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Biomedical subjects

K K Sethi

Publications and source records attributed to K K Sethi.

At least 37 records · Page 2Linked to original sources

Clinical, haemodynamic and echocardiographic study in chronic cor pulmonale.

Thirty patients of chronic cor pulmonale were studied clinically and by chest skiagram, electrocardiography, echocardiography, pulmonary function tests, arterial blood gas analysis and, wherever possible by right heart catheterization. Pulmonary arterial pressures (PAP) correlated significantly only with cardiomegaly on skiagram and with arterial oxygen tension (PaO2). There was no significant correlation between mean PA pressures and prominent pulmonary conus on RVH by ECG, FEV1, PaCO2 or right ventricular outflow tract dimensions by echocardiography. Left ventricular function, as assessed by pulmonary capillary wedge pressure on cardiac catheterization, by LV ejection fraction and fractional shortening on echocardiography was normal in all cases except two (6.67%). There was significant increase in left ventricular posterior wall thickness in the patients studied.

Adult↗

Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones.

A variety of clinical syndromes, including AIDS and neurological disorders, may follow as a consequence of infection with the human immunodeficiency virus type 1 (HIV-1). It is not yet clear, however, to what extent the destruction of lymphocytes and neural cells associated with these conditions is caused by adverse immune responses to HIV-1 or how much is due to cytopathic effects of the virus itself. Here we document the existence of HLA-restricted, HIV-1-specific cytotoxic T lymphocytes in the cerebrospinal fluid of two AIDS patients manifesting neurologic disorders. These cytotoxic T lymphocytes showed dual specificity, recognizing target cells coated with purified HIV-1 envelope glycoprotein (gp 120) or inactivated HIV-1 in the context of HLA antigens. Cytotoxic T-cell clones derived from one of the AIDS patients revealed restriction specificities representing both HLA class I and HLA class II antigens. Considerable phenotypic heterogeneity was observed amongst these clones, some expressing conventional combinations of cytotoxic T-cell surface markers, and others displaying unusual phenotypes. The presence of HIV-specific cytotoxic T lymphocytes in AIDS patients, and in particular in their cerebrospinal fluid, suggests that these cytotoxic effectors may participate in the lymphoid cell and/or neurologic damage observed in such patients.

Acquired Immunodeficiency Syndrome↗

Evaluation of non-radioactive in situ hybridisation method to detect Chlamydia trachomatis in cell culture.

A DNA probe combined with a non-radioactive stain was used to detect inclusions of Chlamydia trachomatis in cell culture. Of 39 positive cultures detected by monoclonal antibodies in combination with direct immunofluorescence, 35 were positive by the DNA hybridisation method, the sensitivity being 89.7%. Staining with iodine showed a sensitivity of 87.2%, corresponding to 34 positive cultures. The specificity of DNA hybridisation method was 100%, as all 162 cultures that were negative by the immunofluorescence method were also negative when assessed by the DNA hybridisation method.

Cells, Cultured↗

Production and characterization of monoclonal antibodies specific for pathogenic serogroups O:3, O:8, and O:9 of Yersinia enterocolitica.

A panel of 7 murine hybridoma derived monoclonal antibodies (MAbs) to Yersinia enterocolitica were produced and characterized by indirect fluorescence assay (IFA) and agglutination reactions. One MAb designated 2D8 (IgG 3) showed specific reactivity both in the IFA and agglutination assays with 70 of the 70 strains belonging to serogroup O:3 of Y. enterocolitica. Three MAbs, 8E9 (IgG 3b), 10G11 (IgG3) and 11G2 (IgG 3), gave unequivocal positive reactions in the IFA and agglutination tests with all the strains representing serogroup O:9 (56/56), but not with serogroup O:3 or O:8 strains. Another MAb coded 1G2 (IgG 1) reacted specially in the IFA test (but not in the agglutination test) with all the strains representing serogroup O:3 (70/70) and O:9 (56/56) indicating that this antibody recognizes an immunodeterminant shared by serogroups O:3 and O:9. Finally, 2 MAbs 4C2 (IgM) and 6G5 (IgM), showed reactivity both in IFA and agglutination assays with "esculin negative" biogroups 1 (pathogenic American strains) strains of serogroup O:8 (12/12), whereas the strains assigned to "esculin positive" biogroup 1 (nonpathogenic) failed to react (6/6). However, 4C2 and 6G5 exhibited narrow cross reactivity with type strains assigned to serogroups O:18, O:20, and O:22. The results of absorption tests and the clear out cell wall immunofluorescence imply that the antigenic molecule(s) recognized by these MAbs are exposed on the bacterial cell surfaces. Some of the MAbs described in this report are useful reagents for precise serotyping of clinical isolates of Y. enterocolitica by simple and rapid slide agglutination assay. They may also allow the development of specific and sensitive tests for probing the presence of pathogenic Y. enterocolitica organism in clinical and food materials.

