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Biomedical subjects

G Kaplan

Publications and source records attributed to G Kaplan.

At least 199 records · Page 11Linked to original sources
PubMed1990

Falls and subjective health rating among the elderly: evidence from two Israeli samples.

Prevention and treatment of falls in the elderly is one of the challenges facing practitioners today. Falls are known to be associated with health status and demographic variables, however relatively little is known about how falls affect the health perceptions of elderly persons. Data from two Israeli samples were analyzed to examine the relationship between reported falls and self-rated health. The first sample was collected in 1978 in home interviews from 96% of residents aged 65 and over of the town of Kiryat Ono (N = 1276). The second sample was collected from a national probability sample of 3494 urban Israelis in 1985, in home interviews. One-year incidence of falls was estimated from both samples at 23-24% for those over 65. Data from both samples showed that recent falls are negatively associated with subjective health rating. In Kiryat Ono, falls interacted with reported chronic conditions, so that the effect of a fall on subjective health status was only apparent in those with few chronic conditions. Among those who reported 4 or more chronic conditions, the occurrence of a fall had no independent effect on subjective health rating. In multivariate analyses of the national data, falls, and particularly those that happened in the home, or that required a visit to the emergency room had a negative effect on subjective health rating, after adjustment for age, sex, education, mobility and visual impairments and use of sleeping pills.

Accidental Falls↗
PubMed1990

Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals.

We report that 11 human immunodeficiency virus 1 (HIV-1)-seropositive patients, including three AIDS patients, were able to generate a cellular immune response to the intradermal injection of low doses (2-10 micrograms) of recombinant interleukin 2 (rIL-2). A dose-dependent zone of induration appeared at the site of injection, peaked at 24 hr, and was accompanied by the local accumulation of T cells, monocytes, and Langerhans cells. Despite the reductions in the CD4+ T-cell counts in the peripheral blood of most patients, CD4+ T-cells could still be mobilized with rIL-2 injections into the skin. The total number of immigrant cells was equivalent to those in HIV-1-seronegative patients, although the CD4+/CD8+ ratio of the dermal population was reduced. In response to rIL-2, major histocompatibility complex (MHC) class II antigen was expressed on the surface of keratinocytes, Langerhans cells, lymphocytes, and macrophages. In addition, the gamma interferon (IFN-gamma)-induced protein IP-10 rapidly appeared in dermal inflammatory cells and keratinocytes. A majority of HIV-1-seropositive patients demonstrated low or absent responses to common skin-test antigens. Those with positive zones of induration were often defective in the cellular expression of the IFN-gamma-induced MHC class II antigen. The simultaneous administration of rIL-2 and soluble antigen at widely separated cutaneous sites led to an enhancement of skin-test antigen reactivity in seropositive patients. The results suggest that local administration of rIL-2 to seropositive patients may act systemically, stimulating cellular immunity to recall antigens, and thus may be of potential benefit in the defense against opportunistic pathogens encountered in HIV-1 infection.

Antigens, CD↗
PubMed1990

Suppression of T-cell proliferation by Mycobacterium leprae and its products: the role of lipopolysaccharide.

Addition of soluble molecules obtained from sonicated Mycobacterium leprae markedly suppressed the proliferative response to the mitogen anti-CD3 of peripheral blood mononuclear cells and isolated T cells. Suppression was nonspecific and occurred with cells from lepromatous and tuberculoid leprosy patients as well as control donors. The purified lipoarabinomannans from M. leprae and Mycobacterium tuberculosis had a similar spectrum of inhibition whereas their deacylated derivatives were without effect. All mycobacterial preparations of either a crude or purified state, which suppressed cellular responses, contained appreciable quantities of bacterial lipopolysaccharide by the Limulus amebocyte assay. Contamination with lipopolysaccharide could account for the extent and nonselectivity of the T-cell suppression. Suppression was also monocyte-dependent and in part due to the release of arachidonate metabolites of the cyclooxygenase pathway.

Antibodies, Monoclonal↗
PubMed1990

Administration of recombinant interleukin-2 reduces the local parasite load of patients with disseminated cutaneous leishmaniasis.

