J Med Assoc Thai, 1983 Mar, 66(3), 176 - 82 Midtrimester abortion by hypertonic saline instillation experience in Ramathibodi Hospital; Suthutvoravut S et al.; PIP: A retrospective study of midtrimester abortions using the intraamniotic instillation of hypertonic saline solution was conducted . All 62 cases admitted to the Ramathibodi Hospital in Bangkok, Thailand for midtrimester abortion in 1980 were terminated by intraamniotic hypertonic saline instillation . The pregnancies were unwanted in 32 (51.6%) of the cases because of family problems, poor socioeconomic status, and deteriorated psychological health . 15 cases (24.2%) were preganancy from rape; 9 (14.5%) had rubella infection during the 1st trimester; and 3 cases (4.8%) were mentally retarded . There was 1 case of renal staghorn calculi post nephrostomy, 1 of multiparity with history of hemophilia in the family, and 1 of failed IUD contraception . The women were between 16-25 years of age in 39 cases, aged 15 or under in 4 cases (6.5%), and over age 35 in 4 cases . In 49 cases (79%) abortion was performed during 16-20 weeks gestation, in 12 cases (19.1%) at 21-24 weeks, and in 1 case at 25 weeks of gestation . The time interval from hypertonic saline instillation to abortion was analyzed in order to evaluate the effect of parity, amount of amniotic fluid withdrawn, and oxytocin augmentation . The mean instillation to abortion time (I-A) was 30.19 +or- 11.25 hours . There were 3 cases which did not receive oxytocin and who spontaneously aborted within 24 hours . Among cases which received oxytocin augmentation, there were 9 who received oxytocin immediately after instillation and 50 who received it 18-24 hours later . The I-A time was 31.22 +or- 11.63 hours in the group that received oxytocin immediately and 31.09 +or- 10.68 in the group receiving it later . There was no statistical difference between the 2 groups . Among the 50 cases which received oxytocin augmentation 18-24 hours later, there was no statistical difference between groups of nulliparity and multiparity . There were 46 cases in which the amount of amniotic fluid withdrawn was noted . In the group in which more than 200 ml of amniotic fluid was withdrawn, the I-A time was 26.81 +or- 7.28 hours . In comparison to the group in which less than 50 ml of amniotic fluid was withdrawn, the I-A time was 28.88 +or- 16.24 hours . There was no statistical difference between the 2 groups . The longer I-A times were found in groups in which 51-1000 ml and 151-200 ml of amniotic fluid were withdrawn . The most common complication was retained placenta (8 cases) . There was only 1 case of hemorrhage . There were 2 cases of fever and 1 case of nausea and vomiting . On follow-up of 46.8% of the cases, 2 cases of cervicitis and 3 cases of vaginitis were found and treated with antibiotic suppositories . Ontogenez, 1983 Mar-Apr, 14(2), 162 - 5 {Sensitivity of the hematopoietic stem cells of anemic animals to actinomycin D}; Domaratskaia EI et al.; It was shown on the model of anemic animals by the method of spleen colonies that non-proliferating CFU-S were resistant against the cytotoxic effect of actinomycin D in concentrations 0.04 to 0.4 micrograms/ml . The entry of CFU-S in proliferation was accompanied by a sharp increase of the sensitivity to the antibiotic in a dose blocking DNA-dependent rRNA synthesis. Am J Trop Med Hyg, 1983 Mar, 32(2), 231 - 57 Appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of Plasmodium cynomolgi; Schmidt LH; Compounds (265) of widely diverse structures were appraised for radical curative activity in rhesus monkeys infected with sporozoites of the B strain of Plasmodium cynomolgi, using an evaluation system that provided a preliminary assessment with from 0.1-1.0 g of compound and tests against one to five active infections . None of 32 compounds in a miscellaneous structure category, none of seven agents of antibiotic origin, none of 12 1,5-naphthyridines, and none of seven 7-aminoquinolines exhibited curative activity at the largest test doses . There was a suggestion that one of 12 newly synthesized pyrocatechols was curative . Two of 20 6-aminoquinolines effected cure at or near maximum tolerated doses . In contrast, 90 of 174 newly synthesized 8-aminoquinolines effected cure; 18 of the 90 being as active as primaquine, eight twice as active, and six four times as active . There were major disagreements between the above results and those recorded by others in mice inoculated with sporozoites of P . berghei yoelii or P . yoelii nigeriensis . These discrepancies were of serious dimensions in evaluations of the 8-aminoquinolines . This, plus previous near flawless performances of P . cynomolgi in identifying agents that would cure naturally acquired P . vivax infections, led to the suggestion that the abbreviated simian model employed in these studies be used hereafter in primary screening of new agents for radical curative activity. J Antibiot (Tokyo), 1983 Mar, 36(3), 301 - 11 Studies on the biological activity of stubomycin; Komiyama K et al.; Stubomycin showed direct cytotoxic activity on mammalian cells, yeast, and fungi, and rapid hemolytic activity on mouse erythrocytes . The rate and extent of the cytotoxic and hemolytic activities decreased at lower temperatures . Studies with radioactive precursors revealed that a marginal cytocidal concentration of the antibiotic inhibited synthesis of DNA, RNA, and protein of leukemic cells at almost the same rate . Stubomycin did not show any mutagenicity on mammalian cells and bacteria i.e . the induction of revertants on six bacterial strains, and chromosomal aberrations, sister chromatid exchanges, and the induction of cells resistant to 6-thioguanine on Chinese hamster cells (DON D-6) . The antagonistic effect of various kinds of lipids including phospholipids, cholesterol, olive oil and squalene was studied . Significant antagonism of stubomycin against anti-Saccharomyces cerevisiae activity was observed with phospholipids except for egg lecithin and with cholesterol . The primary action of the antibiotic seems to be to change the cell surface and ultimately the lysis and death of the cells. Hum Pathol, 1983 Mar, 14(3), 228 - 34 Granulocyte antigen systems and antibodies and their clinical significance; McCullough J; Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems . These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases . Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established . Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies . Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy. Br J Haematol, 1983 Mar, 53(3), 459 - 66 Adverse effects of aneuploidy on the outcome of remission induction therapy for acute nonlymphocytic leukaemia: analysis of types of treatment failure; Preisler HD et al.; Cytogenetic studies were carried out on bone marrow specimens obtained from 98 patients with acute nonlymphocytic leukaemia . Patients were treated with cytosine arabinoside and an anthracycline antibiotic . The remission rate for patients in whom only normal metaphases were detected (NN patients) was 69% while the remission rates were 50% and 40% respectively for patients in whom both normal and abnormal metaphases were seen (NA patients) and for those in whom only abnormal metaphases were noted (AA patients) . Analysis of remission induction failure types suggests that the differences in outcome were related to a tendency for patients with aneuploid leukaemia to be more likely to have drug resistant disease and to the lesser ability of NA and AA patients to survive and receive a second course of therapy if the first course failed to induce a complete remission. Clin Exp Immunol, 1983 Mar, 51(3), 517 - 24 Effect of simple sugars on natural killing: evidence against the involvement of a lectin like mechanism in target recognition; Vose BM et al.; The spontaneous lysis of target cells sensitive to natural killer (NK) activity is accomplished in two distinct phases: (i) binding between target and effector cells and (ii) post-binding events leading to target cell destruction . To test the hypothesis that cell surface carbohydrate(s) might be involved in recognitive and/or lytic events, the binding and cytotoxicity of peripheral blood lymphocytes (PBL) towards NK sensitive K-562 targets was studied in the presence of simple sugars and after treatment of the targets with the antibiotic, tunicamycin . Lysis by peripheral blood lymphocytes was found to be inhibited by N-acetyl glucosamine, N-acetyl galactosamine and alpha-methyl mannoside in a dose-dependent manner under conditions where neither these sugars nor those (fucose, galactose) which had little effect on lysis inhibited the binding of effector cells to targets . Further, growth of K-562 in tunicamycin (which inhibits N-linked glycosylations occurring through the lipid intermediate pathway) with or without subsequent treatment with the enzyme neuraminidase, markedly reduced cell surface expression of sugars monitored by lectin binding . Treated cells showed no loss of NK susceptibility and were frequently more sensitive to lysis . Sugar inhibition profiles were the same as for untreated cells . These data suggest that carbohydrates are not the target sites of NK recognition but that simple sugars may have an inhibitory action at a later stage of the lytic process. J S Afr Vet Assoc, 1983 Mar, 54(1), 67 - 8 The danger of immunising Boergoats against heartwater; Gruss B; Ten 6-toothed Boergoat does and 215 Boergoat kids were injected by the intravenous route with the Onderstepoort heartwater blood vaccine and then temperatured daily . On Day 10, all the does had rectal temperatures in excess of 40 degrees C and were treated with oxytetracycline intravenously, while the kids received an intramuscular injection of the antibiotic . One kid died from heartwater on Day 11 . On Day 15, 7 does had a febrile reaction and all the does and kids were treated as before . Two does died of heartwater on Days 16 and 17 respectively, while 12 kids developed heartwater on Day 17 and 6 kids on Day 18 . All were treated for heartwater . A total of 2 does (20%) and 16 kids (7.4%) died during the experiment. J Pharmacol Exp Ther, 1983 Mar, 224(3), 685 - 91 Inactivation of cytochrome P-450 by a troleandomycin metabolite . Protective role of glutathione; Pessayre D et al.; Troleandomycin, a macrolide antibiotic, has been shown to be demethylated and oxidized into a metabolite which forms an inactive complex with the iron(II) of cytochrome P-450 . The role of glutathione in the metabolism of troleandomycin was investigated . Administration of troleandomycin (1 mmol X kg-1 p.o.) decreased the concentration of glutathione in the liver . The depletion of glutathione was increased in rats pretreated with phenobarbital and decreased in rats pretreated with CoCl2 . In vitro, an inverse relationship was found between the concentration of glutathione in the incubation mixture and the appearance of the cytochrome P-450-troleandomycin metabolite complex . Glutathione, however, did not inhibit the demethylation of troleandomycin and did not destroy the cytochrome P-450-troleandomycin metabolite complex . The in vitro protective effect of glutathione was reproduced by cysteine but not by glycine . In vivo, decreasing the concentration of glutathione in the liver by food deprivation or by the administration of diethylmaleate increased the formation of the cytochrome P-450-troleandomycin metabolite complex . These results indicate that glutathione is depleted by a troleandomycin metabolite in vivo, whereas glutathione protects against the formation of the inactive cytochrome P-450-troleandomycin metabolite complex in vitro and in vivo. Cancer Treat Rev, 1983 Mar, 10(1), 1 - 22 4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data; Ganzina F; 4'-epi-doxorubicin (4'-epi-DX) is a new anthracycline antibiotic . It differs from doxorubicin (DX) by the epimerization of the OH group in position 4' of the aminosugar moiety, and was synthesized in an effort to find agents with a superior therapeutic index to the parent compound doxorubicin (DX) . 4'-epi-doxorubicin binds to DNA and inhibits nucleic acid synthesis and function . The antitumor activity of 4'-epi-DX in several experimental tumors (Leukemias L 1210, P 388, Gross Leukemia, Sarcoma 180 ascitic and solid, C3H/HE mammary carcinoma) is similar to that of DX . However, 4'-epi-doxorubicin has greater antitumor activity than doxorubicin in Lewis lung carcinoma, MS-2 sarcoma lung metastasis, and human melanoma in athymic mice . In chronic toxicity studies there were no qualitative differences between 4'-epi-DX and DX; quantitatively, however, 4'-epi-DX was less toxic . In different experimental models 4'-epi-DX has been shown to be less cardiotoxic than its parent compound . In chronic toxicity studies in the rabbit, histopathologic findings revealed the same pattern of cardiotoxicity for both drugs but less marked with 4'-epi-DX . Distribution studies in mice with tumors showed a lower concentration of 4'-epi-DX in the heart, spleen and kidneys; the hepatobiliary metabolism and excretion of 4'-epi-DX investigated in the rat, indicated that the new analogue was more extensively metabolized than the parent compound . Pharmacokinetics of 4'-epi-DX in humans showed a multiexponential decrease of plasma levels; the same pattern was observed for the metabolite 13-OH epidoxorubicinol but with lower concentrations than the unchanged drug . A high plasma clearance (0.9-1.41/min), a terminal half-life of about 30-40 hr and a large volume of distribution were the main pharmacokinetic characteristics of 4'-epi-DX . A reduction of the dose appears to be appropriate in patients with liver function impairment . Phase II studies with 4'-epi-DX have indicated that the drug produces a pattern of acute toxicity, including acute cardiac toxicity, qualitatively similar to that of DX at identical doses but quantitatively lower, with particular regard to leukopenia and gastrointestinal toxicity . The range of single active doses is between 60 and 90 mg/m2, the most frequently employed doses schedules being 75 or 90 mg/m2 i.v . every 3 weeks . 