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Biomedical subjects

R Farid

Publications and source records attributed to R Farid.

8 recordsLinked to original sources

Molecular and phylogenetic analysis of HIV-1 variants circulating among injecting drug users in Mashhad-Iran.

Genetic and phylogenetic information on the HIV-1 epidemic in Middle-East Countries, and in particular in Iran, are extremely limited. By March 2004, the Iranian Ministry of Health officially reported a cumulative number of 6'532 HIV positive individuals and 214 AIDS cases in the Iranian HIV-1 epidemic. The intra-venous drug users (IDUs) represent the group at highest risk for HIV-1 infection in Iran, accounting for almost 63% of all HIV-infected population. In this regards, a molecular phylogenetic study has been performed on a sentinel cohort of HIV-1 seropositive IDUs enrolled at the end of 2005 at the University of Mashhad, the largest city North East of Tehran. The study has been performed on both gag and env subgenomic regions amplified by Polymerase Chain Reaction (PCR) from peripheral blood mononuclear cells (PBMCs) and characterized by direct DNA sequence analysis. The results reported here show that the HIV-1 subtype A is circulating in this IDUs sentinel cohort. Moreover, the single phylogenetic cluster as well as the intra-group low nucleotide divergence is indicative of a recent outbreak. Unexpectedly, the Iranian samples appear to be phylogenetically derived from African Sub-Saharan subtype A viruses, raising stirring speculations on HIV-1 introduction into the IDUs epidemic in Mashhad. This sentinel study could represent the starting point for a wider molecular survey of the HIV-1 epidemics in Iran to evaluate in detail the distribution of genetic subtypes and possible natural drug-resistant variants, which are extremely helpful information to design diagnostic and therapeutic strategies.

Journal Article↗

A C77G point mutation in CD45 exon 4, which is associated with the development of multiple sclerosis and increased susceptibility to HIV-1 infection, is undetectable in Japanese population.

HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one outcome of Human T-cell lymphotropic virus type 1 (HTLV-1) infection. It remains unknown why the majority of infected people remain healthy whereas only approximately 2-3% develop disease. Recently, heterozygous state of CD45 exon 4 mutation (C77C wild type and C77G mutant) was reported to be associated with development of multiple sclerosis in German patients and increased susceptibility to HIV-1 infection in the United Kingdom. To investigate whether this mutation is associated with the development of HAM/TSP, we studied a group of 164 HAM/TSP patients and 108 asymptomatic HTLV-1 carriers in Kagoshima (HTLV-1 endemic area in Southern Japan) by using PCR-RFLP and subsequent direct sequencing analysis. All 272 subjects showed homozygosity in the CD45 exon 4, suggesting that this mutation is absent or very rare in Japanese population.

Carrier State↗

Prevalence of HTLV type I infection in Iran: a serological and genetic study.

Several publications describe the presence of the human T cell lymphotropic virus type I (HTLV-I) in Jewish individuals born in Mash-had, Iran. We report here the results of HTLV-I serological and genetic studies in the non-Jewish population of Mash-had as well as a neighboring area: Gonbad-Kavous. Seven hundred and seven serum samples from Mash-had (694 healthy individuals and 13 patients with lymphoma) and 90 from Gonbad-Kavous were tested for HTLV antibodies by gelatin particle agglutination assay (PA) and confirmatory Western blots (WBs). Seropositive rates of 3.0% (21 of 694) in Mash-had, 0% (0 of 90) in Gonbad-Kavous, and 100% (13 of 13) in lymphoma cases were observed. HTLV-I DNA sequence were amplified by polymerase chain reaction directly from the fresh PBMCs of seropositive individuals. Phylogenetic analysis of the viral DNA sequence indicated that the HTLV-I present in Mash-had belong to the HTLV-I cosmopolitan clade. Altogether, these data indicate that Mash-had, located in northeastern Iran, is a newly recognized endemic center for HTLV-I.

Amino Acid Sequence↗

Biological electron transfer.

Many oxidoreductases are constructed from (a) local sites of strongly coupled substrate-redox cofactor partners participating in exchange of electron pairs, (b) electron pair/single electron transducing redox centers, and (c) nonadiabatic, long-distance, single-electron tunneling between weakly coupled redox centers. The latter is the subject of an expanding experimental program that seeks to manipulate, test, and apply the parameters of theory. New results from the photosynthetic reaction center protein confirm that the electronic-tunneling medium appears relatively homogeneous, with any variances evident having no impact on function, and that control of intraprotein rates and directional specificity rests on a combination of distance, free energy, and reorganization energy. Interprotein electron transfer between cytochrome c and the reaction center and in lactate dehydrogenase, a typical oxidoreductase from yeast, are examined. Rates of interprotein electron transfer appear to follow intraprotein guidelines with the added essential provision of binding forces to bring the cofactors of the reacting proteins into proximity.

Electron Transport↗

Interethnic differences in drug protein binding and alpha 1 acid glycoprotein concentration.

Interethnic differences in drug responsiveness may in part be accounted for by differences in drug disposition. We investigated the reversible binding interaction by equilibrium dialysis between a representative acidic (warfarin) and basic (lignocaine) drug and drug binding proteins in 20 healthy age and sex matched Iranian and Irish (Caucasian) subjects. The unbound fraction of warfarin and its major binding protein albumin, were similar in the two groups. In contrast unbound lignocaine was higher in Iranian subjects (49.6 +/- 6.96 vs 37.7 +/- 51%, mean +/- SD, p < 0.05) and this was associated with lower plasma concentrations of alpha 1 acid glycoprotein (AAG, 48.8 +/- 10 vs. 60.5 +/- 8 mg/dl p < 0.01) Such alterations may result in differences in drug responsiveness in addition to predictable pharmacokinetic consequences. Protein binding should be included in comparative studies of drugs in subjects of different races.

Adolescent↗

Phylogenetic classification of human T cell leukaemia/lymphoma virus type I genotypes in five major molecular and geographical subtypes.

Proviral DNA was obtained from ex vivo peripheral blood mononuclear cells of 75 human T cell leukaemia/lymphoma virus type I (HTLV-I)-infected individuals who were either asymptomatic or had adult T cell leukaemia or tropical spastic paraparesis/HTLV-I-associated myelopathy. Amplified long terminal repeats (LTRs) were analysed for restriction fragment length polymorphisms (RFLPs). The results, together with previously published LTR data (a total of 180 specimens analysed), showed the presence of 12 different RFLP profiles with four major molecular subtypes. Furthermore, a fragment of 413 bp (nucleotides 22 to 434) of the U3/R region was sequenced for 12 new HTLV-I specimens originating from Central and West Africa (8 cases), Iran (1 case), Caribbean (2 cases) and Reunion Island (1 case). Phylogenetic analysis using three different techniques (maximum parsimony, neighbour-joining and UPGMA) comparing these 12 strains (including four new African HTLV-I variants) with the 30 published partial HTLV-I LTR sequences (nt 120 to 434) showed the existence of clusters of molecular variants in discrete geographical areas. The topology of the phylogenetic trees is thought to reflect HTLV-I evolution and the migrations of virally infected populations in the recent or distant past. Furthermore, there was a nearly perfect concordance between the clustering based on the LTR sequence homologies and the LTR RFLP subtypes suggesting that this rapid and simple technique is well suited to the investigation of HTLV-I molecular epidemiology. These results allow a new phylogenetic classification of HTLV-I genotypes into five major molecular subtypes: Cosmopolitan (C) subtype widespread all over the world, Japanese (J) subtype, West African (WA) subtype. Central African (CA) subtype and Melanesian (M) subtype.

Africa↗