Arch Immunol Ther Exp (Warsz), 1985, 33(6), 851 - 6 Characteristics of Mycoplasma strains isolated from stallion semen; Zgorniak-Nowosielska I et al.; Eleven mycoplasma strains were isolated from the semen of 24 stallions . Eight of these strains were identified as Mycoplasma equigenitalium . Three strains which hydrolized arginine could not be identified . The growth inhibition test with immune sera against M . arginini and M . equirhinis was negative . Antibiotic sensitivity test showed that all strains were sensitive to four antibiotic of tetracycline group (oxytetracyclin, minocycline, transcycline and vibramycin) . Lincomycin and gentamycin appeared to be the most active against all the strains . Comparative analysis of routine semen examination did not reveal any difference between ejaculates infected with mycoplasma and free of these organisms . However, the levels of certain biochemical components of the semen plasma (glycerylphosphorylcholine, ergothioneine, fructose and of the semen plasma (glycerylphosphorylcholine, ergothioneine, fructose and total protein) from mycoplasma-positive ejaculates were significantly lower than in the semen plasma from mycoplasma free ejaculates. Nucleic Acids Symp Ser, 1985, (16), 141 - 4 Protected 2'-deoxyaristeromycin on polymer support: a substitute for the acid labile 2'-deoxyadenosine moiety at the 3'-terminus of oligodeoxynucleotides; Miyashita O et al.; A modified nucleoside antibiotic on polymer support was employed in the solid-phase synthesis of two oligodeoxynucleotides to substitute acid labile 2'-deoxyadenosine(A) at the 3'-terminus of oligomers with acid resistant 2'-deoxyaristeromycin(Ar) . The duplex of the decamer having sticky ends was inserted successfully into the Eco R1 site of pBR322 . E . coli DH 1 was transformed with the Ar-containing plasmid . Inspection of the cloned plasmid pBR2552 by restriction endonucleases revealed that no deletion and insertion occurred near the inserted sequence . This result indicates that Ar can behave as A in DNA replication of the host cells . Therefore, Ar can be used as a substitute for 3'-terminal A in the solid-phase oligonucleotide synthesis. Mol Gen Genet, 1985, 199(3), 401 - 5 Effects of polymyxin B sulfate and polymyxin B nonapeptide on growth and permeability of the yeast Saccharomyces cerevisiae; Boguslawski G; Polymyxin B, a toxic, membrane-affecting antibiotic, can be rendered harmless to yeast cells by enzymatic removal of its fatty acyl moiety . The remaining cyclic peptide portion, polymyxin B nonapeptide, has no significant effect on growth and viability but it drastically reduces mating efficiency . In addition, the cyclic peptide enhances sensitivity of cells to several drugs, presumably by increasing membrane permeability . Mutants resistant to polymyxin B are simultaneously less responsive to the combination of the nonapeptide and the drugs . This indicates that the peptide portion of polymyxin B is the moiety responsible for the permeability changes . The resistance is inherited as a simple recessive trait . The mutation has been mapped to chromosome XV of Saccharomyces cerevisiae. J Basic Microbiol, 1985, 25(5), 325 - 33 Influence of inorganic phosphate on the lipid synthesis of a phosphate-deregulated mutant of Streptomyces noursei; Hanel F et al.; Phosphate-dependent changes of the mycelial lipid composition were studied in the streptothricin-producing parental strain Streptomyces noursei JA 3890 b/2 and its mutant RG 2 . In contrast to its ancestor, the mutant was capable of producing the antibiotic nourseothricin even when large quantities of inorganic phosphate were present in the medium . The apparent insensitivity of the secondary metabolism to phosphate inhibition corresponds to a decreased level of phospholipids in the presence of excessive inorganic phosphate and, during phosphate limitation, to a much higher production of the alkaline phosphatases . A model is discussed which proposed the control by a common genetic element of both the phospholipid and antibiotic production. J Basic Microbiol, 1985, 25(3), 175 - 86 Influence of nourseothricin on growth and secondary metabolism of Streptomyces noursei JA 3890b; Roder B et al.; The nourseothricin-producing S . noursei strain JA 3890b possessed a high degree of resistance to its own antibiotic when grown in submerged cultures started from mycelium samples as inocula . In contrast, both the outgrowth of spores and the development of surface colonies from mycelium samples were severely inhibited in the presence of relatively low concentrations of nourseothricin, suggesting that the producer organism is susceptible to the autotoxic metabolite in particular stages of its development . Nourseothricin production by submerged cultures has been found to be independent of negative feedback regulation by the antibiotic. Pharmacol Res Commun, 1985 Jan, 17(1), 33 - 47 Captopril inhibits sodium and water transport in the toad skin, a model of the distal nephron; Orce GG et al.; Captopril (SQ 14225), an orally active angiotensin I-converting enzyme inhibitor (CEI), increases natriuresis and diuresis in man and experimental animals in vivo, as well as in the isolated perfused rat kidney, raising the possibility of a direct renal action of the drug . We tested this hypothesis by studying its effects in the isolated toad skin, a model of the distal nephron devoid of vascular and nervous influences . When added to the dermal bath, captopril caused a reversible, concentration-related decrease in short-circuit current (SCC), a measure of active transepithelial Na transport . Keeping the toads in 0.1 M NaCl for 4 or more days increased sensitivity to the drug, which then inhibited SCC maximally (49 +/- 12% at 3.4 X 10(-3) M, P less than 0.01, n = 10), suggesting its effect might be modulated by endogenous mineralocorticoid activity . Captopril also inhibited the increase in SCC and in osmotic water permeability caused by neurohypophyseal peptides (NHP) . The increases in SCC by non-peptidic agents (nystatin, a polyene antibiotic, or norepinephrine, an adrenergic agonist) were not altered, ruling out a generalized toxic effect, or any significant inhibition of the Na pump by captopril . The apparently specific effect of the drug on the permeability responses to NHP seems to be exerted proximally to the apical border, since the response of the latter to other agents was preserved . The present data suggest SH groups may be involved, since other CEI lacking such groups (teprotide and MK-422) do not produce such effects . These observations support the notion that a direct tubular effect may be involved in the increased diuresis and natriuresis observed after administration of captopril. Mol Biol (Mosk), 1985 Jan-Feb, 19(1), 177 - 95 {Specific protection of DNA by distamycin A, netropsin and bis-netropsins against the action of DNAse I}; Skamrov AV et al.; Interaction of netropsin, distamycin A and a number of bis-netropsins with DNA fragments of definite nucleotide sequence was studied by footprinting technique . The nuclease protection experiments were made at fixed DNA concentration and varying ligand concentrations . The affinity of ligand for a DNA site was estimated from measurements of ligand concentration that causes 50% protection of the DNA site . Distribution pattern of the protected and unprotected regions along the DNA fragment was compared with the theoretically expected arrangement of the ligand along the same DNA . The comparison led us to the following conclusions: 1 . Footprinting experiments show that at high levels of binding the arrangement of netropsin molecules along the DNA corresponds closely to the distribution pattern expected from theoretical calculations based on the known geometry of netropsin--DNA complex . However, the observed differences in the affinity of netropsin for various DNA sequences is markedly greater than that expected from theoretical calculations . 2 . Netropsin exhibits a greater selectivity of binding than that expected for a ligand with three specific reaction centers associated with the antibiotic amide groups . It binds preferentially to DNA regions containing four or more successive AT pairs . Among 13 putative binding sites for netropsin with four or more successive AT pairs there are 11 strong binding sites and two weaker sites which are occupied at 2 D/P less than or equal to 1/9 and 2 D/P = 1/4, respectively . 3 . The extent of specificity manifested by distamycin A is comparable to that shown by netropsin although the molecule of distamycin A contains four rather than three amide groups . At high levels of binding distamycin A occupies the same binding sites on DNA as netropsin does . 4 . The binding specificity of bis-netropsins is greater than that of netropsin . Bis-netropsins can bind to DNA in such a way that the two netropsin-like fragments are implicated in specific interaction with DNA base pairs . However, the apparent affinity of bis-netropsins estimated from footprinting experiments is comparable with that of netropsin for the same DNA region . 5 . At high levels of binding bis-netropsins and distamycin A (but not netropsin) can occupy any potential site on DNA irrespectively of the DNA sequence . 6 . Complex formation with netropsin increases sensitivity to DNase I at certain DNA sites along with the protection effect observed at neighboring sites. Proc Natl Acad Sci U S A, 1985 Jan, 82(1), 158 - 62 Transfer of genes into hematopoietic cells using recombinant DNA viruses; Karlsson S et al.; The ability of recombinant DNA viruses to transfer genes into hematopoietic cells has been explored . A recombinant simian virus 40 (SV40) in which the early region had been replaced with the chloramphenicol acetyltransferase (CAT) gene driven by the promoter from Rous sarcoma virus (RSV), was constructed . This virus transferred the CAT gene more efficiently into mouse and human bone marrow cells and into the K562, MEL, and WEHI hematopoietic tissue culture cell lines, than the classical calcium phosphate DNA transfer procedure, as shown by assay for CAT activity 48 hr after infection . Recombinant SV40 virions were also shown to be capable of stably transforming Chinese hamster ovary cells by use of an early region recombinant containing the methotrexate-resistant dihydrofolate reductase (DHFR) gene driven by the RSV promoter . The entire DHFR transcriptional unit could be detected in the genome of transformed cells that were also shown to be resistant to methotrexate . A recombinant adenovirus stock containing the neomycin-resistance gene driven by the SV40 early promoter was used to infect the K562 and MEL hematopoietic cell lines to resistance to the antibiotic G418 . Transformation frequency was 10- to 100-fold higher than that obtained with calcium phosphate-precipitated DNA . Most or all of the recombinant adenovirus genome was integrated as 1-3 copies in the transformed cells . These studies show the feasibility of using DNA viruses for introduction of new genetic material into hematopoietic cells. Vutr Boles, 1985, 24(6), 78 - 84 {Pyogenic liver abscesses--diagnostic and surgical problems}; Merdzhanov A et al.; The authors discuss the clinical-diagnostic and surgical problems in the treatment of the pyogenic hepatic abscesses . Eight patients, undergone the operation during the second period after 1971, were out of 18 patients operated (1951--1983) were analyzed in details . An inexplicable predomination of males and affection of all age groups is reported . The abscesses are cryptogenic in 2 of the patients, after operation of the hepaticbiliary system--in 2, after gastric operation--in 3, after abdominal trauma--in 1 . The possible way of penetration of the infection is discussed . In was established that it parallel with the characteristic clinical picture and biochemical deviations, typical for the septic process, a definite diagnosis is made via echography and computer tomography, supported by scintigraphy, angiography, punching of the abscess, inspection graphy of the hepatic region . The treatment is difficult and complex: Antibiotic, generally tonizising and surgical . The choice of the operative approach denends on the localization, number of the abscesses and character (pyogenic, amebic, etc) . The therapeutic tasks are discussed as well as the operation methods applied, punch-aspiration including . The risk of complications and lethality remain high, three patients were discharged healthy, with improvement--2, deceased--3 (sepsis, stress-ulcer, pulmonary embolism). Acta Biomed Ateneo Parmense, 1985, 56(1), 23 - 6 {Use of oral bacteria therapy in childhood during acute enteritis and functional chronic diarrhea . Clinical experience}; Gregori G et al.; There are some theoretical reasons to give an oral bacterial therapy when intestinal ecosystem changes its composition . The authors would verify the clinical effectiveness or oral bacterial therapy during acute and functional chronic diarrhea: even if the course of the illness doesn't become shorter, oral bacterial therapy moreover may be useful in reducing the risk of having casual carries of pathogenic agents and may restore an intestinal ecosystem previously modified by antibiotic therapy. Microbios, 1985, 44(177), 51 - 66 Mechanism of stimulation of Ca2+ uptake by miconazole and ethidium bromide in yeasts: role of vacuoles in Ca2+ detoxification; Eilam Y et al.; The antifungal antibiotic miconazole and the cationic dye ethidium bromide, both caused K+ efflux, membrane depolarization and intracellular acidification in the yeast Saccharomyces cerevisiae . Whereas miconazole inhibited the activity of the plasma membrane H+-ATPase, no such inhibition was observed using ethidium bromide at concentrations up to 600 microM . Low concentrations of both drugs caused marked stimulation of the energy dependent Ca2+ uptake . The extra Ca2+ taken up