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Biomedical subjects

K K Sethi

Publications and source records attributed to K K Sethi.

At least 55 records · Page 3Linked to original sources

Analysis of Ia-antigen(s) positive macrophages in experimental murine toxoplasmosis.

The present study has demonstrated marked increase in the relative percentage of Ia-positive macrophages among the peritoneal macrophage population(s) of BALB/c mice infected intraperitoneally with Toxoplasma gondii or when chronically infected mice were rechallenged with Toxoplasma. The observed increase in Ia-positive peritoneal macrophage numbers coincided with the appearance of interferon-gamma (IFN-gamma) in the sera of infected mice. The appearance of elevated serum IFN-gamma titer was a temporary event but the increased percentage of Ia-positive macrophages persisted. The data presented have documented that antigen-specific proliferation response of vigorously purified Toxoplasma-sensitized T-cells is dependent upon Ia-bearing macrophages. This model is useful for future studies into various aspects of the interaction(s) between parasite antigens and Ia-antigen(s) at the macrophage surface for successful recognition of antigen-specific T-cells.

Animals↗

Sinus node function after autonomic blockade in normals and in sick sinus syndrome.

Electrophysiologic studies were performed in 10 normals and 33 patients with sick sinus syndrome before and after total autonomic blockade with propranolol and atropine. In normals both corrected sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) decreased significantly after autonomic blockade. In patients with sick sinus syndrome the corrected SNRT was abnormal (greater than 450 msec) in 16 (48.5%) cases before and 25 (76%) cases (greater than 285 msec) after autonomic ablation (P less than 0.02). Thirteen of 21 patients (62%) with normal intrinsic heart rate and all 12 cases with abnormally low intrinsic rate after autonomic blockade had abnormal corrected SNRT (greater than 285 msec). Mean SACT measured in 19 patients also shortened significantly following pharmacologic denervation. During control it was prolonged (greater than 226 msec) in 8 patients (44%). After autonomic blockade 2 of 13 patients with normal intrinsic heart rate and 3 of 6 with low intrinsic rate showed abnormal SACT (greater than 151 msec). The data suggest that the majority (76%) of patients with sick sinus syndrome have intrinsic abnormality of sinus node automaticity while in a minority (24%) disturbed autonomic regulation is the pathogenetic mechanism. Patients with normal intrinsic heart rate usually have normal intrinsic SACT, while a significant proportion of those with low intrinsic rate have abnormal perinodal conduction. Subjects with abnormal intrinsic heart rate have more severe disturbances of sinus node function than those with normal intrinsic rate.

Adolescent↗

Analysis of the roles of immune interferon (IFN-gamma) and colony-stimulating factor(s) in the induction of macrophage anti-toxoplasma activity.

Lymphokine-enriched, cell-free supernatants from specific antigen-stimulated spleen cells of toxoplasma-immune mice lacking detectable anti-toxoplasma antibody could generate effective anti-toxoplasma activity within normal (non-immune) murine peritoneal macrophages. Such supernatants also contained high levels of IFN-gamma as well as Ia-antigen(s) inducing activity. Supernatants from ConA stimulated normal (non-immune) spleen cells with high IFN-gamma, as well as CSF-containing supernatants from lung explants, lacked the capacity to induce anti-toxoplasma activity within peritoneal macrophages. ConA-stimulated spleen cell supernatants with high IFN-gamma titers but not CSF-enriched lung explant supernatants could induce the expression of macrophage cell surface Ia-antigen(s). Based on the results of our experiments, we have been able to eliminate the direct (by itself) role of IFN-gamma or CSF in generating macrophage anti-toxoplasma activity. However, the possibility that molecules like IFN-gamma or CSF synergize together with other immune spleen cell-derived factor(s) in the generation of effective macrophage anti-toxoplasma activity has not been ruled out.

Animals↗

Salutary effects of intravenous ajmaline in patients with paroxysmal supraventricular tachycardia mediated by dual atrioventricular nodal pathways: blockade of the retrograde fast pathway.

Electrophysiologic effects of 50 mg iv ajmaline were evaluated in 10 patients with atrioventricular nodal reentrant paroxysmal supraventricular tachycardia (PSVT) utilizing the slow pathway for antegrade and the fast pathway for retrograde conduction. Ajmaline terminated the PSVT in all 10 patients in 17 to 165 sec (mean 94 +/- 49 sec): by ventriculoatrial block in eight, AH block in one, and intra-atrial reentry in one patient. The predrug mean PSVT cycle length of 289 +/- 44 msec (range 240 to 350) increased significantly to 373.5 +/- 60 msec (range 263 to 464; p less than .01) before the tachycardia was terminated. The increase in cycle length was a function of both AH and HA prolongation. In all 10 patients ajmaline depressed conduction through the retrograde fast pathway, as evidenced by the increase in mean ventricular paced cycle length producing ventriculoatrial block from less than or equal to 280 +/- 40 to 438 +/- 93 msec (p less than .001), and the increase in the effective refractory period of the ventriculoatrial conduction system from less than or equal to 241 +/- 42 to less than or equal to 298 +/- 62 msec (p less than .05); the drug abolished ventriculoatrial conduction in four cases. The effective refractory period of the antegrade fast pathway was unchanged after ajmaline (less than or equal to 281 +/- 31 vs less than or equal to 275 +/- 38 msec; p = NS), but conduction through the antegrade slow pathway was depressed (atrial paced cycle length producing AH block 269 +/- 30 msec before and 312 +/- 44 msec after drug; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Contribution of macrophage arginase in the intrinsic restriction of herpes simplex virus replication in permissive macrophage cultures induced by gamma-interferon containing products of activated spleen cells.

