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Biomedical subjects

H C Lane

Publications and source records attributed to H C Lane.

At least 163 records · Page 9Linked to original sources
PubMed1986

Recombinant interleukin-2-induced polyclonal proliferation of in vitro unstimulated human peripheral blood lymphocytes.

Human peripheral blood mononuclear cells as well as T-cell-enriched or T-cell-depleted populations were found to proliferate in response to recombinant interleukin-2 (IL-2) in vitro in the absence of a lectin preactivation signal. This proliferative response was detected at Day 2, peaked at Day 5, and was dependent on the concentration of IL-2 used. At the initiation of culture, these cells did not appear to be activated as determined by the expression of Tac antigens. In cultures of unfractionated T-cell-enriched suspensions, high concentrations of IL-2 resulted in preferential expansion of the OKT8+ population, although both OKT4+ and OKT8+ cells proliferated in response to IL-2 when cultured alone. These studies demonstrate that human lymphocytes obtained by standard fractionation procedures from peripheral blood are capable of proliferation in response to IL-2 without in vitro preactivation signals given by the addition of mitogens or antigens to cultures. These findings suggest that in vivo IL-2, in the absence of other exogenous stimuli, may directly influence immune responses and thus may have a potential role as a clinical immunopharmacologic agent.

Antibodies, Monoclonal↗
PubMed1986

Treatment of cytomegalovirus retinitis with dihydroxy propoxymethyl guanine.

Eight patients with cytomegalovirus retinitis in one or both eyes were treated with 9-(1,3 dihydroxy 2-propoxymethyl) guanine. Of the 14 eyes with retinitis, eight demonstrated more than 90% resolution, four had partial improvement, one failed to respond, and one could not be evaluated. Two of the eight patients had chemotherapy-induced immunosuppression and had ocular remissions for at least several months. The remaining six patients had AIDS or probable AIDS and relapsed in five weeks or less after discontinuation of therapy. Dihydroxy propoxymethyl guanine appears to be effective biologically in treating human cytomegalovirus retinitis without the development of unacceptable side effects but a single course of therapy is not capable of eradicating the virus.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Clinical pharmacokinetics of suramin in patients with HTLV-III/LAV infection.

Suramin has been reported to inhibit the reverse transcriptase activity of a number of retroviruses and to reduce the in vitro infectivity and cytopathic effect of HTLV-III/LAV, the etiologic agent of acquired immune deficiency syndrome (AIDS). The clinical pharmacokinetics of suramin were investigated as part of a pilot study to evaluate the safety and efficacy of this drug for the treatment of patients with diseases caused by HTLV-III/LAV. A dose of suramin 6.2 g was given intravenously over a five-week period to four patients. After the last dose, the plasma half-life of suramin was 44 to 54 days. This is among the longest half-lives reported for any therapeutic substance given to humans. Total plasma levels of suramin were greater than 100 micrograms/mL for several weeks. In vitro activity of suramin was found at concentrations as low as 50 micrograms/mL. Metabolites were not found in plasma, and urinary excretion accounts for elimination of most of the drug. Suramin is approximately 99.7% bound to plasma proteins. The results from these initial clinical pharmacokinetic studies might assist the design of further therapeutic trials of suramin, especially the selection of frequency of dosing and adjustments for renal impairment.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Effect of 9-(1,3-dihydroxy-2-propoxymethyl) guanine on serious cytomegalovirus disease in eight immunosuppressed homosexual men.

Eight immunosuppressed homosexual men with cytomegalovirus viremia--seven with serious bilateral retinitis, one with colitis in addition to retinitis, and one with pneumonitis only--were treated with a new acyclovir derivative, 9-(1,3-dihydroxy-2-propoxymethyl) guanine, which has excellent in-vitro activity against cytomegalovirus. All patients had virologic and clinical improvement, but substantial leukopenia developed in three patients. Both clinical relapses and viral relapses occurred frequently, usually within 30 days after cessation of treatment. 9-(1,3-Dihydroxy-2-propoxymethyl) guanine represents the first clinically and virologically effective agent for the treatment of cytomegalovirus disease, but more effective and less toxic therapeutic regimens for both acute and chronic use must be developed.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Risk of nosocomial infection with human T-cell lymphotropic virus type III/lymphadenopathy-associated virus in a large cohort of intensively exposed health care workers.

