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Biomedical subjects

G Kaplan

Publications and source records attributed to G Kaplan.

At least 109 records · Page 6Linked to original sources
PubMed1997

Sequestration of Mycobacterium tuberculosis in tight vacuoles in vivo in lung macrophages of mice infected by the respiratory route.

Following aerosol infection of mice with Mycobacterium tuberculosis, single mycobacteria or pairs of bacilli were observed within individual phagocytic vacuoles bound by tightly apposed vacuolar membranes. The virulent organism was not observed free in the cytoplasm of the parasitized cells or in the extracellular space of the lung granulomata. This study indicates that in vivo, virulent mycobacteria survive and probably replicate within a unique tight vacuole in the infected phagocyte within the lung.

Administration, Inhalation↗
PubMed1997

Mycobacterial growth and sensitivity to H2O2 killing in human monocytes in vitro.

The intracellular growth and susceptibilities to killing by H2O2 in cultured human monocytes of a number of mycobacterial species including laboratory strains and clinical isolates of Mycobacterium tuberculosis, and Mycobacterium bovis bacillus Calmette-Guerin (BCG) and a clinical isolate of Mycobacterium avium-M. intracellulare were examined. The clinical isolate of M. avium-M. intracellulare did not replicate in freshly explanted monocytes (generation time of >400 h); BCG replicated with a generation time of 95 h, and M. tuberculosis strains CDC551, H37Rv, and H37Ra replicated with generation times of 24, 35, and 37 h, respectively, during the 4-day growth assay. When cultured in monocytes for 4 days, the mycobacteria were variably sensitive to H2O2-induced killing. A positive correlation between the generation time and percent killing of intracellular bacilli was observed. By comparison, mycobacterial strains were similarly sensitive to H2O2 treatment in cell-free culture media and in sonicated cell suspensions. Using a number of inhibitors of reactive oxygen intermediates we determined that other than catalase the inhibitors tested did not affect H2O2-induced killing of intracellular mycobacteria. Our studies suggest that the killing of mycobacteria growing in human monocytes in vitro by the addition of exogenous H2O2 is dependent on the susceptibility to a peroxide-induced killing pathway as well as on the intracellular growth rate of the mycobacteria.

Antioxidants↗
PubMed1997

Thalidomide protects mice against LPS-induced shock.

Thalidomide has been shown to selectively inhibit TNF-alpha production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-alpha has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-alpha and other cytokines and on animal survival. After injection of 100-350 micrograms LPS into mice, cytokines including TNF-alpha, IL-6, IL-10, IL-1 beta, GM-CSF and IFN-gamma were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-alpha levels were reduced by 93%, in a dose-dependent manner, and TNF-alpha mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1 beta, or IFN-gamma. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 micrograms to 300 micrograms in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.

Animals↗
PubMed1997

Height and social class in male adolescents from different ethnic backgrounds in Israel.

The relationship between height and social class, independent of the effect of ethnic background was examined. This is a population-based study of 17-year-old israeli-born Jewish males born between 1966-1969 who underwent routine physical examination prior to army recruitment. Inductees descending from 9 ethnic backgrounds-Germany, Hungary, India, Morocco, Poland, Romania, Russia, Yemen and at least 3rd-generation israeli-born were used for this analysis. Anthropometric data was abstracted from the computerized induction examination; socioeconomic status (SES) was assigned according to the residence of each recruit. Statistical analysis included analysis of variance and chi square test for linear trend. Mean height of the total (reference) group was 173.7 cm, ranging from 172.0 cm in the lowest SES level to 175.1 cm in the highest level. The proportion of individuals above the 85th percentile of height of the reference group, increased linearly from 8.7% (lowest SES) to 18.5% (highest SES) (p < 0.01). The mean height of recruits differed considerably among ethnic groups in each SES level and ranged from 170.8 cm (Yemenites) to 175.4 cm (Russian and Romanian) in the total group. In each ethnic group, height differences between extreme levels of SES were observed ranging from 2.3 cm (Morocco) to 4.3 cm (Russia). We conclude that height among 17-year old israeli-born males is positively associated with SES after controlling for ethnicity.

Adolescent↗
PubMed1996

Fetal pharyngeal distention--is it a normal component of fetal swallowing?

Fetal swallowing is one of the main mechanisms of amniotic fluid circulation. Swallowing mechanisms were studied in 34 healthy fetuses using modern ultrasound technology. The fetal lips and mouth, as well as tongue, pharynx, larynx, trachea and esophagus were surveyed in serial sagittal planes. Fetal swallowing movements were recorded and subsequently analyzed from the videotapes. All neonates were born at term in a satisfactory condition. Twenty-nine infants were breastfed, and five were bottle fed. No feeding problems were reported in these neonates. In 85% of fetuses, swallowing activity started with suckling movements followed by wide opening of the mouth. Next, low frequency tongue movements propelled the fluid bolus into the hypopharynx. In 15% of fetuses, this activity was associated with prolonged pharyngeal dilatation. Prolonged pharyngeal dilatation does not signify fetal neurological compromise as judged by good neonatal outcome and probably represents a normal variant of fetal swallowing.

