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Biomedical subjects

M J Levin

Publications and source records attributed to M J Levin.

At least 181 records · Page 10Linked to original sources
PubMed1980

Increased gastrointestinal absorption of large molecules in patients after 5-fluorouracil therapy for metastatic colon carcinoma.

Chemotherapeutic agents may damage gastrointestinal epithelium and thereby impair the mucosal barrier to bacteria and their products. In order to obtain an objective measurement of gastrointestinal permeability to large molecules, we measured urinary excretion of [14C]polyvinylpyrrolidone administered p.o. (mean molecular weight 11,000) and tobramycin (molecular weight 467) in ten patients receiving 5-fluorouracil therapy for metastatic cancer of the colon. Base-line absorption of [14C]polyvinylpyrrolidone was 0.013 to 0.048% of the administered dose. Dose-related increases in absorption (range, two to 20 fold) occurred after 5-fluorouracil administration, but the dose response differed markedly between individuals. Absorption was maximal 8 to 15 days after the start of therapy, was correlated in time but not necessarily in severity with the presence of gastrointestinal symptoms, and was unaffected by oral nonabsorbable antibiotics. Tobramycin excretion was 8.5 times greater than [14C]polyvinylpyrrolidone excretion, but the two were highly correlated in simultaneous determinations (r, 0.93; p, < 0.001). With the exception of an episode of Escherichia coli bacteremia, infections coincided not with maximal [14C]polyvinylpyrrolidone absorption but with maximal granulocytopenia 17 to 24 days after the start of therapy. The gastrointestinal absorption of polyvinylpyrrolidone provides an objective measurement of mucosal integrity which may have applications in assessing the gastrointestinal toxicity of other cytotoxic agents.

Colonic Neoplasms↗
PubMed1979

Purification and partial characterization of different forms of phosphofructokinase in man.

Phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) from human muscle, brain, heart and granulocytes has been purified using a two or three step purification procedure. The main step is Blue Dextran-Sepharose 4B chromatography with selective elution of phosphofructokinase by formation of the ternary complex ADP or ATP-fructose-6-P-enzyme. Muscle and heart contain only enzyme subunits with a molecular weight of 85,000. This type of subunit is predominnant in brain, where it co-exists with subunits of about 80,000 daltons. A single type of subunits is found in the granulocytes, with a molecular weight of 80,000. Anti-muscle phosphofructokinase antiserum reacts only with M-type enzyme. Anti-granulocyte enzyme antiserum, absorbed by pure brain phosphofructokinase, exhibits a narrow specificity against the so-called L-type enzyme. Anti-brain antiserum, absorbed by pure muscle phosphofructokinase and partly purified red cell enzyme, exhibits a narrow specificity against a phosphofructokinase form predominant in fibroblasts and present in brain (F-type).

Brain↗
PubMed1979

Predictability of peak serum gentamicin concentration with dosage based on body surface area.

We examined gentamicin dosage based on body surface area (60 mg/m2 intravenously every eight hours) as a means of attaining therapeutic but nontoxic serum concentrations in 58 patients ranging in age from 0.7 to 73 years. All but one patient had peak serum levels between 3.4 and 8.0 microgram/ml. The mean serum gentamicin half-life was shorter in patients less than 10 years of age (76 minutes) than in patients aged 10 to 50 years (116 minutes) and in patients aged 50 to 63 years (184 minutes) (all significant at P less than 0.01). We conclude that gentamicin dosage based on body surface area produces uniform peak serum gentamicin concentrations in both children and adults, and that the safety and efficacy of a shorter dosage interval for children deserves investigation.

Adolescent↗
PubMed1979

Immune response to herpesvirus antigens in adults with acute cytomegaloviral mononucleosis.

The immune response of eight patients with mononucleosis caused by cytomegalovirus (CMV) was measured early in their illness--when virus was present in their urine and/or blood--and subsequently during convalescence. Levels of CMV-specific antibody rose early in the illness, but the proliferative response of mononuclear cells to CMV antigen did not reach the level characteristic of CMV-immune donors until several months later. The production of interferon by mononuclear cells in response to CMV antigen was also low early in the illness. Although these patients had prior immunity to herpes simplex virus and varicella-zoster virus, their mononuclear cells responded poorly to antigens prepared from these viruses. The proliferative response to these antigens returned to normal in parallel with the development of a normal response to CMV. It is suggested that acute CMV mononucleosis suppresses the proliferative response of human mononuclear cells.

Antibodies, Viral↗
PubMed1979

Growth inhibition by acycloguanosine of herpesviruses isolated from human infections.

Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID(50)) of 0.15 +/- 0.09 muM. The mean ID(50) for 10 isolates of HSV-2 was 1.62 +/- 0.76 muM, and for four isolates of varicella-zoster virus it was 3.75 +/- 1.30 muM. The ID(50)'s for two cytomegalovirus isolates were 100 and 160 muM, and for four additional isolates of cytomegalovirus no end point (ID(50)) was reached at 200 muM. ACG at a concentration of 200 muM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 muM.

Animals↗
PubMed1978

A practical method for preparation of varicella-zoster immune globulin.

Outdated blood from blood banks in Massachusetts was screened for complement-fixing antibody to varicella-zoster virus (VZV). Approximately 15% of the plasma units had a titer greater than or equal to 16, and one-half of these had a titer of greater than or equal to 32. Plasma units with titers of CF antibody to VZV of greater than or equal to 16 were pooled. This pool had a CF antibody titer of 32 and a titer of fluorescent antibody of 64. Varicella-zoster immune globulin was prepared from the selected plasma pool by alcohol fractionation and analyzed for VZV-specific antibody. Varicella-zoster immune globulin had a fluorescent antibody titer of 2,048 and a neutralizing antibody titer of 1,024. This antibody concentration is equivalent to that in preparations of zoster immune globulin made from plasma of donors recovering from recent VZV infection.

