Detection of HTLV-II in breastmilk of HTLV-II infected mothers.
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Breast Feeding↗
Biomedical subjects
J E Kaplan
Publications and source records attributed to J E Kaplan.
Isolation of an amino-terminal fibronectin-binding protein on human U937 cells and rat peritoneal macrophages.
Several cell-mediated activities for the amino terminus of fibronectin have been documented. In the present study we describe a macrophage surface protein with binding activity directed to the amino terminus of the fibronectin molecule. The binding of a 29-kDa amino-terminal fibronectin fragment to macrophages reached steady state by 30 min and was half-maximal at approximately 2 x 10(-8) M. This binding was specifically inhibited by excess unlabeled 29-kDa fragment or intact fibronectin but not by a 180-kDa fibronectin fragment which lacks the amino terminus. Competitive binding studies of the 70-kDa amino-terminal fibronectin fragment to macrophages revealed a single binding site with KD = 7.14 x 10(-8) M and approximately 8 x 10(4) binding sites/cell. Radiolabeled surface proteins extracted from rat peritoneal macrophages and from the human U937 cell line were applied to an affinity column comprised of the 70-kDa amino-terminal fragment of fibronectin coupled to a solid support. A single trypsin-sensitive radiolabeled protein of 67 kDa, from either cell type, was eluted from this column with urea. This protein showed no immunologic identity with fibronectin, fibrin(ogen), or albumin. The 67-kDa protein exhibited identical apparent molecular weight under reducing and nonreducing conditions, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. We have localized the fibronectin binding activity of this protein to within the 29-kDa amino-terminal domain of fibronectin. The 67-kDa protein eluted from the 70-kDa column failed to bind to a column comprised of the 45-kDa gelatin-binding fragment of fibronectin. Additionally, the 67-kDa protein was specifically eluted from the 70-kDa column by the 29-kDa amino-terminal fragment but not by the 45-kDa gelatin-binding fragment. These data suggest that this 67-kDa protein is a macrophage cell surface binding protein for the amino terminus of fibronectin.
Albumins↗
Seroprevalence of HTLV-1 and HTLV-2 among intravenous drug users and persons in clinics for sexually transmitted diseases.
UNLABELLED: Background. The human T-cell lymphotropic virus Type I (HTLV-I) is associated with adult T-cell leukemia and myelopathy, whereas HTLV-II infection has uncertain clinical consequences. We assessed the seroprevalence of these retroviruses among intravenous drug users and among patients seen at clinics for sexually transmitted diseases (STD clinics). METHODS: We used serum samples that were collected in eight cities in 1988 and 1989 during surveys of human immunodeficiency virus infection among intravenous drug users entering treatment and persons seen in STD clinics. The serum samples were tested for antibodies to HTLV, and positive specimens were tested further by a synthetic peptide-based enzyme-linked immunosorbent assay to differentiate between HTLV-I and HTLV-II. RESULTS: Among 3217 intravenous drug users in 29-drug-treatment centers, the median seroprevalence rates of HTLV varied widely according to city (range, 0.4 percent in Atlanta to 17.6 percent in Los Angeles). Seroprevalence increased sharply with age, to 32 percent in persons over 44 years of age. HTLV infection was more common among blacks (15.5 percent) and Hispanics (10.7 percent) than among whites (4.1 percent), and it was strongly associated with a history of heroin injection (P less than or equal to 0.001). Among 5264 patients in 24 STD clinics, the median rates of HTLV infection were much lower (range, 0.1 percent in Atlanta and Newark to 2.0 percent in Los Angeles). Again, this infection was more common among intravenous drug users (7.6 percent) than among non-drug users (0.7 percent). Eighty-four percent of the seropositive samples from drug-treatment centers and 69 percent of those from STD clinics were due to HTLV-II infection (P = 0.03). CONCLUSIONS: HTLV infections are common among intravenous drug users and are primarily caused by HTLV-II. Among patients seen at STD clinics, HTLV is strongly associated with intravenous drug use, but the retrovirus is also prevalent among non-drug users.
