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Biomedical subjects

S Mahmood

Publications and source records attributed to S Mahmood.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical usefulness of the branched DNA assay version 2 in predicting the efficacy of Interferon treatment in a group of chronic HCV patients based on serotype.

Interferon (IFN) response depends upon pretreatment viral loads and viral genotype/serotype. This study investigated the difference in response to IFN in different viral load groups of 96 chronic hepatitis C patients and compared version 1 (bDNA1.0) and version 2 (bDNA2.0) of the branched DNA assay, according to serotype. On univariate analysis, viral load (P=0.0001, by bDNA 1.0; P=0.0020, by bDNA 2.0,), serotype (P=0.0053) and age (P=0.0073) were significant predictors of IFN response. On multivariate analysis, serotype (odds ratio, 5.44; 95% confidence interval, 1.94-15.24; P<0.01) was a stronger predictor of IFN response than age or viral load (by bDNA2.0). In very high (>6.7 log eq/ml), high (6.0 approximately 6.69 log eq/ml) and low (<6 log eq/ml) viral load groups (by bDNA2.0), complete response was 25, 55 and 92.6% in serotype 2 (sero-2), and 10, 20 and 71.4% in serotype 1 (sero-1), respectively. In sero-2, bDNA2.0 can detect high viral loads underestimated by bDNA1.0. In a low viral load group (by bDNA2.0), IFN response is dependent upon serotype; sero-2 responded better than sero-1. However, in high and very high viral load groups, sensitivities of bDNA1.0 and bDNA2.0 are not effective in clinically distinguishing CR from non-response, and aid in patient selection for IFN therapy.

Journal Article↗
PubMed2001

Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development.

A deficiency of pyruvate dehydrogenase complex (PDC) in humans results in lactic acidosis and neurological dysfunction that frequently results in death during infancy. Using gene targeting technology, a silent mutation was introduced into the murine X-linked Pdha1 gene that encodes the alpha subunit of the pyruvate dehydrogenase or E1 component of the complex. Two loxP sequences were introduced into intronic sequences flanking exon 8 to generate the Pdha1(flox8) allele. In vitro studies in embryonic stem cells demonstrated that deletion of exon 8 ablated PDC activity. Homozygous Pdha1(flox8) females were bred with male mice carrying a wild-type Pdha1 allele and a transgene that ubiquitously expresses the Cre recombinase to produce progeny with a deletion in exon 8, Pdha1(Deltaex8). The majority of progeny were found to be mosaic with the presence of both the flox and deleted alleles, and there were no apparent phenotypic effects associated with the null allele. The mosaic mice were interbred to increase the degree of mosaicism for the Pdha1(Deltaex8) allele in the subsequent generation, resulting in a significantly smaller litter size (54% reduction). Embryos carrying predominantly the Pdha1(Deltaex8) allele were found to be globally delayed in development by 9.5 days postcoitus, with resorption occurring over the following several days. These findings demonstrate an essential role for oxidative metabolism of glucose during the early postimplantation period of prenatal development.

Alleles↗
PubMed2001

Use of intraoperative cytologic assessment of mandibular marrow scrapings to predict resection margin status in patients with squamous cell carcinoma.

PURPOSE: This study assessed the feasibility of intraoperative microscopic assessment of mandibular bone resection margins in patients undergoing segmental resection of mandible for treatment of squamous cell carcinoma. PATIENTS AND METHODS: This prospective pilot study involved 7 consecutive patients undergoing segmental resection of mandible as part of surgical treatment of oral squamous cell carcinoma. Cytologic examination of smear/touch preparations of 35 bone marrow scrapings, including simulated positive margins, was performed. RESULTS: "Malignant" excision margins produced a high cell yield, and it was easy to assign samples to malignant or benign categories on microscopic examination. All the simulated positive margins were easily identified. No false positive results were found. CONCLUSION: Cytologic examination of bone excision margin scrapings is a rapid, inexpensive, and accurate technique. This study confirms its feasibility and accuracy in cases of mandibular resection for squamous cell carcinoma.