in the presence of the drugs was localized within the vacuoles, whereas K+ was lost mainly from the cytosolic pool . The ions Zn2+ and La3+ inhibited the effect of both drugs on the stimulation of Ca2+ uptake . The results indicated that both drugs caused an increase in the permeability of cell membranes to ions, leading to an increase in the influx of Ca2+ into the cytosol along its electrochemical gradient . Consequently, the concentration of Ca2+ within the cytosol increased and in turn led to the enhancement of Ca2+ uptake by the energy dependent vacuolar Ca2+ system, which functioned as a Ca2+ detoxification system. Acta Med Hung, 1985, 42(3-4), 163 - 74 Therapeutical experiments in ulcerative colitis and Crohn's disease; Nagy G et al.; In the period 1963-82 among the patients with aspecific inflammatory bowel disease, the incidence of ulcerative colitis was 3.1 per 100 000 per year, while the frequency of Crohn's disease has doubled during the observation period and now its incidence is 0.58 per 100 000 per year . During the past 20 years, 404 patients with ulcerative colitis were treated . The average follow-up of the patients lasted for 6.6 years . During this period, 40% of the patients could be kept in balance permanently with salicylazosulfapyridine (SASP) monotherapy . A further 34% reacted to SASP plus steroid . The rate of regression was increased by a further 14% when the combination was occasionally completed with a short-term antibiotic or prolonged azathioprine therapy . The inestimable cases and those refractory to treatment made up the other 12% and among them are also the 23 colectomized patients . During the two decades 40 patients with Crohn type ileocolitis were treated . SASP administration by itself was sufficient in only one case among them . In 6 cases steroid, in 4 antibiotics, in 7 azathioprine and in 2 cases metronidazole treatment had to be introduced complementarily . The fact that 21 of the 40 patients had to be subjected to bowel resection in some phase of the disease, shows how impossible it is to evaluate the different therapeutic interventions. Comp Biochem Physiol C, 1985, 81(2), 401 - 4 Actinomycin D and cycloheximide actions on activity of some intestinal enzymes of adult hamster; Andres MD et al.; Actinomycin D, at a dose of 0.25 micrograms/g body wt, produced slight increases in intestinal enzymatic activity on hamsters . At a high dose (1.5 micrograms/g body wt), actinomycin D produced inhibition of lactase activity, whereas maltase, sucrase and alkaline phosphatase activity decreased in males and increased in females . Cycloheximide (1.5 micrograms/g body wt), produced no changes in enzymatic activity . In the male and female hamster, the different actions of the antibiotic can be explained by the variations in the cortisol release produced by stress. Virchows Arch B Cell Pathol Incl Mol Pathol, 1985, 48(3), 219 - 27 Fine structural aspects of the black thyroid induced by minocycline, and the effects of a low iodine diet, propylthiouracil, thyroxine tablet and TSH, on the black discoloration of the rat thyroid; Kurosumi M et al.; Fine structural aspects of the effect of minocycline, an antibiotic of the tetracycline group, on the rat thyroid were studied . In all the rats administered minocycline (100 mg/kg/day) for 21 days, diffuse black discoloration of the thyroid gland occurred . However, when the rats were fed on a low iodine diet, given propylthiouracil (PTU) or thyroxine tablet with minocycline the black pigmentation of the thyroid gland did not take place . On the other hand, black discoloration of the thyroid was accelerated in the rats administered TSH and minocycline simultaneously . Ultrastructurally, numerous dense bodies containing highly electron-dense deposits were seen in the supranuclear region of the follicular epithelial cells of the black thyroid . These dense bodies, which showed positive acid phosphatase activity, are considered to be lysosomes containing minocycline or its derivatives . It is speculated that minocycline is taken up into follicular epithelial cells with iodine, and that the black discoloration of the thyroid gland is intimately related to iodine metabolism. Folia Haematol Int Mag Klin Morphol Blutforsch, 1985, 112(1), 208 - 18 {Bisalbuminemia . Critical review and report of a case of an acquired form in a myeloma patient}; Pola V et al.; Hitherto, bisalbuminemia (double albuminemia) was regarded as a rare finding in serum electrophoresis . In its first part, therefore, the present paper briefly refers to history, systematic, appearance, geography, genetics and laboratory problems of anomaly . By means of own observations made in an acquired form of bisalbuminemia in a patient with a myeloma, problems and practical significance of this serum protein anomaly are then discussed in a second part . This serum protein anomaly is likely to occur more frequently than hitherto assumed and after clarification it may contribute to increase our knowledge about indication and technique of the antibiotic therapy. Acta Derm Venereol, 1985, 65(1), 43 - 52 Clinical manifestations of erythema chronicum migrans Afzelius in 161 patients . A comparison with Lyme disease; Asbrink E et al.; Clinical symptoms were studied in 161 consecutive patients with erythema chronicum migrans Afzelius and in a follow-up study signs of late manifestations were investigated . General symptoms such as headache, fever, myalgia and/or arthralgia were found in about half of the patients with a disease duration of less than or equal to 3 weeks . Three patients had coexisting lymphadenosis benigna cutis . Two untreated patients developed meningitis/meningoradiculitis and one untreated patient arthritis . The importance of a sufficient antibiotic therapy to prevent late manifestations is stressed . Although there are many similarities between erythema chronicum migrans Afzelius and Lyme disease, the results of the present study also point to differences . Multiple skin lesions, pronounced general symptoms, laboratory abnormalities and major symptoms from the joints were less common in patients with erythema chronicum migrans Afzelius than reported in patients with Lyme disease, but a prolonged course of the skin eruption was more common. Cancer Res, 1985 Jan, 45(1), 213 - 6 Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicoumarol in vivo and in vitro; Keyes SR et al.; Previous work by our laboratories demonstrated that dicoumarol can increase the enzymatic activation of mitomycin C (MC) to alkylating species by tumor cell sonicates under hypoxic conditions . To determine whether this increased generation of reactive metabolites would result in increased cytotoxicity, we examined the effect of this combination on the viability of EMT6 cells treated in vitro under hypoxic and oxygenated conditions . Dicoumarol increased the cytotoxicity of MC to these neoplastic cells under hypoxic conditions and decreased the toxicity of the antibiotic to aerobic cells . These findings suggested that dicoumarol might enhance the toxicity of MC to the hypoxic cells of solid tumors, without increasing the toxic side effects of the antibiotic to the host . Treatment of EMT6 tumor-bearing animals with both dicoumarol and MC significantly decreased the survival of the radioresistant hypoxic tumor cells from that obtained with MC alone . In contrast, the leukopenia produced by the antibiotic was not exacerbated by the addition of dicoumarol . These results suggest that a treatment regimen combining dicoumarol and MC might be a useful adjunct to radiation therapy for the eradication of the radioresistant hypoxic cells in solid tumors. Drugs Exp Clin Res, 1985, 11(1), 9 - 15 Experimental studies on aclacinomycin; Tone H et al.; Experimental features of aclacinomycin (ACM), a new antitumour antibiotic of the anthracycline group, are presented . ACM inhibited the growth of experimental mouse tumours and human cancer xenografts from various origins . In CDF1 mice with L1210 cells treated i.p . with ACM in combination with Ara-C for 10 days, a 459% ILS was observed, including 67% of 60-day survivors . The inhibition of RNA and DNA synthesis was examined in L1210 cells . The IC50 values of ACM for incorporations of {14C}-thymidine and {14C}-uridine were 0.30 and 0.038 microgram/ml respectively . The ratio of IC50 . DNA/RNA was 7.9, while with adriamycin (ADR) it was 2.5 . ACM showed no mutagenic activity in the Ames' test and the rec- assay . The cardiac toxicity of ACM was significantly lower than that of ADR . Lower ECG changes, a return to normal after discontinuation of the drug and slighter ultrastructural modifications of the myocardium were demonstrated in hamsters and rabbits . When administered to hamsters i.v . at 5 mg/kg, ACM was eliminated almost completely from the heart muscle after 2 h, while ADR remained at 8 micrograms/g even after 8 h. Cornea, 1985-86, 4(4), 256 - 62 Two treatments of eye bank donor corneas; Farge EJ et al.; The many published studies on sterile procedures used by eye banks have included none until now on ways to optimize sterile handling of corneas procured in the morgues of forensic pathologists . The present study sought to discover if fewer positive cultures would be reported at the time of surgery from corneas which had been treated with an entire bottle of antibiotic (10 ml), as opposed to the more usual method of instilling 10 to 12 drops of antibiotic prior to the corneal excision . The result showed a marginal improvement of 3.1% fewer positive cultures when the entire bottle of antibiotic was used . The findings bolstered the theory that thorough and vigorous washing of the conjunctival sac prior to corneal removal is important and that positive cultures are no more likely when the cornea is shipped away from the eye bank than when used locally. Chromosoma, 1985, 93(2), 165 - 8 SCE induction and harlequin staining in mycoplasma-contaminated Chinese hamster cells; White GR et al.; Chinese hamster V79 and CHO cells infected with Mycoplasma hyorhinis show elevated sister-chromatid exchange (SCE) levels but normal cell proliferation and levels of chromosomal aberrations when compared with uninfected cells . Harlequin staining patterns differ from those seen with uninfected cells at similar levels of bromodeoxyuridine (BrdUrd), indicating that BrdUrd is rapidly depleted from the medium by the mycoplasmal uridine phosphorylase and therefore becomes unavailable over the two cell cycles necessary for harlequin staining . Continuous treatment with the antibiotic minocycline restores the SCE level and harlequin staining to that seen in uncontaminated cells . The results suggest that mycoplasma infection should be suspected if harlequin staining patterns indicate a sudden decrease in incorporation of BrdUrd in cells grown in normal levels of BrdUrd. J Membr Biol, 1985, 87(3), 233 - 9 Osmotic water permeability of small intestinal brush-border membranes; Worman HJ et al.; A stopped-flow nephelometric technique was used to examine osmotic water flow across small intestinal brush-border membranes . Brush-border membrane vesicles (BBMV) were prepared from rat small intestine by calcium precipitation . Scattered 500 nm light intensity at 90 degrees to incident was a linear function of the number of vesicles in suspension, and of the reciprocal of the suspending medium osmolality . When BBMV were mixed with hyperosmotic mannitol solutions there was a rapid increase in the intensity of scattered light that could be fit to a single exponential function . The rate constant for vesicle shrinking varied with temperature and the size of the imposed osmotic gradient . At 25 degrees C and an initial osmotic gradient of 50 mOsm, the rate constant was 1.43 +/- 0.044 sec-1 . An Arrhenius plot of the temperature dependence of vesicle shrinking showed a break at about 25 degrees C with an activation energy of 9.75 +/- 1.04 kcal/mole from 11 to 25 degrees C and 17.2 +/- 0.55 kcal/mole from 25 to 37 degrees C . The pore-forming antibiotic gramicidin increased the rate of osmotically driven water efflux and decreased the activation energy of the process to 4.51 +/- 0.25 kcal/mole . Gramicidin also increased the sodium permeability of these membranes as measured by the rate of vesicle reswelling in hyperosmotic NaSCN medium . Gramicidin had no effect on mannitol permeability . Assuming spherical vesicles of 0.1 micron radius, an osmotic permeability coefficient of 1.2 X 10(-3) cm/sec can be estimated for the native brush-border membranes at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) J Gynecol Obstet Biol Reprod (Paris), 1985, 14(6), 683 - 7 {Prevention of peritoneal adhesions by local treatments . Experimental study in the rat}; Querleu D et al.; Those local treatments that are most used clinically for the prevention of adhesions in the pelvis have been evaluated experimentally using peritoneal abrasion in the rat . In a first experiment these products, namely dexamethasone, high molecular weight dextran, and noxytioline, were compared with a saline solution on the one hand which confirmed the effect of these substances in preventing adhesions, and on the other hand showed that noxytioline was about as effective as dextran 70 and better than corticosteroids . The score for adhesions that were found were; in the control series an average of 9.25, in the dexamethasone series 6, in the dextran 70 series 4.1 and in the noxytioline series 4.00 . This last substance, which has been for less broadly studied than dextran, was then made the subject of a second experiment carried out in the same way as the first, and showing that the anti-adhesion effect was not something that was added on to its anti-bacterial effect because noxytioline alone was more effective than a broad spectrum antibiotic by itself, and adding the two together gave a still better result . It would seem to us that