Search PubMed⌕ Search

Biomedical subjects

S Riazuddin

Publications and source records attributed to S Riazuddin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular characterization of beta-thalassemia in Pakistan.

Beta-thalassemia is one of the most common inherited hemoglobin disorders in Pakistan. The carrier frequency is estimated to be 5.4%. To determine the spectrum of beta-globin gene defects causing beta-thalassemia, we have analyzed a representative sample of 602 alleles from six ethnic groups in Pakistan; 99.2% alleles were characterized, while 0.8% remained unidentified. The spectrum of mutations is heterogeneous and we have found 19 different mutations in all ethnic groups. The four most common mutations, IVS-I-5 (G-->C) (37.7%), codons 8/9 (+G) (21.1%), the 619 bp deletion (12.4%), and IVS-I-1 (G-->T) (9.5%), account for 80.7% of the alleles. There are differences between the ethnic groups and also between provinces. In the four provinces of Pakistan, the IVS-I-5 (G-->C) mutation is more prevalent in Sindh and Balochistan, bordering India in the south and Iran in the southwest, while the codons 8/9 (+G) mutation is more common in the Punjab and the North West Frontier Province, bordering India in the northeast and Afghanistan, respectively. The 619 bp deletion is high (46%) in Gujratis and Memons residing in the Province of Sindh, neighboring the Indian Gujrat.

Alleles↗
PubMed1995

Molecular genetic diagnosis of beta thalassemia in Pakistan.

A set of procedures, based on DNA analysis, has been developed to detect deletions and point mutations causing Beta thalassemia in the Pakistani population. These procedures can be used to analyze the presence of relevant changes in DNA, thus providing a reliable means for screening the high risk families, to provide them genetic counselling and prenatal diagnosis during early pregnancy. We have identified two mutations IVS-1 nt.5 (G--C) and codon 8-9 (+G) in 4 of the 6 families analyzed for these mutations.

DNA Mutational Analysis↗
PubMed1989

Future growth in biotechnology in the developing countries.

Conditions in developing countries are nowhere near what they should be to reap the benefits of modern biotechnology. Be that as it may, there are possibilities in which intelligent thinking and rational planning by the people concerned, combined with input from international agencies and national centres of excellence, can lead to potential economic gains. One possibility is the establishment of collaborative research on a regional basis to tackle common problems and to train each other's manpower in acquired skills. Similarity of circumstances would make these programmes more relevant and cost effective. To ensure the success of joint programmes in the local setting, foreign input in the form of finances, provision of critical laboratory materials, and expert advice in the selection of technically solvable problems becomes inevitable. Thus participation by the developed-country agencies and laboratories in the developing countries presents a purposeful pooling of efforts that will sow the seeds for sustainable development of the developing world. Given that, new technology would prove a boon and a blessing for humanity in general and for the developing world in particular.

Academies and Institutes↗
PubMed1987

Methyl transferases induced during chemical adaptation of M. luteus.

Three peaks of methyltransferase activity specific for MNNG alkylated DNA have been identified from extracts of chemically adapted M. luteus. They are designated as TI to TIII in order to their elution from a Sephadex G-75 column. The first one of these peaks has been purified to homogeneity. TI, is an inducible, unusually salt resistant, heat labile protein which corrects O6-methylguanine in alkylated DNA by the transfer of the O6-alkyl group to a cysteine amino acid in the TI protein. There is a stoichiometric relationship between the loss of O6-methylguanine from the DNA and the production of S-methylcysteine. Partially purified TII & TIII proteins show specificity for O4-alkylthymine and methyl phosphotriesters respectively. The mode of repair by the isolated methyltransferases is similar yet there is no competition for substrate specificity. The apparent molecular weights of TI, TII & TIII proteins are 31Kd, 22Kd, and 13Kd respectively.

Alkylating Agents↗
PubMed1987

DNA glycosylase enzymes induced during chemical adaptation of M. luteus.