4'-epi-DX has shown activity in a variety of tumors such as breast carcinoma, soft tissues sarcomas, NH lymphomas, leukemias, ovarian cancer and gastric cancer . Preliminary evidence of activity has been found in melanoma, rectal cancer and pancreatic cancer suggesting a broad spectrum of activity . As to chronic cardiac toxicity up to now only 2 mild to moderate and reversible CHF have been observed at doses of 1120 and 1235 mg/m2 in about 700 treated patients . Specific and comparative studies are in progress: preliminary findings from a randomized comparison of 4'-epi-DX vs DX in breast cancer indicated that 4'-epi-DX may have a lower cumulative cardiotoxicity. Rev Infect Dis, 1983 Mar-Apr, 5 Suppl 1, S40 - 54 Empiric therapy for pneumonia; Donowitz GR et al.; Bacterial pneumonia remains a serious infectious disease even in the modern era of antibiotics and still causes significant morbidity and mortality . Because of the large number of organisms that may cause pulmonary disease, the inexactness of commonly used diagnostic techniques, and the serious consequences of untreated disease, empiric therapy has become accepted practice . Empiric therapy should be designed for treatment of the most likely etiologic organisms while minimizing the potential adverse effects of "shotgun" therapy: drug toxicity, superinfection, and excessive cost . The recognition of common pneumonia syndromes helps narrow the spectrum of possible etiologic agents and consequently aids in the design of rational empiric antibiotic therapy. Antibiotiki, 1983 Mar, 28(3), 192 - 4 {Effect of heliomycin on the respiration and oxidative phosphorylation of the liver mitochondria of the rat}; Konoshenko GI et al.; The effect of heliomycin and known uncouplers of oxidative phosphorylation on respiration and oxidative phosphorylation was studied comparatively . Heliomycin, as well as 2,4-dinitrophenol, valinomycin and gramicidin S inhibited the mitochondrial synthesis of ATP . This process was inhibited completely by heliomycin at a concentration of 1.5 x 10(-5) M . The synthesis of inorganic pyrophosphate, the other macroergic compound, was also inhibited by heliomycin, ATPase and pyrophosphatase of uncoupled mitochondria being not inhibited by the antibiotic . Like 2,4-dinitrophenol, heliomycin stimulated the synthesis of ATPase and respiration in intact mitochondria . Probably, heliomycin inhibited the synthesis of ATP and pyrophosphate by uncoupling the processes of respiration and oxidative phosphorylation . It was shown earlier that heliomycin, a specific inhibitor of bacterial RNA synthesis, also affected energy metabolism of bacterial cells by inhibiting the synthesis of ATP and active transport. Isr J Med Sci, 1983 Mar, 19(3), 267 - 70 Late postoperative fever--viral infection following multiple blood transfusion; Siegman-Igra Y; The possibility of acquiring a viral infection by blood transfusion, although recognized for nearly 20 yr, is often ignored . Surgeons and internists submit patients to sophisticated, and sometimes invasive, diagnostic and therapeutic procedures without considering this possibility . We report here on two patients in whom febrile illness appeared about 5 wk after surgery . Both had received multiple blood transfusions in the perioperative period . Initial diagnoses indicated typhoid fever in one patient who received chloramphenicol therapy, and endocarditis in the other patient who was given massive combined antibiotic therapy . Both were later diagnosed by serologic methods as having cytomegalovirus and Epstein-Barr virus infection, respectively . Review of the literature reveals that this mechanism of acquiring these frequently asymptomatic viral infections is surprisingly common. J Pharmacol Exp Ther, 1983 Mar, 224(3), 609 - 13 Effect of aminophylline on amphotericin B nephrotoxicity in the dog; Gerkens JF et al.; The polyene antibiotic, amphotericin B, causes an acute reduction in renal blood flow and glomerular filtration rate . The purpose of this study was to evaluate the hypothesis that the renal vascular response to amphotericin B can be blocked by aminophylline . Toward this end, the effect of aminophylline on the renal response to amphotericin B in sodium-depleted dogs was examined . In dogs not treated with aminophylline, amphotericin B (0.5 mg/kg infused i.v . over 20 min) significantly reduced renal blood flow and glomerular filtration by 49.9 +/- 12.6 ml/min (mean +/- S.E.M.) and 23.4 +/- 2.4 ml/min, respectively at 140 min after the amphotericin B infusion . In dogs treated with an intrarenal aminophylline infusion (5 mg/min), the renal blood flow and glomerular filtration rate response to amphotericin B did not differ from that of amphotericin B vehicle . We conclude that aminophylline inhibits the renal response to amphotericin B . The possible clinical relevance of these observations are discussed. Antimicrob Agents Chemother, 1983 Mar, 23(3), 360 - 3 Effects of moxalactam and cefuroxime on mitogen-stimulated human mononuclear leukocytes; Manzella JP et al.; The effect of moxalactam and cefuroxime on mitogen-stimulated human peripheral blood mononuclear leukocytes was studied . Mononuclear leukocytes, mitogen, and antibiotic were added to microtiter wells . Cells were cultured for 3 days, pulsed with tritiated thymidine, and then counted . Compared with control cell cultures, treated cultures showed phytohemagglutinin responsiveness to be depressed by the addition of moxalactam at concentrations of 25 to 200 micrograms/ml (P less than 0.001) and by cefuroxime at concentrations of 50 to 200 micrograms/ml (P less than 0.02 to P less than 0.01) . The depressive effect on blastogenesis was less marked when concanavalin A was used . Unstimulated lymphocyte transformation responses were also depressed by both antibiotics at all concentrations (P less than 0.05) . Preincubation of mononuclear leukocytes with antibiotic for 2 h, followed by washing and culturing in an antibiotic-free medium, did not depress transformation response . When antibiotic was added 24 h after mitogen, depression of response was insignificant . The data from this study suggest that two new beta-lactam antibiotics, at concentrations achievable in serum when used therapeutically, may have immunosuppressant effects . It remains to be established whether these effects are clinically important. J Hosp Infect, 1983 Mar, 4(1), 65 - 9 Metronidazole need not be combined with an aminoglycoside when used for prophylaxis in elective colorectal surgery; Morris DL et al.; A prospective randomized controlled study has compared prophylactic intravenous metronidazole alone with the combination of metronidazole and gentamicin in 100 patients having elective colorectal surgery . There was no significant difference in mortality, infection, dehiscence or postoperative stay between the antibiotic groups . Postoperative sepsis was almost entirely due to aerobic organisms but was associated with minimal morbidity . A significantly higher rate of anastomotic dehiscence and postoperative infection was seen where the quality of bowel preparation was judged to be poor. Br J Clin Pharmacol, 1983 Mar, 15(3), 339 - 46 Effect of cephapirin on tubular reabsorption of amino acids, uric acid and beta 2-microglobulin in man; Arvidsson A et al.; Cephapirin, a beta-lactam antibiotic, was administered intravenously to five healthy subjects in a dose of 1 g . Renal clearances of cephapirin, beta 2-microglobulin, uric acid and amino acids were measured during the experiment and compared to timed control data, i.e . when no cephapirin was given . Renal clearance of cephapirin decreased when plasma concentrations declined . As protein binding of cephapirin is constant over a wide plasma concentration range, this finding may indicate that cephapirin is reabsorbed in the kidney by a saturable process . Renal clearance of endogenous amino acids, particularly those belonging to the basic group increased after cephapirin . There was no change in renal clearance of beta 2-microglobulin which excludes a general toxic effect on tubular reabsorption of endogenous substances caused by cephapirin . A flow dependent increase of uric acid clearance was observed . Our results are suggestive of a competition between cephapirin and amino acids for some common step in the tubular reabsorption process. Cancer Res, 1983 Mar, 43(3), 1049 - 53 Effects of iron, copper, cobalt, and their chelators on the cytotoxicity of bleomycin; Lin PS et al.; Bleomycin is widely used for treating several types of human tumors as well as a variety of experimental tumors . The ability of this antibiotic to bind and to damage DNA has been proposed to be responsible for its antitumor effect . Bleomycin is also a good chelator for several metals, e.g., iron, copper, and others . Bleomycin:metal complexes have been investigated in detail particularly for their action on isolated DNA . The conclusions from these studies indicate that metal-chelated bleomycin either is ineffective or more effective in damaging DNA . In this paper, we tested the effect of iron, copper, cobalt, and their chelators on bleomycin cytotoxicity . Our results suggest that chelating bleomycin with copper or adding an iron chelator (deferoxamine), diethylenetriamine pentaacetic acid, and a copper chelator (penicillamine) shows no effect on bleomycin cytotoxicity . On the other hand, iron dextran and a metal chelator, diethyldithiocarbamate (DDC), with bleomycin show enhanced cytotoxicity . Cobalt-chelated bleomycin is not cytotoxic but is cytotoxic when combined with DDC . We suggest that different mechanisms are contributing to the enhanced toxicity of bleomycin with iron dextran and DDC . Bleomycin acts as a ferrous oxidase which promotes the iron toxicity . In the case of DDC, it can act as a reducing agent or it can help to maintain the bleomycin:metal complex in the reduced form which can generate radicals. Presse Med, 1983 Feb 26, 12(9), 553 - 6 {Chemoprevention with intravenous doxycycline in 40 cases of colonic esophagoplasty}; Saux P et al.; Doxycycline was used to prevent infection in 40 patients undergoing oesophageal surgery (for carcinoma in 35 and for benign lesions in 5) . Treatment began with induction of anaesthesia and continued in doses of at least 200 mg/day for a mean period of 10 days . Concentrations of the antibiotic were measured in the serum and colonic tissue of 20 patients, 2 hours on average after the first injection . Mean serum and tissue levels were 4.1 +/- 0.8 mcg.ml-1 and 2.9 +/- mcg.ml-1 respectively, with a tissue to serum ratio of 0.7 . This ratio remained practically unchanged between the first and fourth hours post-injection . Doxycycline was successful in preventing post-operative infection in 75% of the cases . No infection due to anaerobic organisms was observed. J Biol Chem, 1983 Feb 25, 258(4), 2098 - 101 Thermal regulation of membrane fluidity in Escherichia coli . Effects of overproduction of beta-ketoacyl-acyl carrier protein synthase I; de Mendoza D et al.; Multicopy plasmids bearing the structural gene (fabB) for beta-ketoacyl-acyl carrier protein (ACP) synthase I were constructed in vitro and transformed into various Escherichia coli strains . Introduction of these plasmids into fabB strains resulted in a fabB+ phenotype and a large (8- to 10-fold) overproduction of synthase I activity . Strains carrying these plasmids were also unusually resistant to cerulenin (an antibiotic that specifically inhibits beta-ketoacyl-ACP synthase activity) and overproduced cis-vaccenic acid . Strains (fabF-) lacking beta-ketoacyl-ACP synthase II are deficient in both cis-vaccenic acid synthesis and thermal regulation . Introduction of the fabB plasmids into these strains resulted in the restoration of cis-vaccenic acid synthesis . However, the plasmid-engendered cis-vaccenic acid synthesis of these strains was unaffected by temperature . These results demonstrate that synthase II, the product of the fabF gene, is the sole enzyme regulating the temperature-dependent composition of the membrane phospholipid acyl chains. J Biol Chem, 1983 Feb 10, 258(3), 1775 - 80 Effect of tunicamycin, an inhibitor of protein glycosylation, on the biological properties of acetylcholine receptor in cultured muscle cells; Prives J et al.; We have studied the effect of tunicamycin (TM), an antibiotic which inhibits the glycosylation of nascent proteins, on the properties of the acetylcholine receptor (AChR) at the surface of embryonic chick skeletal muscle cells . The use of two separate assays, specific binding of 125I-alpha-bungarotoxin and carbamylcholine-activated 22Na+ uptake, has allowed us to monitor the effects of impaired glycosylation on the metabolic and functional properties of AChR . A significant decrease in the amounts of surface AChR elaborated in the presence of TM is detected by both measurements . This decrease has been found to reflect an enhanced proteolytic degradation of the underglycosylated AChR . The underglycosylated AChR, expressed on the cell surface in the presence of TM, retains the capability of mediating agonist-activated ionic permeability changes, but displays quantitatively altered interactions with receptor ligands . We conclude that the carbohydrate moiety on AChR may play a role in determining the folding of newly synthesized polypeptides to form a conformation compatible with the metabolic properties and ligand interactions characteristic of glycosylated AChR. Biochem Biophys Res Commun, 1983 Feb 10, 110(3), 959 - 66 Identification of a key structural feature of cobalt(III)-bleomycins: an exogenous ligand (e.g . hydroperoxide) bound to cobalt; Chang CH et al.; A series of cobalt(III) complexes of the anticancer antibiotic bleomycin has been prepared . Mass spectrometry and enzymatic analysis show that the green cobalt-bleomycin complex contains a hydroperoxide (-OOH) group bound to cobalt with unusual stability . Under appropriate conditions, cobalt-bleomycins containing other monodentate ligands to cobalt can be formed; fast-atom bombardment mass spectra of such complexes show peaks for cobalt-bleomycin at the expected mass, and also peaks for the intact complexes at the required higher mass. Nord Vet Med, 1983 Feb, 35(2), 91 - 4 The effect of colistin feeding during the mating, gestation and lactation periods on whelping result in mink; Pekkanen T et al.; Colistin (100000 IU/kg) was given in the feed during the mating, gestation and lactation periods to 49 female standard minks . 