using noxytioline and dextran 70 together does not improve the results achieved by using each substance by itself. Hear Res, 1985, 20(1), 37 - 43 Abolition of the negative endocochlear potential as a consequence of the gentamicin-furosemide interaction; Lee SJ et al.; The DC endocochlear potential and the AC cochlear potential in response to a 4 kHz tone were recorded in pigmented guinea pigs before and during ototoxic damage induced by sequential administration of the aminoglycoside antibiotic, gentamicin, and the loop diuretic, furosemide . Within 4 h significant diminution of the amplitude of the AC cochlear potential was accompanied by an almost complete abolition of the negative diffusion potential revealed by either furosemide administration or terminal anoxia . Thus, one of the effects of this interaction appears to involve a reduction in the potassium permeability of the cochlear partitions. Eur Biophys J, 1985, 12(2), 67 - 73 Molecular shape and dipole moment of alamethicin-like synthetic peptides; Rizzo V et al.; The peptides Boc-(L-Ala-Aib-L-Ala-Aib-L-Ala)n-OMe, with n = 2 (P10) and n = 4 (P20), have been synthesized as purely hydrophobic models of the antibiotic alamethicin, which is known to be a voltage-dependent pore former in membranes and is apparently alpha-helical in lipophilic media . These peptides were investigated in 1-octanol, a solvent which resembles the membrane environment . From dielectric dispersion studies quantitative information on the molecular shape and dipole moments could be derived . Further independent data concerning conformation and extent of aggregation of the peptides were obtained by circular dichroism and ultracentrifuge measurements . The results suggest that the peptides assume the form of elongated particles having a significant amount of ordered secondary structure and carrying a dipole parallel to the long axis . Apparently the monomeric peptide molecules undergo, to some extent, a head-to-tail aggregation which is slightly enhanced at lower temperatures . Based on the high-frequency parts of the dielectric dispersion curves the lengths, diameters, and dipole moments of the monomer particles have been determined as 22.5A, 10A, 36 D (P10) and 28.5A, 12A, 64D (P20). Tierarztl Prax Suppl, 1985, 1, 123 - 31 {Diagnosis of prostatic diseases in the dog using ultrasonics}; Fritsch R et al.; The use of sonography in diagnosing prostate gland diseases has proven very helpful . In contrast to x-raying, it allows the exact determination of the size and position of the prostate, without invasive methods or the danger of side-effects . It also allows the evaluation of its inner construction . For the veterinarian, this is important when weighing the different therapeutic possibilities . Through sonographic findings the kind, extent and localisation of necessary surgery can be decided before hand . The prognosis is facilitated and a continuous control of the intraprostatic process can be carried out, (for example; regression after castration, marsupialisation or antibiotic therapy) . One must point out that, when judging prostate gland diseases, the diagnosis should never be made solely on sonographic results, but only in combination with clinical and laboratory examinations. Arch Int Pharmacodyn Ther, 1985 Jan, 273(1), 167 - 76 The mechanism of gentamicin-inhibited insulin release by isolated islets; Boschero AC et al.; These experiments were performed in order to determine the mechanism of action of the aminoglycoside antibiotic gentamicin on insulin release by isolated islets . Gentamicin significantly reduced the insulin release in the absence as well as in the presence of increasing concentrations of glucose . This effect was immediate and promptly reversible . In the presence of glucose plus high concentrations of K+ the antibiotic did not affect insulin secretion . Gentamicin did not change 86Rb efflux from perifused islets or the glucose metabolism in incubated islets . These data show that gentamicin does not alter the recognition and subsequent metabolism of glucose, and the system responsible for insulin secretion . We suggest that gentamicin reduces glucose-induced insulin release by blocking the entry of Ca2+ into the B-cells. Biochem Biophys Res Commun, 1984 Dec 28, 125(3), 895 - 901 Cloning and expression in Streptomyces lividans of a paromomycin phosphotransferase from Streptomyces rimosus Forma paromomycinus; Perez-Gonzalez JA et al.; The paromomycin producing organism Streptomyces rimosus forma paromomycinus is resistant to this antibiotic and contains a phosphotransferase which inactivates paromomycin . The gene encoding this enzyme has been inserted in the Streptomyces vector pIJ702 and then cloned in Streptomyces lividans, selecting for paromomycin-resistance . Three plasmids have been isolated and one of them, pMJ1, contains a 2.2 kb insert with a single HindIII restriction site . Insertion of foreign DNA in this site blocks the expression of the phosphotransferase enzyme indicating that it is within the cloned gene . These findings provide a new dominant selective marker for Streptomyces cloning vectors with the versatility of insertional inactivation. J Biol Chem, 1984 Dec 25, 259(24), 14997 - 9 Suppression of placental alkaline phosphatase biosynthesis by tunicamycin; Ito F et al.; Placental alkaline phosphatase activity and immunoreactivity were inhibited in a parallel fashion in choriocarcinoma cells by tunicamycin, a protein glycosylation inhibitor . Tunicamycin suppressed placental alkaline phosphatase biosynthesis in addition to inhibiting protein glycosylation in general . An anti-placental alkaline phosphatase-precipitable polypeptide of 58,000 daltons was formed in the presence of this antibiotic . The 58,000-dalton polypeptide had a degradation rate similar to that of the glycosylated phosphatase monomer from control cultures . Tunicamycin suppressed placental alkaline phosphatase mRNA activity leading to the observed decrease in biosynthesis. Am J Med, 1984 Dec 21, 77(6A), 4 - 6 Penetration of cefmenoxime into serum, gynecologic tissues, and heart valves; Daschner FD et al.; Twenty-nine women received 7 g of cefmenoxime before abdominal or vaginal hysterectomy; 20 adult patients received 2 g of cefmenoxime 24 hours and immediately before open heart surgery . In the gynecologic patients, peak cefmenoxime serum concentrations of 23.4 mg/liter were reached within one to two hours after administration of the antibiotic . Cefmenoxime concentrations in myometrium, endometrium, and salpinges also reached their peak one to two hours after administration . Two to three hours later tissue concentrations varied between 1.1 and 5.2 micrograms/g; four hours after application, tissue concentrations were below detectable levels . Cefmenoxime plasma and tissue concentrations were significantly higher in patients undergoing open heart surgery . Subcutaneous tissue and muscle concentrations varied between 2.7 and 38.0 micrograms/g . Cefmenoxime concentrations in cardiac valvular tissue were higher than those in muscle and fat. Biochim Biophys Acta, 1984 Dec 19, 778(3), 435 - 42 Interaction of amphotericin B with membrane lipids as viewed by 2H-NMR; Dufourc EJ et al.; The effects of amphotericin B upon the organization and dynamics of multibilayer membranes of dimyristoylphosphatidylcholine (DMPC) were investigated by means of 2H-NMR . At high amphotericin B concentrations (30 mol% with respect to the lipid) and at temperatures above 25 degrees C, DMPC experiences two different environments which are in slow exchange on the 2H-NMR time scale . In one of these, the lipid is immobilized by the antibiotic, in a molar ratio of approximately 1:1, whereas the lipid unsequestered by amphotericin B is more ordered than in its pure state . This ordering effect is perceived at relatively low antibiotic doses (4%) . The local lipid order, and the relative percentage, of sequestered DMPC, are temperature-independent (up to 65 degrees C), whereas the ordering of the unsequestered lipid domain is not . The perturbation induced by amphotericin B is manifest similarly at the edges as well as in the center of the bilayer . Antibiotic addition leads to large decreases in the transverse relaxation time, T2, of the labelled lipid, but not in the spin-lattice relaxation time, T1 . This indicates an increased density of slow motional modes and little change in rapid motions. Biochemistry, 1984 Dec 18, 23(26), 6697 - 703 Cross-linking of streptomycin to the 30S subunit of Escherichia coli with phenyldiglyoxal; Melancon P et al.; {3H}Dihydrostreptomycin was covalently linked to the 30S subunit of Escherichia coli K12A19 with the bifunctional cross-linking reagent phenyldiglyoxal . The cross-linking was abolished under conditions that prevent the binding of streptomycin, which indicates that the cross-linking occurs at the specific binding site of streptomycin . The cross-linking involved 16S RNA and the ribosomal proteins S1, S5, S11, and S13 . This suggests that the streptomycin binding site is located in the upper part of the 30S subunit, facing the 50S subunit . Unexpectedly, the same extent and pattern of cross-linking were observed with the 30S subunits from a streptomycin-resistant mutant . We have shown previously that streptomycin induces conformational changes in the ribosomes from sensitive bacteria but not from streptomycin-resistant mutants . From this and from the results in the present study, it is suggested that the binding of streptomycin to streptomycin-sensitive ribosomes is a two-step reaction wherein an initial loose interaction at the antibiotic binding site is followed by a conformational rearrangement of the ribosomal particle . The second step would tighten the association with streptomycin and cause interference with protein synthesis . That step would be lacking in streptomycin-resistant mutants. Eur J Biochem, 1984 Dec 17, 145(3), 579 - 86 Kinetic evidence for redistribution of actinomycin molecules between potential DNA-binding sites; Fox KR et al.; The kinetics of interaction between actinomycin D and DNA have been measured by stopped-flow and detergent-dissociation methods . The results are consistent with a model in which the antibiotic initially binds to many sequences on the heterogeneous DNA lattice and subsequently 'shuffles' between the available sites until a thermodynamically determined optimal state of binding is attained . The amplitudes of the two slowest components in the reaction with calf thymus DNA do not vary in parallel as the total level of antibiotic binding is increased; they appear to reflect directly the redistribution of antibiotic molecules along the DNA lattice . The dissociation profile is shown to depend upon the time for which the antibiotic and DNA are premixed, so that for short mixing times a higher proportion of the decay is represented by faster-dissociating species . The rate of appearance of the slowest-dissociating species correlates well with the slowest optical change in the association reaction . Stopped-flow experiments indicate that the antibiotic first binds to sites on natural DNA with an average association constant of 4 X 10(3) M-1 and that it subsequently migrates to sites with higher affinity . Similar experiments performed with poly(dG-dC) are less easily interpreted and seem to indicate that conformational changes or cooperative effects can also occur. Experientia, 1984 Dec 15, 40(12), 1357 - 62 Malaria prophylaxis in travellers: the current position; Sturchler D; Malaria prevention is a main challenge for physicians, nurses, health officers and tour operators . The attack rate of malaria in travellers is 1-10/10,000 departures, and the case fatality rate of imported malaria is around 0.5/100 . Travellers should be informed about the risk they are going to take, how to protect against mosquito bites, about the antimalarials they will have to take and what to do when a malaria breakthrough should occur . The 4-aminoquinolines (chloroquine, amodiaquine) remain the drug of choice for the prevention of Plasmodium vivax and of sensitive P . falciparum infections . The problem is to find an effective and safe drug combination for travellers to areas where P . falciparum is either resistant to chloroquine, to Fansidar (the combination of pyrimethamine plus sulfadoxine) or to both . These travellers will probably best be protected by an individually tailored drug combination, which includes amodiaquine or mefloquine as baseline drugs, and a supplementation with Fansidar, Maloprim (the combination of pyrimethamine with dapsone), paludrine or an antibiotic. Nucleic Acids Res, 1984 Dec 11, 12(23), 9165 - 77 Infrared linear dichroism of oriented DNA-ligand complexes prepared with the wet-spinning method; Fritzsche H et al.; Oriented DNA films prepared by the wet-spinning technique have been complexed with several ligands: the anthracycline antibiotic violamycin BI, the dipeptide L-carnosine, and the oligopeptide antibiotic netropsin . The formation of the DNA-ligand complexes is accompanied by dramatic changes of the conformational flexibility of DNA . The B-A transition which occurs usually between 80% and 70% relative humidity (RH) is more or less suppressed by the ligands . Violamycin BI at a total ligand per DNA base pair ratio, rt, of approximately 0.03 and L-carnosine at rt approximately 1.5 inhibit the B-A transition of approximately 18 and approximately 0.25 base pairs per ligand molecule, respectively . Netropsin at rt = 0.2 induces a very stable B-DNA even at rather low RH (23%) . The total hydration of this complex is significantly higher than for a drug-free DNA film . Netropsin-DNA complexes at rt of 0.02 and 0.01 result in an inhibition of approximately 45 base pairs per drug molecule with respect to the B-A transition. J Comp Neurol, 1984 Dec 10, 230(3), 437 - 43 The distribution of filipin-sterol complexes