Adult↗
Identification of immunodominant epitopes in envelope glycoprotein of human T lymphotropic virus type II.
A series of synthetic peptides derived from the envelope glycoprotein of human T lymphotropic virus type II (HTLV-II) was used in an enzyme immunoassay to determine the immunodominant epitopes of envelope glycoprotein. Of the 11 synthetic peptides spanning the external glycoprotein of HTLV-II (gp52) and the 3 from the transmembrane protein (gp21), 3 peptides from gp52 (termed Env-20(85-102), Env-202(173-209), and Env-203(219-256] reacted with most of the polymerase chain reaction-confirmed HTLV-II specimens (83, 95, and 76%, respectively); all other peptides reacted minimally with these specimens. Env-202(173-209) reacted with a greater percentage (91 to 100%) of specimens from different risk groups, including intravenous drug users (n = 30), North American Indians (n = 13), Guaymi Indians from Panama (n = 22), and routine U.S. blood donors (n = 34), when compared with Env-20(85-102) (73 to 100%) or Env-203(219-256) (68 to 83%). Furthermore, Env-20(85-102) and Env-202(173-209) had some reactivity (8-25%) with sera from HTLV-I-infected individuals, whereas Env-203(219-256) reacted with 58% of HTLV-I specimens. We conclude that peptides Env-20(85-102) and Env-202(173-209) represent the type-specific immunodominant epitopes of HTLV-II external glycoprotein.
Amino Acid Sequence↗
Thrombin induces platelet adhesion to endothelial cells.
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Animals↗
Low risk of mother-to-child transmission of human T lymphotropic virus type II in non-breast-fed infants. The NYC Perinatal HIV Transmission Collaborative Study.
The transmissibility of human T lymphotropic virus (HTLV) type II from mother to child was investigated. Of 236 women enrolled during pregnancy in a study of mother-to-child transmission of human immunodeficiency virus in 1986-1988, 21 (8.9%) were seropositive for HTLV-I/II. All 21 mothers were infected with HTLV-II by synthetic peptide testing and polymerase chain reaction (PCR). HTLV-II-infected women were older (median age, 34 vs. 28 years), more likely to be black (70% vs. 38%), and more likely to report past or current intravenous drug use (85% vs. 56%) than HTLV-II-uninfected women. Of 20 non-breast-fed infants born to 19 of these HTLV-II-infected women, none had detectable HTLV-II by PCR done on peripheral blood mononuclear cells obtained at birth to 36 months of age. Serologic testing of these infants revealed gradual disappearance of HTLV-I/II antibody. While this study does not rule out the possibility of perinatal HTLV-II transmission, the data suggest that it occurs rarely in the absence of breast-feeding.
Adult↗
HIV risk factors in three geographic strata of rural Rakai District, Uganda.
OBJECTIVES: To examine risk factors for HIV-1 infection in three geographic strata (main road trading centers that service local and international traffic, small trading villages on secondary dirt roads that serve as foci for local communications, and agricultural villages off main and secondary roads) in Rakai District, Uganda. DESIGN AND METHODS: Serological, sociodemographic, knowledge/behaviors and health survey conducted in 21 randomly selected community clusters; complete data were collected for 1292 consenting adults. RESULTS: Fifteen per cent of the men and 24% of the women were HIV-1-positive. On univariate analysis, several sociodemographic and behavioral factors were significantly associated with risk of HIV infection, including age, place of residence, travel, occupation, marital status, number of sex partners, sex for money or gifts, history of sexually transmitted disease (STD), and history of injections. On multivariate analysis, age, residence and number of sex partners remained significantly associated with HIV infection in both sexes; a history of STD and not having been circumcised were significant in men. There was a significant interaction between place of residence and reported number of sex partners: for any given level of sexual activity, the risk of HIV infection was markedly increased if the background community prevalence was high. CONCLUSION: Sexual transmission appears to be the primary behavioral risk factor for infection, but the risks associated with this factor vary substantially between the three geographic strata. These data can be used to design targeted interventions.
