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Biomedical subjects

M Ahmad

Publications and source records attributed to M Ahmad.

At least 271 records · Page 15Linked to original sources

Mutagenic activity of certain synthetic steroids: structural requirement for the mutagenic activity in Salmonella and E. coli.

Eight steroids, structurally related to cholesterol, were tested for mutagenic activity in the Ames tester strains. All the test compounds were mutagenic without metabolic activation, although metabolic activation markedly enhanced their activity. A significant decrease in the survival of the radiation-sensitive mutants recA and lexA of Escherichia coli was observed as compared to their wild-type counterpart in the presence of the steroids. The role of recA and lexA genes gains further support from the lambda prophage induction in the lysogen as well as with Salmonella strains triggering the error-prone SOS response. Structural features which appear to be essential for mutagenic activity in these strains of the steroids are (1) reactive thio, sulfonyl or sulfinyl groups at the 6 position and (2) a halogen group at the 3 position of the steroidal nucleus. The mutagenicity appears to involve the formation of H2O2 as well as superoxide and hydroxyl radicals.

Catalase↗

Damage and mutagenesis of bacteriophage lambda induced by high pH.

Bacteriophage lambda-Escherichia coli complexes exhibited remarkable sensitivity to alkaline pH 10.0 at 37 degrees C. The decline in plaque forming units after alkali treatment was more pronounced in complexes with some of the radiation repair defective mutants of E. coli K-12, i.e. uvrArecA, recA, rer and lexA mutants as compared to those of uvrA, recB and wild-type strains. The red gene of lambda phage and recA gene of E. coli seem to have a complementary effect on the alkali induced lesions. Alkaline treatment to lysogenic lambda phage was also found to be mutagenic. An enhanced level of mutagenesis was observed when treated phage particles were allowed to adsorb on treated wild-type bacteria. Moreover, the alkali treatment to lysogen (lambda cI857-E. coli) resulted in prophage induction in nutrient broth even at 32 degrees C. Thus on the basis of these results the role of error prone SOS repair systems in the repair of alkali induced lesions in lysogenic bacteriophage lambda has been suggested.

Bacteriophage lambda↗

Mutagenic activity of aziridinyl steroids and their mechanism of action in biological systems.

The aziridinyl derivatives of steroids, structurally related to cholesterol, were tested for their mutagenic activity in the Ames tester strains. The test compounds were mutagenic without metabolic activation, although metabolic activation markedly enhanced their activity. A significant decrease in the survival of SOS defective mutants, recA and lexA of Escherichia coli was observed as compared with their wild-type counterpart in the presence of the steroids. The role of SOS repair genes gains further support from the lambda prophage induction in the lysogen and beta-galactosidase induction in the Mud strains as well as mutagenesis with Ames tester strains. Structural features which appear essential for mutagenic activity in these strains are (i) a reactive N-aminophthalamide group at the (5,6-b) position and (ii) an acetoxy/chlorine group at the third position of the steroidal nucleus. The individual moieties/groups were not mutagenic per se. These steroids appear to generate H2O2 as well as superoxide and hydroxyl radicals in the model biological system.

Aziridines↗

Ototoxicity due to cis-diamminedichloroplatinum in the treatment of ovarian cancer: influence of dosage and schedule of administration.

Ototoxicity associated with administration of cisplatin was assessed in four groups of patients suffering from advanced ovarian carcinoma. The purpose was to determine the influence of dosage, schedule of administration, and long-term treatment on pure-tone thresholds and other auditory parameters. One hundred and forty-five serial audiograms were obtained in 60 patients and compared with baseline audiograms. The treatment protocol consisted of two different dosages (low--50 mg/m2 and high--100 mg/m2) and three different schedules of administration (short--6 months, extended--12 months, and treatment in blocks--intervening months in which cisplatin was withheld). Using a conservative definition of auditory toxicity and statistical analyses of pure-tone threshold differences between groups, the results indicated that the low dose-short treatment regimens with either monthly administration of cisplatin, or administration in blocks, were the least ototoxic. Ototoxicity was found to increase with increasing cumulative dosages. Hearing loss was primarily in the high frequencies. The most severe ototoxic effects, which include tinnitus and hearing loss in the speech frequency range, were associated with the administration of high dosages over a short period of time. Individual variability in susceptibility to ototoxicity necessitates systematic audiometric monitoring throughout therapy.

