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Biomedical subjects

M Ahmad

Publications and source records attributed to M Ahmad.

At least 253 records · Page 14Linked to original sources
PubMed1992

Kinetics of dipeptidyl peptidase IV proteolysis of growth hormone-releasing factor and analogs.

The kinetics and selectivity of proteolysis of synthetic human growth hormone-releasing factor and analogs by purified human placental dipeptidyl peptidase IV (DPP IV) were studied by HPLC. The initial rates of Ala2-Asp3 cleavage (pH 7.8, 37 degrees C, So = 0.15 mM) were all approx. 5 mumol min-1 mg-1 for the parent hormone, GRF(1-44)-NH2, and the fragments, GRF(1-29)-NH2 and GRF(1-20)-NH2. Lower activities observed for GRF(1-11)-OH, GRF(1-3)-OH, and cyclic lactam analogs indicate S1'-Sn' binding. Assays of [Trp6]-GRF(1-29)-NH2 versus [D-Trp6]-GFR(1-29)-NH2 indicate an S4' binding cavity. Peptides with D-configuration at P2, P1 or P1' and desNH2Tyr1 and N-MeTyr1 analogs of GRF were not cleaved. Catalytic parameters for the P1-substituted analogs [X2,Ala15]-GRF(1-29)-NH2 were found to vary with X as follows, Km: Abu less than Ala less than Pro less than Val less than Ser less than Gly much less than Leu; kcat: Pro greater than Ala greater than Abu greater than Ser greater than Gly much greater than Leu greater than Val; kcat/Km: Abu greater than Pro greater than Ala much greater than Ser greater than Gly = Val much greater than Leu. Km is at a minimum and kcat/Km at a maximum, for a hydrophobic P1 side-chain of about 0.25 nm in length, i.e., the ethyl side-chain of alpha-aminobutyric acid (Abu) is very close to optimal. These results further define the S1 selectivity of DPP IV and may be useful in the design of DPP IV resistant GRF analogs that can be produced by recombinant DNA methods and the design of DPP IV inhibitors.

Amino Acid Sequence↗
PubMed1992

Effect of dehydration on the disposition kinetics of erythromycin in rabbits.

The effect of water deprivation on the physiologic, biochemical, and disposition parameters of erythromycin was investigated in rabbits. The packed cell volume, plasma glucose, and total lipid concentration increased significantly in dehydration. The pharmacokinetic parameters of erythromycin after intravenous administration also changed, suggesting a need for monitoring toxicity of erythromycin in the water-deprived population.

Animals↗
PubMed1992

Cancer-related urinary proteinase inhibitor, EDC1: a new method for its isolation and evidence for multiple forms.

During the past several years, numerous laboratories have reported isolation and purification of proteinase inhibitors from human urine. Many of these molecules were incompletely characterized and some of them may have been artifacts in part because of harsh procedures used for their isolation. Consequently, there is disagreement and confusion regarding the biochemical characteristics of these inhibitors. We previously reported the isolation of a proteinase inhibitor, EDC1, from the urine of a leukemic patient. This molecule, M(r) 30 kDa, was antigenically related to plasma inter-alpha-trypsin inhibitor (IATI) and inhibited the growth of a virally transformed B cell line. Immunoreactive EDC1 was also the major component of low molecular weight proteinuria observed in cancer patients. We now report a new method for the isolation of EDC1 from urine of patients with adenocarcinomas of colon and lung and melanoma and compare its partial amino acid sequence with that of HI 30, a proteinase inhibitor previously isolated from pooled normal urine by Hochstrasser et al. [Hoppe-Seyler's Z Physiol Chem 357:153-162, 1976]. Our method involves i) a batchwise cation exchange, ii) gel filtration chromatography, iii) anion exchange chromatography on FPLC, and iv) reverse phase C18 chromatography on HPLC. This method is mild and results in an overall yield of 0.4 to 1.2 mg of EDC1/liter urine. On the basis of the partial N-terminal amino acid sequence of its N terminal (38 residues) and middle regions (29 residues), EDC1 appears to be identical with HI30. Surprisingly, during this isolation procedure, another proteinase inhibitor, M(r) 22 kDa, which cross-reacted with antisera to EDC1 and IATI, was also isolated. The 22 kDa molecule was a major component of the IATI related urinary molecules and was identical with the 30 kDa EDC1 in which first the 15 N terminal residues were clipped. The lower M(r) inhibitor was not an artifact formed during storage or isolation procedure because the Western blot analysis of fresh cancer and normal urine revealed the 30 and 22 kDa molecules. Thus, both the 30 kDa EDC1 (or HI30) and its clipped variant, the 22 kDa molecule, are physiologic components of IATI related urinary proteinase inhibitors and excretion of both forms may be increased in patients with advanced cancer.