99 similar animals served as control without the antibiotic . The whelping result, expressed as the number of puppies living three weeks post partum per mated female, was 3.22 in the experimental group and 2.67 in the control group . The difference in the whelping result between the groups was mainly due to the significantly greater number of empty females in the control group compared to the experimental group. Mutat Res, 1983 Feb, 107(2), 433 - 45 Characterization of chloramphenicol- and 8-azaguanine-resistant mutants isolated from a continuous rat-liver epithelial cell line; Sudilovsky O et al.; 2 non-tumorigenic, chloramphenicol- and 8-azaguanine-resistant strains have been isolated from the rat-liver cell line K-22, by a 2-step mutagenesis procedure . Their chromosome composition and growth properties have been characterized . Failure of chloramphenicol to inhibit mitochondrial protein synthesis in one of the clones, F1, strongly suggests that resistance to the antibiotic in this strain is due to a mutation in mitochondrial DNA. J Neurosurg, 1983 Feb, 58(2), 270 - 4 Aspergillus infections of the lumbar disc spaces . Report of three cases; Mawk JR et al.; Three cases of lumbar vertebral interspace infection due to the Aspergillus fungus are presented . Two patients responded to vigorous surgical therapy in combination with prolonged administration of antifungal agents . The third patient died of complications related to the antibiotic therapy . Possible etiologies of this unusual problem are reviewed in light of the changing spectrum of nosocomial and spontaneously acquired infectious processes . Combined aggressive medical and surgical therapy is discussed with respect to the known difficulties in eradicating deep-seated osseous mycotic infections. J Clin Gastroenterol, 1983 Feb, 5(1), 55 - 8 Nonhealing duodenal ulceration due to candida; Thomas E et al.; An important role for candida in gastric and duodenal ulcer disease is being increasingly recognized . Causative factors implicated include the frequent use of cimetidine, and immunosuppressive or antibiotic therapy . Concerning cimetidine, there is no clear-cut evidence that the drug depresses cell mediated immunity; on the contrary, there is evidence that delayed hypersensitivity is enhanced . Acid reduction is the alternate and more likely explanation for any role of cimetidine in gastric and duodenal candidiasis . We report a patient with a duodenal ulcer, which repeatedly bled and failed to heal in hospital on standard antacid and cimetidine therapy . Candida was identified in the ulcer and treated, using mycostatin suspension, resulting in complete healing . We feel that candida involvement of duodenal ulcers may be more common than is generally recognized, and may be the cause for nonhealing in certain patients already on optimum therapy. J Clin Microbiol, 1983 Feb, 17(2), 349 - 51 Fusobacterium nucleatum pericarditis; Truant AL et al.; A pericardial effusion was diagnosed by echocardiography in a 49 year old man who suffered acute cough, orthopnea, and chest pain . Because of a positive tuberculin skin test, mycobacteria were initially suspected as the cause of the pericarditis . The patient was therefore treated with antituberculosis drugs . The pericardial effusion failed to resolve, however, and pericardiectomy was performed . Culture of the pericardial fluid yielded pure Fusobacterium nucleatum growth . The patient responded to antibiotic therapy and was in good health 3 weeks after being discharged from the hospital . This represents the first report of F . nucleatum pericarditis. J Cell Biol, 1983 Feb, 96(2), 363 - 72 Distribution of filipin-sterol complexes on cultured muscle cells: cell-substratum contact areas associated with acetylcholine receptor clusters; Bridgman PC et al.; Specialized areas within broad, close, cell-substratum contacts seen with reflection interference contrast microscopy in cultures of Xenopus embryonic muscle cells were studied . These areas usually contained a distinct pattern of light and dark spots suggesting that the closeness of apposition between the membrane and the substratum was irregular . They coincided with areas containing acetylcholine receptor clusters identified by fluorescence labeled alpha-bungarotoxin . Freeze-fracture of the cells confirmed these observations . The membrane in these areas was highly convoluted and contained aggregates of large P-face intramembrane particles (probably representing acetylcholine receptors) . If cells were fixed and then treated with the sterol-specific antibiotic filipin before fracturing, the pattern of filipin-sterol complex distribution closely followed the pattern of cell-substratum contact . Filipin-sterol complexes were in low density in the regions where the membrane contained clustered intramembrane particles . These membrane regions were away from the substratum (bright white areas in reflection interference contrast; depressions of the P-face in freeze-fracture) . Filipin-sterol complexes were also in reduced density where the membrane was very close to the substratum (dark areas in reflection interference contrast; bulges of the P-face in freeze-fracture) . These areas were not associated with clustered acetylcholine receptors (aggregated particles) . This result suggests that filipin treatment causes little or no artefact in either acetylcholine receptor distribution or membrane topography of fixed cells and that the distribution of filipin-sterol complexes may closely parallel the microheterogeneity of membranes that exist in living cells. J Cell Physiol, 1983 Feb, 114(2), 162 - 72 The biochemical and ultrastructural effects of tunicamycin and D-glucosamine in L1210 leukemic cells; Morin MJ et al.; Tunicamycin was found to specifically inhibit the incorporation of a number of sugars into L1210 leukemia cell glycoproteins . This inhibition of glycoprotein biosynthesis led to a cessation of cell growth which was reversible in a dose-dependent and time-dependent manner . After removal of the antibiotic from L1210 cell cultures resumption of sugar incorporation preceded that of thymidine incorporation and the recovery of cell growth . The treatment of cells with tunicamycin resulted in a significant increase in the intracellular pool of UDP-N-acetylglucosamine which occurred concurrently with alterations in cell ultrastructure including distentions of the endoplasmic reticulum and nuclear membranes . Similar ultrastructural changes and increases in the intracellular pools of UDP-sugars were observed in L1210 cells exposed to 5 mM D-glucosamine, which suggested that the antiproliferative effects of tunicamycin may be related to the accumulation in the endoplasmic reticulum of one or more nucleotide sugar precursors of asparagine-linked glycoprotein biosynthesis . However, the biological effects of tunicamycin could be distinguished from those caused by D-glucosamine . Exposure of L1210 cells to tunicamycin resulted in specific alterations in the biochemical composition of the plasma membrane and in the inhibition of cellular agglutination by wheat germ agglutinin which were not apparent following exposure to equitoxic concentrations of the aminosugar . These studies, together with those which demonstrated that recovery of the cellular capacity to synthesize glycoproteins was obligatory for the recovery of cellular proliferation in tunicamycin-treated cells, suggested that inhibition of the synthesis of glycoproteins was the major factor limiting L1210 leukemic cell proliferation. J Bone Joint Surg Am, 1983 Feb, 65(2), 230 - 4 Osteomyelitis of the pelvis in children; Highland TR et al.; We reviewed the records of sixteen patients with osteomyelitis of the pelvis, all of whom were fifteen years old or younger . Eleven of the patients were followed for an average of 3.5 years (range, two to nine years) . Pelvic osteomyelitis in children is an uncommon lesion . Review of the literature gives the impression that this lesion is usually diagnosed late in its course and requires surgical drainage for adequate treatment . The role of the technetium bone scan in making an early diagnosis is important . All of the patients in this series were treated with antibiotic therapy alone, and surgical drainage was not found to be necessary . All of the patients who were followed for at least two years had no recurrence and no permanent sequelae. Dis Colon Rectum, 1983 Feb, 26(2), 116 - 8 Survival after colonic perforation during barium-enema examination . Modified radical surgical debridement; Hardy TG Jr et al.; Four of five patients survived perforation of the colon incidental to barium-enema examination, while the other survived without sequela of infection until hemiplegia and pneumonia supervened two and 36 days, respectively, postoperatively . It is postulated that adequate intravenous fluids, early operation, with complete cleansing by antibiotic irrigation and mechanical debridement of the abdominal cavity, along with excision of the perforated segment of bowel with establishment of an end colostomy or ileostomy and distal mucous fistula, if possible, are keys to survival in these patients . Triple antibiotics, using ampicillin, gentamicin, and clindamycin, or metronidazole, should be administered in all patients as soon as the diagnosis is made, and continued postoperatively as indicated until there is no evidence of infection . An intraluminal intestinal tube, for stichless plication of the small bowel, may be helpful in some patients . A stomacone should be used for a barium enema through a colostomy stoma . Care should be exercised in performing barium contrast studies in patients with inflammatory bowel disease. Cancer, 1983 Feb 1, 51(3), 378 - 80 Phase I study of L-alanosine (NSC 15353); Goldsmith MA et al.; L-alanosine (NSC 15353) is a newly developed antitumor antibiotic which acts as an inhibitor of purine intermediary metabolism . Experimental antitumor activity was demonstrated in a variety of murine neoplasms . A Phase I trial was undertaken on a daily x 5 (d x 5) schedule in 22 evaluable patients . Dose limiting toxicity was an oral mucositis characterized by beefy red oral, lingual and pharyngeal erythema . The maximum tolerated dose is 320 mg/m2/d x 5 every three weeks . The recommended dose for Phase II evaluation is 160 mg/m2/d x 5 every three weeks. Jpn J Antibiot, 1983 Feb, 36(2), 391 - 7 {Cooperative studies on clinical effect of cefotetan for severe infections combined with hematologic disorders}; Shinohara Y et al.; Seventy-six patients with severe infection accompanying hematologic disorders including leukemia and lymphoma were treated with intravenous drip infusion of cefotetan (CTT) . Of the 66 cases in whom the efficacy could be evaluated, 22 cases responded markedly and 16 cases moderately, the effective rate being 57.6% . It is impressed that more cases responded markedly to CTT than to any other antibiotics previously studied . None of the cases revealed serious side effects attributable to CTT . These results indicate that CTT is an effective and safe antibiotic for the treatment of severe infection accompanying hematologic disorders . As CTT was administered to special cases under marked decrease of neutrocyte, the importance of neutrocyte in the treatment of infection was also indicated. Antibiotiki, 1983 Feb, 28(2), 83 - 6 {Characteristic features of protoplast formation and regeneration in Fusidium coccineum}; Zakharova GM et al.; The methods for preparation and regeneration of protoplasts were tested with respect to the strains of F . coccineum markedly differing in their capacity for antibiotic production, sporulation and the growth rate . It was found that the substrate used for the culture growth had a significant effect on the cell wall and sensitivity of the mycelium to lytic enzymes . An enzyme from Hellix pomatia and its combination with lysozyme were used for lysing the culture . The cytological investigation of the time course of the culture lysis revealed a stage-by-stage pattern of protoplast formation by means of fragmentation of the hyphal contents till a ball was formed . Two to 4 protoplasts differing in their size and structure were formed within a cell . The pH value and osmotically stabilizing component had some effect on the rate of protoplast formation . Highly productive strains were characterized by formation of protoplasts heterogenous in their size and by decreased frequency of regenerations . The enzyme-free protoplasts preserved their viability and capacity for germination in osmotically stabilizing media for 72-96 hours of storage at 4 degrees C . On solid media the regeneration frequency reached 38 per cent . The regenerated cells formed colonies morphologically similar to those of the intact culture. J Parasitol, 1983 Feb, 69(1), 129 - 37 Freeze-fracture