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Biomedical subjects

A Nasim

Publications and source records attributed to A Nasim.

At least 55 records · Page 3Linked to original sources

Trends in abdominal aortic aneurysms: a 13 year review.

AIM: To assess changing trends of abdominal aortic aneurysms 1979-1991. DESIGN: Retrospective study from the Leicestershire Health Authority. RESULTS: 727 patients with abdominal aortic aneurysm were treated. Of these 56.4% were admitted for elective repair and 43.6% presented with rupture. There was a significant increase in the number of ruptured aortic aneurysms over this period despite an increase in the number of elective repairs. The overall 30-day mortality of elective repair (including patients with symptomatic but non-ruptured aneurysms) was 8.8%. The overall 30-day mortality of ruptured aneurysms (including patients who were deemed medically too unfit for surgery) was 57.7%. There has been no significant change in elective and ruptured mortality over the study period. There was a significant increase in the median age of patients (69.5 yrs in 1979 to 74 yrs in 1991). CONCLUSION: The increasing incidence of abdominal aortic aneurysms may reflect better diagnostic methods, greater clinical awareness of the condition and increase in the proportion of elderly people in the population.

Adult↗

Video-thoracoscopic lung biopsy in diagnosis of interstitial lung disease.

Lung biopsy remains an important investigation in the diagnosis of diffuse interstitial lung disease despite improved diagnostic yield of high resolution computed tomography scanning. We describe 19 pulmonary wedge biopsies (13 men and 6 women) performed using videothoracoscopic technique. The median age of the patients was 56 years (range 32-72 years). All our patients were suspected to have diffuse interstitial lung disease and were referred for lung biopsy to obtain a histological diagnosis. Thoracoscopic wedge excisions were accomplished under general anaesthesia using high frequency jet ventilation and a percutaneous stapling device. A tissue diagnosis was obtained in all patients: 8 had cryptogenic fibrosing alveolitis, 3 had interstitial pulmonary fibrosis, 2 had emphysema, 2 had extrinsic allergic alveolitis, 2 had sarcoidosis, 1 had non-specific chronic inflammation, and 1 had pulmonary haemosiderosis. There were no operative deaths. There was one failure resulting in conversion to an open procedure. There were three complications: two air leaks and one effusion. Median postoperative hospital stay was 2 days (range 2-7 days). We conclude that videothoracoscopic wedge biopsy is a safe and effective procedure and should be recommended in patients who require a histological diagnosis of diffuse interstitial lung disease.

Adult↗

Endovascular repair of abdominal aortic aneurysm: limitations of the single proximal stent technique.

Endovascular repair of abdominal aortic aneurysm (AAA) has been performed using both a single proximal stent technique and a double (proximal and distal) stent method to anchor a graft in the aneurysm lumen. This study examined the effect of the single proximal stent technique on femoral artery blood flow, renal function and the occurrence of back-bleeding into the aneurysm sac in a canine model; eight dogs were used. Femoral artery blood flow and glomerular filtration rate were not affected by graft-stent insertion. Two graft-stent combinations failed to deploy in the correct position and led to graft thrombosis in one case. The six correctly positioned grafts all showed back-bleeding from around the distal end into the aneurysm sac. The single proximal stent technique for endovascular repair of AAA is inadequate and attention should continue to focus on a double (proximal and distal) stent method or a bifurcated system.

Animals↗

Determination of haemophilia A carrier status from hair samples using polymerase chain reaction technique.

The usefulness of intragenic restriction fragment length polymorphisms (RFLPs) for BclI, HindIII and XbaI, adapted for polymerase chain reaction (PCR), was tested for the detection of haemophilia A carrier status in the consultant of a family in which only haematological information was available on the inheritance of the trait. Hair follicles were used as the non-invasive source of DNA. The mother was found to be homozygous for BclI and heterozygous for HindIII sites, whereas her status as regards informativeness could not be established for XbaI. On the basis of HindIII RFLP, the daughter was found to be a carrier of the haemophilia trait. This was confirmed by sequencing the amplified intron 19 of the mother and the daughter. The RFLP for XbaI did not appear to be suitable for carrier detection using PCR due to the difficulty of establishing homozygosity or heterozygosity from the results of digestion of the amplified product.

Base Sequence↗

The rad16 gene of Schizosaccharomyces pombe: a homolog of the RAD1 gene of Saccharomyces cerevisiae.

The rad10, rad16, rad20, and swi9 mutants of the fission yeast Schizosaccharomyces pombe, isolated by their radiation sensitivity or abnormal mating-type switching, have been shown previously to be allelic. We have cloned DNA correcting the UV sensitivity or mating-type switching phenotype of these mutants and shown that the correcting DNA is encompassed in a single open reading frame. The gene, which we will refer to as rad16, is approximately 3 kb in length, contains seven introns, and encodes a protein of 892 amino acids. It is not essential for viability of S. pombe. The predicted protein is the homolog of the Saccharomyces cerevisiae RAD1 protein, which is involved in an early step in excision-repair of UV damage from DNA. The approximately 30% sequence identity between the predicted proteins from the two yeasts is distributed throughout the protein. Two-hybrid experiments indicate a strong protein-protein interaction between the products of the rad16 and swi10 genes of S. pombe, which mirrors that reported for RAD1 and RAD10 in S. cerevisiae. We have identified the mutations in the four alleles of rad16. They mapped to the N-terminal (rad10), central (rad20), and C-terminal (rad16 and swi9) regions. The rad10 and rad20 mutations are in the splice donor sequences of introns 2 and 4, respectively. The plasmid correcting the UV sensitivity of the rad20 mutation was missing the sequence corresponding to the 335 N-terminal amino acids of the predicted protein. Neither smaller nor larger truncations were, however, able to correct its UV sensitivity.