Five peaks of DNA glycosylase activity showing a preference for MNNG alkylated DNA have been identified from extracts of adapted M. luteus. They are numerically designated as GI to GV in order of their decreasing molecular weights. The first two of these peaks have been highly purified. GI, is a constitutive heat labile protein, 35% stimulated by the presence of 50 mM NaCl, acts exclusively on 3 MeA residues in alkylated DNA, 60-70% inhibited by the presence of 2 mM free 3MeA and has been designated as 3MeA DNA glycosylase enzyme. GII, which is an inducible protein, is heat stable, 28% inhibited by the presence of 50 mM NaCl, removes 3MeA, 3MeG, 7MeA & 7MeG with different efficiency, and has been designated as 3,7 methylpurine DNA glycosylase enzyme. The rate of release of 3 methylpurines is 30 times that of 7MeG. There is no activity of either enzyme on O2-MeC, O2-MeT, O4-MeT or O6-MeG. The apparent molecular weights of GI and GII proteins are 28 Kd and 22 Kd respectively.

Bacterial Proteins↗
PubMed1987

Mutagenicity testing of some medicinal herbs.

Extracts of four brands of a Pakistani local medicine called naswar and six indigenous herbs commonly used as medicine in children were tested for their ability to induce mutations to prototrophy in Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537. Petroleum ether extracts of one brand of naswar, namely green naswar of Peshawar, exhibited mutagenicity in all of the four tester strains. Organic extracts of three herbs, Saussurea lappa, Swertia chiraita, and Skimmia laureola, exhibited mutagenic activity in tester strain TA98. Green naswar of Bannu, grey naswar, red naswar, and the remaining three herbs, namely, Acorous calamus, Azadarachta indica, and Zanthozylum alatum, exhibited no mutagenic activity under the present experimental conditions. The abilities of green naswar of Peshawar and Saussurea lappa to induce mutations was shown to be related to the presence of cyclic aromatic compounds with molecular formulas C34 H44 O9 and C15 H18 O2, respectively. The experimental data are discussed as they relate to the potential hazards of such naturally occurring compounds and to synthetic compounds in excessive and uncontrolled use by the general public in villages in Pakistan.

Animals↗
PubMed1985

Chemical adaptation of M. luteus induces repair functions for O-alkylated DNA pyrimidines.

A partially purified extract prepared from adapted M. luteus cells contains repair functions for oxygen methylated pyrimidine residues present in alkylated DNA. The removal of O2-MeT is mediated by a DNA glycosylase enzyme whereas disappearance of O4-MeT is effected by a methyltransferase in a manner similar to the in situ repair of O6-MeG. O4-MeT methyltransferase enzyme is unusually heat resistant. Synthesis of these repair proteins, which are distinctly different from the previously known inducible 3-MeA DNA glycosylase and O6-MeG methyltransferase activities, forms a part of the adaptive response.

DNA Glycosylases↗
PubMed1984

Adaptive response of Micrococcus luteus to alkylating chemicals.

Wild type M. luteus cells have been adapted by a step-wise treatment with sub-lethal concentrations of MNNG. The adapted cells exhibit 5.7 fold increased resistance to the killing effects of the mutagen and a simultaneous efficient removal of various base modifications present in cellular DNA. A protein extract prepared from adapted cells contains inducible repair functions which can reduce 80-90% of the alkylated DNA content of 06-MeG is effected by a transmethylase and there is no concomitant release of the modified base. However, N-3 MeG is released as a free modified base through the action of a DNA glycosylase. The release of N-3 MeA is unaffected by the induction treatment whereas that of N-7 methylpurine is slightly improved in the adapted cells.

Alkylating Agents↗
PubMed1978

Properties of 3-methyladenine-DNA glycosylase from Escherichia coli.