Adolescent↗
Sensitive and specific polymerase chain reaction assays for diagnosis of human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II infections in HTLV-I/II-seropositive individuals.
To confirm and differentiate between human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II infections, we analyzed by polymerase chain reaction (PCR) samples of peripheral blood lymphocytes from 98 individuals seropositive for HTLV-I/II using pol (SK110/111) and tax (SK43/44) consensus primer pairs. A total of 96 samples (97.9%) were positive by the tax generic probe, while 95 were typed by the HTLV-I and HTLV-II pol probes. The three pol-negative samples were successfully amplified and typed by nested PCR with primers internal to SK110 and SK111. Results of PCR with a lysate of leukocyte nuclei obtained by whole blood lysis were comparable to those obtained with peripheral blood lymphocytes from 16 HTLV-seropositive subjects.
Base Sequence↗
Role of adenosine in platelet-mediated reduction in pulmonary vascular permeability.
Previous studies have shown that platelets decrease 125I-labeled albumin permeability across confluent bovine pulmonary artery endothelial cell monolayers. In the current study, we addressed the role of platelets and platelet-derived adenosine (ADO) in vascular barrier function with cultured endothelial cells and isolated perfused lungs. Both 7 x 10(7) platelets/ml and conditioned media prepared from the same concentration of platelets reduced albumin permeability of endothelial monolayers by 37%. This activity was abolished by pretreatment of the platelets with adenosine deaminase (ADA). ADO (10(-7) M) added directly to the monolayer reduced permeability by 19%. Dipyridamole (10(-6) M), an inhibitor of facilitated ADO uptake, was used to evaluate the contribution of endothelial uptake of ADO in the platelet effect. Dipyridamole pretreatment of the endothelial monolayer did not alter the ability of platelets to decrease albumin permeability. Addition of either an A1- or A2-receptor-specific analogue of ADO to endothelial monolayers revealed that only the A1-analogue possessed permeability-decreasing activity. An isolated perfused guinea pig lung model was used to evaluate the effect of platelets on transvascular water flux as measured by the capillary filtration coefficient (Kf,c). Platelets (4.5 x 10(7) platelets/ml) added to the perfusate reduced Kf,c by 29%. Pretreatment of platelets with ADA abolished this response. The addition of ADO (10(-7) M) reduced Kf,c by 11%. Pulmonary vascular resistance was not changed by any intervention. Our results indicate that ADO is a component in platelet-mediated decreases both in albumin permeability across endothelial monolayers and of the capillary filtration coefficient in isolated perfused lungs.
Adenosine↗
Platelet cGMP, but not cAMP, inhibits thrombin-induced platelet adhesion to pulmonary vascular endothelium.
We have compared the effects of intracellular pathways initiated by nitric oxide and prostacyclin on thrombin-induced platelet adhesion to endothelial cells. Platelet aggregate adhesion was enhanced when endothelial monolayers were pretreated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, decreased platelet aggregate adhesion was seen when platelets were pretreated with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) or 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP). Single platelet adhesion in isolated perfused lungs under flow conditions in the presence of shear was also assessed. Pretreatment of platelets with either Iloprost, in a dose sufficient to decrease platelet aggregation, or 8-bromo-cAMP did not affect platelet adhesion. However, pretreatment of platelets with 8-bromo-cGMP significantly reduced single platelet adhesion to endothelium. These studies illustrate that nitric oxide inhibits platelet adhesion to endothelium in the presence of shear. They further indicate that prostacyclin is also a regulator of this response but has effects more specifically related to the inhibition of platelet aggregation than platelet-endothelium interactions.
8-Bromo Cyclic Adenosine Monophosphate↗
Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS.
Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400-499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance.
AIDS-Related Complex↗
Fibronectin dependent macrophage fibrin binding.