localization of filipin-cholesterol complexes in the plasma membrane of Trypanosoma cruzi; Souto-Padron T et al.; The polyene antibiotic filipin was used as a probe for the detection of cholesterol on the P and E faces of the cell body and the flagellar membranes of epimastigotes of Trypanosoma cruzi . When glutaraldehyde-fixed cells were treated with filipin the filipin-cholesterol complexes were homogenously distributed throughout the parasite's plasma membrane . In some cells, mainly on their P faces, such complexes were arranged linearly forming parallel bands with a distance between the bands similar to that existent between the subpellicular microtubules that are attached to the plasma membrane . Filipin-cholesterol complexes were more abundant in the flagellar membrane than in the membrane that enclosed the cell body . No filipin-cholesterol complexes were seen in the membrane of intracellular organelles . Treatment of living epimastigotes with filipin-induced aggregation of cholesterol and intramembranous particles. J Pharmacobiodyn, 1983 Feb, 6(2), 139 - 40 Covalent binding of cefotaxime to human serum albumin; Toyo'oka T et al.; The covalent binding ratio of cephalosporins (CEZ, CER, CET and CTX) to human serum albumin was examined at pH 7 and pH 10 . The antibiotic equivalents were larger at pH 10 than at pH 7 . The degree in the binding ratio of the 4 cephalosporins was CET greater than CER greater than CTX greater than CEZ at pH 7 and CER greater than CET greater than CTX greater than CEZ at pH 10. Res Commun Chem Pathol Pharmacol, 1983 Feb, 39(2), 311 - 9 The effect of pyrrolnitrin on mitochondrial reactions: the induction of swelling; Kawai K et al.; An antifungal antibiotic, pyrrolnitrin, was found to show very similar biological activities to those of imidazole antimycotics on isolated mitochondria . Pyrrolnitrin caused drastic swelling of mitochondria in isotonic solutions of alkali metal salts and of sucrose without any addition of substrate for the respiratory chain in mitochondria . The swelling induced by pyrrolnitrin was characterized by a biphasic swelling process; a very fast initial swelling and thereafter a very slow speed secondary swelling . The increase of pyrrolnitrin concentration exponentially increased the magnitude of over-all rapid swelling . Pyrrolnitrin enhance the latent ATPase activity of mitochondria at the similar range of concentrations to those needed for the induction of the swelling . The concentrations of pyrrolnitrin where mitochondrial swelling was induced were found to be far lower than those needed for the exhibition of inhibitory effect on the electron transport system of mitochondria. Am J Dis Child, 1983 Feb, 137(2), 118 - 22 Vasculitis, pulmonary cavitation, and anemia during antithyroid drug therapy; Cassorla FG et al.; Two thyrotoxic girls, aged 12 and 16 years, had a clinical picture consisting of purpuric skin rash, nephritis, pulmonary cavitation, hemoptysis, and profound anemia during antithyroid drug therapy . These major toxic manifestations prompted discontinuation of antithyroid drugs and institution of antibiotic and glucocorticoid therapy before the resolution of the severe illness . The girls eventually required ablative doses of radioactive iodine, and one of them had a thyroidectomy for the treatment of thyrotoxicosis . The skin biopsy specimen in one patient was indicative of mononuclear cell cutaneous vasculitis . After recovery, the patients had no evidence Of persistent anemia, nephritis, or pulmonary parenchymal disease. J Ultrastruct Res, 1983 Feb, 82(2), 143 - 55 Variability of the topography of low-density lipoprotein (LDL) receptors in the plasma membrane of cultured human skin fibroblasts as revealed by gold-LDL conjugates in conjunction with the surface replication technique; Robenek H et al.; In this investigation the membrane-perturbing effect of filipin, a polyene antibiotic which reacts specifically with cholesterol or cholesterol-like compounds in cell membranes, has been exploited to study the distribution of coated pits in cultured human skin fibroblasts . The coated pits, showing no filipin-cholesterol complexes, occurred singly or in clusters without apparent localization of either type to a particular region of the fibroblast membrane . Colloidal gold, conjugated to low-density lipoprotein, has proven to be an excellent marker, allowing the localization of low-density lipoprotein receptors on the surface of cultured cells . A pattern similar to that for the coated pits in the plasma membrane fracture faces was observed in the distribution of gold-low-density lipoprotein conjugates in surface replicas, indicating that the low-density lipoprotein receptors are associated with these coated pits . It was shown that there is an apparent heterogeneity in the distribution of low-density lipoprotein receptors, from cell to cell and even among different areas of the same cell membrane . The binding capacity for gold-low-density lipoprotein complexes, as represented by the extent of surface labeling, was directly related to the cell variety within the culture or to the particular experimental procedure . The observation of differences in the distribution of gold-low-density lipoprotein conjugates, even among adjacent coated pits, provides evidence for various stages of activity of the low-density lipoprotein receptors corresponding to incorporation, mobility, and internalization. Biochem Biophys Res Commun, 1983 Jan 27, 110(2), 483 - 90 Repair of potentially lethal and sublethal damage induced by neocarzinostatin in normal and ataxia-telangiectasia skin fibroblasts; Shiloh Y et al.; Neocarzinostatin is a radiomimetic antibiotic with a potent cytotoxic effect which elicits a hypersensitive response in human cells homozygous or heterozygous for the gene for ataxia-telangiectasia . The extent and the time course of potentially lethal damage repair and sublethal damage repair following neocarzinostatin treatment were investigated in human skin fibroblast strains and were found to be remarkably similar to those obtained following X-irradiation . Ataxia-telangiectasia homozygous cells essentially lacked potentially lethal damage repair, but were able to perform some degree of sublethal damage repair following neocarzinostatin treatment . Ataxia-telangiectasia heterozygous cells which show an intermediate degree of neocarzinostatin sensitivity could perform both processes but with somewhat reduced efficiency as compared to normal cells . These observations provide further evidence for a DNA repair defect in ataxia-telangiectasia cells. FEBS Lett, 1983 Jan 24, 151(2), 219 - 22 Compound 48/80-induced permeability change in liposomal membrane; Katsu T et al.; The action of compound 48/80 (a mixture of condensation products of p-methoxy-N-methylphenethylamine with formaldehyde) on liposomal membranes was studied by means of K+-loaded liposomes and a K+ ion-selective electrode . Prompt efflux of K+ was detected when 48/80 was added to the negatively charged liposome suspension, while the monomer of 48/80, p-methoxy-N-methylphenethylamine, did not release K+ from the same liposomes . The mechanism for the action of 48/80 is discussed in comparison with that of a polymyxin, well known as an antibiotic acting on bacterial membranes. Wien Klin Wochenschr, 1983 Jan 21, 95(2), 52 - 5 {Pharmacokinetics and acute signs of cardiac toxicity during doxorubicin therapy}; Lenzhofer R et al.; Doxorubicin (Adriamycin) has shown impressive activity in the treatment of a broad spectrum of malignant tumours . Chronic irreversible cardiac myopathy is the usual cumulative dose-limiting toxicity with this anthracycline antibiotic . In this study acute cardiac reactions following doxorubicin infusions (60 mg/m2) were registered by means of ECG Holter monitoring and measurement of systolic time intervals . The PEPI as well as the PEP/LVET ratio were found to be significantly increased, with a peak at 6 hours following drug infusion (p less than 0.001) . This observation proves the occurrence of transient myocardial dysfunction during doxorubicin treatment . Pharmacokinetic data showed good correlation between the electrocardiographic changes and the tissue distribution of the drug . Doxorubicin-related ventricular arrhythmias were observed in only 2 out of 6 cases . Repeated acute myocardial damage by doxorubicin infusions is considered to be the cause of chronic cardiomyopathy with long-term administration. ZFA (Stuttgart), 1983 Jan 20, 59(2), 79 - 80 {Emergency in general medicine (43) . Septic complications in implanted IUD}; Kuhn W; PIP: Between 2-6% of patients with an IUD will suffer related ascending infections of the inner genital region with possible spread to the pelvic region, independent of length of use . In case of pregnancy with an IUD, septic complications will be more severe . None of the IUD models is regarded as causing infection since the Dalkon Shield has been taken off the market . The symptomatology of the disease develops similar to an uncomplicated ascending adnexitis . It will cause diagnostic problems if it cannot be determined whether the septic focus is located in the inner genital region . With uncharacteristic or absent pathological and gynecological findings by touch, a septic ovarial vein thrombosis has to be considered . The search for the IUD, even with a nonvisible thread, by ultrasound is unavoidable . Further measures include control of the kidney and pulmonary function and leukocytes and blood sedimentation . If an infection develops with an implanted IUD, which is to be classed with the inner genital region, antibiotic therapy can be started provided that no shock signs, no acute abdomen, and no grave feelings of illness are present . If the patient is pregnant it is absolutely necessary to send her to the hospital for examination, even if there are no grave symptoms . Eur J Biochem, 1983 Jan 17, 130(1), 27 - 32 Association of the prolipoprotein accumulated in the presence of globomycin with the outer membrane of Escherichia coli; Inukai M et al.; The prolipoprotein, a secretory precursor of the outer membrane lipoprotein of Escherichia coli, is known to be accumulated in the cell envelope when cells are grown in the presence of a cyclic antibiotic, globomycin . The prolipoprotein was localized in the cytoplasmic membrane when it was separated from the outer membrane by sucrose-density gradient centrifugation . However, when the envelope fraction was treated with sodium sarcosinate, the prolipoprotein was found almost exclusively in the sarcosinate-insoluble outer membrane fraction . The prolipoprotein separated in the cytoplasmic membrane by sucrose-density gradient centrifugation was soluble in sarcosinate and could not form a complex with the outer membrane once solubilized in sarcosinate . Labeling of the two lysine residues at positions 2 and 5 of the prolipoprotein with {3H}dinitrophenylfluorobenzene was enhanced 26-fold when the cells were disrupted by sonication . On the other hand, a tryptic fragment of the ompA protein, which is known to exist in the periplasmic space, increased its susceptibility to {3H}dinitrophenylfluorobenzene only 5.3-times upon disruption of the cell structure . These results indicate that the prolipoprotein accumulated in the presence of globomycin is translocated across the cytoplasmic membrane and interacts with the outer membrane . At the same time, it is attached to the cytoplasmic membrane with its amino-terminal signal peptide in such a way that the amino-terminal portion of the signal peptide containing two lysine residues is left inside the cytoplasm. Biochim Biophys Acta, 1983 Jan 13, 722(1), 43 - 50 Inhibition of mitochondrial oxidative phosphorylation by adriamycin; Muhammed H et al.; The antitumour antibiotic, adriamycin, inhibited oxidative phosphorylation in freshly prepared mitochondria from the heart, liver and kidney of the rat . It abolished respiratory control and stimulated ATPase activity . Succinate oxidation by heart mitochondria was extremely sensitive to the drug when hexokinase was present in the reaction medium . The sensitive site has been identified to lie in the region between the succinate dehydrogenase flavoprotein and ubiquinone of the respiratory chain. Biochim Biophys Acta, 1983 Jan 12, 742(1), 184 - 8 Studies on the complex formed between bacitracin A and divalent cations; Scogin DA et al.; Bacitracin A is a peptide antibiotic which forms stoichiometric complexes with divalent cations, including Ni2+ and Zn2+ . In this paper it is shown that the metal-bacitracin complex contains a group which has a pKa near pH 5.5 . Deprotonation of the group is concomitant with the aggregation and precipitation of the metal-bacitracin complex . Bacitracin A, in the absence of metals, does not contain any group which has a pKa in this range . It is postulated that this group is the N-terminal amino of isoleucine, which was previously postulated not to be directly involved in metal coordination based on proton release measurements . An attempt was made to demonstrate directly that the N-terminal amino group is not coordinated to the metal by examining the reactivity of this group with 2,4,6-trinitrobenzene sulfonate . It was clearly shown that bound metals protect the N-terminal amino group from reacting with this reagent . It is speculated that this metal-protection results from a combination of factors, including steric hindrance. Biochim Biophys Acta, 1983 Jan 5, 727(1), 108 - 14 Melittin and a chemically modified trichotoxin form alamethicin-type multi-state pores; Hanke W et al.; The bee venom constituent, melittin, is structurally and functionally related to alamethicin . By forming solvent-free planar bilayers of small area (approx . 