Adenocarcinoma↗
PubMed1992

Mutagenic activity of oxathiolane steroids: structural requirement for the genotoxic activity in Salmonella and E. coli.

Oxathiolanes and disulfonyl derivatives of steroids were tested for mutagenic activity in the Ames tester strains. The test compounds exhibited mutagenic activity without metabolic activation although metabolic activation markedly enhanced their activity. A significant decrease in the survival of the radiation-sensitive mutants recA, lexA and rer of E. coli was observed as compared to their wild-type counterpart in the presence of the test steroid. Structural features which appear to be crucial for the mutagenic activity in these steroidal drugs are: (i) an electron-donating group at position 3, and (ii) a bulky group anchored at the 5th and 6th positions. The test steroids appear to damage DNA which in turn initiates the SOS repair with the concomitant induction of mutation.

Biotransformation↗
PubMed1992

Pilomatricoma: a retrospective study.

A study of 53 Pakistani patients with pilomatricoma diagnosed at AFIP during 1985-1989 is presented. It constituted 37.2% of all benign adnexal tumors, during the same period. 56.2% of patients were more than 30 years of age. Differences in site, sex, and age distribution from Western reports were observed. Unusual clinical presentations were also noted. This study outlines the clinicopathologic features of pilomatricoma in Pakistan.

Adolescent↗
PubMed1992

Observations of acoustic streaming fields around an oscillating ultrasonic file.

The steady acoustic streaming generated around straight and precurved oscillating ultrasonic files driven by the Piezon-Master 400 unit was examined in the free field and in small channels using a stereomicroscope. In addition, the effect of file-wall contact on streaming production was also investigated. The results indicated that the ultrasonic files can generate acoustic streaming both in the free field and in the small channel. Higher velocity streaming was observed when smaller size files were employed and when the file was precurved. Light file-wall contact did not totally inhibit streaming while severe file-wall contact inhibited movement of the file and, as a result, no streaming was observed. The positions and length scales of the streaming vortices appeared to be influenced by the presence of boundaries. In the free field, two rows of vortices were situated along the sides of the file while in the small channel, the vortices were positioned above the surface of the file. These results indicated that it is possible for acoustic streaming to occur in a confined space as in a root canal provided that severe file-wall contact is avoided. It is therefore recommended that light filing or allowing the file to freely vibrate during some stage of treatment should be carried out in order to generate streaming in the root canal.

Humans↗
PubMed1992

Significance of perioperative blood transfusions in patients undergoing resection of stage I and II non-small-cell lung cancers.

Perioperative blood transfusions (BT) have been reported to reduce survival in patients undergoing curative resection of lung cancers. It is postulated that a state of BT-mediated immunosuppression favors the proliferation of tumor cells not resected during surgery. To evaluate this hypothesis and to determine factors influencing the administration of BT, we retrospectively studied the charts of 127 patients who underwent surgery for stage I and II non-small-cell carcinoma. Thirty (23.6 percent) patients received BT and 97 (76.4 percent) did not. Sex, age, race, smoking history, size and stage of the tumor, histology, extent of resection and preoperative hemoglobin values were analyzed. Only age (p = 0.01) and preoperative hemoglobin values (p less than 0.01) were related to transfusion status. Neither survival nor event-free survival differed significantly between the two groups (p = 0.29 and 0.26 respectively). Our results do not support the hypothesis that perioperative BTs have a significant detrimental effect on survival. A prospective study could clarify this controversial issue; however, such a study would be complex considering the multiple variables that affect survival in patients with non-small-cell lung cancers.