Aged↗
PubMed2001

Selective distribution of oxysterols in atherosclerotic lesions and human plasma lipoproteins.

The presence of oxidized sterols (oxysterols) in human serum and lesions has been linked to the initiation and progression of atherosclerosis. Data concerning the origin, identity and quantity of oxysterols in biological samples are controversial and inconsistent. This inconsistency may arise from different analytical methods or handling conditions used by different investigators. In the present study, oxysterol levels and distribution were analyzed by an optimized GC-MS method, in human atherosclerotic coronary and carotid lesions, in atherosclerotic apolipoprotein E deficient mice (E degrees mice) and in native and in vitro oxidized human low and high density lipoproteins. Oxysterol levels were analyzed with a limit of detection of 0.06 - 0.24 ng, with 25-hydroxycholesterol (25-OH) being the least sensitive. In human coronary and carotid lesions, obtained from endatherectomic samples, 27-hydroxycholesterol (27-OH) was the major oxysterol, with about 85% as sterols esterified to fatty acids. While total cholesterol and oxysterols levels were similar in both kinds of human lesions, oxysterol distribution was significantly different. In coronary lesions the mean levels of 27-OH and 7beta-hydroxycholesterol (7beta-OH) were 38% and 20% of total oxysterols, whereas in carotid lesions their mean levels were 66% and 5%, respectively. Unlike in human aortic lesions, 27-OH was entirely absent in E degrees mice, whereas the level of 7alpha-hydroxycholesterol (7alpha-OH) was 28% of the total oxysterols, vs. 5% in human coronary lesions. As 27-OH is an enzymatic product of cholesterol oxidation, this finding may indicate that such an enzymatic process does not take place in E degrees mice.

Animals↗
PubMed2001

Solubilisation and colonisation of wood ash by ectomycorrhizal fungi isolated from a wood ash fertilised spruce forest.

In Sweden application of granulated wood ash has been suggested as a method to supplement nutrient loss resulting from harvesting of forest residues for bioenergy production. Mycelia of two ectomycorrhizal fungi Piloderma sp. 1 and Ha-96-3, were commonly found to colonise ash granules in a wood ash fertilised spruce forest. Thirty-eight fungal isolates were selected from 10 taxa to investigate the possible role of different ectomycorrhizal fungi in nutrient mobilisation from ash. The taxa were Cenococcum geophilum Fr., Piloderma croceum Erikss. and Hjortst., Piloderma sp. 1, Thelephora terrestris (Ehrenb.) Fr., Tylospora fibrillosa Donk, and five unidentified species, all originating from a wood ash fertilised spruce forest. The isolates were tested for their ability to solubilise tricalcium phosphate (TCP) or hardened wood ash (HWA) in vitro. Ha-96-3, P. croceum and Piloderma sp. 1 were the only taxa which solubilised TCP. Abundant calcium oxalate crystals were formed in TCP and HWA plates with Piloderma sp. 1. Ha-96-3 and two isolates of P. croceum produced intermediate amounts of crystals. Ha-96-1 and T. fibrillosa produced low amounts of crystal but no crystal formation was observed by any of the other isolates. Piloderma sp. 1 from HWA plates had significantly higher concentrations of P, compared to P. croceum or Ha-96-3. Piloderma sp. 1 and P. croceum were further tested for their ability to colonise wood ash in microcosms containing intact mycorrhizal associations. After 7 months Piloderma sp. 1 colonised ash amended patches with a dense, mat like mycelium, whereas P. croceum mycelia avoided the ash patches. Possible differences between these fungi in patterns of carbon allocation were investigated by labelling seedlings with 14CO(2). Piloderma sp. 1 mycelia allocated significantly more 14C to ash patches than P. croceum. P. croceum allocated relatively more 14C to control patches than to the ash patches. The possible role of ectomycorrhizal fungi in mobilisation of nutrients from wood ash is discussed.

Journal Article↗
PubMed2001

Formation of surfactant-like-particle in rat intestine following chronic ethanol feeding.