Amniotic Fluid↗
PubMed1996

Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus.

Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes. Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV. Expression cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAVcr-1). Immunofluorescence analysis indicated that mouse Ltk- cells transfected with HAVcr-1 cDNA gained limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4. Our results demonstrate that the HAVcr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection. This report constitutes the first identification of a cellular receptor for HAV.

Amino Acid Sequence↗
PubMed1996

Plasma cytokines, cytokine antagonists, and disease progression in African women infected with HIV-1.

OBJECTIVES: To examine the relation of circulating cytokines and cytokine antagonists to the progression of human immunodeficiency virus type 1 (HIV-1) disease. DESIGN: Cross-sectional analysis. SETTING: An ambulatory acquired immunodeficiency syndrome (AIDS) research clinic in Kinshasa, Zaire. PATIENTS: 48 women with AIDS, 51 women with HIV infection who were clinically asymptomatic, and 11 female controls who did not have HIV infection, all from Zaire. MEASUREMENTS: Plasma levels of interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, interleukin-8, interferon-gamma, interleukin-1beta receptor antagonist (interleukin-1Ra), and TNF soluble receptor p55 (TNFsRp55) were assayed by specific radioimmunoassays. Plasma levels of interferon-gamma were assayed by commercial enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test was used to assess the significance of mean and median differences between groups. RESULTS: Of the 48 patients with AIDS, circulating interleukin-1beta was detected in 2, TNF-alpha in 4, interleukin-6 in 3, and interleukin-8 in 12. None of these factors were seen in any of the 11 controls. Median values of interleukin-1beta (320 pg/mL), TNF-alpha (210 pg/mL), and interleukin-8 (750 pg/mL) were elevated in HIV-infected asymptomatic patients compared with patients with AIDS (2-, 2.6-, and 18.7-fold higher, respectively; P < 0.001). Interleukin-1Ra and TNFsRp55 levels were substantially higher than interleukin-1beta and TNF-alpha levels in HIV-infected asymptomatic patients (73- and 14-fold, respectively) and were higher than those in patients with AIDS (17.8- and 1.74-fold, respectively). CONCLUSION: High circulating levels of the proinflammatory cytokines interleukin-1beta and TNF-alpha, combined with an excess of their natural inhibitors interleukin-1Ra and TNF-sRp55, were seen in clinically asymptomatic HIV-1-positive African women but not in African women with AIDS or in HIV-negative controls. Circulating cytokine antagonists may play a clinical role in modulating cytokine-associated symptoms in the early phases of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection.

Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-alpha both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patients with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine patients were randomly allocated to treatment with either thalidomide or placebo in a double-blind manner for 21 days. Thirty-two patients completed the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in both plasma TNF-alpha levels and HIV-1 levels. No significant reduction in either TNF-alpha or HIV- 1 levels was observed in patients with HIV-1 infection only. During the study period, patients receiving thalidomide treatment (n=16) showed a significant weight gain (mean +/- SEM: 6.5 +/- 1.2%; p<0.02) relative to placebo-treated patients (n=16). Patients with simultaneous HIV-1 and tuberculosis infections experienced a higher mean weight gain during thalidomide treatment than the group of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing weight gain and possibly reducing TNF-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.

Adult↗
PubMed1996

Relationship between morbidity and extreme values of body mass index in adolescents.

BACKGROUND: Although the association between overweight and cardiovascular risk factors is well documented in cross-sectional and longitudinal studies, reports of adolescent morbidity associated with underweight in industrialized countries are rare. METHODS: This population-based study includes approximately 110,000 17 year old Israeli Jewish males who underwent routine physical examination at army induction centres. Computerized data tapes include overall health profiles, specification of physical and mental conditions, and height and weight measurements. Medically significant conditions are those with sufficient severity to preclude service in a combat unit. RESULTS: Functional limitation is more prevalent at both extremes of the body mass index (BMI) distribution: 149.5/1000 among severely underweight individuals and 164.3/1000 among severely overweight subjects. Overweight was associated with hypertension (14.9/1000 among the severely overweight), as well as joint conditions of the lower extremities, mainly hip, ankle and knee disorders. Functional disorders associated with underweight are bronchial and lung conditions, including asthma (14.2 and 18.9/1000 in the mildly and severely underweight), scoliosis, intestinal conditions and emotional disorders (mainly neurosis). CONCLUSIONS: Both under- and overweight are associated with morbidity at age 17. Intervention programmes should begin at an early age.

Adolescent↗
PubMed1996

Comparable growth of virulent and avirulent Mycobacterium tuberculosis in human macrophages in vitro.

