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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 577 records · Page 32Linked to original sources

The env protein of an infectious noncytopathic HIV-2 is deficient in syncytium formation.

A recent isolate of human immunodeficiency virus type 2 (HIV-2) designated HIV-2ST is deficient in its ability to cause the typical cytopathic effects of HIV infection. The pathogenic potential of HIV-2 in inducing human disease may be less than that of HIV-1, and it is of particular interest to establish the basis for the reduced cytopathogenicity of this isolate in vitro. Utilizing recombinant vaccinia viruses (rVV) carrying the envelope genes (env) of HIV-2ST or those of fully cytopathic HIV-1 or HIV-2 isolates, we have investigated envelope glycoprotein expression, processing, transport, and biological function. Radioimmunoprecipitation and polyacrylamide gel electrophoresis (RIP-PAGE) of rVV-infected cell lysates indicated that the proteins expressed by each recombinant were synthesized, processed, and recognized by specific antisera. Immunofluorescence studies showed that the recombinant env gene products of HIV-2ST and HIV-2ROD reach the cell surface and are retained there in similar amounts. Whereas cells expressing the HIV-1 or HIV-2ROD env gene products were found to undergo fusion with uninfected CD4+ cells, no syncytium formation was observed with three CD4+ cell lines exposed to the cells expressing the envelope glycoproteins of HIV-2ST on their surfaces; one CD4+ lymphoid cell line (SupT1) exhibited few very small syncytia in the presence of recombinant HIV-2ST envelope glycoproteins. The failure of the HIV-2ST envelope glycoprotein to induce cell fusion was not the result of an inhibition by cell-associated CD4, since fusion was also not observed when rVVST-infected CD4- cells were cocultured with CD4+ cells. Thus, the HIV-2ST envelope protein itself is defective in its ability to induce cell fusion. Furthermore, the expression, processing, transport, and surface stability of env products of HIV-2ST are unlikely to be responsible for its attenuation, suggesting that the molecular interactions between its env products and target cell membranes are significantly altered.

CD4 Antigens↗

An investigation of the neurobehavioural effects on workers exposed to organic solvents.

Forty-five workers exposed to the solvents xylene and toluene in varnishing processes in a major heavy electrical industry were studied to find the effect of this exposure on different parameters of behaviour. These were immediate and delayed memory, visual ability, visual learning and psychomotor ability. The findings were compared with those from subjects who were not exposed. Immediate memory and delayed memory were affected among both directly and indirectly exposed workers as compared with those in the controls which remained unaffected. Visual intelligence and memory were most affected by exposure. Psychomotor ability was significantly affected among the directly exposed workers, as compared with the occasionally exposed group which did not show any significant difference from the control workers.

Adult↗

Topical retinoic acid for treatment of solar damage.

Twenty patients with chronic solar damage of the skin were entered in a double-blind, within-patient trial to compare the effect of 0.05% tretinoin cream with a placebo applied once daily for 12 weeks. Sixteen completed the study. Clinical assessment of the individual signs of solar damage were recorded on separate visual analogue scales. After 12 weeks, there were significant improvements in fine wrinkling around the eyes, crease lines around the mouth and cheeks, wrinkling on the dorsum of the hands and yellow discoloration. Overall, 14 of the tretinoin-treated sides were judged to have improved compared to only two of the placebo-treated sides (P = 0.011). Measurement of skin thickness by pulsed A-scan ultrasound revealed that the sides treated with tretinoin were significantly thicker than the placebo-treated sides (P = 0.019). Skin biopsies taken before and after treatment showed an increase in mean epidermal thickness with tretinoin treatment (P = 0.019). The clinical signs of improvement persisted at the follow-up assessment performed 4 weeks after cessation of therapy.

Administration, Topical↗

Interactions between K+ and beta 2-adrenoreceptors in determining muscle vasodilatation induced in the rat by systemic hypoxia.