Ethanol feeding to rats daily for 40 days induces the secretion of surfactant-like-particles in intestine. The isolated lipoprotein particles were enriched with alkaline phosphatase activity and had high phosphatidylcholine content. There was no difference in disaccharidases activities associated with the particles from control and ethanol fed rats. These results suggest that ethanol induced surfactant-like-particles in rat intestine.

Animals↗
PubMed2000

Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities.

BACKGROUND: Human serum paraoxonase (PON1) exists in two polymorphic forms: one that differs in the amino acid at position 192 (glutamine and arginine, Q and R, respectively) and the second one that differs in the amino acid at position 55 (methionine and leucine, M and L, respectively). PON1 protects LDL from oxidation, and during LDL oxidation, PON1 is inactivated. METHODS AND RESULTS: The present study compared PON1 isoforms Q and R for their effect on lipid peroxide content in human coronary and carotid lesions. After 24 hours of incubation with PON1Q or PON1R (10 arylesterase units/mL), lipid peroxides content in both coronary and carotid lesion homogenates (0.1 g/mL) was reduced up to 27% and 16%, respectively. The above incubation was associated with inactivation of PON1Q and PON1R by 15% and 45%, respectively. Lesion cholesteryl linoleate hydroperoxides and cholesteryl linoleate hydroxides were hydrolyzed by PON1 to yield linoleic acid hydroperoxides and linoleic acid hydroxides. Furthermore, lesion and pure linoleic acid hydroperoxides were reduced to yield linoleic acid hydroxides. These results thus indicate that PON1 demonstrates esterase-like and peroxidase-like activities. Recombinant PON1 mutants in which the PON1-free sulfhydryl group at cysteine-284 was replaced with either alanine or serine were no longer able to reduce lipid peroxide content in carotid lesions. CONCLUSIONS: We conclude that PON1 may be antiatherogenic because it hydrolyzes lipid peroxides in human atherosclerotic lesions.

Arteriosclerosis↗
PubMed2000

Endocervical reactive atypia: a histologic-cytologic study.

Of 1,500 cervical tissue specimens, 27 cases showed histologic changes of reactive glandular atypia which we defined as endocervical cells with large hyperchromatic, often irregular nuclei, which did not fulfill the criteria for endocervical adenocarcinoma. Eighteen of these 27 cases had preceding or concurrent cervico-vaginal smears. Six of these showed cells which were similar to those seen in histologic sections. The cytologic characteristics of these cells are defined. To determine if atypia is related to inflammatory-regenerative changes, 29 cases of endocervical polyps were examined, of which 11 showed histologic changes of endocervical reactive atypia; 4 showed these changes cytologically as well. Twenty-eight cases of routine hysterectomy specimens were examined, of which 2 cases showed endocervical reactive atypia, which indicated that the atypical changes were indeed reactive. Nine out of 27 cases were associated with hormonal usage. Fourteen cases were associated with squamous intraepithelial lesions or evidence of human papilloma virus. Follow-up of our 27 index cases revealed no progression to adenocarcinoma. These findings indicate that atypia, as we define it, of the endocervix can be due to inflammatory-reparative changes or possibly related to hormonal usage, and permit its separation from precursor lesions of endocervical adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Functional role of sialic acid in IgG binding to microvillus membranes in neonatal rat intestine.

