lethal challenge with purified endotoxin (P less than .001) . To determine if either of these agents was effective in treating established, overwhelming gram-negative septicemia, we infected rabbits by intraperitoneal injection of Escherichia coli K1 . Animals were treated with moxalactam 1 hr after infection, then randomly assigned to groups receiving either saline, PMB, or NaD . Serial samples of blood were assayed for bacterial concentration, levels of plasma endotoxin, arterial blood gases, and complete blood cell counts . Physiologic functions were monitored continuously . Although levels of bacteremia and endotoxemia were similar in all three groups, rabbits receiving PMB had significantly higher mean arterial blood pressure, blood pH, and bicarbonate concentrations than did control rabbits (P less than .05) . Rabbits receiving NaD fared no better than controls . In this model, PMB moderates some of the deleterious effects of established, overwhelming gram-negative bacterial sepsis.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1761 - 7
Monoclonal antibodies to TEM-1 plasmid-mediated beta-lactamase; Morin CJ et al.; At least 28 plasmid-mediated beta-lactamases have been described in gram-negative bacteria . To assess the relationship among these enzymes, we produced and characterized 28 murine monoclonal antibodies to the TEM-1 plasmid-mediated beta-lactamase . Radial immunodiffusion identified 3 monoclonal antibodies as immunoglobulin M (IgM), 18 as subclass IgG1, 2 as IgG2a, and 5 as IgG2b . Using a newly described enzyme immunoassay, cross-reactivity of 16 of these monoclonal antibodies was tested against 24 plasmid-determined beta-lactamases . The 16 monoclonal antibodies cross-reacted with TEM-2 and TLE-1 and, to a certain extent, SHV-1 . Different levels of cross-reactivity were also observed with OXA-3 (11 of 16), OXA-7 (8 of 16), OXA-1 (2 of 16), OXA-6 (2 of 16), and AER-1 (2 of 16) . Six monoclonal antibodies demonstrated partial neutralization of beta-lactamase activity . This study suggests that common epitopes are shared by nine biochemically distinct plasmid-mediated beta-lactamases . On the basis of cross-reactivities with these monoclonal antibodies, we identified four epitopes on TEM-1, TEM-2, TLE-1, and SHV-1 beta-lactamases.

Biochim Biophys Acta, 1987 Oct 16, 903(3), 519 - 24
Radioprotective effects of lipid A, liposomes, and liposomes containing lipid A in mice; Richardson EC et al.; Lipid A from Gram-negative bacterial lipopolysaccharide (endotoxin) was incorporated into liposomal membranes and examined as a prophylactic radioprotectant compound in lethally irradiated mice . Splenic hematopoietic activity, resulting in increased numbers of spleen cell colonies, was induced both by lipid A alone or more strongly by liposomal lipid A . Increased survival of lethally irradiated animals was induced to a slight extent by liposomes alone, to a greater extent by lipid A, and at the highest level by liposomes containing lipid A . Under conditions where 100% of untreated or saline-treated animals died of acute radiation syndrome after 20 days, more than 90% of the animals pretreated with liposomal lipid A were still alive 30 days after irradiation . We conclude that lipid A had substantial radioprotectant activity by itself, and the activity was enhanced by incorporation into liposomes . Liposomes alone also exhibited mild radioprotectant effects.

Scand J Gastroenterol, 1987 Oct, 22(8), 914 - 8
Mononuclear phagocyte thromboplastin and endotoxin in patients with secondary bacterial peritonitis; Almdahl SM et al.; Endotoxin levels and mononuclear phagocyte thromboplastin activities in samples from peripheral blood and peritoneal fluid were determined in nine patients with secondary bacterial peritonitis (appendicitis with perforation, or diverticulitis) and in five control patients (uncomplicated duodenal ulcer or gallbladder stones) . None or only negligible amounts of endotoxin, always less than 0.01 ng/dl (contamination), and no growth of bacteria were detected in controls . In the patients with peritonitis, peritoneal fluid samples always contained gram-negative bacteria, and large amounts (mean, 31.6 ng/dl) of endotoxin were seen . Plasma from these patients also contained endotoxin (mean, 0.56 ng/dl) despite negative blood cultures . Mononuclear phagocytes from controls had low thromboplastin values, whereas both circulating monocytes and peritoneal macrophages from peritonitis patients showed a substantial increase (multifold) of thromboplastin.