To assess the risk of nosocomial transmission of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), we prospectively evaluated a cohort of 531 health care workers. One hundred fifty of these employees reported percutaneous or mucous membrane exposures to blood or body fluids from a patient with the acquired immunodeficiency syndrome (AIDS) during the treatment of 238 such patients since 1981. None of these 150 employees had serologic evidence of HTLV-III/LAV infection on follow-up from 6 to 46 months after exposure. Of the 150, 46 were studied immunologically and 29 had lymphocytes cultured for HTLV-III/LAV. Results of all studies were normal. Of the 531 employees, 3 (0.56%) had serologic evidence of HTLV-III/LAV infection. All were seropositive at the time of study entry; none reported adverse nosocomial exposures. All acknowledged membership in one or more established risk groups for AIDS. This study provides strong evidence that the risk of nosocomial transmission of HTLV-III/LAV is extremely low.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Effects of suramin on HTLV-III/LAV infection presenting as Kaposi's sarcoma or AIDS-related complex: clinical pharmacology and suppression of virus replication in vivo.

Suramin was given to ten outpatients with acquired immunodeficiency syndrome (AIDS) presenting as Kaposi's sarcoma (KS) or as an AIDS-related complex (ARC). Side-effects associated with the administration of 6.2 g of suramin over 5 weeks included fevers, rashes, urinary abnormalities, and transient rises in hepatic aminotransferases. Peak serum levels of over 100 micrograms/ml were attained. There was evidence of HTLV-III infectivity and replication in lymphocytes from four patients before therapy. The detectable virus level fell in each case by the time of the last dose, and in three cases it became undetectable at the end of therapy. In each case, viral replication was again detected in the weeks or months following the administration of suramin. Despite this in-vivo virustatic effect, no significant clinical or immunological improvement was observed using this short-term regimen. However, the results provide a rationale for investigating longer-term regimens.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition.

We studied purified subpopulations of lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) in order to determine whether intrinsic defects in lymphocyte function, aside from those due to alterations in lymphocyte numbers, were present. Mitogen-stimulated DNA synthesis, production of gamma interferon, production of interleukin-2, and expression of interleukin-2 receptors, although variably decreased in unseparated cell populations, were normal in populations of purified T-cell subsets. In contrast, DNA synthesis in response to the soluble protein antigen tetanus toxoid was decreased in both unseparated and purified T-cell subpopulations. Cell-mixing experiments demonstrated that the hyporesponsiveness of the unfractionated lymphocytes from patients with AIDS was not due to active suppression. We conclude that the lymphocytes of patients with AIDS, although capable of undergoing a normal degree of blast transformation and lymphokine production after mitogenic stimulation, have an intrinsic defect in their ability to recognize and respond to soluble antigen.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The effect of cyclosporine on immunization with tetanus and keyhole limpet hemocyanin (KLH) in humans.

Eleven patients with chronic uveitis treated with Cyclosporine were immunized with keyhole limpet hemocyanin (KLH) and tetanus toxoid. Delayed cutaneous hypersensitivity responses, lymphocyte blastogenic responses, and antibody production were compared with those of similarly immunized control individuals. A significant decrease in delayed cutaneous hypersensitivity (P less than 0.001 for KLH and P less than 0.01 for tetanus toxoid) was observed. No significant differences in blastogenic or antibody responses were noted. These findings demonstrate that the majority of the Cyclosporine-treated patients had intact T cell-dependent antigen responses as measured by both proliferative response and antibody production to primary and secondary antigenic challenges but that other immune functions such as delayed cutaneous hypersensitivity are affected by therapeutic doses of systemic Cyclosporine.

Antibody Formation↗
PubMed1985

Human lymphoblastoid interferon treatment of Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters.

Thirty consecutive patients with the acquired immune deficiency syndrome were treated with intramuscular human lymphoblastoid interferon for Kaposi's sarcoma. Patients were divided into three groups receiving 7.5 million units/m2 per day, 15 million units/m2 per day, or 25 million units/m2 per day for 28 days. Because of dose-limiting toxicity in the highest dose group, all patients received between 6 and 15 million units/m2 per day. There were three partial responses and four minor responses. The responses were not dependent on drug dose, but did correlate with higher total lymphocyte and OKT4-positive lymphocyte numbers and absence of prior opportunistic infection. Patients who had endogenous acid-labile alpha-interferon prior to therapy were more likely to have progressive disease during interferon administration.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Correlation between immunologic function and clinical subpopulations of patients with the acquired immune deficiency syndrome.

