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Biomedical subjects

M A Mahmoud

Publications and source records attributed to M A Mahmoud.

12 recordsLinked to original sources
PubMed2001

Characterization of cryptic flagellin genes in Shigella boydii and Shigella dysenteriae.

Flagellin (fliC) genes of 12 Shigella boydii and five Shigella dysenteriae strains were characterized. Though these strains are nonmotile, the cryptic fliCSB gene, cloned from S. boydii strain C3, is functional for expression of flagellin. It consists of 1,704 bp, and encodes 568 amino acid residues (57,918 Da). The fliCSD gene from S. dysenteriae strain 16 consists of 1,650 bp encoding 549 amino acid residues (57,591 Da) and contains an IS1 element inserted in its 3' end. The two genes are composed of the 5'-constant, central variable and 3'-constant sequences, like other known fliC genes. The two genes share high homology in nucleotide and amino acid sequences with each other and also with the Escherichia coli fliCE gene, indicating that both genes are closely related to the fliCE gene. Comparison of the central variable sequences of six different fliC genes showed that the fliCSB and fliCSD genes share low homology in amino acid sequence with the other fliC genes, suggesting that they encode antigenic determinants intrinsic to respective subgroups. However, Southern blotting using as probes the central variable sequences of several fliC genes showed that four of 12 S. boydii strains have a fliC gene similar to that of Shigella flexneri, and that among five fliC genes from S. dysenteriae strains, one is similar to that of S. flexneri, two are similar to that of S. boydii, and only one is unique to S. dysenteriae. Some of these variant alleles were verified by immunoblotting with flagellins produced from cloned fliC genes. The presence of variant fliC alleles in S. boydii and S. dysenteriae indicates that subdivision into subgroups does not reflect the ancestral flagella H antigenic relationships. These data will be useful in considering the evolutionary divergence of the Shigella spp..

Alleles↗
PubMed2000

Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia.

Endogenous fatty acid synthesis has been observed in certain rapidly proliferating normal and neoplastic tissues. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of lipogenic genes including fatty acid synthase (FAS), the major biosynthetic enzyme for fatty acid synthesis. We have previously shown that SREBP-1, FAS, and Ki-67, a proliferation marker, colocalized in the crypts of the fetal gastrointestinal tract epithelium. This study sought to determine whether SREBP-1 participates in the regulation of proliferation-associated fatty acid synthesis in colorectal neoplasia. An immunohistochemical analysis of SREBP-1, FAS, and Ki-67 expression in 25 primary human colorectal carcinoma specimens showed colocalization in 22 of these. To elucidate a functional linkage between SREBP-1 activation and proliferation-associated FA synthesis, SREBP-1 and FAS content were assayed during the adaptive response of cultured HCT116 colon carcinoma cells to pharmacological inhibition of FA synthesis. Cerulenin and TOFA each inhibited the endogenous synthesis of fatty acids in a dose-dependent manner and each induced increases in both precursor and mature forms of SREBP-1. Subsequently, both the transcriptional activity of the FAS promoter in a luciferase reporter gene construct and the FAS expression increased. These results demonstrate that tumor cells recognize and respond to a deficiency in endogenous fatty acid synthesis by upregulating both SREBP-1 and FAS expression and support the model that SREBP-1 participates in the transcriptional regulation of lipogenic genes in colorectal neoplasia.

CCAAT-Enhancer-Binding Proteins↗
PubMed2000

Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome.

Relapses are common in children with idiopathic nephrotic syndrome, and this prospective study looks into the possibility of decreasing the frequency of relapses in a selected group of such patients. The study includes 36 children with a steroid-dependent, relapsing nephrotic syndrome on a maintenance prednisone therapy of about 0.5 mg/kg every other day. They were prospectively divided into two groups with comparable age and sex distribution and the number of those who had previously received cyclophosphamide therapy. Group 1 patients were advised to take daily prednisone for 5 days, starting at the time of the onset of an upper respiratory tract infection (URI). No such advice was given to those in group 2, and they remained on alternate-day prednisone during URI. At the end of a 2-year follow-up period, the total number of relapses in group 1 was 40 with a mean of 2.2 +/- 0.87 per patient as compared with 99 with a mean of 5.5 +/- 1.33 per patient in group 2 (p = 0.04). We conclude that an increased maintenance prednisone during URI helps decrease significantly the number of relapses in those on alternate-day therapy.

Adolescent↗
PubMed1999

Identification of sequences required for inhibition of oncogene-mediated transformation by pp32.

Oncogenic potential in prostate cancer is modulated in part by alternative use of genes of the pp32 family. This family includes the tumor suppressor pp32, expressed in normal tissue, and the pro-oncogenic genes pp32r1 and pp32r2 that are found principally in neoplastic cells. At the protein level, pp32, pp32r1, and pp32r2 are approximately 90% identical, yet they subsume opposite functions. In this study, we identify the region of pp32 associated with the ability to inhibit oncogene-mediated transformation in a rat embryo fibroblast system, an in vitro correlate of tumor-suppressive activity. Deletion and truncation analysis define a region spanning pp32 amino acids 150-174 as absolutely required for inhibition of transformed foci elicited by RAS and MYC. Comparison of pp32 with the pp32r1 sequence by moving averages of sequence identity reveals divergence over this region; pp32r2 also differs in this region through truncation after pp32 amino acid 131. The deletion experiments and the experiments of nature therefore converge to demonstrate that tumor-suppressive functions of pp32 reside in amino acids 150-174. Identification of this minimal tumor-suppressive region should help elaborate the pathways and mechanisms through which pp32 family members exert their functions.