in photoreceptor synaptic membranes; Cooper NG et al.; The polyene antibiotic filipin, which binds to membrane sterols, has been used to investigate the relative distribution of cholesterol at photoreceptor synaptic junctions in the chick retina . Following anesthesia and aldehyde perfusion fixation, the retina is removed and immersed in fixative solution containing the filipin for 36-48 hours . The retinas are then processed for freeze-fracture . Electron microscopy of freeze-fracture replicas demonstrates that the filipin-sterol complexes are not evident between intramembrane particles of the presynaptic and postsynaptic particle arrays that are present at ribbon and basal junctions . In contrast, the synaptic vesicle fusion zone of ribbon junctions contains large numbers of filipin-sterol complexes which are observed merging with the free margins of the presynaptic particle array . There is a scarcity of such complexes, however, around the free margins of basal junction presynaptic particle arrays . These latter sites do not contain a vesicle fusion zone . Particle-poor areas of membrane that surround postsynaptic particles arrays of ribbon and basal junctions also do not contain filipin binding sites . The nonsynaptic membrane of photoreceptor terminals contains large numbers of filipin-sterol complexes, less tightly packed than in the synaptic vesicle fusion zone . Coated vesicle fusion sites in the presynaptic membrane contain groups of intramembrane particles but the filipin-sterol complexes are excluded from these sites . The observations suggest that synaptic membrane domains which interact with cytoskeletal components, such as clathrin and pre- and postsynaptic densities contain less cholesterol than other domains such as the synaptic vesicle fusion zones. Cell Differ, 1984 Dec, 15(2-4), 93 - 7 DNA transformation of a pluripotent mouse embryonal stem cell line with a dominant selective marker; Wobus AM et al.; The mouse embryonal stem cell line BLC 1 growing on feeder layer was treated with a calcium phosphate/DNA precipitate prepared with DNA of plasmid pAG60 which harbors the Tn5-derived neo gene, thus encoding resistance to G418, an aminoglycoside antibiotic . Transfection performed on feeder layer resulted in the formation of G418-resistant clones T1 and T2/K26 . The stable integration of the transformed neo gene was confirmed by dot hybridization in all descendant cultures of clones T1 and T2/K26 as well as in the tumors derived from them . In vivo and in vitro differentiation revealed the pluripotent status of the transformants . Tumors derived from T1 and T2/K26 contained various tissues with derivatives of all three primary germ layers. Laryngoscope, 1984 Dec, 94(12 Pt 1), 1576 - 9 Necrotizing fasciitis as a lethal complication of peritonsillar abscess; Wenig BL et al.; Abscesses of the peritonsillar region rarely lead to serious complications . Incision and drainage, antibiotic therapy, and subsequent tonsillectomy is the accepted method of treatment . Two cases of fatal necrotizing fasciitis following peritonsillar abscess are presented . The entity of necrotizing fasciitis in the head and neck is discussed with respect to its presentation, diagnosis, and treatment. Geburtshilfe Frauenheilkd, 1984 Dec, 44(12), 792 - 5 {Short-term prevention with cefoxitin in cesarean section}; Heilmann L et al.; In a preliminary prospective study, the febrile morbidity of 60 patients after Caesarean section was determined to investigate the prophylactic effect of a single-dose cefoxitin-application (2 g) intravenously at the time of induction of anaesthesia . Patients were randomly assigned to either the cefoxitin group or a control group without the antibiotic . Each group consisted of 30 patients . Although the numbers of patients were small, a statistically significant reduction (p less than 0.05) of febrile days was found for the cefoxitin group . As compared to previous studies with a three-dose regimen of cefoxitin, the per cent reduction rate of febrile morbidity was similar . In cases with certain risk profiles, such as premature rupture of the membranes or prolonged delivery, a single-dose appears to suffice and is therefore indicated. Contraception, 1984 Dec, 30(6), 535 - 44 Influence of removal of intrauterine contraceptive devices on colonisation of the cervix by actinomyces-like organisms; Mao K et al.; PIP: An overall prevalence rate of actinomyces-like organisms (ALO) in cervical smears of IUD users of 3% (79/2734) was found, with a rate of 2% and 22.6% for copper and inert IUD users . Although the users of the inert IUDs were older, and their devices had been in situ longer, these factors did not account for the significant differences between the 2 types of IUD . 55 patients were counseled and given a leaflet on ALO . 14 IUD users with ALO positive smears who had their devices removed had mild or moderate pelvic pain or discharge . 6 others who were asymptomatic had the IUD removed at their own request . All 55 patients were reexamined 6 months-1 year later and a smear was repeated . Only 1 woman required later removal of the IUD because of dyspareunia with pelvic tenderness . After IUD removal, and without antibiotic therapy, ALO colonization was no longer found 6-12 months later in 100% (20/20) of the cases . This even included the 7 women who had had new copper IUDs inserted immediately after removal of the index device . Jpn J Antibiot, 1984 Dec, 37(12), 2519 - 30 {Pharmacokinetic studies of cefbuperazone in the field of gynecology}; Seiga K et al.; Cefbuperazone (CBPZ), a new cephamycin antibiotic, was studied for the distribution in the genital organs and the excretion to the pelvic dead space exudate by bioassay, and the following results were obtained . CBPZ was rapidly distributed into the various tissues by intravenous drip infusion of 0.5 g and 1.0 g for 1 hour . Those levels depended on serum levels and the ratios (tissue level/serum level) were about 15-25% . Obvious dose response between 0.5 g and 1.0 g of CBPZ was recognized for serum levels as well as tissue levels . Serum and tissue levels were respectively analyzed by two- and three-compartment open model . Consequently, the obtained simulation curve approximated to the observed results . The simulation curve and pharmacokinetic parameters by one-compartment open model were appropriate for CBPZ levels in the pelvic dead space exudate. J Antibiot (Tokyo), 1984 Dec, 37(12), 1587 - 95 B-factor, an essential regulatory substance inducing the production of rifamycin in a Nocardia sp; Kawaguchi T et al.; "Curing" treatment of a rifamycin-producing Nocardia sp . resulted in a mutant deficient in the synthesis of antibiotics . This deficiency was reversed in a medium containing yeast extract . The active substance, named B-factor, which induced rifamycin production in the mutant was purified from yeast extract, and its structure, 3'-(1-butylphosphoryl) adenosine, was determined by structural analysis and chemical synthesis . An extremely low concentration of B-factor (10 ng/ml) caused recovery of rifamycin B synthesis in the mutant and stimulated synthesis of the antibiotic in the parental strain. Br J Obstet Gynaecol, 1984 Dec, 91(12), 1181 - 7 Pelvic inflammatory disease after hysterosalpingography associated with Chlamydia trachomatis and Mycoplasma hominis; Moller BR et al.; A total of 116 women were referred for hysterosalpingography because of primary or secondary infertility . Chlamydia trachomatis was isolated from the cervix of four (3.4%) of the patients whereas Mycoplasma hominis was isolated from 39 (33.6%) of them . Four patients developed acute pelvic inflammatory disease after hysterosalpingography; two of them were chlamydia culture-positive and developed a significant chlamydial antibody response during the course of the disease . One of the other two patients, who developed upper genital-tract infection, was culture positive for M . hominis and developed a significant antibody response to this micro-organism . The results indicate that C . trachomatis should be sought in patients before hysterosalpingography and, if detected, appropriate antibiotic cover should be instituted before the procedure. Br J Haematol, 1984 Dec, 58(4), 633 - 40 Assessment of the drug sensitivity of acute nonlymphocytic leukaemia using the in vitro clonogenic assay; Preisler HD et al.; The ability of an in vitro clonogenic drug sensitivity assay to predict the outcome of therapy for acute nonlymphocytic leukaemia was evaluated using marrow cells obtained from previously untreated or first relapsed patients treated with either cytosine arabinoside/anthracycline antibiotic or high dose cytosine arabinoside remission induction therapy . While the per cent of leukaemic cells killed in vitro was correlated with the outcome of therapy, this drug sensitivity assay provided little or no clinically useful information. Arch Ophthalmol, 1984 Dec, 102(12), 1825 - 9 A fresh look at iontophoresis; Hughes L et al.; The rate of penetration of fluorescein and gentamicin ions into the anterior chamber of the rabbit was increased more than 100-fold by the passage of 1 mamp; the amount of drug that penetrates is better controlled by iontophoresis than by instillation . The potential value, the safety and the limitations of this procedure are discussed, and a theoretical basis for the increase is provided . Practical methods of using iontophoresis in the clinic are described . A 30-s application should result in a therapeutic level of the antibiotic in the anterior segment over a 12-hour period in eyes with an intact epithelium. Arch Surg, 1984 Dec, 119(12), 1372 - 8 A proposed classification of intra-abdominal infections . Stratification of etiology and risk for future therapeutic trials; Meakins JL et al.; Serious studies of ultra-abdominal infections have yielded a mortality that ranges from 3.5% (a composite of antibiotic studies evaluating 1,275 patients) to more than 60% in studies of multiple-organ failure . In reviewing these studies, it is apparent that under the umbrella of "serious intra-abdominal infection," different diseases, processes, and patients are being studied . We define a binomial classification incorporating both an anatomic and a functional approach to intra-abdominal infection . There are ten etiologic classifications of intra-abdominal infections combined with an acute physiologic score (APS), measuring severity of illness, in three gradations . In the patient with undifferentiated intra-abdominal sepsis, the patient will be in class I, II, III, or IV, with a score, A, B, or C, added . Each of the groups V-X, defining a specific infectious category, can also use the APS, which has been verified in patients in intensive care and in those with intra-abdominal infection . It is anticipated that using this approach will provide a technique to evaluate patient groups uniformly in which drug or technical approaches to the management of intra-abdominal infections are being studied . The patients being studied will be more clearly defined, and studies will be comparable from one center to another. Exp Parasitol, 1984 Dec, 58(3), 356 - 64 Tritrichomonas foetus: localization of filipin-sterol complexes in cell membranes; Benchimol M et al.; The polyene antibiotic, filipin, was used as a probe for the detection of sterols in the freeze-fractured plasma membrane and the flagellar membranes of the pathogenic protozoa, Tritrichomonas foetus . A homogeneous distribution of filipin-sterol complexes was seen throughout the plasma membrane, and the membrane of the three anterior and the one recurrent flagella . No or very few filipin-sterol complexes were observed in some specialized regions such as the base of the flagella (necklace), the portion of the recurrent flagellum, and that part of the cell body to which the flagellum was attached . The density of filipin-sterol complexes varied from one cell to the other . In some cells, about 205 complexes/micron 2 were seen . A larger number of filipin-sterol complexes were observed on both faces of the membrane of cytoplasmic structures, probably corresponding to vacuoles . No complexes were seen in the nuclear membrane and in the membrane of the endoplasmic reticulum . Very few or no complexes were observed in the membrane of the hydrogenosomes . Treatment of living cells with filipin induced aggregation of filipin-sterol complexes at some points of the plasma membrane. Cancer Res, 1984 Dec, 44(12 Pt 1), 5638 - 43 Role of NADPH:cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C1; Keyes SR et al.; Hypoxic cells of solid tumors are difficult to eradicate by X-irradiation or chemotherapy; as an approach to this problem, our laboratories are investigating the effects of the bioreductive alkylating agent mitomycin C (MC) on hypoxic cells . This antibiotic was preferentially toxic to EMT6 mouse mammary tumor cells and V79 Chinese hamster lung fibroblasts under hypoxic conditions, but it was equitoxic to Chinese hamster ovary cells in the presence and absence of oxygen . All cell lines catalyzed the formation of reactive metabolites under hypoxic conditions and contained NADPH:cytochrome c reductase and DT-diaphorase, two enzymes which may be responsible for the cellular activation of MC . Although a correlation existed between enzymatic activities and the formation of reactive metabolites from MC, there was no correspondence between these parameters and the degree of cytotoxicity expressed by MC under hypoxic conditions . Purified NADPH:cytochrome c reductase reduced MC in the absence of oxygen, with addition of cytochrome P-450 enhancing, but not participating directly in, the reduction reaction . Addition of NADP+ to cell sonicates substantially reduced NADPH:cytochrome c reductase activity, while the formation of reactive metabolites was affected only slightly; converse results were observed using