Am J Med, 1987 Oct, 83(4), 661 - 5
Septic bursitis in immunocompromised patients; Roschmann RA et al.; A retrospective analysis of 29 patients with septic bursitis was undertaken to ascertain if immunocompromised patients differed in their clinical presentations, type of organisms cultured, and outcome when compared with their non-immunocompromised cohorts . Thirty episodes of septic bursitis occurred in 29 patients, 43 percent of which occurred in immunocompromised patients . Despite similar clinical presentations, the bursae of immunocompromised patients took three times longer to sterilize and had a much higher bursal white blood cell count when compared with the bursae of non-immunocompromised patients . The bacteriologic spectrum was essentially identical in both groups; there were no cases in which gram-negative organisms were recovered from infected bursae . No cases of septic bursitis were seen in neutropenic patients . The most common factors contributing to an immunocompromised state were alcoholism or steroid therapy . A successful resolution of septic bursitis was seen in all the patients in the immunocompromised groups.

J Bacteriol, 1987 Oct, 169(10), 4737 - 42
Variability of the turgor pressure of individual cells of the gram-negative heterotroph Ancylobacter aquaticus; Pinette MF et al.; Cells of Ancylobacter aquaticus were observed under phase microscopy in a chamber to which a measured pressure could be applied . The initial collapse pressure (Ca), i.e., the lowest pressure needed to collapse the most pressure-sensitive gas vesicles, was measured for 69 cells . The cells were taken from cultures in low-density balanced exponential growth, and the experiments were performed quickly so that the bacteria were in a uniform physiological state at the time of measurement . The turgor pressure, Pt, is the difference between the pressure, C, that would cause collapse of vesicles when removed from the cell and Ca . In this paper we focus on the variability of Pt from cell to cell . Part of the observed variability of Ca was due to the variability of the collapse pressure of individual vesicles (standard deviation {SD} = 90 kPa), but because there were about 100 vesicles per cell and because a change in refracted light after the fifth vesicle (approximately) collapsed probably could be detected by the human eye, the pressure would only have an SD of 18.6 kPa due to this type of sampling error . The observed SD of Pt was 42 kPa, indicating that turgor pressure did vary considerably from cell to cell . However, the turgor pressure was independent of cell size . Statistical analysis showed that Pt would decrease 6.9 kPa over a cell cycle, but with too large an SD (19.9 kPa) to be significant . This implies that the observed change in Pt over the cell cycle is not statistically significant.

Drugs, 1987 Oct, 34(4), 459 - 503
The retinoids . A review of their clinical pharmacology and therapeutic use; Orfanos CE et al.; With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses . This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate . The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed . Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy . The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months . This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses . Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses . Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day . In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended . Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day . Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate . Moreover, it has not been shown to increase serum cholesterol levels . However, its clinical efficacy is not yet clearly established . Among the arotinoids, arotinoid ethylester (Ro 13-6298) has revealed the best anti-psoriatic and anti-inflammatory effects at extremely low dose levels . Furthermore, no significant elevations of serum lipids have been observed . Taking its prolonged elimination half-life and its efficacy/side effect ratio into account, the drug is comparable to etretinate . The free arotinoid carboxylic acid (Ro 13-7410) is currently undergoing clinical investigation . Another arotinoid, the parent compound Ro 15-0778, has not demonstrated any convincing clinical efficacy in acne or psoriasis, but topical anti-inflammatory effects were evident in some models.(ABSTRACT TRUNCATED AT 400 WORDS)

Am J Perinatol, 1987 Oct, 4(4), 360 - 2
Failure of endotoxin to cross the chorioamniotic membranes in vitro; Romero R et al.; We have previously reported the detection of endotoxin in the amniotic fluid of patients with gram-negative intra-amniotic infection . Endotoxin or lipopolysaccharide (LPS) is a potent biologic product capable of inducing prostaglandin release from several cell types, and therefore may be involved in the onset of human parturition in the setting of intra-amniotic infection . The experiments outlined in this report were designed to determine whether endotoxin crosses chorioamniotic membranes in vitro . Chorioamniotic membranes obtained at the time of elective cesarean section were placed in Ussing chambers used for transport experiments . Endotoxin was placed in one chamber, and serial timed samples were taken from both chambers for endotoxin quantification, which was performed with the limulus amebocyte gel clot assay . Blue dextran was used to exclude the presence of large defects . Bromophenol blue was used to demonstrate membrane permeability to low-molecular weight substances . Endotoxin failed to cross the chorioamniotic membranes in all experiments (n = 11).