Agglutination Tests↗

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.

Blood Pressure↗

Elevated titers of cell-free interleukin-2 receptor in serum and cerebrospinal fluid specimens of patients with acquired immunodeficiency syndrome.

A sensitive monoclonal antibody based ELISA was used to detect cell-free interleukin-2 receptor (IL-2R) in the body fluids of patients with acquired immune deficiency syndrome (AIDS), a variety of other disease conditions and a control group of apparently healthy (heterosexual and homosexual) males. Two of the 25 control donors showed low titers (1:8) of IL-2 receptor in the serum samples; the cerebrospinal fluid (CSF) specimens from these individuals proved negative. However, serum and CSF specimens from all the 9 patients with AIDS showed significantly elevated titers (range 1:128 to 1:4096) of IL-2 receptor. The presence of moderate titers (range 1:128 to 1:512) of circulating IL-2 receptor could also be detected in all of the 4 patients with acute lymphocytic leukemia. IL-2 receptor was detectable in the CSF and/or serum specimens from 3 of 3 patients with lung cancer, 3 of 4 patients with acute hepatitis B infection, and 2 of 3 patients with multiple sclerosis. IL-2 receptor could not be detected in the serum or CSF specimens originating from patients with legionellosis (3/3), asthma (3/3), or those with non-pulmonary febrile bacterial infections (4/4). It is concluded that soluble IL-2 receptor may be found in serum or CSF specimens from patients with certain (but not all) disease conditions including AIDS. The conspicuously elevated titers of cell-free IL-2R in the body fluids of patients with AIDS may contribute to the drastic impairment of the immune system regulation observed in such patients.

Acquired Immunodeficiency Syndrome↗

Differential effects of autonomic blockade on sinus and atrioventricular nodal function in normals and in intrinsic sinus node dysfunction.

The effect of pharmacologic total autonomic blockade on sinus and atrioventricular nodes was studied in 10 normals and 21 patients with sick sinus syndrome with abnormal intrinsic corrected sinus node recovery time. In normals the intrinsic heart rate (113.3 +/- 11.6 beats/min) was higher than the resting heart rate (87.3 +/- 12 beats/min; P less than 0.001). The AH interval at an identical paced rate decreased from 119 +/- 36 msec to 93 +/- 17.6 msec after autonomic blockade (P less than 0.05). Mean atrial paced cycle length at AH Wenckebach block was not different during control and after drugs (319 +/- 46 msec vs. 311.5 +/- 39 msec; P = NS). Although sinus cycle length shortened in all cases after autonomic blockade, paced cycle length at AH Wenckebach increased (4) or remained unchanged (3) in 7 cases. Maximum normal "intrinsic" paced cycle length at AH Wenckebach was 390 msec (mean +/- 2 SD). In sick sinus syndrome, resting heart rate (66.3 +/- 18.8 beats/min) and intrinsic heart rate (74.6 +/- 16.4 beats/min) were similar (P = NS); AH at identical paced rate: control 136.6 +/- 54 msec, after drugs 130.5 +/- 35 msec (P = NS); cycle length at AH Wenckebach: control 380.5 +/- 73 msec, after autonomic blockade 383 +/- 49 msec (P = NS). Two of 3 cases with abnormal atrioventricular nodal response to atrial pacing during control normalized after autonomic blockade; 9/21 (42.8%) cases developed AH Wenckebach at cycle length greater than 390 msec after autonomic blockade. The data suggest that the autonomic nervous system has differential effects on sinus and atrioventricular nodes. Patients with sick sinus syndrome frequently have abnormalities of "intrinsic" atrioventricular nodal conduction unmasked by autonomic blockade.

Adolescent↗

Verapamil in idiopathic ventricular tachycardia of right bundle branch block morphology: observations during electrophysiologic and exercise testing.