mersalyl . Exposure of cell sonicates to dicumarol inhibited DT-diaphorase activity, while the rate of formation of reactive metabolites of MC was enhanced . The findings suggest that NADPH:cytochrome c reductase and some as yet to be identified enzyme(s) are important for the reductive activation of MC . DT-diaphorase and cytochrome P-450 are not directly involved in the activation of MC, but they appear to modulate the degree of activation to reactive species, which are presumably responsible for the observed cytotoxicity. Drug Intell Clin Pharm, 1984 Dec, 18(12), 984 - 7 Sequential ventricular fluid concentrations of ceftazidime--report of three cases; Polk RE et al.; Three adult subjects, each with a ventriculostomy, received ceftazidime 2g iv q8h for three doses . Serial samples of serum and CSF ventricular fluid were obtained following the third dose; ceftazidime concentrations were measured by high pressure liquid chromatography . In one patient without inflammatory cells in the CSF, ceftazidime CSF concentrations were only approximately 0.3 micrograms/ml . In two other patients who had inflammatory cells and blood in the CSF, concentrations of ceftazidime in ventricular fluid demonstrated a slow rise and decline over an eight-hour period . Although contamination of the CSF by blood in these two patients confounds the interpretation of the concentrations achieved, it is concluded that obtaining serial samples of CSF from a ventriculostomy offers a more realistic appraisal of the dynamics of antibiotic penetration compared with the single-point method. Arch Surg, 1984 Dec, 119(12), 1410 - 8 Evaluation of naloxone for therapy of Escherichia coli shock . Species differences; Hinshaw LB et al.; Dogs and baboons were infused intravenously (IV) with Escherichia coli and treated with the opiate antagonist, naloxone hydrochloride, and the antibiotic, gentamicin sulfate, to determine the therapeutic efficacy of naloxone . Naloxone hydrochloride (2 mg/kg) was injected IV when one fourth of the E coli had been infused and then infused at 2 mg/kg/hr (six hours for dogs and 12 hours for baboons) . Four of five naloxone-treated dogs survived permanently (greater than seven days), while all dogs that were given only E coli died . Arterial BP, blood glucose levels, PCO2, and PO2 were supported at higher levels and lesions of the gastrointestinal tract were prevented in naloxone-treated dogs . A steady decline in blood glucose levels after an initial hyperglycemia was observed in naloxone-treated baboons, indications of peripheral vasoconstriction were noted, and all baboons died within 42 hours. Arch Surg, 1984 Dec, 119(12), 1400 - 4 Ambulatory peritoneal dialysis . Exploratory laparotomy for peritonitis; Schulak JA et al.; We present our experience with performing an exploratory laparotomy for peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . Six of 134 patients undergoing CAPD during the study period underwent surgical intervention because of abdominal sepsis . Two patients had bacterial peritonitis without abscess formation or evidence of visceral perforation and they recovered readily and, in retrospect, may not have required an operation . Of the three patients with fungal abscesses, two died of subsequent bacterial sepsis, while one patient survived, albeit after drainage of a recurrent pelvic abscess . One patient died because of extensive intestinal gangrene that was misdiagnosed as CAPD-related peritonitis initially . Our experience with these cases suggests that fungal peritonitis is a life-threatening complication that may result in both formation of an abscess and death . Therefore, it warrants aggressive antifungal chemotherapy and surgical intervention should an abscess be discovered . In contrast, bacterial peritonitis should be treated with appropriate antibiotic regimens until adequate evidence indicating the presence of a surgical condition is obtained. Surg Gynecol Obstet, 1984 Dec, 159(6), 549 - 52 Extraperitoneal versus transperitoneal drainage of the intra-abdominal abscess; Stone HH et al.; Controversy as to whether the intra-abdominal abscess should be drained extraperitoneally or through formal laparotomy still rages . Arguments for a transperitoneal approach include no need to identify specific locus preoperatively and uniform drainage of all abscesses, especially any otherwise unrecognized pus collection . Proponents for the extraperitoneal route stress failure to contaminate previously uninvolved peritoneal spaces and more reliable avoidance of injury to intestine, predisposing to subsequent intestinal fistula . To resolve this impasse, a prospective study of each method was based upon a schedule of previously randomized treatment options . After 32 months of study, 60 patients had been enrolled without obvious differences between treatment groups with respect to demographic features, preoperative definition and locus of infection, precipitating cause of sepsis, associated diseases, responsible bacteria and antibiotic therapy . With the transperitoneal approach, five patients had hollow viscus injury, while seven eventually had an intestinal fistula develop, causing major problems in four . Despite no obvious intestinal injury with the extraperitoneal route, two transient intestinal fistulas did occur . Seven patients drained transperitoneally had additional abscesses discovered, yet another operation was required to drain at least one complicating abscess in seven of this same group . With the extraperitoneal route, only two patients needed reoperation to drain another abscess . Although there were more deaths and complications in the group drained transperitoneally, morbidity (47 per cent) and mortality (7 per cent) were not significantly different statistically . Such data refute the professed superiority of a transperitoneal approach to intra-abdominal abscess drainage, both from need to reoperative for second abscess as well as incidence of latter intestinal fistula . Best results were noted with abscess identification through computerized tomography followed by extraperitoneal drainage. Blood, 1984 Dec, 64(6), 1146 - 58 T gamma-lymphoproliferative disease and related disorders in humans and experimental animals: a review of the clinical, cellular, and functional characteristics; Reynolds CW et al.; T gamma lymphocytes are those lymphocytes that express receptors for both the Fc portion of IgG and sheep erythrocytes . A very high proportion of normal T gamma lymphocytes are large granular lymphocytes (LGL), the cell responsible for most, if not all, natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) in humans, rats, and mice . In general, these cells are large lymphocytes with prominent azurophilic granules in the cytoplasm . Recently, a group of lymphoproliferative disorders made up predominantly of T gamma lymphocytes has been described . The most common and best studied of these disorders we refer to as "chronic T gamma-lymphoproliferative disease" (T gamma-LPD) . In most cases, this disease represents the abnormal expansion of LGL, which is reflected by an increase in functionally active NK or ADCC effector cells . The chronic T gamma-LPD lymphocytes are generally characterized as E- and EA-rosette positive, acid-phosphatase, and beta-glucuronidase positive and express the pan-T antigens OKT3/Leu-4, OKT11/Leu-5, the suppressor-associated antigens OKT5,8/Leu-2, and the NK-associated antigens Leu-7/HNK-1 . Typically, the patients are older, predominantly males and characteristically have a lymphocytosis of predominantly T gamma lymphocytes with lymphocyte infiltration of the bone marrow and often the spleen . While chronic T gamma-LPD is not usually an aggressive disease, the patients are often neutropenic and have recurrent bacterial infections requiring antibiotic therapy . Some patients have benefited from cytotoxic chemotherapy., but most patients have not required chemotherapy . An experimental LGL leukemia in F344 rats appears morphologically, functionally, and clinically similar to the human chronic T gamma-LPD and serves as an experimental model for further examining the ontogeny and function of LGL and may be applicable for exploring new and more effective means for the treatment of patients with chronic T gamma-LPD. HNO, 1984 Dec, 32(12), 511 - 4 {Granulation tumor of the orbit following ointment treatment of the maxillary sinus}; Brusis T; Attempts to instil an antibiotic ointment into the right maxillary sinus led to the development of a granuloma of the lower eyelid and orbit and the tumour had to be resected . Retroposition of the rectus inferior muscle was carried out by the ophthalmologist to eradicate double images caused by scars . The injection of antibiotic ointments into the maxillary sinus is dangerous. Mol Cell Biol, 1984 Dec, 4(12), 2929 - 31 Hygromycin B phosphotransferase as a selectable marker for DNA transfer experiments with higher eucaryotic cells; Blochlinger K et al.; The DNA coding sequence for the hygromycin B phosphotransferase gene was placed under the control of the regulatory sequences of a cloned long terminal repeat of Moloney sarcoma virus . This construction allowed direct selection for hygromycin B resistance after transfection of eucaryotic cell lines not naturally resistant to this antibiotic, thus providing another dominant marker for DNA transfer in eucaryotic cells. Jpn J Antibiot, 1984 Dec, 37(12), 2364 - 70 {Fundamental and clinical studies of ceftriaxone in the field of obstetrics and gynecology}; Horii T et al.; Fundamental and clinical studies on ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, were carried out with the following results . Following each 1.0 g of drip infusion, transfer of CTRX to female genital organs was found to be excellent . Transfer of CTRX to exudate of the pelvic dead space was also excellent . And high concentration of CTRX was kept for long time after administration . CTRX was given to 7 cases . It was effective for 5 cases and ineffective for 2 cases . The above results demonstrated that CTRX is a safe and effective drug. Jpn J Antibiot, 1984 Dec, 37(12), 2304 - 19 {Pharmacokinetics and clinical studies on ceftriaxone in the field of obstetrics and gynecology}; Cho N et al.; Ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained . The absorption and tissue penetration of CTRX into intrapelvic genital organs were good . The peak serum level in the uterine artery after a single intravenous injection and that after an intravenous drip infusion for 30 approximately 60 minutes, both with 1 g, were 162.5 micrograms/ml and 84.4-93.8 micrograms/ml, respectively . High concentrations were obtained also in genital organ tissues; the maximum concentration was 93.8 micrograms/g by intravenous injection and 56.3-59.4 micrograms/g by intravenous drip infusion . Changes in the tissue concentration were similar to those in the serum, the level over MIC80 against main pathogenic organisms being maintained for a long time . The penetration of CTRX into intrapelvic dead space exudate was good . The level reached a peak of 18.8 micrograms/ml 2 hours after an intravenous injection with 1 g and 13.3 micrograms/ml after 12 hours, while the level over MIC80 against main pathogenic organisms was maintained for a long time . CTRX was effective in 15 out of 16 cases (93.8%) with gyneco-obstetric infections such as intrauterine, intrapelvic, adnexal infections, and postoperative would infections, administered with 1 g twice a day . No side effects were observed. Biochem Pharmacol, 1984 Dec 1, 33(23), 3779 - 86 Studies on the action of nystatin on cultured rat myocardial cells and cell membranes, isolated rat hearts, and intact rats; Aszalos A et al.; The action of nystatin, a polyene antibiotic, was studied in rat myocardial cells, isolated rat hearts, and intact rats . Myocardial cells responded to 10 and 25 micrograms nystatin/ml with arrhythmias that could be minimized by elevated concentrations of K+ and Mg2+ or reversed by washing the cells . Similarly, the isolated heart responded to 100 micrograms nystatin/ml with arrhythmias that could be tempered by addition of elevated concentrations of K+ and Mg2+ . The i.v . injection of the drug caused heart failure in intact animals at the 4-mg/kg dose level . At the subcellular level, nystatin made the myocardial cell membranes more rigid, as measured by electron spin resonance spectrometry . These findings indicate a parallel between physiocochemical changes caused by nystatin in the myocardial cell membrane and the biological changes caused by this drug in myocardial cells, isolated heart, and heart of the intact animal. Exp Cell Res, 1984 Dec, 155(2), 345 - 58 Contribution of alpha-D-galactopyranosyl end groups to attachment of highly and low metastatic murine fibrosarcoma cells to various substrates; Grimstad IA et al.; There are much greater numbers of cell surface terminal, non-reducing alpha-D-galactorpyranosyl groups in highly malignant (metastatic) cells than are found in low malignant cells derived from the same murine fibrosarcoma . We have examined the contribution of these residues to attachment of the cells to various collagens and to plastic . Removal of these carbohydrate groups with alpha-galactosidase or blocking them with lectins from Griffonia simplicifolia seeds or with anti-blood group B antiserum all dramatically inhibited the attachment of both the highly malignant and the low malignant cells . Following removal with the enzyme, the alpha-D-galactopyranosyl end groups were rapidly resynthesized . This resynthesis was inhibited by tunicamycin, an inhibitor of de novo glycoprotein synthesis . This antibiotic also impaired cell attachment and, when used in addition to treatment with alpha-galactosidase, it inhibited cell attachment more than did treatment with the enzyme alone . The effects of all treatments on cell attachment were greater