An Escherichia coli enzyme that releases 3-methyladenine and 3-ethyladenine in free form from alkylated DNA has been purified 2800-fold in 7% yield. The enzyme does not liberate several other alkylation products from DNA, including 7-methylguanine,O6-methylguanine, 7-methyladenine, N6-methyladenine, 7-ethylguanine, O6-ethylguanine, and the arylalkylated purine derivatives obtained by treatment of DNA with 7-bromomethyl-12-methylbenz[a]anthracene. The reaction of the enzyme with alkylated DNA leads to the introduction of apurinic sites but no chain breaks (less than one incision per ten apurinic sites), and there is no detectable nuclease activity with native DNA, depurinated DNA, ultraviolet-irradiated DNA, or X-irradiated DNA as potential substrates. The enzyme is termed 3-methyladenine-DNA glycosylase. It is a small protein, Mr = 19 000, that does not require divalent metal ions, phosphate, or other cofactors in order to cleave base-sugar bonds in alkylated DNA.

Adenine↗
PubMed1977

Micrococcus luteus correndonucleases. II. Mechanism of action of two endonucleases specific for DNA containing pyrimidine dimers.

Py pyrimidine dimers Py correndonucleases I and II from Micrococcus luteus act exclusively on thymine-thymine, cytosine-cytosine, and thymine-cytosine cyclobutyl dimers in DNA, catalyzing incision 5' to the damage and generating 3'-hydroxyl and 5'-phosphoryl termini. Both enzymes initiate excision of pyrimidine dimers in vitro by correxonucleases and DNA polymerase I. The respective incised DNAs, however, differ in their ability to act as substrate for phage T4 polynucleotide ligase or bacterial alkaline phosphatase, suggesting that each endonuclease is specific for a conformationally unique site. The possibility that their respective action generates termini which represent different degrees of single strandedness is suggested by the unequal protection by Escherichia coli binding protein from the hydrolytic action of exonuclease VII.

Alkaline Phosphatase↗
PubMed1977

Micrococcus luteus correndonucleases. I. resolution and purification of two endonucleases specific for DNA containing pyrimidine dimers.

Five peaks of endonuclease activity showing a preference for ultraviolet-damaged DNA have been chromatographically identified from extracts of Micrococcus luteus. They are numerically designated as I to V in order of their elution from phosphocellulose (Whatman P-11) columns. The first two of these peaks have been highly purified by a combination of gel filtration and affinity chromatography and are catalytically homogeneous judging from their effect on transforming DNAs. Peak I, which has an isoelectric point of 4.7, is heat-stable, requires high ionic strength for optimal activity, acts with equal facility on ultraviolet-irradiated native and denatured DNA, and has been designated as Py pyrimidine dimer Py correndonuclease I. Peak II which has a pI value of 8.7, is heat-labile, is inhibited by high ionic strength, acts on ultraviolet-irradiated native but not denatured DNA, and has been designated as Py pyrimidine dimer Py correndonuclease II. Both enzymes are inhibited by Ca2+ and Zn2+, do not show any cofactor or sulfhydryl requirement, act optimally between pH 7.0 and 7.4, and have molecular weights between 11,000 and 15,000. Py pyrimidine dimer Py correndonuclease I requires a dose about 1.6 times that for Py pyrimidine dimers Py correndonuclease II for incision saturation of irradiated phiX174 RFI DNA.

Chromatography, Gel↗
PubMed1977

Micrococcus luteus correndonucleases. III. Evidence for involvement in repair in vivo of two endonucleases specific for DNA containing pyrimidine dimers.

Involvement of Py pyrimidine dimers Py correnconucleases I and II in repair of ultraviolet radiation damage in vivo by Micrococcus luteus has been demonstrated by their absence in the ultraviolet-sensitive mutant DB-7 derived by treatment of the wild type parent with N-methyl-N'-nitro-N-nitrosoguanidine. The necessity for their combined action in DNA repair in M. luteus is shown by: (a) reactivation of ultraviolet-damaged phiX174 RFI DNA in incision-defective hosts after in vivo treatment with both enzymes, (b) correlation between survival after ultraviolet irradiation and the level of the two enzymes, and (c) increased levels of repair synthesis after ultraviolet irradiation of toluenized cells DB-400 with wild type correndonuclease levels when compared with the transformant DB-200 and the mutant DB-7, which lack one or both enzymes.

DNA Repair↗