Plasma fibronectin has been shown to increase the binding of fibrin monomer to macrophages in vitro. In the present study we began characterization of the mechanism underlying this fibronectin activity. Fragments of fibronectin containing the amino terminus enhanced macrophage fibrin binding to the same extent as intact fibronectin on an equimolar basis. However, fibronectin fragments containing the gelatin-binding domain or the cell-binding domain, but lacking the amino terminus, had no effect on fibrin binding. Fibronectin enhanced fibrin binding was not affected by the addition of synthetic peptides containing the RGD adhesion sequence. The ability of fibronectin to augment fibrin binding remained after paraformaldehyde fixation of macrophage monolayers. Fixation did not alter the basal levels of fibrin binding by macrophages. Preincubation of macrophages with exogenous fibronectin did not increase the binding of fibrin. Fibronectin enhanced fibrin binding remained unaltered after the removal of endogenous cell surface fibronectin by capping with F(ab')2 fragments of antibodies to fibronectin. These results suggest that the amino terminus of fibronectin supports the attachment of fibrin to macrophages by an initial fluid-phase interaction that precedes cellular binding and does not require a cellular response.
Amino Acid Sequence↗
Effect of 13-hydroxyoctadeca-9,11-dienoic acid (13-HODE) on thrombin induced platelet adherence to endothelial cells in vitro.
The effect of exogenous 13-HODE on alpha-thrombin induced adherence of platelets to monolayers of cultured pulmonary artery endothelial cells was determined using homologous sheep cells. In a separate series of experiments, endogenous 13-HODE was demonstrated in sheep endothelial cells by reverse phase high pressure liquid chromatography. Levels of endogenous 13-HODE were decreased by alpha-thrombin preincubation. Exogenous 13-HODE (10 microM) reduced the augmented platelet adherence produced by coincubation of alpha-thrombin with platelets and endothelial monolayers, and eliminated the enhancement of platelet adherence produced by preincubation of alpha-thrombin with endothelial monolayers. 13-HODE also reduced the alpha-thrombin induced adherence of platelets to monolayers pretreated with aspirin and to fixed monolayers indicating a direct effect of 13-HODE as opposed to secondary effects mediated by the release of prostacyclin (PGI2) or endothelial derived relaxing factor (EDRF). Platelet adherence to subendothelial matrix was also reduced by 13-HODE. 13-HODE inhibited platelet aggregation initiated by 0.2 U/ml alpha-thrombin but did not affect aggregation initiated by 2.0 U/ml alpha-thrombin. These data provide evidence for the ability of exogenous 13-HODE to attenuate the interaction of thrombin activated platelets with endothelial cells as well as with other platelets.
Animals↗
HTLV-II endemicity among Guaymi Indians in Panama.
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HTLV-II Infections↗
Synthetic peptide-based immunoassays for distinguishing between human T-cell lymphotropic virus type I and type II infections in seropositive individuals.
Until now, serologic tests that distinguish the closely related human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) infections have not been available. Synthetic peptide assays, employing peptides derived from the core and envelope proteins of HTLV-I and HTLV-II (SynthEIA and Select-HTLV tests), were evaluated for the ability to serologically discriminate HTLV-I and HTLV-II infections. Of 32 HTLV-I- and 57 HTLV-II-positive serum specimens from individuals whose infections were confirmed by polymerase chain reaction, the SynthEIA test categorized 29 (91%) as HTLV-I and 50 (88%) as HTLV-II, and 10 (11%) were nontypeable. In contrast, the Select-HTLV test categorized 32 (100%) as HTLV-I and 55 (96%) as HTLV-II, and 2 (2%) were nontypeable. The specificity of both the assays in seropositive serum specimens was 100% in that none of the specimens were incorrectly classified. Additional serum specimens obtained from clinically diseased patients from the United States (n = 8) and asymptomatic carriers and patients from Japan (an endemic population for HTLV-I; n = 40) were categorized as HTLV-I by at least one of the assays, while serum specimens from Guaymi Indians from Panama (an endemic population for HTLV-II; n = 13) were categorized as HTLV-II. Thus, peptide enzyme immunoassays appear to represent a simple technique employing chemically synthesized antigens for discrimination between antibodies of HTLV-I and HTLV-II.