for the highly malignant than for the low malignant cells . With the latter cells, inhibition by lectin was seen only in the absence of serum, whereas the adhesion of highly malignant cells was affected in both the presence and the absence of serum . On their surface membrane the highly malignant cells express much more than do the low malignant cells of a glycoprotein that cross-reacts immunologically with laminin . The basement membrane glycoprotein laminin promotes cell attachment to collagen, and both glycoproteins contain terminal, non-reducing alpha-D-galactopyranosyl groups . Attachment of cells is a requirement for the formation of a metastasis, and thus the laminin-like molecule and the alpha-D-galactopyranosyl end groups (whether on the laminin-related moiety or on other cell surface molecules) may both be important for expression of the most malignant phenotype. J Hosp Infect, 1984 Dec, 5 Suppl A, 57 - 62 Competing risk factors associated with nosocomial infection in two university hospitals; Chavigny KH et al.; An historical cohort study of risk factors associated with nosocomial infection was conducted in two university hospitals on the East and West Coast of the USA . The purpose of the study was to estimate the relative risk ratios (RR) associated with antibiotic therapy, instrumentation, surgical operations and age with nosocomial infection, and to establish the hierarchical relationship of these factors to each other . A high risk cohort of long-staying patients (average length of stay = 30 days), was selected and each patient's chart was analysed retrospectively for infection occurrence and for risk factors . There was no significant difference between hospitals in rates of nosocomial infections, diagnostic categories and utilization of risk factors . Categorical linear regression analysis showed that a four factor model consisting of antibiotic therapy, instrumentation, surgical operations and age accounted for 95 per cent of the variation in nosocomial infection rates . Length of stay was treated as a co-dependent variable . Multivariable stratification analysis yielded aetiologic fractions of 63 per cent attributable to antibiotic therapy, 26 per cent to surgical operations, and 13 per cent to instrumentation . About half the antibiotic therapy was given on admission or at least 4 days before the first hospital-acquired infection . These data support careful assessment of prophylactic antibiotic therapy and infection control policies to reduce risk of nosocomial infection in university hospitals. Antimicrob Agents Chemother, 1984 Dec, 26(6), 892 - 7 Stimulatory, permeabilizing, and toxic effects of amphotericin B on L cells; Brajtburg J et al.; High concentrations of amphotericin B (AmB) killed mouse L cells, but low concentrations increased plating efficiency and stimulated the incorporation of labeled precursors into DNA and RNA . Thus, there were two disparate effects of AmB on L cells, stimulatory and toxic, and they occurred in distinct dose-related stages . AmB also affected the permeability of L cells . In dose-response studies, increases in cell membrane permeability, measured as the loss of K+ ions, occurred along with the stimulation of {3H}uridine incorporation into RNA . In contrast, stimulation of {3H}thymidine incorporation into DNA was only observed in cells recuperating from AmB-induced permeability changes . When the K+ concentration in the medium was lowered to 0.5 from 4.5 mM, or when 1 mM ouabain was added to the cultures, cell killing was potentiated, but the stimulatory and permeabilizing effects of subtoxic concentrations of AmB were unaffected . Furthermore, etruscomycin, a polyene antibiotic without any permeabilizing effects, nevertheless induced an enhancement of plating efficiency and of incorporation of {3H}uridine into RNA and {3H}thymidine into DNA . Our results suggest that the dose-related stimulatory, permeabilizing, and toxic effects of AmB most probably have distinct mechanisms of action and may be independent of one another. Boll Soc Ital Biol Sper, 1984 Nov 30, 60(11), 2143 - 8 {Evaluation of the effect of cloxacillin on human lymphocyte chromosomes through the study of karyotypic changes and sister chromatid exchanges}; Zavarise G et al.; The aim of this work was the evaluation of the possible mutagenic effect of an antibiotic, the Cloxacillin . Therefore the authors have performed the analysis of the chromosomal alterations and the study of the SCE (Sister Chromatid Exchanges) induced with the exposition of cultures of lymphocytes to different concentrations of this drug . The work reveals that Cloxacillin induces chromosomal alterations at high concentrations, while at concentrations similar to its therapeutic levels the drug does not seem to interfere with human DNA. Biochim Biophys Acta, 1984 Nov 28, 802(2), 162 - 8 Evidence of different binding sites for nogalamycin in DNA revealed by association kinetics; Fox KR et al.; The kinetics of association between nogalamycin and DNA have been measured by stopped-flow spectrometry . With a naturally occurring DNA (calf thymus) the reaction profile requires not less than three exponentials for its complete description . By contrast, binding to poly(dA-dT) is fully described by two exponentials which correspond to the two faster components seen with the natural DNA, whereas binding to poly(dG-dC) is a single exponential process whose time constant is about the same as the slowest component measured with calf thymus DNA . In all cases the amplitude of each component in the decay varies considerably with polynucleotide concentration . The results are consistent with a model in which the antibiotic is only able to bind directly to regions of the DNA which are transiently perturbed, probably non-basepaired . As a result, the antibiotic interacts much faster with AT-rich rather than GC-rich DNA sequences, which may provide a basis for its apparent sequence selectivity. Biochim Biophys Acta, 1984 Nov 22, 783(2), 166 - 70 The effects of paromomycin on the fidelity of translation in a yeast cell-free system; Tuite MF et al.; The effects of the aminoglycoside antibiotic paromomycin on the fidelity of translation of the synthetic template poly(U), and two natural mRNAs (rabbit globin mRNA and Brome Mosaic virus RNA), were examined in an mRNA-dependent cell-free system from the yeast Saccharomyces cerevisiae . At antibiotic concentrations that did not inhibit translation (100 microM) optimal mistranslation of all three templates was observed, with the effects declining at higher antibiotic concentrations . Synthesis of the opal termination read-through protein of rabbit beta-globin mRNA was induced by paromomycin, but only in lysates prepared from a {psi+} strain of yeast . The antibiotic did not induce detectable levels of either ochre or amber read-through, but did induce general misreading of Brome Mosaic virus RNA to the same degree in both {psi+} and {psi-} lysates . This misreading was enhanced by addition of the polyamine spermidine. Schweiz Med Wochenschr, 1984 Nov 17, 114(46), 1651 - 5 {How bothersome is fiber bronchoscopy under local anesthesia?}; Langer T et al.; All the 79 (7.4%) complications of 1066 fiberoptic bronchoscopies performed under standardized topical anaesthesia in in- and outpatients were analyzed retrospectively . With the 4.9 mm bronchoscope the transnasal route was possible in all cases, and with the 6.0 mm bronchoscope in 92% . There were no deaths and no major complications, with the exception of one tension-pneumothorax, one pneumonia, one pulmonary edema and one 500 ml hemorrhage . The most frequent complications were minor hemorrhages (4.1%) which occurred mainly after biopsies and were rarely recognized by the patients . laryngospasms (1.5%) and bronchospasms (1.4%) . The rate of complications was higher in patients with a FEV1 of less than 60% predicted (p = 0.02) and in patients with a pO2 below 50 mm Hg (p = 0.06) . We recommend the administration of oxygen during fiberoptic bronchoscopy . Fever within 36 hours after bronchoscopy was observed in 12% and subsided without antibiotic therapy . In the light of these risks, patients should be informed prior to the procedure of the possible occurrence of shortness of breath, hemorrhage and fever. Cancer, 1984 Nov 15, 54(10), 2109 - 21 Familial hemophagocytic lymphohistiocytosis (FHLH) in Israel . I . Description of 11 patients of Iranian-Iraqi origin and review of the literature; Stark B et al.; Eleven patients with familial hemophagocytic lymphohistiocytosis (FHLH) are described . They all belonged to four Jewish families of Iranian and Iraqi origin . Parental consanguinity was found in three families . The age of onset of disease ranged from 6 weeks to 36 months . All patients had fever, wasting, and enlargement of the liver and spleen . In addition, lymph-node enlargement and neurologic complications were common . The most consistent laboratory findings were pancytopenia, atypical lymphomonocytoid cells in the peripheral blood, abnormal liver function test results, and increased cerebrospinal fluid protein . The course was fatal in all patients . Nine of the 11 patients died within 2 weeks to 3 months of presentation, and 2 patients achieved temporary remissions but died of disease within 8 and 24 months, respectively . Response to antibiotic therapy or to the administration of corticosteroids and cytotoxic drugs was unimpressive . Pancytopenia complicated by sepsis or bleeding, hepatic failure, or encephalopathy were the terminal events . This report draws attention to the existence of FHLH in Jews of Iranian-Iraqi origin in whom parental consanguinity is very common. Z Hautkr, 1984 Nov 15, 59(22), 1515 - 21 {Internal versus topical tetracycline therapy of acne}; Schwanitz HJ et al.; The study comprised 49 patients suffering from acne who were treated over a period averaging 4.7 +/- 1.2 months with tetracyclines administered either orally (1000 mg daily for 5 days, then 250 mg daily) or locally (2% alcoholic solution) . Randomization was carried out by means of random numbers . The percentage of pustules among the total acne efflorescences was chosen as clinical parameter for the efficacy of the antibiotic therapy . After treatment, both collectives showed the same significant decline of pustulation . The therapy was finally evaluated on a six-point scale both by the doctor and the patient . In total, there could not be detected any significant difference in the evaluation of local and oral medication. Arkh Anat Gistol Embriol, 1984 Nov, 87(11), 66 - 72 {Features of the structure of the mesenteric and tracheobronchial lymph nodes in rat offspring after exposure to tetracycline}; Savitskaia TN; Ante- and postnatal development of anatomical structures and cells of lymphatic nodes has been studied in rat offspring subjected to tetracycline effect during placentation and organogenesis (the 8th-14th days) and during fetogenesis (the 15th-20th days) . Tetracycline injection during the 8th-14th days of embryogenesis results in certain disturbances of the nodular structure formations, inhibition of lympho- and plasmo-cytopoesis against the background of a sharp increase in number of basophilic granulocytes and tissue basophils . The antibiotic effect on the 15th-20th days of embryogenesis does not disturb the lymph node formation, but produces an increasing number of lymphocytes, plasmocytes, macrophages, eosinophilic granulocytes and tissue basophils in them. Antibiotiki, 1984 Nov, 29(11), 851 - 5 {Antitoxic properties of pantothenic acid derivatives, precursors of coenzyme A biosynthesis, with regard to kanamycin}; Moiseenok AG et al.; The effect of calcium pantothenate (CPN)B 4'-phospho-CPN (PCP), pantetheine (PT) and calcium S-sulfopantetheine (SPN) on acute toxicity of kanamycin sulfate was studied on albino mice . The above derivatives of pantothenic acid except PT lowered the antibiotic toxicity . The coefficient of the antitoxic effect (LD50/ED50) of SPN and PCP was 1.3-1.4 times higher than that of CPN . The combined use of kanamycin (1/5 of the LD50) with CPN, PCP or PT (30 mg/kg bw was equivalent to CPN) for 15 days prevented the increase in the total content of CoA and in the content of the fraction of free CoA and the precursors of its biosynthesis participating in the reaction of N-acetylation in the liver and brain . The contents of these substances were within the normal during the whole experiment . A certain increase in the activity of pantothenate kinase in the liver cytosol due to the use of kanamycin was eliminated by the simultaneous use of PCP and PT . The vitamin-containing compounds PCP and SPN were recommended for the clinical trials as agents preventing complications of kanamycin therapy. Acta Chir Belg, 1984 Nov-Dec, 84(6), 361 - 3 {Conservative treatment of a traumatic biliopleural fistula}; De Groof E et al.; Conservative management of a traumatic biliopleural fistula . A female patient, 13 years of age, developed a right-sided haemothorax after a stab wound in the right para-vertebral region . Pleural effusion reoccurred after thoracic drainage was stopped . Ten days after the injury, thoracic puncture enabled a diagnosis of biliopleural fistula to be made, confirmed by ERCP and CT-scan . The fistula closed after repeat thoracic drainage combined with prophylactic antibiotic therapy. Eur J Cell Biol, 1984 Nov, 35(2), 189 - 99 Filipin as a cholesterol probe . I . Morphology of filipin-cholesterol interaction in lipid model systems; Beknke O et al.; We report some novel morphological observations on the interaction of the polyene antibiotic filipin (crude complex) with cholesterol, studied in non-cellular systems with replication, freeze-fracture, and negative stain techniques . Cholesterol crystals, lecithin liposomes containing 0 to 20 mole% of cholesterol, and liposomes containing 10 mole% of cholesterol and 5 