Adult↗

Synthesis and biological evaluation of mouse growth hormone-releasing factor.

The recently described mouse growth hormone-releasing factor (mGRF) was synthesized by the solid phase procedure, purified by 2 stages of preparative high performance liquid chromatography and fully characterized. The biologic activity of the 42-amino acid peptide (H-His-Val-Asp-Ala-Ile-Phe- Thr-Thr-Asn-Tyr- Arg-Lys-Leu-Leu-Ser-Gln-Leu-Tyr-Ala-Arg-Lys-Val-Ile-Gln-Asp-Ile-Met-Asn- Lys- Gln-Gly-Glu-Arg-Ile- Gln-Glu-Gln-Arg-Ala-Arg-Leu-Ser-OH) was assessed in primary cultures of both mouse and rat anterior pituitary cells and compared to synthetic rat (rGRF) and human (hGRF) growth hormone-releasing factors. mGRF was equipotent to rGRF in mouse somatotrophs but slightly less potent in rat somatotrophs, while hGRF was 3-5 times less potent in both rodent species.

Amino Acid Sequence↗

Comparison between two ultrasonic units in shaping curved canals in teeth using macroradiography.

The efficacy of two ultrasonic units in shaping curved canals in teeth were compared. Twenty teeth were instrumented using the Cavi-Endo unit at a power setting 1 using the technique recommended by the manufacturer. Another group of 20 teeth received similar treatment but were instrumented with the Enac unit. The time taken to instrument each canal was recorded. The pre- and post-instrumented radiographs of the teeth of x 10 magnification were taken using a microfocal technique. The radiographs were subjected to a subtraction technique to result in composite images of the pre- and post-instrumented shapes. The canal shape and the incidence of elbows were evaluated using various measurements taken from the radiographs. The manner the dentine was removed was similar in both groups. All canals exhibited unequal removal along the canal with more dentine being removed at the coronal end. The Enac group exhibited a higher incidence of elbows which occurred further apically than those in the Cavi-Endo group. There was no significant difference between groups in the following: time of instrumentation, amount of apical and coronal canal enlargement, apical deviation and change in width at the elbow. These findings were no different from those of another study using simulated canals.

Chi-Square Distribution↗

Cytokine administration alters the distribution of activated lymphocytes to the lung.

The effects of intraperitoneal injections of recombinant interleukin-1 alpha (IL-1; 250,000 U/day), interleukin-2 (IL-2; 50,000 units/day), interferon-gamma (IFN-gamma; 50,000 U/day) and tumor necrosis factor-alpha (TNF; 100,000 U/day), on the biodistribution of concanavalin A (Con A)-activated, indium-111-labeled lymphocytes were evaluated in BALB/c mice. Syngeneic spleen cells were activated for 48 h in medium with Con A (5 micrograms/ml) and maintained in culture for 72 h in IL-2 (1,000 U/ml). Groups of 12 mice were treated for 4 days with either one of the cytokines or saline. On day 4, mice received 10(7) lymphocytes (3-5 mu Ci) intravenously. Mice were sacrificed at 4 and 24 h following injection and the percent of administered dose per organ was determined. TNF and IL-1 produced a significant increase in lung uptake of radiolabeled lymphocytes at 4 and 24 h, whereas IL-2 and IFN-gamma decreased uptake at both time points. IL-1 increased uptake by liver at 4 and 24 h while IL-2 increased uptake only at 4 h. We conclude that the distribution of activated lymphocytes following adoptive transfer is altered by cytokines. This finding may have important implications for cell delivery during adoptive immunotherapy.

Animals↗

Amino acid sequence analysis of proteins in the human corneal stromal cell membrane.