Three patients with disseminated cutaneous leishmaniasis received three intranodular injections of 10 micrograms of recombinant interleukin 2 (rIL-2) at 48-h intervals. After 7 and 14 days, 4-mm punch biopsies were taken of control and injected nodules and processed for histology, electron microscopy, immunocytochemistry, and parasite culture. Control sites exhibited loose infiltrates of parasitized macrophages and T cells predominantly of the CD8+ phenotype. Amastigotes were present in large numbers and were found distributed within tightly apposed endosomes and larger vacuoles. After the administration of rIL-2, there was a prominent influx of T cells, predominantly of the CD4+ phenotype, and an increased number of plasma cells. At 7 days, leishmanial amastigotes were present in either the same or somewhat reduced numbers but predominantly within large, lucent vacuoles. By 14 days the number of amastigotes was strikingly lower. Lymphokine-treated skin sites became sterile in two patients, as evaluated by parasite culture after rIL-2 injection. The results suggest that the local administration of rIL-2 induces a beneficial enhancement of the cellular immunity with a consequent disposal of parasites in the cutaneous site.

Adolescent↗
PubMed1990

Intradermal recombinant interleukin 2 enhances peripheral blood T-cell responses to mitogen and antigens in patients with lepromatous leprosy.

Thirty-one patients with lepromatous leprosy received recombinant interleukin 2 (IL-2) intradermally in doses ranging from 10 to 30 micrograms. Before injection and at time intervals of 2-21 days thereafter, samples of peripheral blood mononuclear cells (PBMC) were obtained. Single or multiple injections (1-3) of IL-2 did not modify the total number of circulating lymphocytes or the number of T cells and the CD4/CD8 T-cell ratio. However, IL-2 had a pronounced influence on the [3H]thymidine incorporation in response to various stimuli 4-8 days after intradermal IL-2. Stimulation indices of three- to sevenfold above pre-IL-2 levels were observed with the polyclonal activator phytohaemagglutinin (PHA) and enhanced thymidine incorporation occurred in the presence of antigens to which the patients were already sensitized, such as purified protein derivative and BCG. IL-2 had no effect on the unresponsive state of lepromatous leprosy patient T cells to the antigens of Mycobacterium leprae.

Administration, Cutaneous↗
PubMed1990

Neutralization of poliovirus by cell receptors expressed in insect cells.

To examine the interaction of the poliovirus receptor (PVR) with virus and the role of the PVR in virus entry, the PVR was expressed in insect cells. Poliovirus bound to insect cells infected with a recombinant baculovirus (AcPVR) carrying cDNA encoding the PVR. Antibodies raised against PVR expressed in bacteria immunoprecipitated a 67-kilodalton polypeptide from cytoplasmic extracts of AcPVR-infected cells. Treatment of AcPVR-infected cells with tunicamycin revealed that the PVR is a glycoprotein containing N-glycosidic linkages and that carbohydrate accounts for nearly 50% of its molecular weight as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When PVR was solubilized from AcPVR-infected insect cells and incubated with poliovirus, viral infectivity was neutralized. Sedimentation analysis revealed that irreversibly altered 135S particles were formed after incubation of poliovirus at 37 degrees C with solubilized extracts of AcPVR-infected insect cells. These results demonstrate that poliovirus eclipse may result from interaction with the cell receptor at neutral pH in the absence of membranes and suggest that soluble receptors may be effective antiviral agents against picornaviruses.

Animals↗
PubMed1990

Heterogeneous expression of poliovirus receptor-related proteins in human cells and tissues.

Portions of the cellular receptor for poliovirus were expressed in Escherichia coli as fusion proteins with the product of the trpE gene. One of two antireceptor antisera obtained by immunizing rabbits with the fusion proteins blocked poliovirus infection. Western immunoblot analyses demonstrated that poliovirus receptor-related proteins were expressed in HeLa cells and a variety of human tissues, including those that are not sites of poliovirus replication. Tissue-specific variation in electrophoretic mobility, immunoreactivity, and subunit arrangement of poliovirus receptor-related proteins was observed. These results demonstrate that poliovirus tissue tropism cannot be explained by a limited distribution of receptor polypeptide, but may be the result of alternative splicing, posttranslational modifications, or both. In addition, the widespread but heterogeneous expression of the receptor suggests that the protein may have an important endogenous function.

Blotting, Western↗
PubMed1989

Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.

Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.

Esterases↗
PubMed1989

[Inflammatory arthropathies in patients with human immunodeficiency virus infection].