to 40 mole% of sphingomyelin were incubated for varying lengths of time with filipin at different cholesterol: filipin molar ratios . The resulting filipin-induced lesions (FIL) were pleomorphic in all systems studied . In replicas of crystals, FIL appeared as ridges which were either straight, or curved into C- and S-shaped figures or closed circles . Negatively stained preparations showed FIL as white lines of the same configurations and in addition revealed a delicate veil attached to individual FIL . FIL, fused by their veils into clusters or large sheets ("holey sheets"), were shed from crystals . Incubation of liposomes for 1 h at cholesterol:filipin molar ratios of 4:1, 2:1, 1:1, and 1:5, demonstrated that cholesterol detection (i.e . formation of FIL) depend upon the ratio of cholesterol to filipin . At a 1:1 molar ratio FIL formed on liposomes containing 10 mole% cholesterol or more, but detectability increased to 5 mole% at the 1:5 ratio . Increasing the molar ratio of cholesterol:filipin to 2:1 and 4:1 decreased cholesterol detectability to between 10 and 20 mole% . Increasing concentrations of sphingomyelin decreased cholesterol detectability at the 1:1 cholesterol:filipin ratio; further, FIL in sphingomyelin-containing liposomes tended towards larger diameters . Filipin induced aggregation of liposomes and linked them together by holey sheets, providing evidence for filipin-induced extraction of cholesterol from liposomes . Taken together our morphological observations on filipin-cholesterol interaction in non-cellular systems raise pertinent questions as to the feasibility of filipin as a cholesterol probe in cellular systems. J Anim Sci, 1984 Nov, 59(5), 1125 - 8 Efficacy of nosiheptide as a growth promotant for growing-finishing swine--a cooperative study; Cromwell GL et al.; A cooperative study involving 296 pigs was conducted at two experiment stations and at a commercial research farm to evaluate the efficacy of nosiheptide as a growth promotant for growing-finishing swine . At each station, five or six replicate pens of four or five pigs/pen were fed a fortified, corn-soybean meal basal diet with 0, 5.5, 11 or 22 ppm nosiheptide . Initial and final weights averaged 11 and 92 kg, respectively . Daily gain increased quadratically (623, 664, 669, 678 g/d; P less than .03) and feed/gain decreased quadratically (3.35, 3.24, 3.24, 3.28; P less than .02) with increasing level of nosiheptide . Breakpoint analysis indicated that gain plateaued at 6.8 ppm and feed/gain at 5.5 ppm of nosiheptide . Averaged across all levels of nosiheptide, gain and feed/gain during the growing phase (11 to 52 kg body weight) were improved by 13.1 and 7.6%, respectively, by feeding the antibiotic . For the entire growing-finishing period, gain was improved by 5.3% and feed/gain by 2.9% in pigs fed nosiheptide . Although there were large differences in gain and feed/gain, the responses to dietary treatments were similar among the three stations . The results indicate that nosiheptide is an effective growth-promoting agent for growing-finishing swine. J Antibiot (Tokyo), 1984 Nov, 37(11), 1344 - 56 Structure and properties of major largomycin FII chromophore components; Gonda SK et al.; Largomycin FII, a protein antitumor antibiotic of molecular weight 29,300 daltons, contains a chromophore that is separable under mild denaturing conditions . The chromophore complex was found to be considerably less stable than the holoprotein towards light and heat, suggesting a protective effect of the protein on the chromophore . Separation of the chromophore into several components was achieved using high performance liquid chromatography, and the biological activity of the isolated components was determined . Data gathered from UV, IR, proton and carbon NMR, and fast atom bombardment mass spectrometry indicated that all the chromophore components belong to the pluramycin class of antitumor agents . Pluramycin A and deacetylpluramycin A were found to be the two major components. Arch Surg, 1984 Nov, 119(11), 1325 - 8 Complications of renal dialysis access procedures; Connolly JE et al.; The complications of 2,179 dialysis access procedures of various types have been reviewed in an effort to determine their possible prevention and management . Scribner arteriovenous shunts or central venous catheters were preferred for temporary dialysis . Infection was a common complication of central venous catheters, but responded well to removal of the catheter . Brescia-Cimino fistulae were preferred for long-term dialysis, but were often not possible because of inadequate veins or the need for relatively urgent hemodialysis . The most useful secondary shunt was the straight forearm synthetic polytetrafluoroethylene (PTFE) graft whose most common complication was thrombosis due to intimal hyperplasia at the venous anastomosis . In most cases, this complication could be corrected by patch grafting or by extension bypass . Infection was infrequent with PTFE shunts and, when localized, was sometimes successfully treated by drainage, antibiotic therapy, and topical povidone-iodine . The principal complications of long-term peritoneal dialysis were peritonitis and tunnel infection that responded to antibiotic therapy and/or removal of the catheter . Compulsive care in access insertion and meticulous management during dialysis has permitted very satisfactory long-term hemodialysis and peritoneal dialysis. Am J Clin Pathol, 1984 Nov, 82(5), 611 - 5 Rhinosporidiosis . A report of two cases from Arkansas; Jimenez JF et al.; Two human native cases of ocular-conjunctival rhinosporidiosis from Arkansas are believed to be the first documented reports in this part of the country . The common mode of infection was accidental injury to the eye by possible contaminated soil-dust . The appearance of the polypoid growth was relatively fast, 6-16 days, and unresponsive to topical antibiotic and steroid treatment . Surgical excision, with one recurrence in one case, was the elective treatment . Both patients are asymptomatic 10-12 months after treatment, respectively, with no evidence of other recurrence, dissemination, or major complications . From 1939 to September, 1983, only nine cases of conjunctival rhinosporidiosis were reported in the United States. Clin Orthop, 1984 Nov, (190), 266 - 72 The influence of etiology on the results of coccygectomy; Bayne O et al.; The results of coccygectomy for coccygodynia seem not to have been correlated with etiologic factors and were investigated in 48 cases (10 men and 38 women) with an average follow-up period of seven years . The following four etiologic groups were designated: I, direct trauma; II, spontaneous in origin; III, coccygodynia associated with spinal surgery; and IV, postpartum . Groups I and IV had a 75% recovery rate from pain and Group II had a 58% recovery rate . No satisfactory results were obtained in Group III . The incidence of infection was 16.6% . Few satisfactory results were obtained in cases of deep infection . While this operation is effective in many cases, it is seldom successful for pain associated with lumbar disc disease requiring lumbar laminectomy and spine fusion . Prophylactic antibiotic therapy is clearly indicated. Radiology, 1984 Nov, 153(2), 357 - 61 Aortic root abscess resulting from endocarditis: spectrum of angiographic findings; Miller SW et al.; Abscesses in the aortic root are a serious complication of infective endocarditis and require accurate diagnosis for antibiotic and surgical management . Nineteen cases of endocarditis of a native valve or prosthetic valve and adjacent abscess cavities were identified with angiography . Of 6 patients with endocarditis of a native valve, 5 had bicuspid aortic valves and all had severe aortic regurgitation . Of 13 patients with endocarditis of a prosthetic aortic valve, all had paravalvular regurgitation . Abscesses in the aortic root were saccular, ranged from 1 to 3 cm in diameter, and, depending on sinus of origin, extended beneath the main and right pulmonary arteries or into the interventricular septum or mitral anulus . Fistulas were detected into the mitral anulus in 8 patients, and into the right ventricle in 3 patients . No complications from the catheterization were recorded during the 48-hour follow-up. Gastroenterology, 1984 Nov, 87(5), 1091 - 103 Structural features of and cholesterol distribution in M-cell membranes in guinea pig, rat, and mouse Peyer's patches; Madara JL et al.; Evidence suggests that M cells, which are antigen-sampling epithelial cells that overlie the domes of Peyer's patches, have an apical plasma membrane that differs from that of absorptive cells . We examined the structural features of rat, mouse, and guinea pig M-cell apical membranes and compared them with those of dome and villus absorptive cell apical membranes using electron microscopy of thin sections and freeze-fracture replicas . We also determined the distribution of morphologically detectable cholesterol in M-cell plasma and intracellular membranes in dome epithelium exposed to the polyene antibiotic, filipin . The areal density of P-face intramembrane particles was significantly less on M-cell microvilli than on microvilli of dome absorptive cells and villus absorptive cells . Areal densities of E-face intramembrane particles were similar on M-cell and absorptive-cell microvilli . M-cell apical plasma membranes were rich in cholesterol, displaying numerous filipin-induced membrane lesions in thin sections and freeze-fracture replicas . In contrast, apical membrane endocytic pits and coated vesicles in M cells failed to show filipin-induced membrane lesions . These findings suggest that, compared with the apical membranes of absorptive cells, those of M cells have a low protein to lipid ratio and an abundance of morphologically detectable cholesterol except in domains involved in endocytosis . Additionally, a subpopulation of dome epithelial cells displayed distinctive tight junctions with high strand counts and unusual depth . Although the cell type associated with these modified tight junctions could not be identified with certainty, their interspecies frequency paralleled the interspecies frequency of M cells in dome epithelium . These expanded tight junctions may result from physical tension caused by epithelial shape changes induced by intraepithelial lymphoid trafficking or, alternatively, may help buttress M cells that have attenuated cytoplasmic processes due to the presence of central hollows. J Hand Surg {Am}, 1984 Nov, 9(6), 894 - 8 A functional treatment method for interphalangeal pyogenic arthritis; Wittels NP et al.; A treatment plan for pyogenic arthritis has been devised in which the accessory collateral ligaments are resected through radial and ulnar midaxial incisions . The surgical wound is debrided and copiously irrigated with an antibiotic solution, and intravenous antibiotics are instituted before operation and continued after operation . Physical therapy is begun within 24 hours of surgery and includes active range of motion (ROM) of all joints, dynamic splinting, and hand therapy to ensure both full flexion and extension . Forty patients were treated with this method within a 6-year period . Of five interphalangeal (IP) joints of the thumb, four regained 0 degree to 60 degrees full ROM and one gained 15 degrees to 65 degrees limited ROM . Of the two distal IP joints, one regained full ROM and the other became fused . Among the 33 proximal IP joints, 13 regained full ROM of 110 degrees and 13 regained limited ROM . Good functional results were obtained with this treatment plan in lieu of amputation, which previously was the most likely treatment. Am Heart J, 1984 Nov, 108(5), 1326 - 34 Gonococcal endocarditis: a case series demonstrating modern presentation of an old disease; Fernandez GC et al.; Gonococcal endocarditis appeared with striking frequency in the preantibiotic era compared with its surprising rarity today . We present a series of four episodes of gonococcal endocarditis, which presented to our institution in the last 2 years, after no cases in the previous decade . Three episodes involved the aortic valve and required emergency aortic valve replacement . One episode involved the tricuspid valve and was successfully cured with antibiotic infusion alone . Combining our four patients with the available 25 well-documented gonococcal endocarditis cases reported in the English medical literature during the antibiotic era, we demonstrated that the disease incidence may be increasing, that infections more often involve left-sided cardiac structures (particularly the aortic valve), and that the association with a quotidian fever curve, rash and arthritis, and overt gonococcal infection is less common than previously reported . These patients frequently present with fulminant and dramatic valvular insufficiency without immediately positive blood cultures and complete echocardiographic evaluation seems to provide a valuable aid in making a presumptive diagnosis of endocarditis and directing appropriate clinical management. Ann Intern Med, 1984 Nov, 101(5), 683 - 91 The pregnant surgical patient: medical evaluation and management; Barron WM; Nonobstetric disease requiring surgery may complicate pregnancy and jeopardize maternal and fetal well-being . Surgery may be safely done if the physician is aware of anatomic and physiologic alterations during gestation that necessitate an altered approach to diagnosis and management . Fetal exposure to all diagnostic and therapeutic agents should be minimized, particularly during organogenesis . However, the risk to the fetus of diagnostic irradiation is justifiable when information essential to maternal health is likely to be obtained . Furthermore, the broad range of available antibiotic, analgesic, and anesthetic agents provide the physician with options for treatment that have an