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Biomedical subjects

M J Kramer

Publications and source records attributed to M J Kramer.

35 records · Page 2Linked to original sources
PubMed1979

Correlation by scanning electron microscopy of in vitro and in vivo effects of amoxicillin and ampicillin on the morphology of Escherichia coli.

The effect of in vitro incubation with subinhibitory and inhibitory doses of amoxicillin or ampicillin on the morphology of E. coli 257 was evaluated by scanning electron microscopy (SEM). No effect, with either penicillin was seen at 1/16 X MIC (0.39 microgram/ml). Filament formation was the major effect seen with both agents at 1/8, 1/4 and 1/2 X MIC but only with ampicillin at the MIC (6.25 microgram/ml). Cells incubated with amoxicillin at the MIC were primarily short rods with bulbous swellings. This morphological difference between the two antibiotics was dose-related since ampicillin, at 2 X MIC, also caused the formation of short rods with bulbous swellings. SEM examination of omentum from amoxicillin and ampicillin treated mice 2 h after infection with E. coli 257 indicated a correlation of morphological effects seen in vitro and in vivo with the respective antibiotics. For example, following a single subcutaneous treatment with amoxicillin and ampicillin at 250 mg/kg, the plasma concentrations 2 h later (the time of infection) were 8.2 and 7.7 microgram/ml respectively but short rods with bulbous swellings were seen in amoxicillin-treated mice whereas filaments were found in the ampicillin-treated mice.

Amoxicillin↗
PubMed1978

Activity of 10-chloro-5-(2-dimethylaminoethyl)-7H-indolo [2,3-c]-quinolin-6(5H)-one hydrochloride against experimental tumors in mice and rats.

10-Chloro-5-(2-dimethylaminoethyl)-7H-indolo [2,3-c]-quinolin-6(5H)-one hydrochloride (CIQ) was shown to exert significant antitumor activity against the Ehrlich carcinoma and sarcoma 180 transplantable tumors in mice by the intraperitoneal (ip) or oral (po) routes and when incorporated into diet. A solid tumor induced in BALB/c mice by the subcutaneous (sc) implantation of nonproducer murine sarcoma virus-transformed BALB/3T3 cells was also inhibited by CIQ after ip or po treatment but there was no effect against leukemia L1210 ascites or a transplantable murine renal adenocarcinoma. When tested in rats, CIQ significantly reduced the growth of Flexner-Jobling carcinoma, Murphy-Sturm lymphosarcoma and Walker 256 carcinosarcoma when administered by the ip or po routes. Pretreatment, but not posttreatment, with CIQ slightly inhibited the humoral antibody response of mice to sheep red blood cells. CIQ therefore differs from immunosuppressive agents such as imuran, methotrexate, cytosine arabinoside, or 6-mercaptopurine which affect the antibody response of mice to sheep erythrocytes when administered after immunization.

Adenocarcinoma↗
PubMed1976

Synthesis of tetrazole ribonucleosides and their evaluation as antiviral agents.

Synthesis of 1-beta-D-ribofuranosyltetrazole and two 5-substituted derivatives, i.e., the 5-carboxamide and 5-acetamide, is described. The stereochemical structure of the parent tetrazole ribonucleoside has been established by means of nuclear Overhauser effect and x-ray crystallography. By analogy to the parent compound, the two 5-substituted tetrazole nucleosides are also assigned the beta configuration on the basis of the NMR coupling constant of the anomeric proton and the site of N-ribosylation is determined by 13C NMR studies. Results are also presented on antiviral testing of these synthetic tetrazole nucleosides against influenza A2/Asian/J-305 virus infection in mice.

Animals↗
PubMed1976

Synthesis of tetrazole ribonucleosides and their evaluation as antiviral agents. 2. 5-Amino-1-(beta-D-ribofuranosyl)-1H-tetrazole and 5-amino-2-(beta-D-ribofuranosyl)-2H-tetrazole.