Plasma membrane proteins from human corneal stromal fibroblasts were isolated and separated by two-dimensional polyacrylamide gel electrophoresis. Separated polypeptides were electroeluted onto polyvinylidene difluoride (PVDF) membranes and individual polypeptides were subjected to NH2-terminal amino acid sequence analysis. Of a total of 33 polypeptides sequenced, 26 were found to be blocked at their NH2-terminus. Seven major membrane polypeptides were sequenced and further analyzed. One polypeptide, designated #18, was determined to be homologous to the beta subunit of prolyl hydroxylase/protein disulfide isomerase/thyroid hormone-binding protein. The other six polypeptides were found to have no significant sequence homology with any known polypeptides, as revealed by a protein data base homology search. Polypeptide Bands #90, #102, and #103 were found to have the same NH2-terminal amino acid sequence and the same overall molecular weight, yet separated from one another according to pI. These three polypeptides probably arose from differential posttranslational modification of the same original protein. Synthetic peptides were prepared from the #18 and #19 sequence and antibodies were produced. Immunostaining of cultured human corneal stromal cells and frozen sections of corneas demonstrated that these membrane polypeptides were present in corneal keratocytes, both in vitro and in vivo. Antibody against #18 stained fixed cultured corneal fibroblasts in a very fibrous pattern, with more intense staining in the perinuclear region of the cell, while antibody against #19 stained the cell surface in a much more uniform pattern. In sections of human cornea, both antibodies stained only the keratocytes in the stroma, but they also appeared to stain epithelial cells.

Amino Acid Sequence↗

Phycochemical studies on Scinaia fascicularis (Bonnemaisoniales, Rhodophyta).

The sterol composition of marine red alga, Scinaia fascicularis (Bphirg.) Huisman has been studied and cholesta-5, 20, 24-trien-3beta-ol, 22-dehydrocholesterol, brassicasterol, 24-methylene cholesterol, 24-methyl cholesterol, nor 31-cycloartanol, ergost-5-en-3,25-diol and lanostan-3beta-ol were identified through mass and 1H-NMR spectroscopy. All of them were present in more or less equal amount. The fatty acid methyl esters, analysed through GC-MS, were found to be methyl laurate, tridecylate, myristate, pentadecylate, palmitate, margarate, stearate and nonadecylate. Methyl myristate was present in largest and laurate in smallest quantity, no unsaturated fatty acid could be detected.

Journal Article↗

Phycochemical investigations on Centroceras clavulatum (Ceramiales, Rhodophyta).

The methanolic extract of a marine red alga Centroceras clavulatum (C. Ag.) Mont., collected from the coast of Karachi, was studied for its fatty acid and sterol compositions. The analysis of fatty acid methyl esters by GC-MS revealed the presence of methyl laurate, tridecylate, myristate, pentadecylate, palmitate, margarate, nonadecylate, arachidate, behenate, tricosanoate and pentacoeanoate among saturated and methyl palmitoleate and heptadecylenate among unsaturated acids. The sterol composition divulged the presence of 22-dehydrocholeaterol, cholesterol, 24-methyl-cholesterol and beta-sitosterol, identified through main spectrometry and 1H-NMR spectroscopy.

Journal Article↗

Localization of technetium-99m-glucarate in zones of acute cerebral injury.

The potential structural similarity of technetium-99m-labeled glucaric acid (99mTc-glucarate) to that of fructose suggests that this agent may enter cells by a sugar transport system. Studies with LLC-PK1 cells demonstrated inhibition of 99mTc-glucarate uptake by fructose, confirming this potential relationship. Since anaerobic metabolism can use either glucose or fructose, we hypothesized that 99mTc-glucarate may concentrate in areas of acute ischemic injury. To test this hypothesis, 63 adult rats with middle cerebral artery (MCA) occlusion followed by reperfusion were injected with 99mTc-glucarate and in vivo and ex vivo images were acquired. Seven animals were also studied with 18FDG and high resolution PET imaging. The radionuclide images were compared to the results of triphenyl tetrazolium chloride (TTC) staining and conventional histopathology. Thirty-five rats had significant accumulation of 99mTc-glucarate and no TTC staining (indicating infarction) in the involved hemisphere. Of the remaining 28 rats with TTC staining (suggesting viability) of the involved hemisphere, 16 (57%) had 99mTc-glucarate accumulation. In the seven rats that were studied with both 99mTc-glucarate and 18FDG, 99mTc-glucarate accumulated at the center of the occluded MCA territory while 18FDG activity was decreased in this region. These results suggest that 99mTc-glucarate is a sensitive marker of acute severe cerebral injury, but its mechanism of localization is probably different from that of 18FDG.