Am J Perinatol, 1987 Oct, 4(4), 356 - 9
Do blood and meconium affect the detection of endotoxin in amniotic fluid with the limulus amebocyte gel clot assay?
Romero R, Kadar N, Lafreniere D, Durum S, Hobbins JC, Duff GW.
The limulus amebocyte lysate (LAL), assay is the most sensitive technique for the detection of endotoxin in biological fluids . Because endotoxin is a component of gram-negative bacteria, the assay has been employed in the detection of gram-negative bacterial contamination of biological fluids . The LAL assay is rapid, inexpensive, easy to perform, and requires little laboratory expertise . When used in conjunction with the gram stain examination of amniotic fluid, it improves the detection of intra-amniotic infection before the availability of culture results . However, the usefulness of the LAL assay in the detection of endotoxin in other body fluids is limited by the presence of an inhibitor to the gelation of the assay . The studies reported in this communication were undertaken to establish if amniotic fluid contains such an inhibitor . Sterile amniotic fluid (AF) samples obtained from 93 patients by transabdominal amniocentesis before labor were used to determine the ED 50 dose of endotoxin necessary for a positive LAL result . The ED 50 dose of endotoxin required for gelation was significantly higher when AF--rather than pyrogen-free saline--was used as the diluent, implying that inhibitors are in fact present (ED 50 = 58.3 pgm/ml) . The presence of blood or meconium in the AF did not enhance inhibition significantly: ED 50 doses were 58.3 pgm/ml and 56.2 pgm/ml, respectively . This is not significantly different from the ED 50 of clear amniotic fluid.

Proc Soc Exp Biol Med, 1987 Oct, 186(1), 21 - 6
Suppressed in vitro blastogenic responsiveness of rat spleen cells after continuous infusion of endotoxin by an implanted osmotic pump; Spitzer JA et al.; Continuous infusion of a gram-negative bacterial endotoxin in relatively small doses into rats by means of an implanted osmotic pump was studied . The model system was designed to examine the effects of endotoxin on the blastogenic response of spleen cells to the endotoxin itself and to a nonspecific T-cell mitogen, concanavalin A (Con A) . Rats were implanted with an osmotic pump which delivered saline for the first 42 hr to provide postsurgical recovery before the onset of endotoxin infusion . Previous studies had shown that during the first 1-4 days after administration of endotoxin marked alterations of metabolism and some changes in physiologic parameters such as blood pressure and in vitro myocardial performance occurred . In the present study the blastogenic responsiveness of spleen cells to endotoxin itself as well as to the nonspecific T-cell mitogen Con A was markedly decreased after several days of continuous administration of endotoxin . Control animals receiving only saline for the same period of time showed a similar depression of blastogenic responsiveness to the lipopolysaccharide (LPS), as well as to Con A, however, with a delay of 2-4 days before comparable levels of suppression became evident . These results indicate that marked alterations of immune competence as measured by blastogenesis of spleen cells to Escherichia coli LPS and to a mitogen such as Con A may occur after implantation of an osmotic pump, with or without continuous infusion of endotoxin . Further studies seem warranted to determine the role of the foreign body reaction to the osmotic pump as well as to the endotoxin administered by the pump.

Chemioterapia, 1987 Oct, 6(5), 346 - 9
Further characterization of the in vitro and in vivo activity of ciprofloxacin against mycoplasmas; Furneri PM et al.; The aim of this study was the evaluation of some parameters which might better characterize ciprofloxacin: the influence of inoculum, serum and medium . Resistance development, hamster protection and mycoplasmacidal concentrations were also investigated . Ciprofloxacin showed moderate antimycoplasmal activity, both in vitro and in vivo . The minimum inhibitory concentrations (MICs) for Ureaplasma urealyticum, if compared to those shown by erythromycin, are lower, but higher than those obtained with tetracyclines . Unlike the macrolides, ciprofloxacin suffers from change of inoculum size, but no single step resistance induction was reported both in ureaplasmas and mycoplasmas . If Mycoplasma pneumoniae pneumonia or genital infections due to U . urealyticum carry out gram-negative rod isolation, ciprofloxacin can be considered a valid therapeutic agent for these mixed infections.

