PubMed Health⌕ Search

Biomedical subjects

M M Lederman

Publications and source records attributed to M M Lederman.

At least 91 records · Page 5Linked to original sources
PubMed1992

Suppression of interleukin-2 and interleukin-2 receptor expression in Jurkat cells stably expressing the human immunodeficiency virus Tat protein.

The Jurkat T cell line was stably transfected with an Epstein-Barr virus-based episomal replicon designed to express high levels of the HIV-1 Tat protein. After selection in hygromycin B, high-level Tat activity was detected in 3 of 18 transfected cell lines. After stimulation with phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), Tat transfectants with high Tat expression showed diminished expression of interleukin-2 (IL-2) and the interleukin-2 receptor alpha chain (IL-2R) when compared to untransfected Jurkat cells or Jurkat cell lines transfected with the parent control plasmid. Sublines derived from the high-level Tat transfectants with reduced Tat activity showed normalization of PHA/PMA-induced IL-2 expression. Northern analysis showed diminished expression of IL-2 and IL-2R mRNA in the stimulated Tat transfectants. Inhibition of IL-2 and IL-2R expression by the HIV-1 Tat protein may contribute to the immune suppression that characterizes HIV-1 infection.

Cell Line↗
PubMed1992

Incidence of lymphomas and other cancers in HIV-infected and HIV-uninfected patients with hemophilia.

OBJECTIVE: To determine the types and rates of cancers occurring in excess in the presence of infection with the human immunodeficiency virus type 1 (HIV-1). DESIGN: Cohort analytic study of HIV-infected and HIV-uninfected subjects followed for up to 12 years. SETTING: Fifteen hemophilia treatment centers. PATIENTS: A total of 1701 patients with hemophilia, of whom 1065 (63%) were HIV-1 seropositive. MAIN OUTCOME MEASURES: Morphologic classification and incidence rates of cancers. MAIN RESULTS: The incidence of non-Hodgkin's lymphoma after HIV seroconversion averaged 0.15 case per 100 person-years (95% confidence interval [CI], 0.08 to 0.25) and rose exponentially with increasing duration of HIV infection. Although the greatest absolute risk of lymphoma was in the oldest age group, the relative increase compared with general population rates was 38-fold in subjects 10 to 39 years old and 12-fold in older subjects (P less than .05). The CD4+ T-lymphocyte levels for lymphoma cases were similar to HIV-positive subjects without the acquired immunodeficiency syndrome (AIDS) who had been infected for the same length of time. The incidence of Kaposi's sarcoma was increased 200-fold (95% CI, 20 to 700). The incidence of cancers other than non-Hodgkin's lymphoma and Kaposi's sarcoma were not increased in the HIV-positive subjects (ratio of observed to expected cases, 0.9 [95% CI, 0.4 to 1.9]). The HIV-negative subjects had no significant increase in cancer incidence. CONCLUSIONS: HIV infection has restricted effects on cancer incidence that are only partly explained by immunosuppression. Paradoxically, improvements in therapy of HIV infection that prolong survival may lead to further increases in HIV-associated lymphoma.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Duration of fever during treatment of infective endocarditis.

We reviewed the duration of fever among 123 patients treated for infective endocarditis at University Hospitals of Cleveland between 1972 and 1984. One half of these patients became afebrile within 3 days after initiation of antibiotic therapy and nearly three quarters were afebrile after 1 week of therapy. After 2 weeks of therapy, nearly 90% had defervesced. Endocarditis due to Staphylococcus aureus or gram-negative bacilli, and culture-negative endocarditis, were associated with prolonged fever. Microvascular phenomena, major vessel embolization, or vegetations seen on 2-D echocardiogram also were associated with prolonged fever. Multivariate analysis revealed that only microvascular phenomena or major vessel embolization were independently associated with longer duration of fever. Endocarditis-associated mortality among patients who remained febrile after 1 week of therapy was 18%, and this was greater than the 2% mortality among patients who defervesced (p less than 0.002). These data suggest that prolonged fever during treatment of infective endocarditis is often due to tissue infarction or vascular injury. Prolonged fever also identifies patients at higher risk of a fatal outcome.