Animals↗

Alpha-thalassaemia: prevalence and pattern in northern Pakistan.

The level of Hb Bart's is directly related to the inheritance of alpha-thalassaemia gene. Hb electrophoresis for Hb Bart's in the cord blood is a very simple method of finding out the prevalence of alpha-thalassaemia gene in a given population. A study was, therefore, carried out to find out the prevalence of alpha-thalassaemia gene in the population of northern Pakistan by estimating the concentration of Hb Bart's in 500 cord blood samples during the period 1986-87 at AFIP Rawalpindi. Hb Bart's was detected in 12 neonates, thus indicating a rate of 2.4% of general population as carrier of alpha-thalassaemia gene. Two distinct groups were recognized. The first group was composed of 9 (75%) neonates, in which Hb Bart's levels varied between 2.0% to 3.5%, while the second group of 3 neonates (25%) showed a level of 5.8% to 6.3%. The former group was considered to be carrying alpha-thalassaemia-2 gene and the latter group as carrier of alpha-thalassaemia-1 gene. Neither Hb H disease nor Hb Bart's hydrops foetalis syndrome was detected in this series.

Female↗

Role of prostaglandin synthesis inhibitors in the passage of ureteric calculus.

Diclofenac sodium, one of the prostaglandin synthesis inhibitors was evaluated in terms of passage or movement of ureteric stones upto the size of 0.5 cm in a series of 80 patients. Forty-six (57.5%) patients passed the stone within a period of 4 weeks. This frequency of stone passage was significantly higher when compared with stone passage of similar size in other series (P less than 0.001). In 17 (56.6%) out of 30 patients, stone moved from upper and middle ureter to the lower ureter which is also significant from therapeutic point of view. Complete pain relief was achieved in 67 (84%) patients. No side effects of the drug noted in this series. The sequence of events following ureteral obstruction by the stone, based on recent experimental and clinical studies is discussed and possible mechanism of action of diclofenac sodium was highlighted.

Adolescent↗

The pattern of malignant tumours in northern Pakistan.

A retrospective study of 14,018 malignant tumours from northern Pakistan is presented. The data reflects the pattern of cancer distribution in this region. Among males most common sites are lymphnode, leukemia, skin, prostate, colorectal, bone and stomach and in females breast, skin, ovary, leukemia, gall-bladder, thyroid and bone. The distribution of malignant tumours in various districts of northern Pakistan and different ethnic groups like Pathans, Punjabis and Urdu speaking have also been outlined. Age standardized cancer ratio (ASCAR) was calculated to compare the data from the neighbouring countries of the region. Prostatic cancer in males and gall-bladder carcinoma in females is more frequent in our material as compared to other countries of the region. Comparison of the pattern of malignant tumours in North and South has also been highlighted.

Female↗

Toxoplasmic lymphadenitis--a clinicopathological study.

Forty-three cases of toxoplasmic lymphadenitis were studied. They constituted 0.5% of all lymph node biopsies and 4.2% of reactive lymphadenitis. The histological findings supporting a diagnosis of toxoplasmosis were correlated with serological studies. The condition primarily affects young men, causing cervical lymph node enlargement and varying degrees of fatigue, malaise, cough and fever. It is usually self-limited. This study emphasizes the need for clinicians to consider toxoplasmosis in the differential diagnosis of lymphadenopathies.

Adolescent↗