Histopathology, 1987 Oct, 11(10), 1093 - 9
Cerebral infarction due to systemic necrotizing vasculitis in a patient with rheumatic heart disease, subacute bacterial endocarditis and status epilepticus; Mizutani T et al.; Systemic necrotizing vasculitis involving cerebral blood vessels is described in a 30-year-old man with rheumatic heart disease and subacute bacterial endocarditis . Fever, anaemia, splenomegaly and positive blood cultures for Gram-negative bacteria were found on admission . The fever resolved with antibiotic therapy on the third hospital day but he then developed hemiplegia and multifocal seizures . The seizures progressed to uncontrollable status epilepticus accompanied by congestive heart failure and the patient died 20 d after admission . At autopsy, exudative and necrotizing vasculitis involving medium- to small-sized arteries was seen in the brain, the heart and the skeletal muscles . Rheumatic myocarditis and endocarditis and old rheumatic mitral valve deformities were also present . In addition, verrucous endocarditis in the mitral valve and Lohlein's focal glomerulonephritis were noted . We discuss the possible mechanism of the systemic necrotizing vasculitis in relation to rheumatic fever.

Am J Obstet Gynecol, 1987 Oct, 157(4 Pt 1), 815 - 9
Infection and labor: the detection of endotoxin in amniotic fluid; Romero R et al.; Intra-amniotic infections are frequently caused by gram-negative organisms . Lipopolysaccharide, or endotoxin, is a component of the cell wall of these bacteria . The Limulus amebocyte lysate assay is the most sensitive test clinically available for the detection of endotoxin in biologic samples . The diagnostic value of the Limulus amebocyte lysate assay test for the detection of intra-amniotic infection has been examined and compared with that of the Gram stain . The Gram stain had a 60.8% sensitivity and 9.6% false positive rate . The Limulus amebocyte lysate assay had a 69% sensitivity and a 4.8% false positive rate . When both tests were used in combination, the sensitivity improved to 95.6%, whereas the false positive rate was 14.3% . The Limulus amebocyte lysate assay test is a rapid, sensitive, inexpensive, and simple test for the detection of gram-negative intra-amniotic infections.

Life Sci, 1987 Sep 21, 41(12), 1507 - 15
Hepatic prolactin binding is rapidly altered by endotoxin in lactating mice; Carr JK et al.; Endotoxin or lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, produces profound physiologic changes in most mammals . The effects of LPS on ovine prolactin (oPRL) binding by hepatic membranes of lactating mice is explored in this report . Specific 125I-oPRL binding by liver membranes from LPS-responder C3HfB/HeN mice increased two-fold within fifteen minutes of the injection of LPS, while no change was observed in the non-responder C3H/HeJ mice . Specific 125I-insulin binding did not change . Scatchard analysis of equilibrium binding of oPRL to C3HfB/HeN liver membranes indicated that within fifteen minutes of LPS injection, a receptor of differing binding affinity appears and then disappears by one hour post-injection . We propose that these rapid alterations in the specific binding of oPRL by liver membranes from LPS-injected, lactating C3HfB/HeN mice are due to the transient creation or unmasking of a novel class of PRL receptor.

Ther Drug Monit, 1987 Sep, 9(3), 306 - 10
Positive impact of a therapeutic drug-monitoring program on total aminoglycoside dose and cost of hospitalization; Crist KD et al.; A prospective evaluation was undertaken to assess the impact of an aminoglycoside therapeutic drug-monitoring (TDM) program on the total dose of aminoglycoside antibiotics, the duration of therapy, the number of serum concentrations determined, the length of hospital stay, and the potential cost reduction in 221 patients with proven or suspected gram-negative infections . The patients were allocated to a group that received individualized aminoglycoside doses (study) or to a group that did not (control) . The mean total dose of gentamicin or tobramycin per patient course of therapy was 1,258 mg in the study group and 1,981 mg in the control group (p less than 0.0001) . The mean duration of therapy was 5.9 and 10.3 days per patient in the study and control group, respectively (p less than 0.0001) . The mean length of hospital stay was 8.4 days in the study group and 11.8 days for the control (p less than 0.005) . The type and site of infection, number of serum concentration determinations, and mortality were not statistically different for the groups . These data indicate that a TDM program can markedly reduce the total dose of aminoglycoside, which can potentially reduce tissue accumulation and toxicity . In addition, the hospital costs were $725 less per patient in the study group, which would produce a savings of approximately $640,000 per year at our institution.