Cultured peritoneal macrophages (PM) from adult mice of strain DBA/2 (but not C57BL/6) supported productive replication of HSV, as monitored by infectious virus yield and electron microscopy. In contrast, PM of DBA/2 origin, when pretreated with supernatants of Con A-stimulated spleen cells containing immune interferon (IFN-gamma) activity, manifested remarkable intrinsic restriction to HSV replication. The acquisition of this intrinsic restriction to virus replication correlated with the generation of appreciably elevated levels of arginase in supernate of treated PM. Addition of incremental doses of exogenous arginine in the culture medium led to the abrogation of induced restriction to HSV replication in DBA/2 PM, indicating the critical role of arginase in the phenomenon. Furthermore, anti-HSV activity of arginase levels released into the culture medium of IFN containing supernate-treated PM became apparent when assayed on PM, which were precultured in arginine-deficient medium for 24 hours before virus infection and exposure to arginase containing preparation. Taken together, these observations indicate that macrophage arginase can mediate intrinsic restriction to HSV replication in PM.

Animals↗

Protection of mice from fatal herpes simplex virus type 1 infection by adoptive transfer of cloned virus-specific and H-2-restricted cytotoxic T lymphocytes.

A cloned culture of secondary anti-herpes simplex virus (anti-HSV) cytotoxic T lymphocytes (CTL) generated in vitro when adoptively transferred to intact or cyclophosphamide (CP) pretreated syngeneic mice protected the recipients from death following intraperitoneal infection with HSV-1. This in vivo protective effect conferred by anti-HSV CTL was virus-specific and H-2K/D-restricted. Twenty-four h after HSV-1 infection of BALB/c mice (intact or CP-pretreated) relatively high levels of serum interferon-gamma were observed in the recipients of syngeneic anti-HSV CTL and this event may explain, at least in part, the CTL-mediated protective effect.

Animals↗

Effects of monoclonal antibodies directed against herpes simplex virus-specified glycoproteins on the generation of virus-specific and H-2-restricted cytotoxic T-lymphocytes.

Passive transfer of monoclonal antibodies specific for herpes simplex virus type 1 (HSV-1) glycoproteins gC or gD resulted in the generation of highly potent HSV-specific and H-2-restricted primary cytotoxic T-lymphocytes (CTL) in the lymph nodes of recipients provided they were injected at 12 h post-infection. When the same antibody was injected at 3 h before HSV infection, the recipients failed to generate primary anti-HSV CTL. Rather, lymph node cells from such donors proved unsuitable for the initiation in vitro of a secondary anti-HSV CTL response by restimulation.

Animals↗

Hybridoma-derived monoclonal immunoglobulin M antibodies to Legionella pneumophila serogroup 1 with diagnostic potential.

Mouse hybridomas were isolated by fusing P3-X63-Ag 8.653 myeloma cells with spleen cells from mice that had been repeatedly immunized with Legionella pneumophila serogroup 1 organisms. In one fusion, three independent hybridoma cultures which secreted antibodies that reacted with the immunizing strain in the indirect immunofluorescent-antibody test were selected for cloning. Representative continuously growing clones, one of each hybridoma, which remained stable in producing high-titer antibodies were examined in detail. Extensive specificity tests revealed that these hybridoma-derived monoclonal antibodies were specifically directed against L. pneumophila serogroup 1 organisms and showed no cross-reactions in the indirect immunofluorescent-antibody test either with the other known serogroups of L. pneumophila or with other unrelated bacterial species. The three monoclonal antibodies F4/CB5/K18, F/4CB5/K104, and F4/JD3.8/K101 belonged to the immunoglobulin M class and were capable of agglutinating serogroup 1 organisms of L. pneumophila exquisitely. These monoclonal antibodies against L. pneumophila with defined fine specificity should enable purification and subsequent analysis of the corresponding antigenic determinant(s) and can also be used for the preparation of unlimited supplies of standard diagnostic reagents for the identification of L. pneumophila in the tissues and body fluids.

Animals↗

Selective blockade of retrograde fast pathway by intravenous disopyramide in paroxysmal supraventricular tachycardia mediated by dual atrioventricular nodal pathways.