Age Factors↗
PubMed1992

Biopharmaceutical studies of spirobishexahydropyrimidine.

Oral administration of spirobishexahydropyrimidine showed an increase in the activity of serum transaminases, lactate dehydrogenase and alkaline phosphatase. Biological half life and other pharmacokinetic parameters showed rapid absorption and slow elimination of the drug.

Alanine Transaminase↗
PubMed1992

Anorectal melanoma in northern Pakistan.

Melanoma of the anorectum is a rare malignancy. At Armed Forces Institute of Pathology (AFIP), 11 cases were diagnosed over a 10 year period (1981-1990) constituting 14.2% of all primary malignant melanomas. The anorectum was the commonest site for noncutaneous melanomas (45.8%). The age group commonly affected was the fifth to seventh decade (72.7%). Most of the tumours were extensive involving both anal canal and rectum. The proportion of anorectal melanoma is much higher in our study as compared to western reports (0.4-1.6%). The distribution of noncutaneous melanomas in our population also differs, with a relatively lower proportion of ocular melanomas (33.3%) which are the commonest (80%) in western studies (JPMA 42: 155, 1992).

Adult↗
PubMed1992

Non-Hodgkin's lymphoma--clinicopathological pattern.

A study of histopathological and clinical features of non-Hodgkin's lymphoma in 495 consecutive cases, diagnosed at AFIP during 1984-1989 is presented. Children below the age of 15 years were not included in this study. The relative frequency of non-Hodgkin's lymphoma was 4.29% in our material. Non-Hodgkin's lymphoma was more frequent than Hodgkin's disease, ratio being 2.44:1. Lymphadenopathy (78.78%), fever (33.08%), weight loss (31.62%) and anemia (30.14%) were the main presenting features. New working formulation was used for morphological characterisation. Follicular lymphoma constituted 8.08% of all cases. Follicular lymphoma was seen only in older age whereas diffuse lymphoma occurred in all age groups. Intermediate and high grade lymphoma represented 73.54% of all NHL. Small lymphocytic lymphoma was common in low grade tumours (13.13%). Extra nodal lymphoma was encountered in a significant proportion (21.22%), gastrointestinal tract being the most frequent site. This study outlines certain interesting features of NHL in Pakistan.

Adolescent↗
PubMed1991

Vascular smooth muscle expresses a truncated Na+, K(+)-ATPase alpha-1 subunit isoform.

By regulating transmembrane Na+ and K+ concentrations and membrane potential, the Na+,K(+)-ATPase plays an important role in regulating cardiac, skeletal, and smooth muscle function. A high degree of amino acid sequence and structural identity characterizes the three Mr 100,000 Na+,K(+)-ATPase alpha subunit isoforms expressed in cardiac and skeletal muscle. Strikingly, vascular smooth muscle utilizes alternative RNA processing of the alpha-1 gene to express a structurally distinct Mr approximately 65,000 isoform, alpha 1-T (truncated). Analysis of both its mRNA and protein structure reveals that alpha-1-T represents a major, evolutionarily conserved, truncated Na+,K(+)-ATPase isoform expressed in vascular smooth muscle. This demonstrates an unexpected complexity in the regulation of vascular smooth muscle Na+,K(+)-ATPase gene expression and suggests that a structurally novel, truncated alpha subunit may play a role in vascular smooth muscle active ion transport.