The present study was designed to determine whether there was a significant correlation between the clinical presentation of patients with AIDS or AIDS-related illnesses and the degree of their underlying immunologic abnormalities. In 17 patients who presented with opportunistic infections, the mean number of T4 lymphocytes was 34/mm3 and the mean proliferative response to phytohemagglutinin 26,000 cpm; in 12 patients who presented with Kaposi's sarcoma alone, the mean number of T4 cells was 231/mm3 and the mean proliferative response to phytohemagglutinin, 32,809 cpm; and in nine patients with the lymphadenopathy syndrome, the mean number of T4 cells was 703/mm3 and the mean proliferative response to phytohemagglutinin, 49,317 cpm. These findings suggest that those patients who present with opportunistic infections as their initial clinical manifestation of AIDS may represent a subgroup with a more severe immunologic derangement prior to clinical diagnosis. Thus, in those who have a predisposition to Kaposi's sarcoma, this disease will often develop, prior to the development of T cell dysfunction, to the degree of that in those who present with opportunistic infections. This finding is of importance in attempts to understand the pathogenesis of this syndrome and in the design of therapeutic trials.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Human B-cell proliferation in response to recombinant interleukin 2 is not due to T-cell help.

Positively selected human B-cell suspensions with no detectable T cells and containing more than 99.5% B cells both at the initiation and termination of culture were shown to proliferate in response to interleukin 2 (IL-2) in a dose-dependent fashion. The lack of influence of residual T cells on this proliferative response was demonstrated in experiments where T cells were added back in increasing numbers to B-cell suspensions. No detectable enhancing effect on B-cell proliferation was noted when 2.5% T cells were purposely added back to culture, a proportion far in excess of that which might be expected to contaminate B-cell suspensions under the present methodology. In contrast, when 10% T cells were added back to B-cell cultures, an enhanced proliferation of B cells was observed suggesting that the lack of effect of lower numbers of T cells was due to their inefficiency in helping B-cell proliferation in response to IL-2. Therefore, it is concluded that highly purified IL-2 is capable of triggering human peripheral blood B cells to proliferate and that this proliferation is not due to T-cell help.

Animals↗
PubMed1985

Oligoclonal immunoglobulins in patients with the acquired immunodeficiency syndrome.

Analysis of serum samples from patients with the acquired immunodeficiency syndrome (AIDS) was performed by high-resolution zone electrophoresis. A high incidence of monoclonal and oligoclonal immunoglobulins was detected in the sera of 24/27 patients with Kaposi's sarcoma and in 2/15 patients with opportunistic infections. The presence of monoclonal bands was independent of whether or not the patients had experienced an opportunistic infection. These findings indicate a monoclonal or oligoclonal B-cell activation occurring in a much higher frequency in AIDS patients with Kaposi's sarcoma, thus suggesting that similar mechanisms may be operative in the malignant or pseudomalignant proliferation of B-cells and endothelial cells in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Immunologic abnormalities in the acquired immunodeficiency syndrome.

The immune systems of patients with AIDS are characterized by a profound defect in cell-mediated immunity which is predominantly due to a decrease in the number and function of the helper/inducer T lymphocytes, particularly the antigen-reactive cells. This defect is manifested primarily as decreases in delayed-type hypersensitivity reactions and decreased in vitro proliferation to soluble antigen. A variety of secondary manifestations of immunologic dysfunction occur, some of which result from a lack of effective inducer-cell function, others from the occurrence of opportunistic infections. Among these secondary phenomena are decreased cytotoxic lymphocyte responses, polyclonal B-cell activation, decreased monocyte chemotaxis, and a number of serologic abnormalities. The primary cause of this defect in the antigen-reactive helper/inducer T lymphocyte is infection with a class of T-cell tropic retroviruses known as HTLV-III or LAV. This virus is capable of selectively infecting T4 + lymphocytes and can be isolated consistently from patients with AIDS or AIDS-related conditions. Despite substantial knowledge concerning the nature of the immune defect in AIDS and its causative agent, little progress has been made in developing effective therapies for this uniformly fatal illness. Because the incidence of this disease continues to increase, and patients stricken with this illness have a median survival of two years, additional investigation in this area is greatly needed. Continued effort aimed at delineating the precise nature of the immune defect in these patients should be of value in attempting to enhance our understanding of the human immune system in both normal and disease states.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The acquired immunodeficiency syndrome (AIDS): an update.