A close parallelism exists between sialylation and endocytotic activity of the small intestine during postnatal development in rats. Thus, the binding of 125I-labelled IgG to microvillus membranes and its relationship to membrane sialic acid has been studied in suckling rat intestine, during (a) postnatal development; (b) cortisone-induced precocious maturation, and (c) after desialylation of brush borders by neuraminidase treatment. Neuraminidase-treated membranes exhibited low (42%, p < 0.001) IgG binding. The observed decrease in IgG binding to desialylated membranes was associated with a decrease in the value of affinity constant, (-Ka = 0.4 x 10(6) M-1 in control and 0.23 x 10(6) M-1 in desialylated membranes). The number of IgG-binding sites (2.3 nmol/mg protein) was unchanged under these conditions. A similar decrease (50%) in IgG binding to brush borders was also observed in cortisone-injected pups. This was associated with reduced sialic acid (37%) content of the membranes compared to the controls. The value of -Ka was reduced from 0.4 x 10(6) M-1 in the control to 0.3 x 10(6) M-1 in the hormone-injected pups. The number of binding sites (n) was decreased from 2.2 to 1.4 nmol/mg protein under these conditions. Low concentrations of calcium (0.1-1.6 mM) in the incubation medium enhanced IgG binding (p < 0.001) to brush borders in pups but there was no change in binding of IgG to the membranes at 2 mM Ca2+ concentration compared to controls. Addition of Zn2+ or Mg2+ did not affect IgG binding under these conditions. These findings suggest a functional role of Ca2+ and sialic acid residues of the membrane glycans in IgG-receptor interactions in suckling rat intestine.

Animals↗
PubMed1999

IgG binding and expression of its receptor in rat intestine during postnatal development.

The binding of 125I labelled IgG to the microvillus membranes (MVM) has been studied during postnatal development of rat intestine. The levels of mRNA encoding IgG receptor were also analyzed by liquid hybridization under these conditions. The IgG binding to MVM reached maximum levels by day 12 and showed a gradual decline upon weaning. The FcRn mRNA was markedly low in adult rats and was maximum during second week of postnatal development. Administration of cortisone or thyroxine to suckling rats, induced precocious decline of both IgG binding and the receptor expression. However, insulin administration did not affect the receptor expression. Scatchard analysis of IgG binding to MVM in cortisone injected pups revealed that the observed inhibition in IgG binding was a consequence of a decrease, both in the affinity constant (-Ka) as well as in the number of receptor sites (n) while thyroxine administration caused a reduction in the number of receptor sites from 2.29 in control to 1.14 nmoles/mg protein in thyroxine injected pups. These observations indicate that expression of IgG receptor during postnatal development is a hormone regulated process.

Animals↗
PubMed1998

Structural aspects of the inhibitory effect of glabridin on LDL oxidation.

The inhibitory effects of glabridin, an isoflavan isolated from licorice (Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by copper ions or mediated by macrophages were studied, in order to evaluate the contribution of the different parts of the isoflavan molecule to its antioxidant activity. The peak potential (E1/2) of the isoflavan derivatives, their radical scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and their ability to chelate heavy metals were also analyzed and compared to their inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation, glabridin (1), 4'-O-methylglabridin (2), hispaglabridin A (3), and hispaglabridin B (4), which have two hydroxyl groups at positions 2' and 4' or one hydroxyl at position 2' on ring B, successfully inhibited the formation of conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1-3 exhibited similar activities, whereas compound 4 was less active. In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by these isoflavans (1-4) at a similar order of activity to that obtained in copper ion-induced LDL oxidation. On the other hand, 2'-O-methylglabridin (5), a synthesized compound, whose hydroxyl at 2'-position is protected and the hydroxyl at 4'-position is free, showed only minor inhibitory activity in both LDL oxidation systems. 2',4'-O-Dimethylglabridin (6), whose hydroxyls at 2'- and 4'-positions are both protected, was inactive. Resorcinol (7), which is identical to the phenolic B ring in glabridin, presented low activity in these oxidation systems. The isoflavene glabrene (8), which contains an additional double bond in the heterocyclic C ring, was the most active compound of the flavonoid derivatives tested in both oxidation systems. The peak potential of compounds 1-5 (300 microM), tested at pH 7.4, was similar (425-530 mV), and that for compound 6 and 8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2, 3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were able to chelate iron, or copper ions. These results suggest that the antioxidant effect of glabridin on LDL oxidation appears to reside mainly in the 2' hydroxyl, and that the hydrophobic moiety of the isoflavan is essential to obtain this effect. It was also shown that the position of the hydroxyl group at B ring significantly affected the inhibitory efficiency of the isoflavan derivatives on LDL oxidation, but did not influence their ability to donate an electron to DPPH or their peak potential values.

