Search PubMed⌕ Search

Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 181 records · Page 10Linked to original sources
PubMed1993

Safety and immunogenicity of a fully glycosylated recombinant gp160 human immunodeficiency virus type 1 vaccine in subjects at low risk of infection. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group Network.

Recombinant gp160 derived from human immunodeficiency virus type 1 (HIV-1)IIIB and produced in mammalian tissue culture cells using a vaccinia virus expression system (rgp160-mam) was evaluated as a vaccine in combination with alum and deoxycholate adjuvant. Sixty low-risk, uninfected subjects received 12.5 micrograms, 50.0 micrograms, or adjuvant control at 0, 1, 6, and 12 months in a randomized, double-blind dose-escalation study. A single injection of 200 micrograms of vaccine was given at 18 months in an open study to 9 vaccines who had received 50 micrograms. The vaccine was safe. Six of 16 subjects receiving 50 micrograms developed neutralizing antibody to HIV-1IIIB. Seven of the 9 boosted with 200 micrograms of vaccine at 18 months developed neutralizing antibodies. Lymphocyte proliferation to rgp160-mam and baculovirus-derived rgp160 and rgp120 was induced in both groups (12.5 and 50.0 micrograms) and appeared after the first dose. Further studies with higher doses of rgp160-mam and vaccines derived from other strains of HIV-1 are warranted.

AIDS Vaccines↗
PubMed1993

The morphology and function of rabbit hepatocytes isolated using ethylenediaminetetraacetate.

The enzyme digestion technique using collagenase is used in most studies that describe hepatocyte isolation, including those in which hepatocytes are isolated for transplantation. The use of collagenase, however, has several drawbacks. We describe the use of a highly concentrated ethylenediaminetetraacetate solution for isolation of hepatocytes followed by purification using a Percoll gradient in the rabbit model. Isolated hepatocytes were then preserved at 4 degrees C for up to three days in either University of Wisconsin solution or Dulbecco's modified eagle's medium. Morphological studies of hepatocytes at 24 hr and 72 hr in either medium were performed using Papanicolaou and PAS stains of cytopreparations for the presence of glycogen. Similarly, functional studies of the preserved hepatocytes included LDH release, total tissue water content, and amount of 99m-technetium mebrofenin uptake. The use of EDTA perfusion for hepatocyte isolation was highly reproducible in this model. The cell yield was comparable to that achieved previously using collagenase. The morphologic studies demonstrated pure hepatocytes with well-preserved architecture when preserved for up to three days in UW solution. Functional studies showed a statistically significant lower LDH release and total tissue water content and a higher technetium-99m mebrofenin uptake for hepatocytes preserved in UW solution. We conclude that a pure and viable hepatocyte suspension can be obtained from rabbit livers using concentrated EDTA solutions. These hepatocytes can be well preserved at 4 degrees C for up to 72 hr in UW solution, based on morphologic and functional criteria.

Adenosine↗
PubMed1993

The emergence of chronic peer victimization in boys' play groups.

This investigation utilized a contrived play group procedure to examine the behavioral patterns leading to chronic victimization by peers in middle childhood. 30 play groups, each of which consisted of 6 unacquainted African-American 6-year-old or 8-year-old boys, met for 45-min sessions on 5 consecutive days. Play group interactions were videotaped and then examined. 13 boys who came to be chronically victimized by their play group peers were identified, along with matched nonvictim contrasts. Victims demonstrated lower rates of assertive behaviors, such as persuasion attempts and social conversation initiatives, and higher rates of nonassertive behaviors, such as submissions to peers' social initiatives, than contrasts. This nonassertive behavior pattern appears to have preceded the development of chronic victimization. Children who eventually emerged as victims were pervasively submissive, beginning in the initial 2 sessions. However, marked individual differences in victimization by peers did not become apparent until the final 3 sessions. These data provide evidence of strong linkages between submissive social behavior and the emergence of chronic victimization by peers.

Child↗
PubMed1993

The significance of polymicrobial growth in urine: contamination or true infection.

Urine growing more than one organism is usually considered contaminated. During 1980-1984, among 198 episodes of urosepsis with at least one identical organism in blood and urine, there were 62 with polymicrobial growth from urine. The significance of the multiple growth from urine was confirmed in 12 episodes by the growth of more than one identical organism in blood and urine and in 21 episodes by repeated growth of the same mixture of organisms in multiple urine specimens. Escherichia coli had a higher tendency to invade blood stream than other Gram-negative organisms, such as pseudomonas and proteus. In specific populations with high risk of polymicrobial infection, multiple growth in urine should be carefully evaluated with appropriate colony count and identification of each isolate.

Adolescent↗
PubMed1993

Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes.