Articular manifestations were observed in 10 patients (8 men, 2 women, aged from 23 to 46 years) with human immunodeficiency virus (HIV) infection. All men were homosexuals, except for an intravenous drug addict. One woman was a native of Gabon and the other had multiple transfusions. The joint diseases were of the polyarthritis and acute oligoarthritis types, affecting mainly the knees and ankles but also the wrist and fingers; the spine was involved in one case. The synovial fluid present in 4 patients contained 5,000 to 27,000 cells per cubic millimeter, with a strong predominance of polymorphonuclears. In 3 cases, infective viral particles were found in the fluid with anti-HIV antibodies. In 2 patients biopsy of the synovial membrane provided evidence of non-specific subacute synovitis. All X-ray films, including those of the sacro-iliac joint, were and remained normal. The course of the joint disease was acute and regressive in 5 cases, chronic and prolonged in the remaining 5 cases. In 5 patients the arthropathies were the first clinical manifestations of the HIV infection. Three patients who had stage IV C AIDS died; the others were in stages II (5), III (1) or IV E (1) and did not progress to a more severe stage. This study shows that various types of inflammatory arthritis may occur in HIV positive patients. In most cases the arthritis is reactive, but certain data suggest that it may be directly related to the virus in some patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2.

Human rIL-2 (10-30 micrograms) was injected intradermally into the skin of patients with lepromatous leprosy with high bacillary loads. All patients responded to the lymphokine with local areas of induration that peaked at 24 h and persisted for 4-7 d irrespective of whether the site was "normal skin" or a nodular lesion. Within 24 h there was an extensive emigration of T cells and monocytes into the site. The percentage of the dermis infiltrated by mononuclear cells increased by more than sevenfold, peaking at 4 d and persisting for greater than 15 d. Both CD4+ and CD8+ T cells entered the site. T cells of CD4+ phenotype predominated at 2-7 d but by 11 d, CD8+ cells were predominant. Considerable numbers of T6+ Langerhans' cells appeared in the dermis by 72 h and persisted for 3 wk. By 4 d the thickness of the overlying epidermis had increased twofold, and keratinocytes were expressing MHC class II antigen and the IFN-gamma-induced peptide IP-10. Starting at 48 h, there was an extensive destruction of mononuclear phagocytes that contained structurally intact or fragmented M. leprae observed at the electron microscope level. The organisms, either free or contained within endocytic vacuoles, were discharged into the extracellular space and then reingested by blood-borne monocytes. This was followed by marked reductions in the number of acid-fast organisms in the injected site, evident as early as 4-7 d and more marked at 2-3 wk after injection. 13 of 15 patients exhibited a disposal of acid-fast bacilli ranging from 5- to 1,000-fold with a mean value of approximately 100-fold. The administration of IL-2 leads to the generation of an effective cell-mediated immune response, recapitulating an antigen-driven event and leading to striking local reductions in M. leprae. In comparison with the purified protein derivative of tuberculin reaction, bacilli are cleared more promptly, although emigratory cells persist for a shorter time.

Adult↗
PubMed1989

The generation of antigen-specific, major histocompatibility complex-restricted cytotoxic T lymphocytes of the CD4+ phenotype. Enhancement by the cutaneous administration of interleukin 2.

We have examined an in vitro system in which PBMC from purified protein derivative (PPD)-sensitized patients generate CTL after in vitro activation with antigen. These cells selectively destroy mycobacterial antigen PPD-pulsed monocyte targets. These CTL are of the CD4+ phenotype and exhibit MHC class II restriction. After exposure to antigen these cells require 5-7 d for maximal development, whereas, a separate antigen-independent population is generated within 3-4 d. CD8+ cells are poorly, if not at all, cytotoxic under similar conditions. Cells with properties of the NK and LAK lineage are also present in these cultures and kill other specific targets. Human rIL-2 was injected into the skin of lepromatous patients at 10-micrograms doses, given at 48-h intervals, for three doses. Peripheral blood cells obtained 8-14 d after the initiation of IL-2 injection demonstrated enhanced antigen-dependent destruction of monocyte targets. The efficacy of antigen-dependent and -independent populations and their amplification by IL-2-dependent mechanisms is discussed in terms of the local destruction of parasitized macrophages and the subsequent disposal of M. leprae.

Antigens, Bacterial↗
PubMed1989

The consequences of current constraints on surgical treatment of appendicitis.

