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Biomedical subjects

P S Venkateswaran

Publications and source records attributed to P S Venkateswaran.

16 recordsLinked to original sources

The connection domain is implicated in metalloporphyrin binding and inhibition of HIV reverse transcriptase.

We have shown that heme and zinc protoporphyrin inhibit both human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptases (RTs) and, in combination with other nucleoside and non-nucleoside inhibitors, exert an additive effect on HIV-1 RT inhibition. Screening of a phage peptide library against heme resulted in the isolation of a peptide with sequence similarity to sequence 398-407 from the connection subdomain of both HIV-1 and HIV-2 RTs, suggesting that this highly conserved region of HIV RTs corresponds to the binding site for metalloporphyrins and a new site for inhibition of enzyme activity. Inclusion of a synthetic peptide corresponding to the exact sequence 398-407 of HIV-1 RT in RT inhibition assays had a protective effect on metalloporphyrin inhibition, as it was able to reverse the inhibitory effect of both metalloporphyrins on HIV-1 RT activity. Furthermore, intrinsic fluorescence assays indicated that these metalloporphyrins bind to synthetic peptide 398-407 as well as to intact dimeric HIV-1 RT. The identification of this novel inhibition site will help to expand our understanding of the mode of action of metalloporphyrins in RT inhibition and will assist in the design and development of more potent metalloporphyrin RT inhibitors for the management of HIV infection.

Amino Acid Sequence↗

Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus.

A viricide capable of eliminating hepatitis B virus (HBV) from chronic carriers should, theoretically, decrease the risk of primary hepatocellular carcinoma. Extracts of Phyllanthus amarus have been shown to inhibit the DNA polymerase of HBV and woodchuck hepatitis virus (WHV) in vitro. Three of four recently infected WHV carriers treated i.p. with P. amarus extract lost WHV, animals infected for greater than or equal to 3 months showed a decrease in virus levels. Preliminary results in human carriers treated orally with P. amarus for 1 month indicated that approximately 60% of the carriers lost HBV during the observation period.

Animals↗

Interaction of fucoidan from Pelvetia fastigiata with surface antigens of hepatitis B and woodchuck hepatitis viruses.

A sulfated polysaccharide isolated from Pelvetia fastigiata, a marine algae, was found to inhibit in vitro the reaction of the surface antigen of hepatitis B virus (HBsAg) or of woodchuck hepatitis virus (WHsAg) with antibody to HBsAg (anti-HBs). The polysaccharide was composed mainly of 1----2 linked L-fucose-4-sulfate with some (less than 10%) 1----3 linkages. The inhibition of the reaction of HBsAg with anti-HBs or of WHsAg with anti-HBs was found to be directly proportional to the molecular size of the polysaccharide. Comparison of its inhibitory activity with that of carrageenans and dextran sulfates showed that, in addition to the size, the configuration of the component sugar and the presence of deoxy sugar may play a role in the inhibition of reaction of HBsAg or WHsAg with anti-HBs. The fucose sulfate polymer, fucoidan, however, had no effect in vivo on woodchuck hepatitis virus in woodchuck chronic carriers.

Animals↗

Hepatitis B virus and hepatocellular carcinoma--treatment of HBV carriers with Phyllanthus amarus.

Extracts of Phyllanthus amarus inhibit the DNA polymerase of HBV and related viruses. Woodchuck carriers of woodchuck hepatitis virus (WHV) were treated intraperitoneally with P. amarus extract. Three of four animals which had been recently infected lost the virus. Animals infected for about 3 months or more had a decrease in virus levels. Human carriers of HBV were treated orally for 1 month. About 60% of the carriers lost HBV, which did not return during the observation period. Fractions containing active principles are now being isolated and characterized.

Animals↗

Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus.

In a preliminary study, carriers of hepatitis B virus were treated with a preparation of the plant Phyllanthus amarus for 30 days. 22 of 37 (59%) treated patients had lost hepatitis B surface antigen when tested 15-20 days after the end of the treatment compared with only 1 of 23 (4%) placebo-treated controls. Some subjects have been followed for up to 9 months. In no case has the surface antigen returned. Clinical observation revealed few or no toxic effects. The encouraging results of this preliminary study recommend continued evaluation of this plant and the active principles isolated from it.

Adolescent↗

Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.

An aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus (WHV) DNA polymerase and binds to the surface antigen of WHV in vitro. The extract, nontoxic to mice, was tested for antiviral activity in woodchucks (Marmota monax). In a trial using six long-term WHV-carrier woodchucks, five treated animals showed a faster decrease in woodchuck hepatitis virus surface antigen titer compared to one untreated control. In animals recently infected with WHV, the extract was effective when administered i.p. in three out of four animals in reducing and within 3-6 weeks eliminating both the surface antigen titer and DNA polymerase activity in serum. The treatment was discontinued after 10 weeks, and the treated animals have remained free of detectable markers of WHV for more than 45 weeks. In contrast, three untreated controls remained positive for both markers for WHV. One of the controls died after 8 weeks; the other two controls have remained positive for WHV markers for more than 45 weeks. In a third trial with long-term carriers, test animals treated subcutaneously with the extract for 12 weeks did not respond; but on switching the mode of administration to i.p., two out of the five animals showed a significant decrease in woodchuck hepatitis virus surface antigen titer compared to controls.

Animals↗

Type variation of strains of Streptococcus pneumoniae in capsular serogroup 15.

The repeated finding of two capsular types of Streptococcus pneumoniae in serogroup 15 in infected exudate from the middle ear led to the demonstration of type variation in pneumococcal types 15B and 15C. Determination of the chemical composition of the capsular polysaccharides of the pneumococci in serogroup 15 showed that the observed variation was related to the presence of an O-acetyl group in the capsular polysaccharide of type 15B which was lacking from the otherwise identical polysaccharide of type 15C. The phenomenon appears similar to that reported in several other bacterial species in which it has been ascribed to labile inversion of a segment of DNA.

Antigens, Bacterial↗

Filamentous capsulated streptococci from the human respiratory tract: chemical and immunochemical characterization of a glycoprotein capsular antigen of provisional binary capsular type 87.

A filamentous alpha-hemolytic streptococcus of provisional capsular type 87 isolated from the human respiratory tract has been shown to be binary capsulated. One of the capsular antigens appears to be a glycoprotein; the other appears to be a polysaccharide. Transformation reactions with deoxyribonucleic acid from streptococcus type 87 and a number of noncapsulated pneumococci yielded transformed pneumococci with either a glycoprotein capsule or a polysaccharide capsule, but not with both. Capsular precipitin (quellung) reactions were observed when streptococcus type 87 was treated with homologous antiserum or with antisera to either of the two distinct capsular transformants. Each of the transformed pneumococci gave a quellung reaction with its homologous antiserum or with antiserum to streptococcus type 87, but neither reacted with antiserum to the heterologous transformant. Chemical analysis showed the glycoprotein antigen of streptococcus type 87 to contain, in addition to amino acids, glucose, galactose, glucosamine, and phosphate. The amino acid composition of the glycoprotein capsular antigens from streptococcus type 87 and of those from transformed pneumococci were similar, showing only minor differences. The glycoprotein capsular antigen from streptococcus type 87 gave two closely associated precipitin bands with homologous antiserum or antisera to transformed pneumococci with the glycoprotein capsule. That the two precipitin bands represent two unrelated proteins is precluded largely on the basis of the unlikely probability of 100% cotransformation of the genes coding for both proteins in the pneumococcal transformants that were isolated. Chemical analyses of the various fractions of the glycoprotein indicate that the two precipitin bands may represent a glycoprotein and its corresponding apoprotein.

Amino Acids↗

Filamentous capsulated streptococci from the human respiratory tract: chemical and immunochemical characterization of the polysaccharide capsular antigen of provisional binary capsular type 87.

The polysaccharide capsular antigen of the filamentous binary capsulated streptococcus of provisional type 87 and the polysaccharide capsular antigens of two pneumoccal strains transformed with deoxyribonucleic acid of streptococus type 87 have been purified and analyzed with regard to their component monosaccharides. The purified polysaccharides from the three strains were immunochemically identical. Each was found to contain rhamnose, glucose, galactose, galactosamine, and phosphate. Rhamnose was the immunodominant sugar.

Antigens, Bacterial↗

Isolation and characterization of a phosphonomycin-resistant mutant of Escherichia coli K-12.

A mutant was isolated from Escherichia coli K-12 which showed increased resistance towards phosphonomycin, a new bactericidal antibiotic recently isolated from strains of Streptomyces. Evidence is presented which suggests that this mutant is resistant to lysis by phosphonomycin because of a lower affinity of phosphoenolpyruvate: uridine diphospho-N-acetylglucosamine enolpyruvyl transferase for this antibiotic. This mutant was also found to be temperature-sensitive in growth. At 42 C mutant cells grew poorly, and the rate of incorporation of (3)H-diaminopimelic acid into trichloroacetic acid-insoluble material was also greatly reduced. Genetic studies indicate that the increased resistance toward phosphonomycin and temperature sensitivity in growth of this mutant are probably the consequences of a single mutation.

Anti-Bacterial Agents↗