In spontaneously breathing anaesthetized rats, both moderate and severe hypoxia caused increases in [K+] in venous efflux from hindlimb muscle, from 4.3 to 4.6 and from 3.8 to 4.4 mM respectively; the increases were accentuated to 5.2 and 5.7 mM after beta 2-receptor blockade with I.V. sotalol. Sotalol also potentiated the vasodilatation evoked in hindlimb muscle by moderate hypoxia, but reduced that evoked by severe hypoxia. We propose that K+ released from muscle during hypoxia contributed to the local vasodilatation. Further, we suggest that this effect was enhanced in moderate hypoxia by blockade of the beta 2-mediated uptake mechanism for K+ in skeletal muscle, but outweighed in severe hypoxia by blockade of the beta 2-mediated dilator action of circulating catecholamines on vascular muscle.

Animals↗

Molecular characterization of an attenuated human immunodeficiency virus type 2 isolate.

Naturally occurring strains of human immunodeficiency virus (HIV) can vary considerably in their in vitro biological properties, and such differences may also be reflected in their in vivo pathogenesis. In an attempt to define genetic determinants of viral pathogenicity, we have molecularly cloned, sequenced, and characterized an attenuated isolate of HIV type 2 (HIV-2/ST) that differs from prototype HIV-2 strains in its inability to fuse with and kill susceptible CD4-bearing target cells. A proviral clone, termed JSP4-27, was identified to be transfection competent and to fully exhibit the noncytopathic and nonfusogenic properties of its parental isolate. Nucleotide sequence analysis of this clone revealed a genomic organization very similar to that of cytopathic HIV-2 strains and an overall nucleotide sequence homology of 88 to 90%. Amino acid sequence comparison confirmed the integrity of all major viral gene products in JSP4-27 but identified two amino acid sequence substitutions in its envelope fusion region. To investigate whether these mutations were responsible for the nonfusogenic phenotype of JSP4-27, we amplified, cloned, and sequenced the envelope fusion regions of four additional HIV-2/ST strains, two of which represented in vitro-generated, fusogenic and cytopathic variants of HIV-2/ST. The analysis showed that all HIV-2/ST strains examined, including the fusogenic variants, contained the same amino acid sequence changes. On the basis of these findings, we conclude that the attenuated phenotype of JSP4-27, and that of its parental virus, is not due to a direct alteration of the envelope fusion domain. Our results also show, for the first time, that individual replication-competent proviral clones can be representative of attenuated strains of HIV.

Amino Acid Sequence↗

HLA-DP and coeliac disease: family and population studies.

We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DP alpha polymorphism (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34% of control subjects, p less than 0.001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin dependent diabetes mellitus. The association with coeliac disease was further investigated. Msp I DP beta polymorphism was studied in 52 healthy subjects and 59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac disease compared to 11.5% of control subjects (p less than 0.001). Furthermore, nearly all subjects with the DP alpha 3.5 kb fragment also had the DP beta 4.9 kb fragment. However, disease frequency was still increased in the DP alpha 3.5 positive/DP beta 4.9 negative group. In seven families, each with at least two affected members, while the DP alpha 3.5 fragment was frequently present in patients it did not preferentially segregate with any particular HLA haplotype--for example, those associated with DR3 or DR7--and therefore is not part of an extended haplotype associated with coeliac disease. We therefore conclude that a gene(s) in the HLA-DP region predisposes to coeliac disease independently of the HLA-DR/DQ regions.

Celiac Disease↗

Permeability pulmonary edema following lung resection.

The etiology of edema associated with pulmonary resection was investigated in five patients during the immediate postoperative period. Three patients received pneumonectomy while two patients had one lobe resected. All patients suffered from severe respiratory distress and had x-ray evidence of diffuse interstitial pulmonary edema within 12 hours of surgery. Hemodynamic data were obtained with radial and pulmonary artery catheters. Edema fluid was obtained along with blood samples for simultaneous determination of protein and albumin content. All patients studied had normal or high cardiac output, normal cardiac filling pressures, and edema fluid protein to serum protein ratio of 0.6 or greater suggestive of permeability changes contributing to edema fluid accumulation. Calculated shunt fraction exceeded 25 percent in all patients. Pulmonary edema has been noted in patients following pulmonary resection in the early postoperative period. In patients reviewed here, two factors appeared to be significant. First is an increase in pulmonary capillary pressure associated with passage of a normal to high cardiac output in a reduced volume pulmonary vascular bed. The second factor, as demonstrated by protein content in the edema fluid, is injury to the alveolar capillary membrane.

Blood Proteins↗

Synthesis and antiinflammatory activity of 2H-tetrazol-2-acetic acids, esters and amides.