100 microns 2) on the tip of fire-polished glass pipettes we could observe single melittin pores in these membranes . An increase in the applied voltage induced further non-integral conductance levels . This indicates that melittin forms multi-level pores similar to those formed by alamethicin . Trichotoxin A40, an antibiotic analogue of alamethicin, also induces a voltage-dependent bilayer conductivity, but no stable pore states are resolved . However, chemical modification of the C-terminal molecule part by introduction of a dansyl group leads to a steeper voltage-dependence and pore state stabilization . Comparing structure and activity of several natural and synthetic amphiphilic polypeptides, we conclude that a lipophilic, N-terminal alpha-helical part of adequate length (dipole moment) and a large enough hydrophilic, C-terminal region are sufficient prerequisites for voltage-dependent formation of multi-state pores. Biochemistry, 1983 Jan 4, 22(1), 13 - 21 A rapid method for analysis of ligand binding to deoxyribonucleic acid and soluble nucleoproteins using streptomycin: application to steroid receptor ligands; Spelsberg TC; A method is described which allows the rapid analysis of the binding of practically any molecules to DNA or to protein--DNA complexes (termed nucleoacidic protein or NAP) . The antibiotic streptomycin sulfate, a soluble aminoglycoside, is used to precipitate the DNA after the ligand binding . Comparison of different sources and commercial batches of the antibiotic is described . Optimal conditions for precipitating DNA or NAP and the application of this method to the binding of the chick oviduct progesterone receptor to soluble NAP are described . The streptomycin method can be used with DNA molecules whose size ranges from 750 base pairs to greater than 50 000 base pairs . The method works with a DNA or NAP from a variety of sources, including synthetic homo- or heteropolymers . The precipitation of DNA or NAP by streptomycin occurs rapidly and has minimal effects on the steroid receptor complex or binding of the steroid receptor to DNA or NAP . The requirements and limitations of the method as well as the optimal conditions for binding of the progesterone receptor to DNA or NAP are described. Digestion, 1983, 27(1), 36 - 43 Regulation of gastric mucosal DNA synthesis during fasting and refeeding in rats; Majumdar AP; The effects of 1-4 days of fasting and 3-24 h of refeeding of 4-day fasted rats on the rate of {3H}-thymidine incorporation into DNA in vitro (referred to as DNA synthesis) and the activity of thymidine kinase and DNA polymerase were measured in the oxyntic gland mucosa . Ad libitum fed rats served as control . Starvation for 1-4 days significantly depressed the activity of mucosal thymidine kinase (39-58%) and DNA polymerase (26-36%), when compared with the initially fed control . Mucosal DNA synthesis, measured in 3- and 4-day fasted rats, was also markedly decreased (80-90%) compared to the fed control . Refeeding of 4-day fasted rats significantly stimulated DNA synthesis and the activity of thymidine kinase and DNA polymerase . However, whereas DNA polymerase and thymidine kinase attained their respective peak activity (84 and 340% above the 4-day fasted level) after 3 and 6 h of refeeding, DNA synthesis was significantly stimulated (700% above the 4-day fasted control) after 9 h of refeeding . Administration of actinomycin-D prior to refeeding reduced the magnitude of stimulation of mucosal thymidine kinase and the rate of DNA synthesis, but had no effect on DNA polymerase activity which was found to be stimulated to the level of non-antibiotic treated rats . The current results demonstrate that following refeeding mucosal DNA polymerase and thymidine kinase activities are increased before DNA synthesis is significantly stimulated . Blocking of the maximal stimulation of mucosal thymidine kinase lowers the magnitude of the subsequent rise in DNA synthesis caused by refeeding. Digestion, 1983, 26(4), 236 - 8 Factors preceding relapse of ulcerative colitis; Isgar B et al.; The effect of intercurrent diarrhoea on relapse of ulcerative colitis was investigated . Diarrhoea resulting from travel abroad, gastroenteritis or antibiotic usage resulted in an approximately 50% relapse rate . With regard to colonoscopy and barium enema, only the latter was followed by relapse and this may reflect differences in the preparation for the procedure. Ann Biol Clin (Paris), 1983, 41(1), 13 - 6 {Comparison of the results of antibiograms obtained from blood culture broth and after isolation on agar media with the Autobac 1}; Flandrois JP et al.; The authors compare the results of antibiotic sensitivity tests performed within 4 hours with the aid of the Autobac 1 machine, using blood culture medium and following isolation on agar plates . There was concordance in about 90 p . cent of cases . The first test is not suitable for sensitivity to trimethoprim and the beta-lactamines, as was already observed in the study using the MS-2 machine . The authors discuss the various sources of error and compare the results obtained from the two machines. Wien Med Wochenschr, 1983, 133(7), 183 - 7 {Pilot studies with aclacinomycin in patients with breast cancer or gastrointestinal tumors}; Rainer H et al.; Aclacinomycin (ACM), a new anthracycline antibiotic compound, was given intravenously q x 3 to 6 weeks in a dosage of 4 x 60 mg/4 days to 10 patients with metastasizing breast cancer and 5 patients with gastric carcinoma . Breast cancer patients, prior to ACM had extensive cytotoxic and hormonal treatments, gastric cancer patients received ACM as a first chemotherapeutic tumor treatment . No life-threatening hematologic toxicities could be noticed . All patients experienced moderate to severe gastrointestinal toxicities . No patient had considerable hair loss . 4 patients showed clinical signs of cardiac dysfunction: 1 ECG changes, 4 developed edema of lower extremities, 2 developed pericardial effusion . Moreover, 1 patient developed significant elevation of the pulmonary capillary wedge pressure (PCW) and prolongation of the systolic time intervals indicating pulmonary congestion grade I to II (Braunwald) . No significant increase in heart volume was registered . Clear signs of cardiotoxicity could be demonstrated in patients pretreated with adriamycin exclusively . In animal experience, ACM had been reported as less cardiotoxic as compared to adriamycin . Present studies seem to indicate ACM being considerably cardiotoxic at relatively low cumulative dosages . Among the 15 patients there was one with metastatic breast cancer pretreated with adriamycin and resistant to that drug in whom partial remission was achieved . The other patients did not objectively respond to ACM therapy . 3 out of 5 patients with gastric cancer had stabilisation of the disease but no objective response. Mol Pharmacol, 1983 Jan, 23(1), 133 - 40 Correlation of structure and activity in ansamycins . Molecular structure of sodium rifamycin SV; Arora SK; The crystal and molecular structure of the sodium salt of rifamycin SV (clinically known as rifacin) as the monohydrate ethanol solvate has been determined to study the conformation of the ansa chain in unsubstituted rifamycins and also to clarify the metal complexation with rifamycins . The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions (estimated standard deviations in parentheses) of a = 12.061 (2), b = 13.936 (2), and c = 24.731 (4) A . The structure was solved by direct methods and refined to an R factor of 0.069 . The conformation of the ansa chain differs from that of other active rifamycins, e.g., rifampcin and rifamycin B at the joining point of the ansa chain to the naphthohydroquinone chromophore . The conformation of the middle part of the ansa chain, which is essential for activity against DNA-dependent RNA polymerase, remains the same . The sodium ion is penta-coordinated and has a trigonal bipyramidal geometry . The intermolecular hydrogen bonding involves O(9), O(10), O(5), and O(6) through water and ethanol molecules . A two-step mode of action of rifamycins has been postulated, and the conformations of antibiotics suitable for penetration of the membrane barrier and that for antibiotic-enzyme complex formation have been suggested. Ann Med Interne (Paris), 1983, 134(1), 51 - 4 {Gonococcal endocarditis . A new case}; Baudouy PY et al.; The authors report the case of a 35 year old female hospitalised for gonococcal endocarditis with mitral valve vegetations infecting pre-existing asymptomatic rheumatic mitral incompetence . Apyrexia was rapidly obtained with antibiotic therapy; the valvulopathy was well tolerated from the hemodynamic viewpoint; the echocardiographic appearances of the vegetations were stable . However, the patient died during the third week of a cerebral haemorrhage, probably due to rupture of a mycotic arterial aneurysm . The authors suggest that the difficulties encountered in the fight against sexually transmitted diseases may result in a recrudescence of this type of disseminated gonococcal infection. Pathology, 1983 Jan, 15(1), 67 - 73 Histological assessment of orthotopic aortic valve leaflet allografts: its role in selecting graft pre-treatment; Armiger LC et al.; Histopathological studies of human cardiac valve grafts recovered at autopsy or re-operation, together with long-term clinical follow-up of valve graft recipients, have indicated that the success of grafts is largely dependent upon the extent to which they are replaced by host fibrous connective tissue . To find the valve preparation technique with least inhibitory effect on tissue ingrowth after grafting, various sterilizing and storage procedures were evaluated using a series of aortic valve leaflet allografts in dogs . To facilitate evaluation, a method for rapidly assaying relative degrees of colonization of grafts was first devised . Application of this method has unequivocally identified a newly-formulated antibiotic solution as the pre-treatment most compatible with host tissue ingrowth. J Nat Prod, 1983 Jan, 46(1), 108 - 11 Non-competitive inhibition of hepatic and intestinal aryl hydrocarbon hydroxylase activities from rats by rifampin; Wu CL et al.; Rifampin is a semisynthetic antibiotic which is known to alter hepatic cytochrome P-450 mediated drug metabolizing enzymes . Using benzo(a)pyrene as the substrate we have shown that rifampin acts as a non-competitive inhibitor of hepatic microsomal aryl hydrocarbon hydroxylase in vitro at or below 0.10 mM and that it is also a non-competitive inhibitor of intestinal aryl hydrocarbon hydroxylase at or below 0.075 mM . These results suggest that the administration of rifampin with other drugs may result in altered drug biotransformation. Clin Ther, 1983, 5(3), 279 - 83 Cyclacillin in the treatment of acute sinus infections and exacerbations of chronic infections; Ordonez FH; Cyclacillin was used to treat 40 patients with bacterial sinus infections, either acute or exacerbations of chronic infections . The drug was administered orally in a dosage of 500 mg every six hours for ten days, although three patients required extended treatment . More than 70% of the patients had remission of symptoms in six days, and all but the aforementioned three had remission in ten days or less . More than 90% of the patients had a moderate to good response; only two patients had a poor response . The only side effects were gastrointestinal disorders, which disappeared with administration of antacids . No side effects were noted in 72.5% of patients . Cyclacillin proved to be an effective and well-tolerated antibiotic for infections of the paranasal cavities. Cancer Biochem Biophys, 1983, 6(3), 137 - 42 Evidence for the lack of relationship between inhibition of nucleic acid synthesis and cytotoxicity of adriamycin; Siegfried JM et al.; The ability of adriamycin-sensitive and -resistant Sarcoma 180 cells to incorporate thymidine and uridine into macromolecular material following exposure to this antibiotic was directly compared to the degree of cell survival by measuring in the same population precursor incorporation and cloning efficiency in soft agar after different intensities of drug exposure . The concentration and time dependence of inhibition of these processes by adriamycin wer compared . No correlation between the ability to incorporate radioactive precursors into DNA and RNA and the extent of cell survival was observed except ay very toxic drug concentrations . The results indicate that the extent of inhibition of precursor incorporation into DNA and RNA following drug exposure is not predictive of cell survival . This finding implies that the effect of adriamycin on nucleic acid synthesis is not directly coupled to cytotoxicity. Crit Care Med, 1983 Jan, 11(1), 10 - 2 Selection criteria for pediatric critical care transport teams; Smith DF et al.; The primary goal of an interhospital critical care transport program is to provide quality medical care during transit as close as possible to that available in the receiving ICU . Critically ill pediatric patients are transported between hospitals by a variety of transport teams . The skills possessed by physicians, nurses, respiratory therapists, and paramedics overlap . To determine the criteria for selection of the team members for these patients, we reviewed the medical records of 115 pediatric patients transported to this facility in 1978 and 1979 . Patients were categorized by diagnosis, severity of illness at the time of transport, and the monitoring and life support required during transport . Our data indicate the medical transport team members should have skills required for pediatric critical care diagnosis and management including endotracheal intubation and assisted ventilation; insertion of peripheral, central venous, and arterial catheters; fluid and electrolyte therapy; antibiotic