Age Factors↗
PubMed1989

Heightened complement sensitivity of acquired immunodeficiency syndrome lymphocytes related to diminished expression of decay-accelerating factor.

Although the human immunodeficiency virus can induce cytopathic changes in human lymphocytes in vitro, the mechanism(s) underlying progressive lymphopenia in patients with AIDS and AIDS-related complex has not been elucidated. To investigate this issue, peripheral blood lymphocytes of AIDS and AIDS-related complex patients and healthy control subjects were examined for their ability to resist homologous complement-mediated lysis. Upon sensitization with monoclonal antibodies to major histocompatibility complex class I antigen, as much as 48% lysis of patients' cells was observed in as little as a 1:32 dilution of human serum compared to 18 +/- 8% (mean +/- SD) lysis of controls' cells even in a 1:8 dilution of human serum. To investigate the mechanism of the abnormal complement sensitivity, AIDS and AIDS-related complex cells were analyzed for expression of decay-accelerating factor (DAF), a complement regulatory protein that functions intrinsically in blood cell membranes to prevent complement activation on their surfaces. Flow cytometric assays using anti-DAF monoclonal antibodies demonstrated that patients' lymphocytes and monocytes were DAF-deficient, in contrast to their polymorphonuclear leukocytes, which showed normal DAF levels. Expression of DAF was diminished on CD4+ as well as CD8+ T-lymphocyte subpopulations as opposed to expression of CD3, which was comparable in patients and controls. Incubation of normal lymphocytes with anti-DAF monoclonal antibodies or phosphatidylinositol-specific phospholipase C, an enzyme that cleaves DAF, enhanced lysis. Conversely, reconstitution of patients' cells with exogenous DAF reduced their lysis. The findings of heightened complement sensitivity and DAF deficiency of patients' lymphocytes in vitro suggest the possibility that the DAF deficit may contribute to the progressive lymphopenia of AIDS in vivo.

AIDS-Related Complex↗
PubMed1989

Serious infectious complications of corticosteroid therapy for COPD.

We report seven elderly patients with COPD who developed serious infectious complications during prolonged treatment with high doses of corticosteroids. Infections included invasive pulmonary aspergillosis, Herpes simplex stomatitis and esophagitis, cytomegalovirus pneumonia, bacterial sepsis, fungemia and meningitis due to Cryptococcus neoformans. Each of the three patients who developed invasive aspergillus pneumonia died. The efficacy of prolonged therapy with high doses of corticosteroids in patients with COPD is not proven. These cases illustrate the potential for serious infections in patients with COPD treated with corticosteroids.

Aged↗
PubMed1989

Tendency to serious sequelae of infection with the human immunodeficiency virus in sibships with hemophilia.

Cofactors for the clinical expression of infection due to the human immunodeficiency virus (HIV) are not well understood. We asked if there was a familial tendency to the development of complications of HIV infection. We examined 35 hemophilic sibships in which at least two brothers with classic hemophilia (factor VIII deficiency) were infected with HIV. Twenty-four (34%) of the 70 patients had serious sequelae of infection, and 46 (66%) were asymptomatic or had only lymph node enlargement. Using Fisher's exact test, we found the concordance among siblings for serious sequelae of HIV infection was greater than would be expected by chance. When analysis was restricted to include only siblings known to be infected for more than two years, this concordance was still present. In the study population, birth order and mean yearly usage of factor VIII concentrate were unrelated to the outcome of HIV infection. The data indicate a familial tendency to serious complications of HIV infection. The factor(s) responsible for this familial tendency are currently under investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cardiomyopathy associated with the acquired immune deficiency syndrome.

Three cases of congestive cardiomyopathy complicating the acquired immune deficiency syndrome (AIDS) are reported. In one case, acute cardiac decompensation resulted in prolonged but ultimately reversible cardiogenic shock. In the second case, clinical signs of cardiac disease were precipitated by acute renal failure and fluid overload. In the third, congestive heart failure developed spontaneously and responded promptly to administration of diuretics but the patient died suddenly, apparently due to an arrhythmia. The etiology of cardiomyopathy in AIDS is unclear and the manifestations of cardiomyopathy in this setting range from subclinical to life threatening.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Defective accessory function of monocytes in human immunodeficiency virus-related disease syndromes.