Synthesis of 5-amino-1-(beta-D-ribofuranosyl)-1H-tetrazole and 5-amino-2-(beta-D-ribofuranosyl)-2H-tetrazole is described. X-Ray crystallography was first used to establish the stereochemical configuration of the two isomers. By conducting 13C NMR analysis on these isomers with known structures, i.e., N1beta, a correlation is developed for determining the N-ribosyl attachment site of tetrazole ribonucleosides. Results are also presented on antiviral testing of these synthetic 5-aminotetrazole ribonucleosides against influenza A2/Asian/J305 virus infection in mice.

Amitrole↗
PubMed1976

Antiviral activity of 10-carboxymethyl-9-acridanone.

Intraperitoneal administration of 10-carboxymethyl-9-acridanone sodium salt (CMA) protected at least 50% of mice tested from otherwise lethal infections with Semliki forest, coxsackie B1, Columbia SK, Western equine encephalitis, herpes simplex, and pseudorabies viruses. The protective effect against influenza A2/Asian/J305 and coxsackie A21 viruses was less but was statistically significant. When administered either subcutaneously or orally, CMA protected at least 50% of mice against Semliki forest and pseudorabies viruses; the effect against coxsackie B1 and herpes simplex viruses was less but was statistically significant. Initiation of treatment could be delayed from 2 to 24 h after infection of mice with coxsackie B1, herpes simplex, Semliki forest, and Western equine encephalitis viruses without loss of an antiviral effect. CMA did not inactivate Semliki forest or coxsackie B1 viruses on contact and was without effect against any of the viruses tested in tissue culture by the tube dilution assay. The humoral antibody response in mice to both influenza virus and sheep erythrocytes was unaffected by CMA. After administration of CMA, an interferon-like substance was induced in mice or mouse cell culture but not in rabbits or rabbit cell culture.

Acridines↗
PubMed1975

Mersalyl: a diuretic with antiviral properties.

Mersalyl (Salyrgan), an organic mercurial diuretic, was tested against human and animal viruses with in vivo model infections in mice and tissue culture systems. Mersalyl was active against coxsackieviruses A21 and B1 in mice if administered intraperitoneally immediately after infection. No effect was observed if intraperitoneal treatment was delayed 1 or 2 h postinfection, or if treatment was administered either subcutaneously or per os. Topical treatment with a 5% aqueous solution of mersalyl produced a statistically significant effect against herpes simplex dermatitis in mice but the substance was inactive against systemic infections in mice with herpes simplex as well as Columbia SK, influenza, Semliki Forest, and Sendai viruses. Contact inactivation of coxsackieviruses A21 and B1 and herpes simplex virus was observed, but mersalyl was inactive in tissue culture against coxackieviruses A21 and B1, herpes simplex, influenza, rhinovirus, Semliki Forest, Sendai, and vaccinia viruses.

Animals↗
PubMed1971

Transformation of mouse 3T3 cells by murine sarcoma virus: release of virus-like particles in the absence of replicating murine leukemia helper virus.

Small numbers of virus-like particles were observed by electron microscopy in each of two cloned lines of 3T3 cells transformed by murine sarcoma virus, even though these lines were free of detectable quantities of infectious leukemia and sarcoma virus. The morphology and occurrence of the particles were identical to those of the murine leukemia-sarcoma group. Moreover, the particles incorporated uridine and had a buoyant density of 1.16 g/ml in sucrose gradients. No evidence of sarcoma or leukemia virus infectivity was associated with the particles in cells of several susceptible species under various conditions, including both cosedimentation with leukemia virus and infection in the presence of inactivated Sendai virus. The particles may represent a form of murine sarcoma virus deficient in one or more of the viral components necessary for infectivity.

Animals↗
PubMed1971

Ultrastructural analysis of the effects of penicillin and chlortetracycline on the development of a genital tract Chlamydia.