J Clin Invest, 1987 Sep, 80(3), 605 - 12
Inhibition of endotoxin-induced priming of human neutrophils by lipid X and 3-Aza-lipid X; Danner RL et al.; Lipid X, a precursor of lipid A (the toxic moiety of endotoxin), has been shown to protect animals from the lethal effects of endotoxin challenge . We investigated the mechanism of action of lipid X and 3-aza-lipid X, a diamino-analogue, in vitro, using the ability of lipopolysaccharide (LPS) to prime neutrophils for an enhanced release of toxic oxygen radicals . Lipid X and 3-aza-lipid X inhibited LPS-induced neutrophil priming in a concentration-dependent manner . At high concentrations, 3-aza-lipid X was a partial agonist of priming . Lipid X was found to inhibit LPS-induced priming by directly interacting with the neutrophil in contrast to polymyxin B, which neutralized LPS by binding to it . Increasing concentrations of lipid X shifted the LPS dose response curve of neutrophils rightward but did not prevent maximum priming at higher LPS concentrations, a finding consistent with competitive inhibition . These results suggest that lipid X, a compound structurally related to lipid A, may block neutrophil priming by competing with LPS for cellular binding sites . Lipid X appears to have a novel mechanism of inhibiting LPS effect and may have efficacy in the treatment of gram-negative sepsis.

Orthop Rev, 1987 Sep, 16(9), 659 - 62
Eikenella corrodens infection of the hand--a case report and literature review; Weinberg A et al.; Eikenella corrodens, a gram-negative, slow-growing rod, belongs to the normal flora of mucous membranes . Infections of the hand including this pathogen, are described in human bite and clenched fist injuries . Our case demonstrates another possibility of wound contamination with normal oral flora causing Eikenella corrodens infection . The consequences due to the delay of appropriate therapy are discussed.

Rev Infect Dis, 1987 Sep-Oct, 9 Suppl 5, S512 - 6
Characterization of a nontoxic monophosphoryl lipid A; Johnson AG et al.; Gram-negative bacterial endotoxins constitute some of the strongest immunologic adjuvants known . Precluding their use as adjuvants in humans has been the exquisite toxicity of these compounds in extraordinarily small amounts . With the acquisition of precise knowledge of the structure of the active moiety, detoxifying procedures have been developed . These have resulted in the isolation of a monophosphoryl lipid A with a much reduced toxicity that retains the capacity to act as an adjuvant in young mice as well as in immunodeficient aging mice.

Rev Infect Dis, 1987 Sep-Oct, 9 Suppl 5, S503 - 11
Review of the molecular requirements of endotoxic actions; Nowotny A; Old and new data are compiled to confirm earlier claims and to substantiate new concepts regarding the structural requirements of endotoxic reactions . The major points can be summarized as follows . (1) Recent results obtained by the use of synthetic analogues of lipid A structures proved unequivocally that the lipid moiety of the endotoxin is the carrier of toxic properties . Incomplete or attenuated structures are inactive in some or all toxic reactions, depending on the extent of deviations from the structure of the native product . (2) On the other hand, some beneficial reactions can be initiated not only by the complete structures but by their structural remains, which are no longer toxic . (3) Some of the split products in the lipid-free and polysaccharide-rich preparations can induce beneficial reactions . (4) Gram-negative bacteria can produce endotoxin-unrelated and beneficial compounds . Conventional endotoxin preparations are heterogeneous and often contain some of these unrelated substances . (5) Elucidation of the exact structural requirements of endotoxic reactions has just begun . It appears to be safe to predict that individual reactions will require highly specific structures or physicochemical properties . The potential rewards of such research might be quite significant by facilitating our understanding of the molecular events of the beneficial effects of endotoxins and by directing the search for preparations with therapeutic applications.