Animals↗
PubMed1998

Echocardiography in the diagnostic evaluation of syncope.

To assess the role of echocardiography in patients with syncope, we studied 439 consecutive adults who were referred over a 7-year period. Of all patients, 251 (57.2%) were women, who were generally younger than male referrals. All 439 patients had interpretable echocardiographic studies. Results showed that of patients younger than 40 years of age, 72.8% had scans that were normal and 18.5% had mitral valve prolapse (MVP). All (other) patients in this age group with abnormal echocardiographic findings (8.7%) had either abnormal physical findings over the heart, an abnormal electrocardiogram, or an abnormal chest radiograph. In patients 60 years old and older, 29.6% had scans interpreted as normal and 4.6% had MVP (approximately half of these patients had at least moderate mitral regurgitation). The study demonstrates that patients younger than 40 years of age with syncope are likely to have a normal Doppler echocardiography or MVP without significant mitral regurgitation. Thus additional abnormal findings (e.g., heart murmur, abnormal electrocardiogram, or abnormal chest radiograph) may be needed before the patient is referred to the echocardiography laboratory.

Adolescent↗
PubMed1998

Association of fatty liver with increased ratio of visceral to subcutaneous adipose tissue in obese men.

We studied the association of fatty liver with subcutaneous and visceral obesity in 46 male and 36 female patients with body mass index (BMI) over 22 kg/m2. The correlation coefficient between the ratio of the visceral adipose tissue to the subcutaneous adipose tissue (V/S) and the computed tomography (CT) number of the liver was -0.299 (P < 0.05) and that between the V/S ratio and the ratio of the CT number of the liver to that of the spleen (CT-L/CT-S) was -0.335 (P < 0.05) in the males. Partial correlation analysis after making correction for BMI showed an increased correlation coefficient of -0.485 (P < 0.05) between the V/S ratio and the CT-L/CT-S ratio in the males. The odds ratio in the males for CT-L/CT-S below 1.0 and V/S above 1.0 was 3.25 with a 95% confidence interval of 1.02 to 9.39. No such association between the V/S ratio and the CT-L/CT-S ratio was present in the female patients. Multiple regression analysis with serum level of alanine aminotransferase, a marker of fatty liver, as an independent variable revealed a partial regression coefficient of -17.7 for CT-L/CT-S (P < 0.05) in the males and -21.7 (P < 0.05) in the females, validating the CT-L/CT-S ratio as an index of fatty liver. The results indicate the association of fatty liver as determined by the CT-L/CT-S ratio with visceral obesity in males.

Adipose Tissue↗
PubMed1998

Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study.

OBJECTIVE: To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)--clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)--were recorded. RESULTS: Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (-32 vs. 4%, P = 0.001), total cholesterol (-7 vs. -0.3%, P = 0.004), and total-to-HDL cholesterol ratio (-12 vs. -0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. -2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (-18 vs. -6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction. CONCLUSIONS: Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of "definite CHD events" in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.

Adult↗
PubMed1998

Effect of chronic ethanol feeding on intestinal alkaline phosphatase activity in rats.

The effect of chronic ethanol feeding has been studied on intestinal alkaline phosphatase (IAP) activity. The enzyme was assayed using p-nitrophenyl phosphate (PNPP), phenylphosphate (PhP) and beta-glycerophosphate (beta GP) as the substrates. Feeding of ethanol for 10 days did not effect the enzyme activity but it was markedly elevated in animals fed ethanol for 20 or 30 days. However, ethanol administration to rats, for over 6 wk exhibited a decline in IAP activity, both in the soluble and membrane fractions of intestine. Kinetic studies revealed an enhancement in Vmax with no change in apparent Km after 30 days of ethanol feeding and a decrease in Vmax after 6 wk of ethanol ingestion. These results were confirmed by assaying the enzyme activity in non-denatured polyacrylamide gels using 5-bromo-4-chloro-3-indoly1 phosphate (BCIP) as the substrate. These findings suggest differential changes in IAP activity in response to ethanol feeding in rats.

Alcoholism↗