The developmental cycle of a genital tract Chlamydia (MRC-1/G) growing in irradiated monkey kidney cell monolayers was analyzed by electron microscopy. Growth was essentially similar to that of C. psittaci and ocular isolates of C. trachomatis. Penicillin (50 units/ml) interfered with the growth cycle by producing greatly enlarged initial bodies which sometimes measured 3 mum instead of the normal 1 to 1.3 mum in diameter. In contrast to penicillin, chlortetracycline (10 mug/ml) did not grossly distort morphology of the initial body but had a definite inhibitory effect on the formation of elementary bodies depending upon the time postinfection the antibiotic was added. If added 24 hr or later postinfection, typical inclusions containing elementary bodies were formed. When administered 18 hr postinfection, the transition of initial bodies to elementary bodies was prevented, and the inclusion was much smaller when examined at 48 hr in comparison to a control without chlortetracycline. Addition of the drug at 6 or 12 hr postinfection resulted in very small inclusions which contained only one or two chlamydiae of an initial body type. It was not possible to detect chlamydiae when chlortetracycline was added immediately after adsorption (0 hr), and cells were examined by light and electron microscopy at 48 hr.

Journal Article↗
PubMed1970

Electron Microscopy of the Phagocytosis of Capsulated Bacillus anthracis.

The phagocytosis of capsulated vegetative cells of Bacillus anthracis in the mouse spleen was studied by thin sectioning techniques of electron microscopy. Mice were injected with autoclaved suspensions of capsulated and noncapsulated vegetative cells via the tail vein. The animals were killed 5, 10, and 30 min and 4 hr postinjection, with the central portion of the spleen being removed and procssed for electron microscopy. Fixation was with 2% KMnO(4) for 2 hr. Results of this study indicated that phagocytosis of autoclaved, capsulated anthrax bacilli was through the normal phagocytic process. The vesicular membrane or phagosome membrane was still present around these killed, capsulated organisms 4 hr postinjection. It is concluded that such cells possess no toxic principle to account for the supposed destruction of the phagosome membrane previously reported.

Journal Article↗
PubMedDate not supplied

Effects of three recombinant human leukocyte interferons on drug metabolism in mice.

Three recombinant human leukocyte interferons (IFLrA, IFLrD, and a hybrid IFLrA/D) that differ markedly in their antiviral activity in murine L cells were examined for their effects on hepatic microsomal drug metabolism in adult female CD-1 mice. When administered for 1 or 3 consecutive days, IFLrA/D, which exhibited the highest antiviral activity in murine L cells, caused a dose-dependent decrease in cytochrome P-450 content and in the rate of metabolism in vitro of benzo[a]pyrene, hexobarbital, 7-ethoxycoumarin, benzphetamine, and zoxazolamine. The concentration of cytochrome b and the activity of NADPH-cytochrome c reductase were also depressed when IFLrA/D was administered for 3 days. Similar but somewhat smaller changes were observed following treatment of mice with IFLrD, which possessed approximately 1% of the antiviral activity of IFLrA/D in murine L cells. In contrast, IFLrA, which was essentially devoid of antiviral activity in the mouse cell line, failed to depress cytochrome P-450 levels and in vitro drug metabolism activity in a consistent or dose-dependent manner. Cytochrome P-450 content and the in vitro rate of metabolism of benzphetamine and zoxazolamine were maximally depressed 8-24 hr after a single intraperitoneal injection of 1.5 micrograms of interferon per mouse; at this time the interferons were no longer detectable in serum. Near-normal levels of cytochrome P-450 and in vitro drug metabolism activity were restored by 48 hr after a single injection of interferon. Treatment of mice with 1.5 micrograms of IFLrA/D once daily for 3 days prolonged hexobarbital sleeping time but not zoxazolamine paralysis time, whereas neither of these was influenced by treatment with IFLrA or D. The results indicate that an interferon-dependent process reduces the level of microsomal cytochrome P-450 in liver and potentiates the pharmacological actions of certain drugs in mice.

Animals↗