Electrophysiological effects of 2 to 2.5 mg/kg iv disopyramide were studied in 10 patients with dual nodal pathways who used a slow pathway for anterograde and a fast pathway for retrograde conduction during paroxysmal supraventricular tachycardia (mean cycle length 308.5 +/- 37 ms; range 260-370 ms). Disopyramide terminated the tachycardia in six cases by production of ventriculoatrial block in five and by sinus overdrive in one. In the remaining four patients cycle length of the paroxysmal supraventricular tachycardia increased significantly from 270 +/- 8 ms to 377.5 +/- 28 ms. In all 10 patients disopyramide depressed retrograde fast pathway conduction manifest by an increase in mean ventricular paced cycle length producing ventriculoatrial block from less than or equal to 296.5 +/- 25 ms to 358 +/- 60 ms, and increase in retrograde fast pathway effective refractory period from less than or equal to 246 +/- 34 ms to 325 +/- 36 ms; the drug abolished ventriculoatrial conduction in two cases. Anterograde slow pathway and fast pathway conduction properties were unchanged after disopyramide (atrial paced cycle length producing AH block 292 +/- 30 to 306.5 +/- 30 ms; effective refractory period of anterograde fast pathway less than or equal to 274 +/- 56 to 284 +/- 44 ms, before and after the drug, respectively) suggesting that anterograde conduction was not crucial either for sustainment or for failure to initiate paroxysmal supraventricular tachycardia after the drug. Paroxysmal supraventricular tachycardia could not be reinduced in six cases after disopyramide. In the other four the ventricular paced cycle lengths producing ventriculoatrial block (318 +/- 41 ms) and effective refractory period of retrograde fast pathway (320 +/- 28 ms) were shorter than the cycle length of reinduced paroxysmal supraventricular tachycardia (367.5 +/- 35 ms) allowing perpetuation of the tachycardia. We conclude that disopyramide breaks atrioventricular nodal re-entrant tachycardia by specific blockade of the retrograde fast pathway though the effect on anterograde atrioventricular nodal conduction is variable.

Adult↗

Direct demonstration and isolation of Legionella pneumophila (serogroup 1) from bathroom water specimens in a hotel.

Legionella pneumophila serogroup 1 organisms were isolated from one sample of water originating from a shower head in a bathroom of a hotel. Seven of the 16 swab specimens collected from 2 different sites of the hotel bathrooms revealed fluorescing bacteria in direct fluorescent antibody test. The significance of present observations in relation to the cluster of L. pneumophila infections diagnosed recently in Berlin among a group of visitors who stayed in this hotel has been discussed.

Baths↗

Establishment of hybridoma cell lines secreting anti-Legionella pneumophila serogroup 1 monoclonal antibodies with immunodiagnostic potential.

Three independent hybridoma cell lines (F4/CB5/K18, F4/CB5/K104, F4/JD3.8/K101) producing monoclonal antibodies that reacted specifically against cell surface molecule(s) of Legionella pneumophila serogroup 1 have been established. These monoclonal antibodies belong to IgM class and are capable of agglutinating exquisitely serogroup 1 organisms. These hybridoma-derived monoclonal antibodies can be used for the preparation of standardized immunodiagnostic reagents for detection and rapid identification of Legionnaire's disease bacterium in clinical laboratories and will also enable purification and subsequent characterization of the serogroup 1 specific molecule(s) of L. pneumophila.

Animals↗

Generation of cytolytic T-cell cultures displaying measles virus specificity and human histocompatibility leukocyte antigen restriction.

In the present study, peripheral blood lymphocytes from eight randomly selected, healthy, measles virus-seropositive donors were used to initiate and expand T-cell cultures during secondary immune response in vitro. Five of the donors yielded continuously growing T-cell cultures which showed reproducible strong lytic activities towards measles virus-infected autologous fibroblasts. Uninfected or herpes simplex virus-infected targets were weakly susceptible to these effectors. By contrast, T-cell cultures from three other seropositive donors expressed comparable lytic activities for measles virus- or herpes simplex virus-infected targets, but not for uninfected autologous targets. The five T-cell cytolytic cultures which revealed measles virus specificity also displayed human histocompatibility leukocyte antigen (HLA)-A and HLA-B restriction, i.e, were lytic for targets sharing HLA-A or HLA-B or both with them. Additionally, it was found that a monoclonal anti-HLA antibody (W6/32) could effectively block the measles virus-specific and HLA-A- and HLA-B-related lytic activities of these cytotoxic T-lymphocytes. The specificity of this blocking effect was reflected by the inefficacy of a monoclonal anti-HLA-DR antibody to block the cytotoxic T-lymphocyte-mediated lysis.

Cells, Cultured↗

IgG Fc-binding receptors on spermatozoa.

The ability of human and mouse spermatozoa to bind immunoglobulin to their surfaces was investigated by a binding assay using radioiodinated Ig. The results suggest that spermatozoa of both human and mouse origin possess Fc receptors, i.e. they have the ability to bind Fcgamma region. This association of Fc-binding receptor activity on spermatozoa surfaces is likely to raise some technical problems in certain conventional assays used to monitor the presence of membrane antigen(s) on spermatozoa.

Animals↗