therapy; cardiovascular monitoring; and pharmacological life support . The team members should be chosen based on the particular skills needed for a transport with a goal of providing the patient care required on a consistent basis. Z Naturforsch {C}, 1983 Jan-Feb, 38(1-2), 67 - 73 Sensitive fluorimetric assay for adenosine deaminase with formycin as substrate; and substrate and inhibitor properties of some pyrazolopyrimidine and related analogues; Wierzchowski J et al.; The nucleoside antibiotic formycin, 7-amino-3-(beta-D-ribofuranosyl)pyrazolo(4,3-d)pyrimidine, a structural analogue of adenosine, is deaminated about 10-fold faster by adenosine deaminase than adenosine itself, and is therefore a superior substrate for both routine assays and kinetic studies with the purified enzyme . The luminescence properties of formycin have been profited from to develop a fluorimetric assay for adenosine deaminase which is considerably more sensitive than the spectrophotometric procedure widely employed with adenosine as substrate . Examples are presented of its application to routine assays of adenosine deaminase levels in cellular extracts, as well as to kinetic studies with the purified enzyme, including the properties of some pyrazolopyrimidine and purine substrates and inhibitors. Gerontology, 1983, 29(2), 89 - 96 Genetic effects on the longevity of cultured human fibroblasts . III . Correlations with altered glucose-6-phosphate dehydrogenase; Holliday R et al.; The level of heat-labile glucose-6-phosphate dehydrogenase (G6PD) has been measured in skin fibroblast cultures from premature ageing or DNA repair deficient genetic syndromes . The short in vitro longevity of Werner's syndrome, progeria, Cockayne's syndrome, ataxia telangiectasia, Fanconi's anaemia, and Bloom's syndrome cultures was correlated with the appearance of a significant fraction of heat-labile enzyme . Long-lived control cultures contain a low level of altered enzyme until they become senescent . The evidence that heat-labile G6PD molecules are derived from errors in synthesis, or from other causes, is critically assessed . It is shown that normal cells grown in medium containing the antibiotic, paromomycin, which is known to reduce the fidelity of ribosomal translation, produce a significant fraction of altered G6PD. Dev Pharmacol Ther, 1983, 6(1), 55 - 63 Age-related effect of cycloheximide on lipid peroxidation in rough and smooth microsomes of rat liver; Pushpendran CK et al.; Cycloheximide, at a nonlethal dose of 2 mg/kg body weight, has different effects on microsomal in vivo lipid peroxidation in different age groups . In general, the antibiotic increases microsomal lipid peroxidation in newborn and 1-year-old rats, but decreases it in 15- and 75-day-old rats . Low doses of cycloheximide induces lipid peroxidation in vitro whereas higher doses cause inhibition . The degree of change differs in the two microsomal fractions . The sucklings are more susceptible to such a change than the older rats . In vivo lipid peroxidation in rat liver homogenate and rough and smooth microsomes declines as a function of age . Smooth microsomes show more lipid peroxidation than the rough in the different age groups. Eur J Clin Pharmacol, 1983, 24(1), 109 - 12 Elimination of cefroxadine (CGP-9000) from patients undergoing dialysis; Nieto MJ et al.; The pharmacokinetics of cefroxadine was studied in 17 patients with terminal renal impairment, 10 of whom were undergoing 5 h dialysis sessions . The antibiotic was administered as a single oral dose of 500 mg . Cefroxadine followed a single compartment open kinetic model . During the interdialysis period in patients with terminal renal impairment, an average Cmax of 26.59 micrograms/ml and a tmax of 3.65 h were reached, which are greater than in patients with normal renal function . The serum half-life was reduced from 23.55 h in the interdialysis periods to 3.40 h during the dialysis sessions . The average extraction coefficient was 0.249 . It is recommended that a 500 mg dose cefroxadine should be administered at the end of each dialysis session if the interdialysis period is 48 h. Arch Biochem Biophys, 1983 Jan, 220(1), 39 - 45 Purification and characterization of beta-ketoacyl-ACP synthetase I from Spinacia oleracea leaves; Shimakata T et al.; beta-Ketoacyl-acyl carrier protein (ACP) synthetase I was purified 180-fold from crude extracts of spinach leaves . The purified preparation was completely free from other component enzymes of the de novo fatty acid synthetase (FAS) system . Its molecular weight was estimated to be 56,000 by gel filtration . The apparent Km value for malonyl-CoA in the presence of ACP and malonyl-CoA:ACP transacylase was 4 microM . Purified synthetase I was highly active with acyl-ACP having chain lengths from C2 to C14, with hexanoyl-ACP being the most effective substrate, but palmitoyl-ACP was far less effective and stearoyl-ACP almost inactive . The antibiotic, cerulenin, strongly inhibited synthetase I activity . The inhibition by cerulenin was protected by prior incubation with hexanoyl-ACP, decanoyl-ACP, and myristoyl-ACP . The synthetase was inhibited by 1 mM p-CMB and 5 mM NEM, but not by 1 mM arsenite. Antimicrob Agents Chemother, 1983 Jan, 23(1), 59 - 62 Nafcillin-induced platelet dysfunction and bleeding; Alexander DP et al.; This paper describes two cases of nafcillin-induced platelet dysfunction, with positive rechallenge data for one patient . Nafcillin resulted in abnormal bleeding times in both patients and a clinically apparent bleeding episode in one of the cases . Platelet function tests were performed on one patient during the initial therapy and after rechallenge with nafcillin . Platelet aggregation showed abnormal responses to ADP, collagen, and epinephrine . Platelet count and morphology were normal . Nafcillin should be recognized as another antibiotic which causes platelet function abnormalities and clinical bleeding episodes. J Med Chem, 1983 Jan, 26(1), 25 - 9 Pyrrolopyrimidine nucleosides . 18 . Synthesis and chemotherapeutic activity of 4-amino-7-(3-deoxy-beta-D-ribofuranosyl)pyrrolo{2,3-d} pyrimidine-5-carboxamide (3'-deoxysangivamycin) and 4-amino-7-(2-deoxy-beta-D-ribofuranosyl)pyrrolo{2,3-d} pyrimidine-5-carboxamide (2'-deoxysangivamycin); Maruyama T et al.; A multistep synthesis, using the nucleoside antibiotic toyocamycin as the starting material, has furnished 6,2'-S-cyclosangivamycin (6) . Desulfurization of 6,2'-S-cyclosangivamycin (6) with Raney nickel has provided 2'-deoxysangivamycin (7) . Treatment of sangivamycin (1c) with sodium iodide and alpha-acetoxyisobutyryl chloride has furnished 4-amino-7-{2-O-acetyl-3-deoxy-3-iodo-5-O-(2,5,5-trimethyl-4-oxo-1, 3-dioxolan-2-yl)-beta-D-xylofuranosyl}-pyrrolo{2,3-d} pyrimidine-5-carboxamide (8a) . Dehalogenation of 8a with 10% palladium on charcoal was followed by a removal of the blocking groups with ammonium hydroxide to give 3'-deoxysangivamycin (9) in 49% overall yield . The reaction of sangivamycin (1c) with diphenyl disulfide and tributylphosphine gave 5'-(phenylthio)-5'-deoxysangivamycin (10) . Treatment of 10 with Raney Nickel afforded 5'-deoxysangivamycin (11) . Antitumor evaluation showed that 3'-deoxysangivamycin had significant activity against the murine leukemia L1210 both in vivo and in vitro, although it was less potent on a molar basis than the parent compound sangivamycin . The 2'- and 5'-deoxysangivamycins did not show significant antitumor activity. J Med Chem, 1983 Jan, 26(1), 11 - 5 Adriamycin analogues . Preparation and biological evaluation of some novel 14-thiaadriamycins; Seshadri R et al.; Condensation of 14-bromodaunorubicin with thiols in methanol, in the presence of potassium carbonate, resulted in the formation of 14-thia analogues of the antitumor antibiotic adriamycin . However, similar condensation of N-(trifluoroacetyl)-14-iododaunorubicin with thiols invariably led to a redox reaction, with the formation of N-(trifluoroacetyl)daunorubicin and disulfides . Accordingly, N-(trifluoroacetyl)-14-bromodaunorubicin was used for reaction with thiols to yield thia analogues of the clinically active but non-DNA-binding adriamycin analogue N-(trifluoroacetyl)adriamycin 14-valerate (AD 32) . Reaction of 14-bromoadunorubicin with alpha, omega-alkanedithiols gave bis(thiaadriamycin) analogues as potential difunctional intercalating agents . The aforementioned products, plus two related phenylselena derivatives, were examined for in vitro growth inhibition, in vivo antitumor activity, and, where appropriate, DNA binding . A number of agents, most notably 14-(carbethoxymethyl)-14-thiaadriamycin and N-(trifluoroacetyl)-14-phenyl-14-selenaadriamycin, were active against murine L1210 leukemia in vivo . Several of the amino glycoside unsubstituted 14-thiaadriamycin analogues exhibited DNA-binding properties equivalent to those of adriamycin. Am J Vet Res, 1983 Jan, 44(1), 68 - 71 Absorption in calves of amoxicillin, ampicillin, and oxytetracycline given in milk replacer, water, or an oral rehydration formulation; Palmer GH et al.; Oxytetracycline, amoxicillin or ampicillin suspended in milk replacer, water, or a glucose-glycine-electrolyte solution (GGES) was orally given to calves (n = 64) . Oxytetracycline suspended in milk replacer gave lower relative bioavailability than when suspended in water (P less than 0.01) or in GGES (P less than 0.001) . Seemingly, the 63% binding (only partly reversible) of oxytetracycline suspended in milk replacer was responsible for low serum concentrations, whereas the greater water absorption from the GGES was responsible for improved uptake of antibiotic . Amoxicillin suspended in milk replacer had a delayed absorption, compared with that suspended in water, but the relative bioavailabilities from milk replacer and water were similar . In contrast, peak serum concentration and bioavailability were higher (P less than 0.05) when amoxicillin was suspended in GGES than when suspended in water . Binding of amoxicillin with milk replacer was comparatively low (16%) and was reversible . Ampicillin suspended in GGES gave a higher peak serum concentration (P less than 0.05) than when suspended in milk replacer . It, therefore, appeared that these antibiotics were more bioavailable when suspended in GGES than when suspended in water or especially in milk replacer . Oxytetracycline was bound particularly strongly to milk replacer. Lab Invest, 1983 Jan, 48(1), 80 - 9 Distribution of filipin-sterol complexes in plasma membranes of the kidney . II . The thin limbs of Henle's loop; Orci L et al.; Thin limbs of Henle from the rat kidney were investigated by freeze fracture electron microscopy after incubation of the tissue with the polyene antibiotic, filipin, a morphologic probe for membrane cholesterol . Distinct patterns of distribution of filipin-sterol complexes were found in plasma membranes of epithelial cells from each of the four thin limb regions examined . In particular, adjacent cells in the thin ascending limb had either heavily or poorly labeled apical membranes, whereas in the lower part of long descending thin limbs, all apical membranes were poorly labeled . In contrast, both apical and basolateral membranes of short descending limbs were heavily labeled with filipin-sterol complexes . These results demonstrate the existence of plasma membranes with different properties both within specific segments of Henle's loop (ascending thin limb) and between different thin limb segments (short and long descending limbs). Dis Colon Rectum, 1983 Jan, 26(1), 59 - 60 Diverticulitis of the midrectum; Chiu TC et al.; Diverticulitis of the rectum is a rare condition . This report covers patient history, diagnosis, and treatment involved in such a case . The patient presented with a history of rectal pain and muscle spasm of six months' duration . After several available examinations had been completed, i.e., digital examination, sigmoidoscopy, and barium-enema examination, the diagnosis of a rectal diverticulum was made . Initially, conservative treatment, including high-fiber diet and sitz baths, proved effective . Approximately nine months later, the patient developed severe rectal pain, unrelieved by previously effective measures . After the above-described examinations had been repeated, the rectal wall was found to be ulcerated and inflamed, and a diagnosis of diverticulitis of the rectum was made . Antibiotic therapy and evacuation of the 3- to 4-cm mass under anesthesia resulted in subsidence of symptoms and resolution of the mass . Segmental resection will be considered if the diverticulum becomes infected again. Rev Fr Mal Respir, 1983, 11(6), 907 - 13 {Mycotic aneurysms of the intrapulmonary arteries: unusual manifestation of right-sided endocarditis}; Godin N et al.; We report the case of a 27 year old man admitted to hospital for investigation of radiological opacities of recent origin . A diagnosis of mycotic aneurysms was made on a surgical biopsy . Although a right sided endocarditis could not be detected clinically, a trial of antibiotic therapy was instituted . However, no improvement occurred . The patient died, following a massive pulmonary haemorrhage . The necropsy revealed an active right sided endocarditis with multiple aneurysms of the intra-pulmonary arteries. Eur J Drug Metab Pharmacokinet, 1983, 8(1), 43 - 9 Pharmacokinetic study of doxycycline polyphosphate+ after simultaneous ingestion of milk; Saux MC et al.; Pharmacokinetic parameters of doxycycline polyphosphate were studied in healthy volunteers after oral administration of a single 200 mg dose of this antibiotic with a breakfast containing or not 200 ml of whole milk . Ingestion of milk had only mild effect upon absorption parameters of doxycycline; only a moderate increase of the lag-time was significant . Elimination parameters