Clin Chest Med, 1987 Sep, 8(3), 543 - 56
Strategies for the prevention of pneumonia; Niederman MS; Pneumonia remains a major source of morbidity and economic cost to our society, despite the availability of new antibiotics for therapy . To truly reduce the impact of this illness, serious efforts at preventing infection must be undertaken . In the area of community-acquired infections, safe and effective vaccines are available against S . pneumoniae, the most common pneumonic pathogen, and influenza . High-risk individuals (Table 2), who should be considered for vaccination, include: the elderly; residents of chronic-care facilities; and patients with chronic cardiac, respiratory, renal, and hematologic illnesses . Influenza vaccine is effective in preventing infections in such high-risk populations, including the elderly . There is some controversy about the efficacy of pneumococcal vaccine in an at-risk population with severe co-morbid illness, but there is little doubt that the vaccine is effective in a more healthy elderly population . Both patients and physicians fail to appreciate the safety and utility of these vaccines as evidenced by their low rates of use . Remarkably, only about 10 per cent of appropriate persons have ever received the pneumococcal vaccine, even though it needs to be given only once in a lifetime . In the area of nosocomial pneumonia, several strategies for prevention have proven to be useful . Most promising is the use of topical antibiotics in the upper and lower airway . Although the efficacy of this approach is well established, its safety has been questioned in prior studies . For many reasons, this position should be reevaluated, and this therapy should be considered for use in carefully selected patients at risk, using modern techniques of aerosol therapy . Active investigation into vaccines against gram-negative bacterial look to yield promising results in the future . In addition, passive "serum" therapy with preformed antibodies is a strategy for preventing gram-negative lung infection that has shown use in animal studies and may circumvent certain logistical problems of vaccine therapy . Infection control methods and sensible handling of respiratory therapy equipment are simple, yet effective, means for preventing contamination of the airway in mechanically ventilated patients . Finally, for patients both in and out of the hospital, an understanding of the nature of host defense impairments leading to pneumonia will allow for strategies to boost host defenses.(ABSTRACT TRUNCATED AT 400 WORDS)

Arch Intern Med, 1987 Sep, 147(9), 1642 - 4
Gentamicin resistance among gram-negative bacillary blood isolates in a hospital with long-term use of gentamicin; Mylotte JM; Between 1977 and 1985, gentamicin was the only formulary aminoglycoside at the Buffalo Veterans Administration Medical Center . During this time, there was a significant increase in the amount of gentamicin purchased . Amikacin represented 11% or less of the total aminoglycoside purchased in the same period, but purchases of this agent also significantly increased . Because of this long-term use of gentamicin, a retrospective analysis of gentamicin resistance among gram-negative bacillary blood isolates was performed . The results of this review revealed no significant change in the overall incidence of gram-negative bacteremia; approximately 75% of these bacteremic episodes were hospital acquired . The mean yearly gentamicin-resistance rate of gram-negative blood isolates was 13.2% (range, 6% to 18%) with no significant change in the rate for the period reviewed . However, for certain strains there were fluctuations in the percentage of resistance from year to year, suggesting that clusters of infections due to these organisms had occurred . Bacteremic infection due to resistant organisms was a major contributor to the overall level of gentamicin resistance among blood isolates . Amikacin resistance among gram-negative blood isolates was rare . In conclusion, despite the predominant use of gentamicin there was no change in the gentamicin resistance rate among gram-negative bacillary blood isolates during a nine-year period . The rate of gentamicin resistance among blood isolates appeared to be related to outbreaks/clusters of infections due to resistant strains rather than the frequency of use of gentamicin.

J Infect Dis, 1987 Sep, 156(3), 456 - 62
Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits; Tauber MG et al.; We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis . Both antibiotics were similarly effective in reducing bacterial titers . Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 +/- 0.8 to log10 2.8 +/- 0.7 ng/ml (P less than .01) . This result was associated with an increase in brain water content (405 +/- 12 g of water/100 g of dry weight compared with 389 +/- 8 g in untreated controls; P less than .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls . The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A . These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edema.