Amino Acid Sequence↗

Cellular recovery, DNA repair and mutagenesis--a tale of two yeasts.

In studies related to recovery and repair mechanisms following DNA damage, one problem that has been frequently addressed concerns the effects of DNA repair on both spontaneous and induced mutagenesis. Among the eukaryotic organisms which served as unique and valuable systems for investigating this problem are the two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe. With the basic genetics well worked out in both, these yeasts have provided the experimental tools for comparative analysis of mechanisms of DNA repair which show a great deal of diversity between the two unicellular eukaryotes. Since the present issue focuses on the contributions of R.H. Haynes to the area of DNA repair and mutagenesis, we have chosen to discuss those specific aspects of our studies which are directly or indirectly related to or influenced by his research in this field. These include: (i) liquid holding recovery, (ii) production of two strand mutations and the concept of heteroduplex repair, and (iii) understanding of pathways of repair through construction of supersensitive mutants in yeast.

DNA Repair↗

Schizosaccharomyces pombe ras1 and byr1 are functionally related genes of the ste family that affect starvation-induced transcription of mating-type genes.

We have further investigated the function of the ras1 and byr1 genes, which were previously shown to be critical for sexual differentiation in fission yeast cells. Several physiological similarities between strains containing null alleles of these genes supports the idea that ras1 and byr1 are functionally closely related. Furthermore, we have found that byr1 is allelic to ste1, one of at least 10 genes which when mutated can cause sterility. Since ras1 had previously been found to be allelic to ste5, both ras and byr genes are now clearly shown to be a part of the ste gene family, thus confirming their close functional relationship. The observation that the mating-type loci could overcome the sporulation block of ras1 and byr1 mutant strains prompted investigation of the role of the ras-byr pathway in the induction of the mating-type gene transcripts upon nitrogen starvation. By Northern analysis of RNA preparations from strains carrying wild-type or mutant ras1 alleles and grown to different stages of the growth cycle, we have shown that ras1 plays an important role in inducing the Pi transcript of the mating-type loci and the mei3 gene transcript. These observations provide a molecular basis for the role of the ste gene family, including ras1 and byr1, in meiosis and indicate that further characterization of other ste genes would be very useful for elucidating the mechanism of ras1 function in fission yeast cells.

Alleles↗

Cloning and analysis of a gene involved in DNA repair and recombination, the rad1 gene of Schizosaccharomyces pombe.

We have cloned the rad1 gene of Schizosaccharomyces pombe by complementation of the rad1-1 mutant, which is deficient in DNA repair and recombination. The coding region of the gene is 582 base pairs long and contains no introns. The predicted product is a strongly acidic, 22-kilodalton protein containing 194 amino acid residues. This gene does not exhibit significant homology to any other known repair gene. The major transcription start site is at 27 base pairs upstream of the putative start codon. Insertion mutagenesis revealed that besides the coding region, at least 151 base pairs of 5'-flanking sequence are required for full complementing activity. A strain carrying a null allele of rad1 was constructed and found to have a phenotype closely similar to that of the rad1-1 mutant. Expression in Escherichia coli of the coding region yielded a protein product of a size close to that predicted from the DNA sequence. This product reacted with antibodies raised against a synthetic peptide with a sequence from that predicted for the protein product. We have localized the rad1 gene to NotI fragment E of the S. pombe genome.

Amino Acid Sequence↗

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↗

A gene which encodes a predicted protein kinase can restore some functions of the ras gene in fission yeast.

The ras1- mutation of the fission yeast Schizosaccharomyces pombe interferes with sexual differentiation by preventing conjugation and causing inefficient sporulation. From a gene library, we have isolated a gene, byr1+, which when in high copy number restores efficient sporulation to ras1- strains. byr1+ encodes a putative 340-amino acid protein product, the sequence of which strongly suggests that it functions as a protein kinase. Gene disruption experiments show that loss of byr1+ function does not interfere with mitotic growth but it completely prevents both conjugation and sporulation. byr1 is thus another important gene in the sexual differentiation pathway and we believe that at least part of ras1 function is to act directly or indirectly through byr1 to modulate protein phosphorylation.

Amino Acid Sequence↗

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↗

Purification and characterization of the extracellular alpha-amylase activity of the yeast Schwanniomyces alluvius.

The extracellular alpha-amylase activity of the yeast Schwanniomyces alluvius has been purified by anion-exchange chromatography on DEAE-cellulose and gel-filtration chromatography on Sephadex G-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and N-terminal amino acid analysis of the purified sample indicated that the enzyme preparation was homogeneous. The enzyme is a glycoprotein having a molecular mass of 52 kilodaltons (kDa) estimated by SDS-PAGE and 39 kDa by gel filtration on Sephadex G-100. Chromatofocusing shows that it is an acidic protein. It is resistant to trypsin but sensitive to proteinase K. Its activity is inhibited by the divalent cation chelators EDTA and EGTA and it is insensitive to sulfhydryl-blocking agents. Exogenous divalent cations are inhibitory as are high concentrations of monovalent salts. The enzyme has a pH optimum between 3.75 and 5.5 and displays maximum stability in the pH range of 4.0-7.0. Under the conditions tested, the activity is maximal between 45 and 50 degrees C and is very thermolabile. Analysis of its amino acid composition supports its acidic nature.

Amino Acids↗