The acquired immunodeficiency syndrome (AIDS) is a disease which is characterized by a profound defect in cell-mediated immunity leading to opportunistic infections and unusual neoplasms such as Kaposi's sarcoma. It is caused by a retrovirus of the human T cell leukemia/lymphoma virus family and has been termed HTLV-III/lymphadenopathy-associated virus. The virus selectively infects the T4 helper/inducer subset of T cells, accounting for the profound defects in immunity noted in AIDS patients. AIDS is transmitted sexually, and by blood and blood products, accounting for its relative confinement to specific risk groups. The disease is now seen worldwide, and as of September 1984, approximately 6,000 cases have been reported in the USA alone. There is no effective treatment for the disease at present, and the mortality of the full-blown syndrome approaches 100%. Hopefully, with the recent isolation of the causative agent of the syndrome, effective therapies and vaccinations will be forthcoming.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Clonal analysis of T lymphocytes in the acquired immunodeficiency syndrome. Evidence for an abnormality affecting individual helper and suppressor T cells.

Purified helper-inducer (T4+) and suppressor-cytotoxic (T8+) lymphocytes from eight patients with acquired immunodeficiency syndrome (AIDS) and eight healthy heterosexual donors were examined by limiting dilution analysis for their ability to be clonally expanded. It was demonstrated that viable T4+ and T8+ lymphocytes from patients with AIDS had markedly reduced proportions of clonable cells compared to the healthy donors (T4 = 1:255 vs. 1:34, P = 0.06; T8 = 1:355 vs. 1:55, P = 0.01). However, the cloned T cells that were obtained from the patients with AIDS demonstrated normal proliferation in response to phytohemagglutinin and alloantigen, and normal ability to help or suppress pokeweed mitogen-driven IgG synthesis. These results strongly suggest that, in addition to a quantitative diminution of T4+ lymphocytes in AIDS, there is an intrinsic functional defect in the surviving T4+ and T8+ lymphocytes, which is reflected by a severe decrease in their potential for clonal expansion.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Kaposi's sarcoma causing pulmonary infiltrates and respiratory failure in the acquired immunodeficiency syndrome.

Although an aggressive form of Kaposi's sarcoma often develops in patients with the acquired immunodeficiency syndrome, most patients die due to opportunistic infections rather than the direct effects of this tumor. Because Kaposi's sarcoma has caused pulmonary dysfunction in a number of our patients, we attempted to characterize features of pulmonary dysfunction induced by Kaposi's sarcoma. In 66 patients with Kaposi's sarcoma treated between 1982 and 1984 there were 30 episodes of pulmonary dysfunction that resulted in a biopsy. Six episodes were due to pulmonary Kaposi's sarcoma alone, and 6 additional episodes were due to Kaposi's sarcoma and associated opportunistic infections. Clinical and radiologic features of pulmonary Kaposi's sarcoma an infection were indistinguishable. Pulmonary Kaposi's sarcoma could only be documented in large tissue sections available from open-lung biopsy or autopsy samples. Because chemotherapy or radiation therapy appears to provide palliation, clinicians should recognize Kaposi's sarcoma as a cause of pulmonary disease in patients with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1985

NIH conference. The acquired immunodeficiency syndrome: an update.

The acquired immunodeficiency syndrome continues to be a major public health problem in the United States, and recently its spread worldwide has accelerated. The syndrome is caused by a human retrovirus transmitted by sexual contact and via blood or blood products. The virus has been isolated, characterized, and cloned, and in addition to its presence in blood, it has been found in body tissues and fluids including brain, semen, and saliva. Although the syndrome in the United States is still largely confined to male homosexuals and intravenous drug users, there is increasing evidence, particularly from Zaire, that the virus can be spread by heterosexual contact. Attempts at immune reconstitution with lymphocytes and lymphokines have resulted in some transient improvement in immune function but without clinical effect, indicating the need for specific anti-retroviral therapy in combination with immune reconstitution.

Acquired Immunodeficiency Syndrome↗