Electrophysiologic studies before and after administration of verapamil were performed in three young patients with recurrent sustained ventricular tachycardia (VT) of right bundle branch block morphology. VT was not provoked by maximal treadmill testing in any patient. Electrophysiologic findings at induction of VT suggested reentry in the first patient and triggered automaticity in the second. Findings were inconclusive in the third patient. Intravenous verapamil terminated the VT in all the three cases. Oral verapamil prevented laboratory induction of sustained VT in the latter two patients. However, VT could be provoked during exercise in both while on oral verapamil therapy. These findings suggest that different mechanisms may underlie ventricular tachycardia dependent upon slow-response tissue; the role of oral verapamil in the treatment of such VT needs further investigation.

Adult↗

Electron microscope observations on the interaction of Mycoplasma fermentans with Trichomonas vaginalis.

Cultures of Trichomonas vaginalis were found to be contaminated with Mycoplasma fermentans. By means of electron microscopy the interaction between the prokaryotic organisms and the trichomonads was examined. Cells of M. fermentans were observed in the medium; some of them were attached to the surface of the trichomonads and others were observed in membrane-bounded vacuoles of trichomonads. They were also present in the ground substance of the cytoplasm. The mycoplasmas divided by binary fission like other prokaryotes. The most obvious change occurring in the infected trichomonad cells was an increase in number of vacuoles containing mycoplasmas.

Animals↗

Contribution of immune interferon (IFN-gamma) in lymphokine-induced anti-toxoplasma activity: studies with recombinant murine IFN-gamma.

Recombinant E. coli-derived murine interferon gamma (cDNA IFN-gamma) per se induced resident mouse peritoneal macrophages (MPM) and mouse embryo cells to exert marked antitoxoplasma activity. This capacity of cDNA IFN-gamma was abrogated by a specific antiserum to cDNA IFN-gamma which could only neutralize the antiviral activity mediated by this product, whereas a rabbit antiserum directed against murine IFN-alpha/beta proved ineffective in neutralizing these functions. It has been found that rabbit antiserum to cDNA IFN-gamma could also neutralize IFN-gamma-mediated antiviral activity present in crude lymphokine-enriched supernatants of antigen-stimulated toxoplasma-sensitized spleen cells (Toxo-LK) but proved ineffective in abolishing the capacity of Toxo-LK to trigger macrophage anti-toxoplasma activity. The data obtained suggest that macrophage anti-toxoplasma activity induced by Toxo-LK may be an interplay of multiple factor(s) and that Toxo-LK preparations contain soluble factor(s) other than IFN-gamma, which can induce macrophages to kill intracellular Toxoplasma. Experiments in which crude Toxo-LK preparations were incubated with lectin concanavalin A (Con A) showed that this treatment resulted in a block of anti-toxoplasma arming factor(s) activity, as well as a significant reduction of IFN-gamma-mediated antiviral activity present in Toxo-LK. By contrast, no significant difference was observed in the macrophage anti-toxoplasma activity mediated by Con A or untreated cDNA-IFN-gamma.

Animals↗

Wide QRS supraventricular tachycardia due to coexisting Mahaim and Kent pathways.

In two patients with Wolff-Parkinson-White syndrome, we observed the unusual coexistence of functional Mahaim and accessory atrioventricular pathways. In the first patient, three types of reciprocating tachycardia were demonstrable: (1) anterograde conduction over the atrioventricular (AV) node with right bundle branch block (RBBB) and retrograde conduction via a right-sided atrioventricular accessory pathway; (2) anterograde conduction through the AV node with RBBB and retrograde conduction via two (right-sided and septal) anomalous pathways; and (3) anterograde conduction through nodoventricular fibers and retrograde conduction over a right-sided accessory pathway. In the second patient the reentry circuit was comprised of AV node fasciculoventricular fiber in an anterograde direction and a right-sided accessory pathway in a retrograde direction. We believe this to be the first report of triple accessory pathways, consisting of two atrioventricular and one nodoventricular connection, demonstrated by intracardiac electrophysiologic study.

Adolescent↗

Topographical localization of distinct antigenic domains of Toxoplasma gondii with the aid of monoclonal antibodies.

In the present study, a panel of six individual hybridoma derived antibodies produced against the BK strain of Toxoplasma gondii were evaluated for their reactivity in an immunofluorescence test. Each of the six monoclonal antibodies demonstrated a unique pattern of fluorescence localized to distinctive regions on the toxoplasmas. Although all of the six detected antigenic determinants which were shared by at least four different T. gondii strains, monoclonal antibody TG-E4A17 has disclosed hitherto unrecognized population differences among the BK or PH strain parasites. The fact that some of the antigenic molecules are restricted to distinct regions of the toxoplasmas may have implications in the infections process/immune response.

Animals↗