It is not clear whether the accessory function of monocytes from subjects with human immunodeficiency virus (HIV)-related diseases such as acquired immunodeficiency syndrome (AIDS) and persistent generalized lymphadenopathy (PGL) is intact. In this study, the accessory function of monocytes from healthy subjects (n = 9) and subjects with AIDS (n = 4) and PGL (n = 5) was assessed by adding graded numbers of monocytes to lymphocytes stimulated with either tetanus toxoid or phytohemagglutinin. By nonparametric analysis, it was determined that a significantly greater number of monocytes was required for half-maximal responses of lymphocytes from subjects with PGL (for tetanus toxid but not phytohemagglutinin) and from those with AIDS, compared with healthy subjects. To address whether this observed difference was a result of a defect in accessory function of monocytes or a result of altered responsiveness of lymphocytes, a mixing experiment was performed between monocytes and lymphocytes obtained from a patient with PGL but without symptoms and an HLA-D-matched healthy sib. Dysfunction of both monocytes and lymphocytes was evident. Thus, this report provides data that monocytes in HIV infection are defective in accessory function for lymphocyte responses to soluble stimuli. We speculate that such dysfunction of monocytes may contribute to the progressive disturbance of the immune response that occurs during HIV infection.

AIDS-Related Complex↗
PubMed1987

Augmentation of skin test reactivity and lymphocyte blastogenesis in patients with AIDS treated with transfer factor.

Nine patients with the acquired immunodeficiency syndrome (AIDS) were administered four doses of pooled transfer factor obtained from the lymphocytes of three healthy controls and three homosexuals with stable lymphadenopathy and serum antibody to the human immunodeficiency virus. Before receiving transfer factor, all patients exhibited anergy to skin test antigens. After four weeks of transfer factor therapy, six of seven patients tested had at least one skin test response. Lymphocyte blastogenic responses to phytohemagglutinin rose from a stimulation index of 6.77 +/- 1.31 before treatment to 19.77 +/- 6.24 after four weeks of transfer factor therapy. Smaller but significant increases were also seen in blastogenic responses to antigens. Improvements in immune responses diminished after administration of transfer factor was halted. Thus, administration of transfer factor to patients with AIDS resulted in partial immune reconstitution. Further studies are indicated to examine the clinical efficacy of this immune response modifier in the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Lymphocytes of persons with the acquired immunodeficiency syndrome and related conditions express reactivity with the monoclonal antibody 4D12 reflective of in vivo lymphocyte activation.

We observed that lymphocytes obtained from healthy persons generally expressed infrequent reactivity with the monoclonal antibody 4D12, an antibody raised against a cell line infected by the human T-lymphotropic virus type I. As had been observed previously, persons bearing HLA-B5 cross-reactive antigens and certain other allotypes had frequent lymphocyte reactivity with 4D12. Lymphocytes obtained from persons infected by the human immunodeficiency virus were highly reactive with 4D12 as were lymphocytes obtained from persons with other viral or bacterial infections. Flow cytometric studies revealed greater 4D12 reactivity by larger lymphocytes, and in vitro studies demonstrated that lectin-stimulated lymphocytes acquired 4D12-reactive antigens. There was also a significant correlation between expression of 4D12-reactive antigens and the presence of the interleukin-2 receptor as recognized by the monoclonal antibody anti-Tac. Thus, the monoclonal antibody 4D12 recognizes a lymphocyte surface antigen frequently expressed among persons with various acute and chronic infections. This antigen is a marker of lymphocyte activation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Epidemiology of human T cell leukemia virus type I infection in East Sepik Province, Papua New Guinea.

A serological survey of 317 healthy residents of rural Papua New Guinea (PNG) showed a 26% prevalence of antibodies to human T cell leukemia virus type I (HTLV-I). Antibody to HTLV-I was detected in 16% of children less than or equal to 10 years old (including an 18-month-old child) and increased to greater than or equal to 24% in subjects greater than 20 years old. Prospective examination for antibody in 104 residents of one village revealed a seroconversion rate of 13% over a one-year period. The mean titer of antibody in these subjects (1:183) was lower (P less than .0005) than that in persons who were persistently seropositive (1:718). Analysis for clustering of infected subjects suggested that personal contact within the home played a role in the horizontal spread of HTLV-I. These data indicate that HTLV-I infection has a higher prevalence in PNG than in other endemic parts of the world, exposure occurs at an early age, and infection and/or seroconversion is common in adults as well as in children.