The various steps of differentiation and maturation in spermatogenesis are well characterized and offer a convenient system to explore the possibility that p53 plays a role in cell differentiation in vivo. In situ hybridization experiments indicate that the p53 gene is expressed in tetraploid primary spermatocytes at the meiotic pachytene stage of the first round of spermatogenesis in young mice. An analysis of spermatogenic cells treated with anti-p53 antibodies reveals that the p53 protein is expressed in a discrete tetraploid cell population, with size and cellular structure parameters characteristic of midpachytene spermatocytes. The specific kinetics of p53 expression in the first round of spermatogenesis and its localization in adult testicular sections, coupled with the fact that the protein is expressed in the largest cells with lower DNA density, suggest that p53 expression is confined to the tetraploid primary spermatocytes of the meiotic pachytene phase. These observations identify p53 protein as a potential member of the meiosis control protein family.

Animals↗
PubMed1992

Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines.

The lysis of infected host cells by virus-specific cytolytic T lymphocytes (CTL) is an important factor in host resistance to viral infection. An optimal vaccine against human immunodeficiency virus type 1 (HIV-1) would elicit virus-specific CTL as well as neutralizing antibodies. The induction by a vaccine of HIV-1-specific CD8+ CTL in humans has not been previously reported. In this study, CTL responses were evaluated in HIV-1-seronegative human volunteers participating in a phase I acquired immune deficiency syndrome (AIDS) vaccine trial involving a novel vaccine regimen. Volunteers received an initial immunization with a live recombinant vaccinia virus vector carrying the HIV-1 env gene and a subsequent boost with purified env protein. An exceptionally strong env-specific CTL response was detected in one of two vaccine recipients, while modest but significant env-specific CTL activity was present in the second vaccinee. Cloning of the responding CTL gave both CD4+ and CD8+ env-specific CTL clones, permitting a detailed comparison of critical functional properties of these two types of CTL. In particular, the potential antiviral effects of these CTL were evaluated in an in vitro system involving HIV-1 infection of cultures of normal autologous CD4+ lymphoblasts. At extremely low effector-to-target ratios, vaccine-induced CD8+ CTL clones lysed productively infected cells present within these cultures. When tested for lytic activity against target cells expressing the HIV-1 env gene, CD8+ CTL were 3-10-fold more active on a per cell basis than CD4+ CTL. However, when tested against autologous CD4+ lymphoblasts acutely infected with HIV-1, CD4+ clones lysed a much higher fraction of the target cell population than did CD8+ CTL. CD4+ CTL were shown to recognize not only the infected cells within these acutely infected cultures but also noninfected CD4+ T cells that had passively taken up gp120 shed from infected cells and/or free virions. These results were confirmed in studies in which CD4+ lymphoblasts were exposed to recombinant gp120 and used as targets for gp120-specific CD4+ and CD8+ CTL clones. gp120-pulsed, noninfected targets were lysed in an antigen-specific fashion by CD4+ but not CD8+ CTL clones. Taken together, these observations demonstrate that in an in vitro HIV-1 infection, sufficient amounts of gp120 antigen are produced and shed by infected cells to enable uptake by cells that are not yet infected, resulting in the lysis of these noninfected cells by gp120-specific, CD4+ CTL.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Vaccines↗
PubMed1992

Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event.

A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains in various human T-cell systems, including peripheral blood lymphocytes, at 0.14-1.4 microM, without being toxic to the host cells at 2.2 mM. The bicyclam JM2763 is active against 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant HIV-1 strains and acts additively with AZT. Mechanism of action studies revealed that the bicyclams (i.e., JM2763) interact with an early event of the retrovirus replicative cycle, which could be tentatively identified as a viral uncoating event.

Antiviral Agents↗
PubMed1992

Humanization of immunotoxins.

The construction and expression of a chimeric gene encoding a mouse/human antibody to the human transferrin receptor fused to the gene for angiogenin, a human homolog of pancreatic RNase, are described. F(ab')2-like antibody-enzyme fusions were prepared by linking the gene for human angiogenin to a chimeric anti-transferrin receptor heavy chain gene. The antibody-enzyme fusion gene was introduced into a transfectoma that secretes the chimeric light chain of the same antibody, and cell lines were cloned that synthesize and secrete the antibody-enzyme fusion protein of the expected size at a concentration of 1-5 ng/ml. Culture supernatants from clones secreting the fusion protein caused inhibition of growth and protein synthesis of K562 cells that express the human transferrin receptor but not toward a non-human-derived cell line that lacks this receptor. Whereas excess antibody to the same receptor did not itself inhibit protein synthesis, it was able to completely prevent the protein synthesis inhibition caused by the fusion protein. These results indicate that the cytotoxicity is due to a transferrin receptor-mediated mechanism involving the angiogenin portion of the fusion protein and demonstrate the feasibility of constructing recombinant antibody-RNase molecules capable of killing tumor cells bearing the transferrin receptor. The significance of the acquired cytotoxicity of a mouse/human chimeric antibody linked to a human protein may bear importantly in human therapeutic strategies that use mouse antibodies linked to toxins from plants or bacteria to target tumor cells. It is expected that the humanization of immunotoxins will lead to less toxicity and immunogenicity than currently available reagents.