Antibodies, Viral↗
PubMed1978

Combined activity of minocycline and amphotericin B in vitro against medically important yeasts.

The capacity of minocycline to enhance the activity of amphotericin B against Candida albicans, Torulopsis glabrata, Cryptococcus neoformans, and non-albicans Candida was examined in vitro utilizing a time-killing curve technique. Synergism was apparent at 4 h with 5 of 5 strains of C. albicans, 8 of 8 strains of C. neoformans, and 1 of 12 strains of non-albicans Candida. Synergism was apparent at 24 h with the remaining 11 strains of non-albicans Candida and all 5 strains of T. glabrata. C. neoformans was the most susceptible of the yeasts to the minocycline-amphotericin B combination; seven strains showed a 3-log or greater reduction in colony count in 4 h and all strains showed this reduction in 24 h at amphotericin B concentrations of 0.4 mug/ml or less in the presence of minocycline.

Amphotericin B↗
PubMed1978

Specificity of the blastogenic response of human mononuclear cells to herpesvirus antigens.

Peripheral blood mononuclear (PBM) cells from donors with a history of prior infection with herpes simplex virus, varicella-zoster virus, and/or cytomegalovirus were cultured for 2 to 8 days with glycine-extracted antigens prepared from these viruses and from infectious bovine rhinotracheitis virus. The proliferative response of PBM cells from all donors was specific during the first 6 days in culture. During this period the cellular immune responses of the seronegative donors were clearly different from those of the seropositive donors. The responses of PBM cells in culture with any of the human herpesvirus antigens studied was not influenced by prior infection of the donor with one or more other human herpesviruses. In contrast, although no donors had antibody to infectious bovine rhinotracheitis virus, the PBM cells from some of them had a proliferative response to this bovine herpesvirus, which increased with time. This nonspecific response appears to be a host-associated function which may be related to recognition of a common herpesvirus antigen.

Antibody Specificity↗
PubMed1978

Proliferative and interferon responses by peripheral blood mononuclear cells after bone marrow transplantation in humans.

The capacity of peripheral blood mononuclear cells from bone marrow transplant recipients to proliferate and produce interferon in response to mitogens and specific antigens was tested. Proliferation in response to phytohemagglutinin or pokeweed mitogen occurred in cells from more than 90% of the recipients, and interferon was present in 60 to 70% of the supernatants from these cultures, even when tested as soon as 8 weeks after transplantation. Proliferation in response to bacterial antigens was infrequent, and interferon release was not detected. In the early post-transplantation period (less than 13 weeks), cells from only two of four cytomegalovirus (CMV) antibody-positive patients proliferated normally in response to CMV antigen and interferon release was detected only once. In the late post-transplantation period (more than 13 weeks), in only two of five instances did cells proliferating in response to CMV antigen release interferon. The response to CMV antigen of mononuclear cells from many transplant recipients differs from that of cells from normal controls.

Antigens, Viral↗
PubMed1977

Antifungal activity of four tetracycline analogues against Candida albicans in vitro: potentiation by amphotericin B.

The antifungal activities of four tetracycline analogues in combination with amphotericin B (AmB) were determined against 20 strains of Candida albicans. When a microtiter checkerboard technique was used, minocycline (less than or equal to 10 microgram/ml) acted synergistically with AmB against all strains, whereas doxycycline had a reduced effect, and demeclocycline and tetracycline had no potentiating effect at this concentration. Killing-curve experiments with two strains of C. albicans demonstrated that the combination of minocycline and AmB produced a decrease in number of colony-forming units (cfu) of greater than 2 logs in 4 hr and a 4-log decrease in cfu in 24 hr at concentrations (minocycline, 0.64 microgram/ml; AmB, 0.1 microgram/ml) that were subinhibitory when each agent was used alone and that are readily achieved in human serum and body fluids with conventional doses. The killing-curve technique indicated that doxycycline had an intermediate degree of synergistic activity, whereas tetracycline had no synergistic activity at clinically relevant concentrations.

Amphotericin B↗
PubMed1976

Mechanism of interferon action: further evidence for transcription as the primary site of action in simian virus 40 infection.

Interferon inhibits the replication of simian virus 40 (SV40) in monkey cells and reduces markedly the formation of both early virus protein (i.e. SV40 T antigen) and early SV40 RNA. This suggests that in SV40 infection interferon acts primarily by inhibiting transcription. To test this conclusion further, we examined alternative mechanisms which might explain these results and made the following observations. (1) The quantity of input SV40 DNA in the nucleus 24 h post infection (p.i.) was the same in interferon-treated and control cells. Thus interferon does not appear to diminish the quantity of SV40 DNA template available for transcription. (2) Chemical inhibitors of protein synthesis did not mimic the selective inhibition of early SV40 RNA formation induced by interferon, indicating that the transcription of early SV40 RNA is not dependent upon the prior synthesis of any virus-induced protein. Thus a block in translation cannot readily explain the reduced formation of early SV40 RNA in interferon-treated cells. (3) Fractionation of SV40 infected cells after a one-hour labelling period showed that interferon produced a comparable reduction in the quantity of early SV40 RNA in the nucleus and the cytoplasm. Thus the observed inhibition of early SV40 RNA is not due solely (if at all) to enhanced cytoplasmic degradation. These results indicate that the primary effect of interferon in SV40 infected monkey cells is either to inhibit the transcription of early virus RNA or to enhance its turnover in the nucleus.

Cell Line↗
PubMed1975

Fatal disseminated adenovirus infection in a renal transplant recipient.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.

Adenoviridae↗