Antibodies, Viral↗
Evaluation of a recombinant human T-cell lymphotropic virus type I (HTLV-I) p21E antibody detection enzyme immunoassay as a supplementary test in HTLV-I/II antibody testing algorithms.
To evaluate the usefulness of a human T-cell lymphotropic virus type I (HTLV-I) recombinant p21E immunoassay as a supplementary test in HTLV-I/II serologic testing algorithms, we used this assay to test 378 serum samples previously categorized as positive, indeterminant, or negative for HTLV-I/II antibody, as defined by U.S. Public Health Service guidelines. We found this test to be highly sensitive for detecting antibody to HTLV-I/II env (99.4%) but slightly less specific (96.0%), particularly among samples from intravenous drug users. Our data suggest that this test is most appropriately used to confirm the absence of env antibody in samples which are repeatably reactive in an HTLV-I/II screening assay and gag reactive only by immunoblotting. Because of the high sensitivity of this recombinant p21E test, a negative result in this context could preclude radioimmunoprecipitation testing. However, pending further evaluation of the specificity of this assay, samples testing positive for p21 env antibody may require confirmation by radioimmunoprecipitation, particularly in situations in which the results will be used for diagnostic purposes or blood donor counseling.
Algorithms↗
Role of platelet-activating factor in mediating tumor necrosis factor alpha-induced pulmonary vasoconstriction and plasma-lymph protein transport.
We assessed the role of platelet-activating factor (PAF) in mediating the pulmonary hemodynamic and lymph flow responses to tumor necrosis factor-alpha (TNF alpha). The effects of the PAF receptor antagonist WEB 2086 on TNF alpha-induced pulmonary vasoconstriction and increased pulmonary transvascular plasma-lymph protein transport were examined. Control (n = 7) and WEB-2086-pretreated (n = 7) sheep prepared with chronic lung lymph fistulas were challenged with recombinant human TNF alpha (12 micrograms/kg over 0.5 h). Ex vivo challenge of platelet-rich plasma (PRP) with 10(-8) M PAF resulted in aggregation of platelets from control TNF-challenged sheep, but not of platelets from WEB-treated sheep similarly challenged with TNF. The control TNF-alpha-challenged sheep developed hemoconcentration, leukopenia, and neutropenia. TNF alpha resulted in increases in pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) within 15 min, and the values were sustained for the 5-h experiment duration. Pulmonary lymph flow (Qlym) and pulmonary transvascular protein clearance rate (Qlym x lymph-to-plasma protein concentration) were increased within 30 min and remained elevated for 5 h. The WEB-2086-treated sheep developed similar leukopenia and neutropenia after TNF alpha challenge, but the initial increases in Ppa and PVR were significantly reduced (p less than 0.05). However, WEB 2086 did not prevent the threefold increases in Qlym and transvascular protein clearance induced with TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Longitudinal evaluation of neuropsychological function in homosexual men with HIV infection: 18-month follow-up.
Subjects were 21 men with persistent generalized lymphadenopathy (PGL, n = 13) or AIDS-related complex (ARC, n = 8), who were not receiving anti-retroviral medication, and 21 controls. At baseline, mild cognitive impairment was detected in language, memory, attention, and visual and auditory processing, primarily in patients with ARC. On follow-up, the ARC group showed continued impairment and abnormalities on new measures of distractibility and activities of daily living. Although mild decline in verbal memory was noted for some patients, overall neuropsychological profiles did not show deterioration. Nomenclature for the pattern of mild, stable neuropsychological changes in patients with cognitive symptoms is discussed. Two interdisciplinary panels have recommended the term HIV-1-associated minor cognitive/motor disorder. Unlike the term AIDS dementia, it does not imply progression or a diagnosis of AIDS.
AIDS Dementia Complex↗