Animals↗
PubMed1992

Androgenic-anabolic steroid abuse and platelet aggregation: a pilot study in weight lifters.

The abuse of anabolic-androgenic steroids by athletes has recently been associated with the development of myocardial infarction and stroke. Because platelets play a pathogenic role in these disorders, the authors hypothesized that androgenic steroid abuse among weight lifters was associated with increased platelet aggregation as measured in vitro. Twenty-eight study participants were recruited. Twelve denied current androgen use. However, 8 of these 12 tested positive for urinary androgens. Nonsignificant trends toward increased platelet counts and increased platelet aggregation to adenosine diphosphate were noted when androgen users were compared to nonusers. However, when stratified by age, older (greater than 22 years) androgen users required lower concentrations of collagen to produce 50% aggregation of test platelets than did younger (less than or equal to 22 years) androgen users (1.47 versus 3.35 micrograms/ml; p = .01). Further subgroup analysis revealed nonsignificant trends toward increased adenosine diphosphate-induced aggregability and nonsignificant trends in the platelet count in older weight lifters. Subsequent studies using collagen threshold aggregometry revealed no age-dependent effect in 17 other men (aged 18 to 46 years) not specifically selected for activity (r = .17). This study suggests an association between androgen use, age, and increased platelet sensitivity to collagen in weight lifters and may be helpful in explaining recent thrombotic disease in androgen users. It additionally calls into question the validity of subjective reporting when assessing androgen use among weight lifters.

Adolescent↗
PubMed1992

Disseminated intravascular coagulation with renal and liver damage as the predominant manifestations of recurrent relapses in systemic juvenile rheumatoid arthritis.

Relapses of systemic juvenile rheumatoid arthritis associated with intravascular coagulation are rare. This paper describes a patient who, over a two year period, had two relapses, each accompanied by evidence of liver and renal damage and disseminated intravascular coagulation. The patient was not receiving non-steroidal anti-inflammatory drugs, and all laboratory and clinical manifestations of her disease rapidly resolved after treatment with prednisone. It is therefore believed that the hepatocellular damage, in addition to the disseminated intravascular coagulation, was a direct manifestation of disease activity. A possible pathogenic role for tumour necrosis factor is suggested.

Adult↗
PubMed1992

Combined effect of captopril and aspirin in renal hemodynamics in elderly patients with congestive heart failure.

Captopril and aspirin have been claimed to adversely affect renal function. This study was designed to evaluate the safety of concomitant administration of both drugs in patients with moderate to severe congestive heart failure (CHF). The study group consisted of 10 patients with a mean age of 77.6 +/- 4.4 years and a mean New York Heart Association functional class of 2.6 +/- 0.5. Captopril was administered in a rapidly escalating dose regimen over a 4-day period to a maximum dose of 75 mg/day. Aspirin 0.25 g/day was added from day 5 on. Renal plasma flow (RPF) was measured by iodohippurate scan and the creatinine clearance test (Ccr) was used as an index of glomerular filtration rate (GFR). Both Ccr and RPF remained unchanged throughout the study period; 48.9 +/- 16; 48.2 +/- 16.5; 49.4 +/- 16, and 222 +/- 67, 241 +/- 97, 237 +/- 88 ml/min, for days 0, 4, 9, respectively. Only 1 patient developed a significant decrease in Ccr following the administration of captopril. This patient had a further decrease when aspirin was added. The decrease in Ccr was accompanied by a marked reduction in filtration fraction and in mean arterial pressure. Our data suggest that the administration of aspirin to elderly patients with moderate CHF treated with captopril is relatively safe and is not associated with further deterioration in renal function.

Aged↗
PubMed1992

[Immunologic factors in habitual abortion].

Recent advances in immunology have discovered two immunological factors in part of the patients with habitual first-trimester abortions. Antibody formation against the major histocompatibility antigens (HLA = human leukocyte antigen) which can be demonstrated during normal pregnancy is often not detectable in these patients, sometimes presumably because of compatibility in the HLA antigens between mother and fetus. In a high percentage of these patients immunotherapy by subcutaneous leukocyte injections can lead to antibody formation and successful pregnancy. As another immunological factor, a genetic variant of the complement-inactivating leukocyte differentiation antigen CD46 (= TLX antigen, = membrane cofactor protein) could be identified, which can be seen more frequently in patients with habitual abortions as compared to healthy controls. Both factors seem just to contribute to a predisposition for early-pregnancy abortions rather than to be an absolute barrier, as they can also be seen in normal pregnancy and successful carriages can also occur without any therapy in early-pregnancy aborters with an immunological background.

Abortion, Habitual↗