Microbiol Sci, 1987 Sep, 4(9), 270 - 3
Contribution of immunogold labelling to study of the outer membrane of gram-negative bacteria; Ryter A; The immunogold labelling technique is beginning to make a significant contribution to the study of several biological systems . In the case of Gram-negative bacteria, immunogold labelling performed either on whole cells or on thin sections has recently begun to facilitate the study of outer membrane biogenesis, the topology of membrane proteins, and protein export.

Rev Infect Dis, 1987 Sep-Oct, 9 Suppl 5, S630 - 8
Strategies for the treatment of endotoxemia: significance of the acute-phase response; Warren HS et al.; Shock during gram-negative bacterial sepsis continues to be a major clinical problem . Its development is assumed to be due to the release of toxic lipopolysaccharide (LPS) from the bacterial cell wall . Consequently, research efforts have turned toward treatment to counteract the effects of LPS . Possibilities include methods based on the blocking of over-exuberant intrinsic host responses to LPS and on the neutralization of LPS with pharmacologic agents or passively infused antibodies directed at different parts of the molecule . Evidence exists to support the concept that some LPS-induced (acute-phase) host responses may play a role in protection against LPS.

Am J Med, 1987 Sep, 83(3), 499 - 502
Appropriateness of antibiotic therapy in long-term care facilities; Jones SR et al.; The objective of this study was to examine the appropriateness of antibiotic therapy in nursing homes . Information was abstracted from infection control reports and patients' charts for a three-month period at two nursing homes in Portland, Oregon . A panel of two board-certified infectious disease specialists and one hospital pharmacist reviewed the information and rated the appropriateness of each prescription using a previously developed scale . Among the 120 infections, treatment was rated as appropriate in 49 percent, as inappropriate in 42 percent, and as unjustified in 9 percent . Cephalosporins received the lowest percent of appropriate ratings (27 percent) . The primary reason for an inappropriate rating was that a more effective drug was recommended for empiric therapy of gram-negative bacillary infections . These bacteria are often resistant to oral antibiotics . There were no significant differences in appropriateness by type of organism, infection site, or clinical outcome . Physician education and the development of systems and guidelines for optimal management in this population are appropriate actions for the future.

Infect Immun, 1987 Sep, 55(9), 2290 - 2
Deficiency of peptidoglycan and lipopolysaccharide components in Rickettsia tsutsugamushi; Amano K et al.; Analyses of chemical composition in whole cells of Rickettsia tsutsugamushi were performed and compared with those of the other rickettsiae and gram-negative bacteria . The results indicated that R . tsutsugamushi does not contain detectable amounts of 3-deoxy-D-mannooctulosonic acid, heptose, muramic acid, or glucosamine (less than 2, less than 2, less than 3, and less than 3 nmol/mg, respectively) . The microorganism was found to contain four kinds of fatty acids (16:0, 18:0, 18:1, and 18:2), but not hydroxy fatty acids . Furthermore, in analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver or Coomassie blue staining, lipopolysaccharide bands were not detected in preparations treated with proteinase K . It is concluded that R . tsutsugamushi has little or no peptidoglycan or lipopolysaccharide.

Rev Infect Dis, 1987 Sep-Oct, 9 Suppl 5, S639 - 43
Reactivity of antibodies to core glycolipid with gram-negative bacteria; Shenep JL et al.; Studies of the cross-reactivity of antibodies to core glycolipid with assorted isolated, heterologous lipopolysaccharides (LPSs) confirm the conservation of core glycolipid epitopes among gram-negative bacterial species . However, the accessibility of core glycolipid epitopes to antibody in the intact bacterial cell may be affected by the cell surface structure . In studies with 125I-labeled monoclonal antibodies to core glycolipid that cross-react with isolated LPS, the degree to which antibodies can bind to LPS in the outer membrane of intact, viable, gram-negative bacterial cells was found to vary with the strain of bacteria tested . Sequestration of bacterial cell-bound LPS from antibody was confirmed in a smooth strain of Escherichia coli by means of immunoelectron microscopy . The inability of antibody to bind to membrane-bound LPS suggests that such sequestered LPS may also be unable to effect toxicity in the infected host until liberated by bacterial cell breakdown.

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