In this study, we sought to identify changes in the picture of a selected surgical condition during an interval of time that has brought about radical departures from previously established policies and programs. As a direct consequence, the patients take a more circuitous route to the surgeon. A significant number of patients with acute appendicitis in 1986 (37 percent) and 1987 (29 percent) suffered a prolonged delay in hospitalization or surgical referral compared with patients in 1980. This delay was accompanied by a more advanced stage of disease that ultimately caused a markedly increased morbidity (13 percent in 1986 and 24 percent in 1987, compared with 5 percent in 1980) and subsequent extended length of stay. This deterioration in patient care and failure at cost containment had previously been examined for conditions that can be operated electively. This study documents that the constraints also affect the treatment of patients whose initial condition requires urgent operative treatment. With specific relation to patients with acute appendicitis, surgeons recognize the value of the negative appendectomy. It appears the so-called gatekeepers must find a way to accept a certain negative hospitalization to referral rate. If current constraints will not allow this, the policies and programs behind the constraints should be changed.

Acute Disease↗
PubMed1989

Influence of Mycobacterium leprae and its soluble products on the cutaneous responsiveness of leprosy patients to antigen and recombinant interleukin 2.

Experiments were carried out in the skin of patients with leprosy to examine whether suppressor cell populations either exist in the skin of multibacillary lepromatous leprosy patients, can be activated with antigen, or are induced to emigrate into a cutaneous site from the circulation. For this purpose, purified protein derivative of tuberculin, a delayed-type antigen that generates a cell-mediated immune response, was introduced into the skin alone or with nonviable Mycobacterium leprae bacilli. Areas of induration and the resulting numbers and phenotypes of emigratory cells were not influenced by M. leprae and its products. Further studies examined the ability of M. leprae and its soluble products to modify the cutaneous response to intradermal injection of recombinant interleukin 2 (IL-2), a lymphokine that mimics a cell-mediated response. Neither the simultaneous injection of M. leprae and IL-2, nor the prior injection of M. leprae followed in 2 days by IL-2, nor the prior administration of IL-2 followed in 4 days by M. leprae, into the same skin site, modified the zone of induration generated by IL-2. In addition, the immunocytochemical and histopathological evaluation of biopsy specimens of skin sites showed no difference between sites injected with IL-2 and sites injected with IL-2 and M. leprae. We conclude that suppressor T cells, if they exist, do not influence the gross or microscopic responsiveness of a cell-mediated skin reaction to antigen and IL-2. IL-2 did, however, enhance the responsiveness of skin-test-positive tuberculoid patients and family contacts to M. leprae antigens by a synergistic effect on the zone of induration and local cell accumulation.

Adolescent↗
PubMed1989

Effect of multiple interferon gamma injections on the disposal of Mycobacterium leprae.

The effect of multiple intradermal injections (four to six) of 10 micrograms of interferon gamma on the number of Mycobacterium leprae in the skin of patients with polar lepromatous leprosy and borderline lepromatous leprosy was evaluated. To achieve a maximum zone of induration and cell emigration a preparatory dose of the lymphokine was required. A second group of three injections, given 3-4 days after the initial series, resulted in lesser degrees of induration and was more in keeping with a partial local hyporesponsive state. A marked emigration of T cells and monocytes into the dermis resulted from injections of interferon gamma and persisted for greater than 21 days. A preponderance of CD4+ cells in the infiltrate was seen within a few days and CD4/CD8 ratios remained elevated for greater than 5 weeks. The bacillary load of injected sites evaluated 21 days after lymphokine administration was reduced in 14/17 patients by factors ranging from 5- to 1000-fold. This occurred predominantly within diffuse lesions and occurred rarely in nodular sites. Biopsy samples of injected sites taken 6 months later demonstrated progressive 10-fold reductions in bacilli and the continued presence of a granulomatous response.

Administration, Topical↗
PubMed1989

Subtypes of suicidal and assaultive behaviors in adolescent psychiatric inpatients: a research note.

Among 129 adolescent psychiatric inpatients, four subgroups of suicidal and/or assaultive behaviors were identified. A suicidal-only subgroup with no evidence of assaultive behavior was characterized by depression, drug abuse and environmental stresses. An assaultive-only subgroup with no evidence of suicidal behavior exhibited aggressive symptoms and violence at home. A subgroup with both suicidal and assaultive behaviors experienced accidents and family violence. A fourth subgroup had neither suicidal nor assaultive behavior. This subgroup showed eating disorders, depression, minimal assaultiveness and few peer friendships.

Adolescent↗