acceptable degree of risk to fetal health . Anesthesia and surgery are tolerated considerably better by the fetus than is maternal hypotension, hypoxia, or sepsis . When an operative procedure is urgently or emergently indicated, pregnancy should not delay timely intervention. EMBO J, 1984 Nov, 3(11), 2575 - 80 Hyper-accurate ribosomes inhibit growth; Ruusala T et al.; We have compared both in vivo and in vitro translation by ribosomes from wild-type bacteria with those from streptomycin-resistant (SmR), streptomycin-dependent (SmD) and streptomycin-pseudo-dependent (SmP) mutants . The three mutant bacteria translate more accurately and more slowly in the absence of streptomycin (Sm) than do wild-type bacteria . In particular, the SmP bacteria grow at roughly half the rate of the wild-type in the absence of Sm . The antibiotic stimulates both the growth rate and the translation rate of SmP bacteria by approximately 2-fold, but it simultaneously increases the nonsense suppression rate quite dramatically . Kinetic experiments in vitro show that the greater accuracy and slower translation rates of mutant ribosomes compared with wild-type ribosomes are associated with much more rigorous proofreading activities of SmR, SmD and SmP ribosomes . Sm reduces the proofreading flows of the mutant ribosomes and stimulates their elongation rates . The data suggest that these excessively accurate ribosomes are kinetically less efficient than wild-type ribosomes, and that this inhibits mutant growth rates . The stimulation of the growth of the mutants by Sm results from the enhanced translational efficiency due to the loss of proofreading, which more than offsets the loss of accuracy caused by the antibiotic. J Bacteriol, 1984 Nov, 160(2), 533 - 40 Mutants of Aspergillus nidulans blocked at an early stage of sporulation secrete an unusual metabolite; Butnick NZ et al.; Mutants of Aspergillus nidulans defective in conidiation (asexual sporulation) can be classified according to whether they are blocked before or after induction of conidiation . Mutants blocked before induction (preinduction mutants) appear to be unable to respond to the inducing stimulus and thus are defective in one of the earliest events in the sporulation process . Three preinduction mutants have been isolated and characterized . Each was found to exhibit the same pleiotropic phenotype: they also were defective in sexual sporulation and secreted a set of phenolic metabolites at a level much higher than did wild type or mutants blocked at later stages of conidiation . One of the metabolites has been identified as the antibiotic diorcinal (3,3'-dihydroxy-5,5'-dimethyldiphenyl ether) which is known to be involved in the synthesis of certain farnesyl phenols of unknown function . These results suggest that preinduction mutants are blocked in a phenolic metabolic pathway, one or more product of which participates in the initiation of sporulation. Clin Rev Allergy, 1984 Nov, 2(4), 319 - 28 Etiologic factors in the development of chronic middle ear effusions; Kraemer MJ et al.; Many factors increase the risk for CMEE in children . We believe the most important include recurrent purulent otitis media, chronic nasal congestion, atopy, and household cigarette smoke exposure . The risk of each of these in causing middle ear disease increases with the chronicity of the exposure . The risk may be additive, with a combination of these factors . CMEE undoubtedly develops through several mechanisms . It is important to look for specific risk factors, as their identification may afford potential approaches toward the prevention of recurrences . Theories such as prophylactic antibiotic administration, pneumococcal vaccination, pharmacologic therapy with antihistamines, decongestants and/or steroids, immunotherapy, and the avoidance of household irritants may be selectively beneficial for the appropriate individual . In an attempt to facilitate strategies to prevent acute middle ear disease as well as recurrent and chronic effusions, further understanding of the etiology, pathogenesis, and risk factors is prerequisite . Additional controlled studies in all of these areas are essential so that we may expand our knowledge base and offer more definitive recommendations to our patients and their families. Tsitologiia, 1984 Nov, 26(11), 1267 - 72 {Cytophotometric study of the granules formed in frog erythrocytes incubated in solutions of acridine orange, chloroquine and daunorubicin}; Veselkina MN et al.; Granules arising in the cytoplasm of Rana temporaria erythrocytes incubated in either solution containing acridine orange, chloroquine or antibiotic daunorubicine were studied cytophotometrically . The stuff concentrations in the granules were estimated under various conditions of incubation . The stuff concentrations in the granules appeared to be 1000-fold higher than in the incubation solutions . The average concentration in the granules did not depend on either the initial concentration of the stuff solution or the incubation time . The stuff concentration in the granules decreases with the increase of the granule size . Mechanisms of cation-acid segregation and accumulation by living cell are discussed. Proc Soc Exp Biol Med, 1984 Nov, 177(2), 247 - 52 Folate deficiency and pancreatic acinar cell function; Elseweidy M et al.; The present study was designed to determine the effect of folate deficiency on pancreatic acinar cell function . In the first series of experiments, three groups of rats were fed ad libitum regular rat feed, folate-deficient diet, or an equivalent amount of folate-sufficient diet . In the second series of experiments, rats were either fed ad libitum or rendered folate deficient by a purified folate-deficient diet; half of the folate-deficient group was replenished with oral folate . Body weight, pancreatic weight, DNA {methyl-14C}thymidine incorporation into DNA, RNA, {8-14C}adenine incorporation into RNA, protein content, synthesis of proteins, amylase content, and basal and bethanechol-stimulated amylase secretion were determined . The parameters were the same in the rats fed a folate-sufficient diet as in those fed a regular rat feed . Feeding a folate-deficient diet resulted in impaired DNA synthesis as evidenced by diminished incorporation of {methyl-14C}thymidine into DNA . There was no change in secretion of amylase . Similar results were obtained in the second series of experiments . These studies indicate that folate deficiency (rather than antibiotic content of the diet) impaired pancreatic function . Folate deficiency may therefore contribute to pancreatic injury in malnutrition and alcoholism. J Foot Surg, 1984 Nov-Dec, 23(6), 445 - 50 Crush and avulsion injuries of the foot: their evaluation and management; Graziano TA et al.; It is difficult to assess the damage resulting from crush or avulsion injuries so they may be treated adequately . The authors present a systematic approach to evaluating tissue involved in foot trauma . They also discuss antibiotic and tetanus prophylaxis and a technique of bacterial quantification that is helpful in determining the advisability of primary or delayed wound closure. Ann Allergy, 1984 Nov, 53(5), 370 - 8, 394 Otitis media with effusion in childhood; Marshall SG et al.; OM and OME are common disorders of childhood . Middle ear disease is related to anatomic abnormalities, prior episodes of AOM, chronic rhinitis, allergy, age, sex, race, season, perinatal factors, viral infections, and irritant exposure . ET dysfunction plays an important role in OME, as does the presence of bacteria or bacterial products in the middle ear . Viral infection, nasal allergy, previous episodes of OM and primary mucosal disease all may contribute to this chronic disorder . Diagnostic evaluation involves an appropriate personal and environmental history, a physical examination, pneumatic otoscopy, tympanometry, pure tone audiometry, and (if indicated) allergic and immunologic evaluation . Treatment may include environmental control, antibiotic therapy, decongestants and/or antihistamines, topical corticosteroids, and possibly immunization or allergic immunotherapy (hyposensitization) . In order to facilitate strategies to prevent acute and recurrent OM as well as chronic effusion, further knowledge regarding the etiology, pathogenesis, and risk factors is essential . Well designed, controlled studies are imperative to provide further understanding and more effective treatment of this common, chronic and often very frustrating medical problem. Mol Cell Biol, 1984 Nov, 4(11), 2549 - 52 Efficient transfer of cloned DNA into human diploid cells: protoplast fusion in suspension; Litzkas P et al.; A method for fusion of protoplasts bearing amplified plasmids and human diploid fibroblasts or other cell types in suspension is described . Transient expression of plasmid-encoded proteins occurs in up to 50% of the human cells, as demonstrated for simian virus 40 T antigen by immunofluorescence and the Escherichia coli xanthine-guanine phosphoribosyl transferase by autoradiography . In contrast, frequencies of stable transformants were similar to those obtained by the CaPO4 coprecipitation technique . However, experiments with both methods involving the recombinant pRSVneo (in which the Rous sarcoma virus long terminal repeat regulates expression of the antibiotic-inactivating aminoglycoside phosphotransferase) revealed a much higher frequency of colonies in G418 selective medium with constructions in which the early region of simian virus 40 DNA was present as well . We propose a role for the simian virus 40 T antigen in enhancing stable transformation in this system. Mol Cell Biol, 1984 Nov, 4(11), 2381 - 8 Asparagine-linked glycosylation in Saccharomyces cerevisiae: genetic analysis of an early step; Barnes G et al.; Asparagine-linked glycosylation is a form of covalent modification that distinguishes proteins that are either membrane bound or are in cellular compartments topologically outside of the cell from those proteins that remain soluble in the cytoplasm . This type of glycosylation occurs stepwise, with core oligosaccharide added in the endoplasmic reticulum and subsequent modifications occurring in the golgi . We used tunicamycin, an inhibitor of one of the earliest steps in the synthesis of N-linked oligosaccharide, to select for mutants that are resistant to this antibiotic . Genetic, biochemical, and physiological experiments led to the following conclusions . The synthesis of N-linked oligosaccharide is an essential function in cells . In contrast to mammalian cells, yeast cells do not transport tunicamycin by a glucosamine transport function . We identified a gene, ALG7, that is probably the structural gene for UDP-N-acetylglucosamine-1-P transferase, the enzyme inhibited by tunicamycin . Dominant mutations in this gene result in increased activity of the transferase and loss of the ability of the cell to sporulate . In addition, we identified another gene, TUN1, in which recessive mutations result in resistance to tunicamycin . The ALG7 and TUN1 genes both map on chromosome VII. J Antibiot (Tokyo), 1984 Nov, 37(11), 1370 - 5 Control of ammonium ion level for efficient nanaomycin production; Tanaka Y et al.; The addition of a small amount of NH4+ to a complex medium increased nanaomycin production by Streptomyces rosa subsp . notoensis OS-3966 . The best NH4+ donor for nanaomycin production was NH4+-saturated natural zeolite, with which the maximum titer of nanaomycin E was 760 micrograms/ml, about four fold higher than the control titer . In contrast, lowering NH4+ levels by adding NH4+-trapping agents such as untreated natural zeolite reduced antibiotic production. J Virol, 1984 Nov, 52(2), 370 - 6 Herpes simplex virus cloned DNA fragments induce coumermycin A1 resistance in Escherichia coli; Pearson RE et al.; We have taken a new approach to identify and fine map previously undescribed herpes simplex virus (HSV) functions . In experiments described in this report the antibiotic coumermycin A1 was used to select two HSV type 1 BamHI fragments cloned in pBR322 that confer partial resistance to drug-susceptible Escherichia coli . The genes encoding these HSV functions have been designated cour-1 and cour-2 and have been fine mapped to the HSV sequences . HSV-cour1 is located at the left end of BamHI-F near HSV type 1 genomic map coordinate 0.645 . cour-2 maps to BamHI-M', which is a 159-base-pair internal component of the alpha ICP4-coding sequence located in the reiterated sequences of the S component . In pBR322 both inserts apparently rely on the tet promoter for expression . Additionally, cour-2 functions when present as a BamHI insert in pUC7 . The analysis of cour-2 "maxi" cell proteins reveals the presence of proteins produced by the fusion of HSV-1 BamHI-M' sequences and the sequences of the vector genes, i.e., the major tet product for pBR322 and the modified beta-galactosidase for pUC7 . These data suggest that the development of bacterial assays for fusion products of eucaryotic DNA open reading frames in plasmid vectors may be a useful technique for initiating gene function studies. J Clin Oncol, 1984 Nov, 2(11), 1270 - 6 Sudden death in cancer patients receiving lithium; Lyman GH et al.; Lithium carbonate may attenuate the incidence and severity of infection associated with cancer chemotherapy but does not appear to improve patient survival . Of 100 patients with small-cell lung cancer receiving an identical regimen of cyclophosphamide, doxorubicin, and vincristine, 40 were assigned to treatment with lithium concurrently . To date, 60 patients have died, including 14 who died suddenly of apparent cardiovascular causes without evident progression of neoplastic disease or concurrent illness . Thirteen of the 14 sudden deaths were among 50 patients with clinical or electrocardiographic evidence of cardiovascula