of doxycycline were impaired by milk; a decrease of the terminal half-life from 28 h to 15 h, and apparent decrease of the enterohepatic circulation and an increase in total body clearance from 40 to 62 ml/min . were observed. J Emerg Med, 1983, 1(2), 133 - 6 Fournier's disease: necrotizing gangrene of the male genitalia; Mabry RM et al.; Fournier's disease, a necrotizing subcutaneous infection involving the male genitalia, was first described by the French venereologist Jean Alfred Fournier in 1884 . Its characteristic triad of abrupt onset in young, previously healthy males, rapid progression to gangrene, and absence of a discernable cause appear to have been altered, at least partially, by the advent of the antibiotic era . We present a case report, with discussion of the clinical and pathophysiological mechanisms involved in this rare and malignant infectious process. Invest New Drugs, 1983, 1(3), 249 - 51 The treatment of acute leukemia with continuous infusion L-Alanosine; Weick JK et al.; L-Alanosine, an antitumor antibiotic was administered by members of the Southwest Oncology Group (SWOG) to 22 patients with resistant acute non-lymphocytic leukemia . The drug was administered by continuous infusion for five days at a starting dose of 125 mg/m2/day . Mucositis was dose-limiting in 15 patients and no marrow aplasia was attained . As administered, L-Alanosine is not an effective single agent in acute leukemia. Haemostasis, 1983, 13(6), 385 - 93 Diminished osmotic and chemically induced haemolysis of human erythrocytes following exposure to contrast media molecules; Paul J et al.; Radiocontrast molecules (RCM) used in coronaroangiography and/or urography diminished their osmotic fragility when they were incubated for 30 min with human erythrocytes . The shift of the osmotic fragility curve towards lower NaCl concentration is related to the hypertonicity of RCM, but in addition, at a given osmolality (100 +/- 5 mosm/kg), RCM at the concentration of 4-10% v/v increase the resistance to osmotic lysis or even suppress it . Similar protection is observed towards erythrocyte lysis induced by a detergent (saponin), polyenic antibiotic (filipin) or non-polyenic cholesterol-specific agent (digitonin) . The effect is (1) proportional to the amount of RCM present, (2) independent of hypertonicity of the molecule, and (3) related to the nature of acidic molecules . A weak insertion of RCM into the erythrocyte membrane is suggested since it was suppressed by a single washing of the cells. Nucleic Acids Symp Ser, 1983, (12), 119 - 22 Inhibition of S-adenosylhomocysteine hydrolase by purine nucleoside analogues; Ishikura T et al.; To find out potent inhibitors of S-adenosylhomocysteine hydrolase (SAHase), several deazaadenosine analogues synthesized in this laboratory and some naturally occurring nucleoside analogues were examined with SAHases from yellow lupin seeds and rabbit liver . Neplanocin A, an antibiotic, inhibited both enzymes more potently than aristeromycin which was also an antibiotic and known as one of the most potent inhibitors of SAHase . The 3-deazaadenine derivatives (2'-deoxy, arabinosyl, xylosyl) inactivated lupin SAHase as potent as 3-deazaadenosine . Whereas, inhibitory activities of 1-deazaadenosine, its derivatives, and 7-deazaadenosine (tubercidin) were very weak. Acta Otorhinolaryngol Belg, 1983, 37(4), 624 - 34 Surgical treatment of sinusitis; Hellmich S; There is no doubt that there is a considerable number of cases of acute and chronic sinusitis, which can be cured only by surgical intervention . The modern philosophy should be: to choose a surgical technique as conservative as possible and as radical as necessary according to the individual case . To achieve this goal, an exact knowledge of the anatomy and pathology of the paranasal sinuses, as well as a full command of the available diagnostic methods (including sinuscopy) are essential . The sometimes dangerous complications of acute ethmoiditis in children usually can be solved by simple displacement of the middle turbinate to the center and uncapping of the ethmoidal cells assisted by antibiotic and antiphlogistic treatment . The surgical treatment of choice in cases of acute recurrent or chronic maxillary sinusitis in children (often combined with bronchial or allergic problems) is the installation of a nasoantral window from the inferior meatus, to guarantee adequate drainage . In adults, the radical techniques of Caldwell-Luc (maxillary sinus) and Riedel (frontan sinus) should be used in selected cases only . They should be replaced--if possible--by osteoplastic methods or modified techniques (frontal and maxillary sinus) or bimeatal-transnasal approach under endoscopic control (maxillary and ethmoidal sinus) . Healthy and reversibly damaged mucosa should be saved; but at the cost of sacrificing the nasal function instead. Acta Neuropathol (Berl), 1983, 61(3-4), 291 - 9 Toxic effects of adriamycin on the central nervous system . Ultrastructural changes in some circumventricular organs of the mouse after intravenous administration of the drug; Bigotte L et al.; Recent experimental studies have shown that the cytotoxic antibiotic adriamycin (doxorubicin) after systemic administration can enter the so-called circumventricular organs (CVO) of the brain of the mouse . The present experiments were performed to find out whether such penetration of the brain is associated with signs of neurotoxic injury . For this purpose, light- and electron-microscopic observations were carried out on three of these organs: the neurohypophysis (NH), median eminence (ME), and postremal area (PA) . Pronounced widening of the extracellular space indicating the presence of edema was present in all the regions, particularly in animals examined within 3 days of injection of the drug . Many degenerated axon terminals were observed in the NH and ME . The glial cells within these regions showed rarefaction of the nuclear chromatin, nucleolar segregation, and also cytoplasmic changes . The PA presented marked cellular changes resulting in degeneration of neurons, which was most evident 30 days after the injection . Hence, regions of the CNS outside the blood-brain barrier can be reached by adriamycin after systemic administration, and the drug can induce morphological changes there . The doses of the drug used in the present experiments were comparable to those given to patients for the treatment of malignant tumors. Neurochirurgie, 1983, 29(4), 229 - 33 {Analysis of infectious sequelae of 1000 neurosurgical operations . Effects of prophylactic antibiotherapy}; Raggueneau JL et al.; Postoperative infections: cellulitis at the site of skin incision and/or meningitis, were reported in 5.1 p . cent of 1 000 cases treated by neurosurgery in Pr R . Houdart's department between december 1980 and march 1982 . Statistically significant factors predisposing to infection were: emergency surgery, opening of the sinus, presence of a foreign body, and operation lasting more than 5 hours . The age of the patient, diabetes, or previous corticoid therapy did not significantly alter the risk of infection . Prophylactic antibiotic therapy had been administered to 37 p . cent of patients, but this had not affected the incidence of general infection, a statistically significant effect being observed only after operations lasting for more than 5 hours . The risk of infection was high after craniotomies and major after external ventricular shunts (valves) . For the latter type of operation it was not possible to determine factors favorable for infection: neither duration of surgery, nor age of patient, nor absence of antibiotic therapy . The risk of postoperative infection was low (less than 1 p . cent) in the absence of factors favorable for its development, but its frequency increased considerably in patients presenting one or more other intercurrent infections . It is therefore possible to recognize surgical and general factors influencing infection, but prophylactic antibiotic therapy has only a weak effect on morbidity modification. Intervirology, 1983, 20(2-3), 101 - 7 Biogenesis of vaccinia: analysis by three-factor crosses reveals mutual influence on stability of drug resistance and temperature sensitivity when both markers occur in some recombinant virus isolates; Essani K et al.; Recombination analysis with 5 temperature-sensitive (ts) mutants of vaccinia virus, relegated to the E category phenotype and mimicking closely the effects produced by the antibiotic rifampicin, was undertaken to determine whether the genetic loci determining this phenotype were clustered on the genetic map . Optimum conditions for analysis were established with respect to the MOI and duration of incubation . At an MOI of 5-10, consistent values of recombination frequency (RF) were obtained, but became significantly lower when the MOI was 1 or less . Constant RF values were recorded when the duration of the infection was 8-24 h . These values were increased 3-fold by extending the incubation to 36 h . Under the standard conditions for analysis adopted, each mutant partner was added at an MOI of 10 and incubation was for 18 h . The map of group E mutants drawn from RF values obtained by 2-factor crosses was confirmed by 3-factor cross analysis, in which recombinants carried both the ts mutations and the rifampicin-resistance (R) marker . Both 2- and 3-factor cross data revealed that the 5 group E mutations were not clustered on the vaccinia virus genome . Surprisingly, after recombining ts 7743 with rifampicin resistance (R), different isolates of ts 7743 R could be mapped at two loci to the right or left of another isolate, ts 9383 . Characterization of five independent plaque isolates of the progeny arising from a ts 7743 R parent showed that one isolate possessed a cold-sensitive phenotype (33 degrees/40 degrees = 1:26), two isolates retained their original ts character, and two became phenotypically like wild type (wt) with respect to thermosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Clin Pharmacol, 1983, 25(3), 333 - 8 The influence of uremia on the accessibility of phosphomycin into interstitial tissue fluid; Fernandez Lastra C et al.; The entry and persistence of phosphomycin in interstitial tissue fluid (ITF) were studied in 9 patients with normal renal function and 8 patients with varying degrees of renal impairment, all of whom received a single i.v . dose of 30 mg/kg . ITF was obtained from skin blisters produced by suction . The antibiotic followed a two-compartment open kinetic model . In patients with normal renal function, phosphomycin is incorporated rapidly into the ITF reaching a level of 60.4 micrograms/ml 60 min after administration . There was no statistically significant difference between the elimination rates from serum and ITF . The serum half-life of the slow disposition phase was 1.75 h in patients with normal renal function . There was a linear correlation between the elimination half-life of phosphomycin in serum and ITF in subjects with differing degrees of renal impairment. Drug Chem Toxicol, 1983, 6(3), 267 - 77 Acute toxicity of some silver salts of sulfonamides in mice and the efficacy of penicillamine in silver; Horner HC et al.; The silver salt of 2-metanilamido-5-chloropyrimidine (AgMCP) and the sodium, amminosilver and trimethylphosphite-silver salts of 3',5'-dichlorobenzenesulfonanilide (NaDBS, AgNH3DBS and AgP(OCH3)3DBS were synthesized as possible antibiotic of antiparasitic drugs . All the organosilver compounds were extremely water-insoluble . For animal studies these, and other reference compounds, were given as fine suspensions in an Emulphor-safflower oil mixture . The ip LD50's in mice in mmol/kg were: 1.67 for NaDBS, 0.22 for silver acetate (AgAc), 0.15 for AgP(OCH3)3DBS, 0.13 for AgMCP and 0.10 for AgNH3DBS . When given by mouth, 15 mmol AgAc/kg produced a high mortality, but none of the organosilver compounds caused death in maximal doses (1.9 to 2.6 mmol/kg) that could be given based on considerations of total volume and stability of the suspension . All the silver compounds, including AgAc, produced a similar toxic syndrome with initial hyperexcitability, ataxia, central nervous depression, labored breathing, loss of righting reflex and death . Most deaths occurred between 12 and 24 hours after dosing . In contrast, animals given NaDBS often died within 3 hours although the major signs were very similar to those produced by the silver compounds . When given ip as a single dose 30 minutes after AgAc, D-penicillamine was effective in reducing mortality, but it had no effect on the mortality of the organosilver compounds . Histological studies revealed similar patterns of silver deposition, especially in the liver and kidneys, at 6, 18 and 24 hours after the organosilver compounds and after AgAc . We conclude that the presence of silver contributes significantly to the acute toxicity of these sulfonamides although they may dissociate free silver less readily than does AgAc. Biol Res Pregnancy Perinatol, 1983, 4(3), 123 - 6 Gentamicin monitoring in low-birth-weight newborns; Rameis H et al.; The pharmacokinetics of gentamicin in premature newborns is influenced by many noncalculable variables . Nevertheless, and despite its narrow therapeutic range, this aminoglycoside antibiotic is usually prescribed according to a fixed schedule . Gentamicin was monitored in 22 severely sick, low-birth-weight newborns on combination therapy of various antibiotics including gentamicin . Dosage regimen of gentamicin was prescribed according to Eichenwald and McCracken {1978} . Serum gentamicin concentrations were measured by radioimmunoassay before infusion, 30 min after, and 3 h after infusion of the antibiotic . In 22 prematures desirable serum gentamicin concentrations with a mean elimination half-life (t 1/2) of 5.3 h; in 2 prematures, levels with a mean t 1/2 of 2.3 h; in 7 prematures, possible toxic levels with a mean t 1/2 of 8.3 h; and in 2 prematures, definite toxic levels with a prolonged t 1/2 up to 17 h were observed . Most of the prematures with possible or definite toxic gentamicin levels were not older than 1 week . This is explained by the immaturity of the kidneys and the retention of aminoglycosides . A satisfactory correlation between postnatal age and gentamicin elimination half-life was found, which might be caused by postnatal maturation of the glomerular function . In prematures in the 1st postnatal week we recommend reducing the daily dose by prolonging the dosage interval, e.g., from 12 to 18 h, or reducing the single gentamicin doses . Gentamicin monitoring seems advisable for detecting toxic serum concentrations and accumulation and for revealing an insufficient dosage of this aminoglycoside antibiotic. Vet Med Nauki, 1983, 20(3-4), 47 - 51 {LDH activity and isoenzyme spectrum in the leukocytes of cows with catarrhal mastitis and chronic endometritis}; Deianov M; The activity of lactatedehydrogenase (LDH) in the leukocytes of cows affected with mastitis and endometritis was found to drop strongly to the detriment of the aerobic fractions of LDH1 and LDH2 . The processes of anaerobic glycolysis in such animals ran more intensely their course . The antibiotic therapy raised the functional activity of the white blood cells. Vet Med Nauki, 1983, 20(3-4), 40 - 6 {Toxicity, tolerance and blood concentrations of iron and tylosin with the use of preparation FV-82}; Dilov P et al.; A pharmacologic evaluation was made of a technologic model of a liquid drug form (code name phi B-82), having the following composition: tylosine tartrate 3500000 UI, cyanocobalamine 0.008 g, pyridoxin hydrochloride 0.500 g, tartaric acid 0.100 g, and feridextran (dextrofer-100) up to 100 cm3; pH from 5.5 to 6.5, and Fe3+ 100 mg/cm3 . It was found that phi B-82 at i/m application to rabbits, subcutaneous injection to albino mice, and intra-abdominal introduction to albino rats and mice at rates that were equal to ED100 and 3 to 5 times higher than those used with pigs did not lead to local and total lack of tolerance . The acute toxicity (LD50) of phi B-82 at intra-abdominal application to 18-20 g albino mice was 29.2 cm3/kg . The single muscular application to guinea pigs at 2 cm3 per kg of body mass showed good absorption of the preparation - it did not differ essentially from those of dextrofer-100 and aquaous solution of tylosine tartrate used in equivalent amounts . The bacteriostatic concentrations of tylosine were maintained for 24 hours . It was shown that the optimal effect would be produced by a combined preparation having the qualities of the feridextrane complexes with a rapid absorption and those of the erythropoietic vitamins of the B12 group and B6 along with the participation of tylosine as an antibiotic. J Foot Surg, 1983 Fall, 22(3), 212 - 7 Chronic osteomyelitis associated with monofilament wire fixation; Varzos PN et al.; Infections following osteotomy and internal fixation must be treated aggressively . The plan of treatment should include the following: 1) continued immobilization of the part during healing, 2) removal of any internal fixation device after the osteotomy site is stable, 3) debridement of necrotic debris, and 4) use of an appropriate antibiotic over a sufficient time period (including a few weeks after removal of an internal fixation device) . A report was made of a case of chronic osteomyelitis that may have resulted from undertreatment of a postoperative infection. Zentralbl Chir, 1983, 108(11), 641 - 6 {Treatment and treatment results of infections of the hand with gentamicin PMMA minichains}; Asche G; Soft tissue and bone infections often require lengthy treatment . In most cases this will result in a poor function . The treatment can be shortened by surgical revision and highly effective local antibiotic therapy with Gentamycin-PMMA-minichains. Biomed Biochim Acta, 1983, 42(2-3), 189 - 94 A three-stage chromatographic procedure for cordycepin . Quantitative estimation in rat brain tissue; Musaev NI et al.; A technique for the quantitative estimation of intraperitoneally injected unlabelled cordycepin in the acid soluble pool (ASP) isolated from rat brain tissue has been suggested . It consists of consecutive chromatography of ASP on columns of Dowex 1 X 8, Dihydroxyboryl-SP500 and Sephasorb-HP . As a result, the fraction containing 2'-deoxyriboadenosine and 3'-deoxyriboadenosine (cordycepin) was isolated from the brain tissue ASP of experimental animals which were given a cordycepin injection . The 2'-deoxyriboadenosine fraction was isolated from tissue ASP of control animals which were not given an injection of this antibiotic . Brain tissue antibiotic content was estimated by the difference in mumolar nucleosides quantity values in the two fractions (control/experiment). Scand J Infect Dis Suppl, 1983, 41, 187 - 91 Intensive care treatment in septic shock; Lundberg D et al.; Deaths in septic shock continue to occur at a high frequency despite current treatment programs . However, the mortality can be substantially decreased with a close bedside attendance of patients at risk and if the patient is transferred to an intensive care unit for intensive treatment and monitoring as soon as shock is suspected or established . The treatment program consists of adequate antibiotic administration in combination with massive doses of steroids and aggressive infusion therapy supplemented with cardiovascular drugs according to the hemodynamic response to the initial treatment. Mol Gen Genet, 1983, 192(3), 471 - 6 Possible plasmid involvement in turimycin production in Streptomyces hygroscopicus; Zippel M et al.; Streptomyces hygroscopicus JA 6599 is the producer of the macrolide antibiotic turimycin . Mapping analysis by conventional matings and protoplast fusion techniques were carried out . The sequence of auxotrophic markers determined by using the method of minimizing the frequency of quadruple crossover recombinants, could be shown to be in accordance with the related marker sequence of Streptomyces coelicolor after both conjugation and protoplast fusion . However, the tur locus could localized between chromosomal markers only assuming quadruple crossover . Moreover, after conventional crosses the tur marker has to be localized at quite another site than after protoplast fusion . Regarding also our results on the evidence of extrachromosomal DNA in strains of S . hygroscopicus, the following hypothesis is proposed: the structural genes for turimycin biosynthesis are localized on the bacterial genome, but plasmid-borne genes might be involved in the control of the antibiotic production in a yet unknown way, possibly by inducing chromosomal rearrangements. Leuk Res, 1983, 7(1), 67 - 75 Recognition of drug resistance during remission induction therapy for acute non-lymphocytic leukemia: utility of day 6 bone marrow biopsy; Preisler H et al.; While the majority of patients under 70 years of age with acute non-lymphocytic leukemia enter remission when treated with a combination of cytosine arabinoside and an anthracycline antibiotic, 20-45% of patients do not . The reasons for treatment failure in these patients vary from drug resistant disease to death from infection or bleeding shortly after remission induction therapy is initiated . Clearly, more intensive remission induction therapy should be administered only to those patients for whom the therapy being employed is of insufficient intensity . Bone marrow biopsies after six days of therapy have been performed on 53 patients who received 65 courses of remission induction therapy . Eighty-eight per cent of the remissions occurred in patients whose marrow cellularity was less than 62.5% on day 6 while 78% of patients who had drug resistant disease had day 6 marrow cellularities which exceeded 62.5% . Hence, a bone marrow biopsy performed after six days of therapy permits the recognition of the majority of patients who will enter complete remission or alternatively who need more aggressive therapy. J Cancer Res Clin Oncol, 1983, 105(2), 162 - 5 Phase II trial of aclacinomycin A in acute leukemia and various solid tumors; Schutte J et al.; Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models . A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response . All suffered from recurrent and advanced tumors . Pretreatment consisted of at least four different chemotherapeutic agents (range: 4-9) . Lung cancer patients (3/9) were irradiated to the mediastinum . Eighteen patients were pretreated with doxo- or daunomycin . The dose for solid tumors was 2-3 mg/kg given on 3 consecutive days every 3 weeks . Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used . Marked reductions of leukocyte counts were achieved in leukemia patients . The overall response rate was about 15% in solid tumors, but major objective responses (CR + PR) have not been observed . Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced . Cumulative cardiotoxicity was not evaluated in this trial . Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics. Z Allg Mikrobiol, 1983, 23(6), 359 - 65 Effect of the autoregulator from Streptomyces griseus JA 5142 on surface cultures of blocked mutant ZIMET 43682; Grafe U et al.; Zero time addition of the autoregulator (L-factor) from S . griseus (Lkm+Amy+) to surface cultures of its bald mutant ZIMET 43 682 (Amy-Lkm-) restored the capacity to form both anthracycline-type antibiotic leukaemomycin and aerial mycelium . The pertinent mycelia displayed the same growth rate and cellular levels of nucleic acids as the asporogeneous phenotype but the composition of fatty acids and phospholipids as well as the ratio of cytochromes b and c were altered . These differences indicate alterations in the cellular architecture of substrate and aerial hyphae . The results suggest that the autoregulator triggers the onset of a complex programme of differentiation at a very early stage. J Membr Biol, 1983, 74(2), 131 - 8 Ultrastructural characterization of cholesterol distribution in toad bladder using filipin; Stetson DL et al.; The polyene antibiotic filipin was used to characterize the cholesterol distribution in the membranes of the toad bladder epithelium in freeze-fracture replicas . The apical membranes of granular and mitochondria-rich cells incorporate moderate amounts of filipin while the basolateral membranes of both cell types incorporate substantially greater amounts . Intracellular membranes, in general, take up very little filipin . The major exception to this is the granule membrane, which appears to be rich in cholesterol . An inverse correlation was found between the density of filipin-sterol complexes in the apical membrane and the incidence of granules in the cytoplasm . This suggests that fusion of granules with the apical membrane may be responsible for variation in the concentration of cholesterol in the apical membrane . Thirty minutes following vasopressin exposure, there is no consistent change in the cholesterol content of the apical membrane of granular cells as measured by the incidence of filipin-sterol complexes . The lack of change in the amount of membrane cholesterol indicates that the vasopressin-induced increase in transepithelial water permeability is not mediated by a change in cholesterol content of the apical membrane. Mol Immunol, 1983 Jan, 20(1), 89 - 99 Use of Trypanosoma equiperdum infected rabbits as a source of splenic mRNA; construction of cDNA clones and identification of a rabbit mu heavy chain clone; Bernstein KE et al.; Rabbits were infected by Trypanosoma equiperdum and the splenic mRNA was isolated . In vitro translation of this RNA and immunoprecipitation with anti-light chain, anti-heavy chain, anti-mu and anti-VH antibodies demonstrated that T . equiperdum infection elicits large quantities of splenic mRNA encoding mu and kappa chains . The mu and gamma heavy chains and the kappa light chains synthesized in the cell-free translation system were specifically immunoprecipitated by antisera to heavy chain VHa and light chain kappa b allotypes . In vitro labeling of spleen cells from trypanosome-infected animals demonstrated that the biosynthetically labeled IgM has a mu chain of higher molecular weight than the mu chain synthesized by in vitro translation, a difference that is largely abolished when cellular glycosylation is blocked with the antibiotic tunicamycin . Enrichment for heavy chain or light chain mRNA was achieved by fractionating mRNA from trypanosome-infected animals on a sucrose gradient . cDNA clones carrying mu heavy chain sequences were produced using a 'one tube' protocol and identified by cross species hybridization and hybridization selection . Infection of rabbits with T . equiperdum followed by sucrose gradient enrichment of splenic mRNA has provided sufficient quantities of mRNA encoding mu heavy chain suitable for cDNA cloning. J Cancer Res Clin Oncol, 1983, 105(3), 250 - 7 Chemotherapeutic study on Yoshida sarcoma ascites cells implanted into the glandular stomach of rats . Monotherapy with 5-fluorouracil, methyl-CCNU, mitomycin C, adriamycin, and cytosine arabinoside, and combination therapy with respective two-drug combinations; Eichler G et al.; The chemotherapeutic activity of five cytostatic drugs was investigated experimentally in monotherapy and in two-drug combinations, using Yoshida sarcoma cells implanted into the wall of the glandular stomach of Sprague-Dawley rats . In monotherapy, the antibiotic agent mitomycin C and the nitrosourea methyl-CCNU exhibited the highest cytotoxic activity in this tumor model . In combination therapy, the combination of these two drugs was superior to all the other