A series of 5-(pyridyl)-2H-tetrazol-2-acetic acids (16-21), esters (10-15), and amides (22-27) was synthesized in order to investigate the effect of 5-substituents (R1 = 2-, 3- or 4-pyridyl) and alpha-substituents (R2 = H, Me) on anti-inflammatory activity. The point of attachment of the R1-pyridyl substituent influenced potency. The relative potencies in the acetic acid ester, acetic acid and acetamide classes of compounds were 2- and 4- greater than 3-pyr, 2- and 3- greater than 4-pyr, and 4- greater than 2- and 3-pyr, respectively. In the acetic acid ester and acetamide classes, compounds having a R2 hydrogen substituent were generally more potent than corresponding methyl substituted compounds, whereas, in the acetic acid class the reverse applied. The relative order of anti-inflammatory potency was generally amide greater than ester greater than acid. 2-[5-(4-Pyridyl)-2H-tetrazol-2-yl]acetamide (26) was the most effective antiinflammatory agent in the series, reducing inflammation by 53% at 3 and 5 hr after a 25 mg/kg po dose.

Acetamides↗

Highly selective vagotomy in the treatment of peptic ulcer diathesis.

The results of highly selective vagotomy in 174 Indian patients have been analysed. Compared to other procedures on the stomach, HSV has a definite advantage both on long term as well as on short term basis. HSV has therefore become the procedure of choice in the treatment of duodenal ulcer disease provided the expertise is available locally. HSV has also been used now in the treatment of ulcer complications and benign gastric ulcer disease.

Duodenal Ulcer↗

A comparative therapeutic trial of sucralfate and ranitidine in initial healing and relapse rate of duodenal ulcer.

The present study was carried out to examine the comparative efficacy of sucralfate and ranitidine in the treatment of duodenal ulcer. Sixty-six patients with endoscopically diagnosed duodenal ulcer were studied in a 4-6 weeks randomised, single blind trial comparing sucralfate 1 gm T.D.S. one hour before meal and 1 gm nocte (34 pts) with ranitidine 300 mg nocte (32 pts). Six patients (four on sucralfate and 2 on ranitidine) failed to complete the study. Endoscopy after four weeks of treatment showed an ulcer healing rate of 57% in the sucralfate group compared with 73% in ranitidine group (p greater than 0.1). At six weeks these figures had risen to 87% and 90% respectively (p less than 0.5). After one year followup study 69% of sucralfate treated ulcers relapsed whereas the relapse rate was 82% in ranitidine treated ulcer group (p less than 0.1). It was observed that the relapse was earlier in the ranitidine group as compared to sucralfate group (p less than 0.01 at 3 months and p less than 0.05 at 6 months). Asymptomatic recurrence was seen in 15% (6/40) patients. Sucralfate was not only as effective as ranitidine in short term healing of duod. ulcer but also delayed the relapse of ulcer in long term followup after initial healing with the drug.

Acute Disease↗

Extracellular enzymes of pulmonary fluid and their bactericidal effects on Mycobacterium tuberculosis.

The enzyme activity and bacillary content of cell free pulmonary lavage fluid has been compared in infected and immunized infected animals. Increased enzyme production was found as a result of macrophage activation. Marked decrease in the number of tubercle bacilli was observed in immunized infected animals. The active enzyme production is considered to be the impact of availability of enzyme specific substrate, particularly cell wall components of tubercle bacilli viz. arabinogalactan, arabinomannan and sulphatides. These macromolecules are considered as active substrates for the action of arabinosidase (EC:3.2.1.55), mannosidase (EC:3.2.1.24) and sulphatase-C (EC:3.1.6.1).

Animals↗

Mold contamination of automobile air conditioner systems.

Eight cars belonging to patients who were found to have exacerbation of allergic rhinitis and bronchial asthma after turning on the air conditioner in their cars were examined. Mold concentrations inside the passenger compartment with the a/c turned off and at different climate control settings were lower than concentrations in the outside air. After turning on the air conditioner to "Max", cultures obtained at various intervals revealed that mold concentrations decreased significantly with time. Furthermore, placement of a filter at the portal of entry of outside air significantly reduced the mold concentration in the passenger compartment.

Air Conditioning↗