Adolescent↗
PubMed1987

Molluscum contagiosum and the acquired immunodeficiency syndrome: clinical and immunological details of two cases.

We report here the clinical and immunological findings in two patients with molluscum contagiosum poxvirus infection and the acquired immunodeficiency syndrome (AIDS). These cases support earlier evidence that the molluscum contagiosum virus may act as cases support earlier evidence that the molluscum contagiosum virus may act as an opportunistic pathogen. There is now evidence that members of all five families of double stranded DNA-containing human viruses have been associated with unusual clinical manifestations in AIDS patients, and the significance of DNA virus infections in patients with AIDS is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Diagnosis of nosocomial pneumonia in intubated, intensive care unit patients.

The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients. We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection. Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates. Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status. Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status). Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 0.05); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection. No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course. By univariate analysis, infected patients had a longer duration of intubation (p less than 0.05), higher Gram's stain grading for neutrophils (p less than 0.05) or bacteria (p less than 0.005), higher bacterial colony counts (p less than 0.05), and more frequent detection of elastin fibers in tracheal aspirates (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Fibronectin and cellular cytotoxicity: evidence against a role for fibronectin in natural killer activity.

We investigated a possible role for fibronectin (Fn) in natural killer (NK) cell activity against K562 tumor cells. Plastic plates that had been incubated with Fn at 60 micrograms/ml bound 49.6% +/- 12.8% (mean +/- SEM) of K562 cells; plates coated with three other proteins bound essentially no tumor cells (P less than 0.01). In similar experiments, 12.6% +/- 4.7% of nonadherent lymphocytes bound to plates that had been coated with 60 micrograms/ml Fn; plates coated with other proteins bound less than or equal to 10% of these cells. Lymphocytes that bound to Fn-coated plates appeared to be slightly enriched for NK cells as assessed by morphology and by cytotoxic activity. Despite these findings, neither NK cytotoxic activity nor binding to K562 targets was affected by the addition of any of three anti-Fn antibody preparations, nor by the addition of exogenous Fn at concentrations found in plasma (300 micrograms/ml). Although Fn appears to bind both to K562 targets and to lymphocyte preparations that contain NK cells, it does not appear to have a functional role in mediating NK cell activity against K562 tumor cells.

Cell Adhesion↗
PubMed1986

Staphylococcal protein A primed leukocytes enhance the autologous mixed lymphocyte reaction.

Human peripheral blood mononuclear cells (PBMC) were preincubated for 3 days in medium alone or with various mitogens then washed and irradiated. The preincubated cells then were cultured with autologous T-cells in an autologous mixed lymphocyte reaction (AMLR). Staphylococcal protein A (SPA) pretreatment of PBMC enhanced autologous T-lymphocyte proliferation from 1375 +/- 321 cpm (mean +/- SEM untreated PBMC) to 42,467 +/- 7,985 cpm (SPA primed PBMC) (p less than 0.01). The ability of SPA treated PBMC to enhance the AMLR was not simply a reflection of their proliferation in preculture, as PBMC precultured with phytohemagglutinin and concanavalin A showed greater proliferation than SPA-treated PBMC yet only minimally enhanced the AMLR. Kinetic studies and pre-exposure of PBMC to graded doses of gamma radiation showed that SPA augmentation of the AMLR was mediated by 2 components which differed in kinetics and radiosensitivity. Although incubation of PBMC with SPA did not increase the percentage of cells with detectable surface Ia antigen, SPA did increase the density of Ia in the preincubated cells. Cell separation studies revealed that SPA enhancement of the AMLR was not mediated by T-cells, but was mediated by a non-adherent non-E-rosetting fraction of cells. SPA enhancement of the AMLR was associated with an increased Ia density in the stimulator population but not with an increase in Ia positive cells and was mediated by proliferation-dependent and proliferation-independent mechanisms.

Antigens, Surface↗