The relative virulence and avirulence of Mycobacterium tuberculosis strains H37Rv and H37Ra were previously defined using animal infection models. To investigate host species' specificity of mycobacterial virulence, growth of the 2 M. tuberculosis strains in human monocyte-derived macrophages in vitro was studied. Mycobacterial growth was evaluated by acid-fast staining, electron microscopy, and colony-forming units (cfu) assay. As expected, the 2 strains demonstrated significantly different growth rates in mouse macrophages in vitro (53 h for H37Rv, 370 h for H37Ra). In marked contrast, in human macrophages the average division times of the strains were nearly equal (80 h for H37Rv and 76 h for H37Ra by cfu measurement, and 96 h for H37Rv and 104 h for H37Ra by acid-fast staining). These findings indicate that observations of mycobacterial virulence in murine systems may not necessarily translate to the human system, in which different mechanisms to control mycobacterial growth may be expressed.

Animals↗
PubMed1996

Determination of cystic fibrosis carrier frequency for Zuni native Americans of New Mexico.

The Zuni native Americans of the Southwest have an incidence of cystic fibrosis of approximately one in 333 or seven and one-half times that found for Caucasians. Earlier studies indicated that dF508 was not among the cystic fibrosis mutations causing this disease. Through a collaborative study the R1162X mutation was found on 12 out of 12 cystic fibrosis chromosomes from six Zuni patients. Because of the relative high incidence of cystic fibrosis, we undertook a study to determine the carrier frequency of the R1162X mutation among randomly sampled individuals. We found the carrier frequency in the general population for the R1162X to be 6.7%, a very significant number when compared with the carrier frequency for all cystic fibrosis mutations in the Caucasian population of approximately 4%.

Adult↗
PubMed1996

Nonadherent cultures of human monocytes kill Mycobacterium smegmatis, but adherent cultures do not.

Human peripheral blood monocytes are permissive for the growth of Mycobacterium tuberculosis, but the fate of nonpathogenic Mycobacterium smegmatis in these cells is not known. Since M. smegmatis may be used as a host with which to express and screen for M. tuberculosis genes needed for survival in monocytes, we determined whether human peripheral blood monocytes could restrict the growth of Mycobacterium smegmatis. Adherent human peripheral blood monocytes were permissive for the growth of M. smegmatis, as measured by ex vivo [3H]uracil uptake. However, human peripheral blood monocytes which were cultured nonadherently in Teflon wells were able to restrict the growth of M. smegmatis while remaining permissive for the growth of M. tuberculosis H37Ra. The loss of viability of M. smegmatis in nonadherent cells was correlated with an increase in nonspacious phagocytic vacuoles. The killing of M. smegmatis was not blocked by NG-monomethyl-L-arginine, suggesting that it was not due to the production of reactive nitrogen intermediates. Incubation of the monocytes for 1 to 7 days before infection had no effect on the fate of M. smegmatis, suggesting that adherence versus nonadherence, and not differentiation, was the key determinant for the difference in functional ability. Nonadherent human peripheral blood monocytes may be a more appropriate model than adherent cells for the study of factors employed by bacterial to survive within monocytes and for selection screening of bacterial genes needed for intracellular survival.

Blood Bactericidal Activity↗
PubMed1996

H2O2 induces monocyte apoptosis and reduces viability of Mycobacterium avium-M. intracellulare within cultured human monocytes.

Mycobacterium avium-M. intracellulare, an intracellular parasite of mononuclear phagocytes, rarely causes disease in immunocompetent individuals. In contrast, in human immunodeficiency virus type 1-infected patients, M. avium-M. intracellulare can infect almost every tissue and organ. This suggests that immunocompetent individuals have a protective mechanism to control or prevent the infection. How mycobacterial may be killed by the host immune response is unclear. We have recently reported that induction of apoptosis of Mycobacterium bovis BCG-infected macrophages with ATP4- was associated with killing of the intracellular mycobacteria. In the present study, a long-term culture of M. avium-M. intracellulare-infected monocytes was used to further evaluate the interaction between M. avium-M. intracellulare and primary human monocytes. In our system, M. avium-M. intracellulare parasitized the human monocytes and appeared to replicate slowly over 14 days within the host cells. To examine the role of apoptotic mechanisms in survival or death of intracellular mycobacteria, M. avium-M. intracellulare-infected human monocytes were treated with a monoclonal antibody to Fas receptor (APO-1/CD95) or with various concentrations of H2O2. Although both of these exogenous agents induced monocyte apoptosis, optimal killing (65% reduction in CFU) of intracellular M. avium-M. intracellulare was observed only when M. avium-M. intracellulare-infected cells were treated with 10 mM H2O2. Fas-induced apoptosis did not affect M. avium-M. intracellulare viability. Our results suggest that not all stimuli of monocyte apoptosis induce killing of intracellular M. avium-M. intracellulare. Since release of H2O2 following phagocytosis of mycobacteria has been documented, H2O2-induced apoptotic death of M. avium-M. intracellulare-infected monocytes and its association with killing of the intracellular bacilli may be a physiological mechanism of host defense against M. avium-M. intracellulare.

Acquired Immunodeficiency Syndrome↗