Amino Acid Sequence↗
PubMed1991

Induction of cytokine messenger RNA and secretion in alveolar macrophages and blood monocytes from patients with lung cancer receiving granulocyte-macrophage colony-stimulating factor therapy.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation and differentiation of hematopoietic progenitor cells. Although preliminary data are available from clinical trials, the effect of GM-CSF on gene expression of immunocompetent cells in treated patients has not been studied. We previously demonstrated that in vitro treatment with GM-CSF also enhances maturation-related anti-tumor activities in mononuclear phagocytes. The purpose of the present study was to examine the effects of in vivo recombinant GM-CSF therapy on alveolar macrophages and blood monocytes, to determine if these cells demonstrated differential expression of cytokine genes, cytokine production, and tumoricidal activity. Alveolar macrophages and blood monocytes were isolated from 13 patients receiving a range of GM-CSF doses (60-250 micrograms/m2/day) by continuous infusion over a 2-week period. Both monocytes and macrophages were isolated prior to therapy and at day 10 of the infusion. Monocytes, in addition, were isolated on day 3 of infusion. Results indicated that GM-CSF therapy enhanced expression of tumor necrosis factor, interleukin 1, and interleukin 6 mRNA in both monocytes and alveolar macrophages. Differential responses, however, were observed in cytokine secretion; monocytes demonstrated enhanced secretion of all three cytokines by day 3 of treatment, but alveolar macrophages showed only enhanced interleukin 6 secretion at day 10. Monocyte tumoricidal activity after in vitro lipopolysaccharide stimulation was also significantly elevated by day 3 of treatment, but at day 10 activity was not statistically different from pretreatment values in either monocytes or alveolar macrophages. These data indicate that GM-CSF exerts striking time-dependent modulatory effects on gene expression and functional activities of monocytes and alveolar macrophages in vivo, although the responses of the two cell types differ with respect to cytokine secretion.

Gene Expression Regulation, Neoplastic↗
PubMed1991

Myocardial accumulation and clearance of technetium 99m teboroxime at 100%, 75%, 50% and zero coronary blood flow in dogs.

Sequential changes in the regional distribution of technetium 99m Teboroxime (SQ30217) were evaluated in nine dogs with graded coronary artery stenosis, occlusion and reperfusion of either the left anterior descending or left circumflex arteries. 99mTc-Teboroxime accumulation recorded by planar imaging was compared with directly measured coronary blood flow (Doppler) and regional myocardial perfusion (microspheres). Serial images were recorded beginning at the time of injection and continuing for the next 18 min. The data were summed from minutes 2-3, 3-6, 4-8 and 9-18 after injection for comparison with the other parameters. Myocardial clearance of Teboroxime was analysed at each level of blood flow. There was a linear relationship between the Teboroxime activity ratio (abnormal/normal) and coronary blood flow (r = 0.96) and regional myocardial perfusion (r = 0.99). Zones of diminished perfusion were least apparent in the summed images recorded during minutes 2-3. In later images, the lesions were well visualized. The myocardial clearance half-times at 100%, 75% and 50% flow were not significantly different, while clearance half-time at total occlusion was significantly (P less than 0.01) faster. In the 3-6, 4-8 and 9-18 minutes summed images, the Teboroxime activity ratio increased significantly (P less than 0.01) after reperfusion compared with total occlusion.

Animals↗
PubMed1991

Biochemical changes during the development of the miracidium of Gigantocotyle explanatum.

Analysis of various biochemical components during the development of the miracidium of G. explanatum showed marked changes, particularly in glycogen, protein and DNA levels. Though the total lipids remained more or less unchanged, alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids and phospholipid fractions were also recorded. Such changes could be intrinsically programmed for the cellular differentiation and organogenesis in larval amphistomes.

Animals↗
PubMed1991

Behavioral and biochemical consequences of perinatal exposure of mice to instant coffee: a correlative evaluation.

In the present study, the lasting effects of prepartum and perinatally consumed instant coffee by female mice on the behavior as well as on the level of activities of certain enzymes in the tissues of their male offspring have been investigated. The behavioral observations of nonsocial investigation, defense, displacement, latency to threat and naso-nasal contact has decreased significantly in offspring of treated mothers, while the threat, attack, latency to threat and attack and number of fights have increased significantly. Hence, coffee has proven to be an inducer of hyperactive behavior in these offspring. Such effects are both dose dependent and duration-of-treatment dependent. Moreover, variations were detected in the level of AChE activity in the brain tissues of these offspring together with variations in the levels of AcPase and AlPase activities in their liver, kidneys and testes. Such variations in these organs have developed in utero, making these enzymes convenient markers in teratological studies.

Acetylcholinesterase↗