Animals↗
PubMed1999

Primary hyperoxaluria in infants: medical, ethical, and economic issues.

OBJECTIVES: Survey on the current medical approach to and the economic issues affecting infants with primary hyperoxaluria type 1. METHODS: Questionnaire to specialized centers worldwide. RESULTS: Seventy-eight infants were identified: 44% were of Muslim origin and 56% were not. The consanguinity rate was 76% and 0%, respectively. Thirty-three percent were treated in developing countries (group 1) and 67% in developed countries (group 2). Initial presentation (4.9 +/- 2.8 months) consisted of failure to thrive (22%), urinary tract infection (21%), and uremia (14%). Radiologic findings included nephrocalcinosis (91%), urolithiasis (44%), or both (22%). The diagnosis was based on family history, tissue biopsy, and urine oxalate level in most patients from group 1 and on urine oxalate and glycolate levels, alanine:glyoxalate aminotransferase activity, and DNA analysis in patients from group 2. Therapeutic withdrawal was the final option for 40% of children; financial reasons were given for 10 of 17 patients from group 1 and 0 of 9 from group 2. End-stage renal disease started at 3.2 +/- 6.4 years of age and was present in half of the patients at the time of diagnosis. Fifty-two percent of the patients died: 82% in group 1 versus 33% in group 2; 33% of patients who underwent transplantation died versus 71% of those who did not. CONCLUSION: The management of primary hyperoxaluria type 1 in infants is a major example of the ethical, epidemiologic, technical, and financial challenges that are raised by recessive inherited diseases with early life-threatening onset. In certain circumstances, oxalosis can be regarded as a condition for which therapeutic withdrawal may be an acceptable option.

Developed Countries↗
PubMed1994

Molecular characterization of intact, but cryptic, flagellin genes in the genus Shigella.

Flagellin genes (fliC) were detected in two species of the genus Shigella. The fliCSF gene cloned from Shigella flexneri produced normal-type flagella in an Escherichia coli delta fliC strain while the fliCSS genes from two Shigella sonnei strains produced curly-type flagella and their expression is repressible by Salmonella FljA repressor. The fliCSF gene (1650 bp) shared high similarity with the E. coli fliCE gene not only in the 5' and 3' constant sequences but also in the upstream and downstream sequences. The fliCSS genes (1572 bp) shared high similarity with the Salmonella typhimurium fliCS gene in the operator and 3' constant sequences and also shared high similarity with the fliCE gene in the downstream sequence, suggesting that the fliCSS gene has undergone horizontal transfer and recombination. Differences in nucleotide sequences of the central variable regions among the four fliC genes, including fliCE and fliCS, suggest that they started differentiation in each lineage approximately 80 million years ago. Loss of motility in Shigella seems to be evolutionarily a recent event.

Amino Acid Sequence↗
PubMed1992

Seropositivity to hepatitis C virus (HCV) in Saudi children with chronic renal failure maintained on haemodialysis.

Twenty Saudi children (mean age: 7.7 years) with chronic renal failure who had received several blood transfusions were screened for antibodies to hepatitis C virus (anti-HCV), antibodies to the human immunodeficiency virus (anti-HIV) and antibodies to the various markers of hepatitis B virus (HBV). Prevalence of anti-HCV antibodies was significantly higher in these patients (45%) than in controls (1%) (p less than 0.001). In contrast, the exposure rate to HBV was similar in both groups (15.0% in patients vs 16.8% in controls). These results underscored the high risk of acquiring HCV infection in patients on haemodialysis irrespective of age. Currently, practices such as screening blood for HBsAg and other preventive measures seem to be effective in controlling HBV but not HCV infection in patients on haemodialysis. Perhaps, as with HBV, a stringent policy regarding HCV should be implemented if HCV is to be controlled. None of our patients or controls was anti-HIV positive.

Adolescent↗
PubMed1985

Coronary hemodynamics in hypertensive heart disease: basic concepts and clinical consequences.

Myocardial hypertrophy may influence coronary hemodynamics variably. Therefore, coronary blood flow (CBF) (gas chromatic argon technique) was determined in patients with left ventricular (LV) hypertrophy, with or without dilatation, associated with exclusively normal coronary arteriogram: 12 patients with hypertrophic obstructive cardiomyopathy (HOC) (LV mass to volume (M/V) ratio: 3.66 + 0.52 g/ml), 22 patients with hypertensive heart disease due to essential hypertension (EH) (LV M/V ratio: 2.12 + 0.26 g/ml), 18 patients with hypertensive dilatation (M/V ratio: 1.6 + 0.48 g/ml), 6 patients with aortic stenosis (LV M/V ratio: 1.99 + 0.41 g/ml), 12 patients with aortic incompetence (AI), 20 patients with normal heart function. CBF was determined as (A) controls and (B) following the intravenous injection of dipyridamole (0.5 mg/kg body weight). Coronary reserve (CR) was calculated as the ratio of coronary resistance before and after dipyridamole. Normal CR averaged 4.89 + 0.11 similar values despite marked LV hypertrophy, were present for both HOC (4.4 + 0.19) and as (4.66 + 0.12), whereas CR was considerably reduced in the concentrically hypertrophied hypertensive hearts (3.22 + 0.19) (p less than 0.001). Moderate decrease of CR was found in AI and in dilated EH. The results indicate that nonhypertensive hypertrophy, despite LV mass augmentation, may have normal CR, whereas at a comparable degree of LV hypertrophy, hypertensive hypertrophy has specific reduction in CR. Independent from vascular effects, ventricular dilatation may deteriorate CR because of an abnormal component of coronary vascular resistance.

Cardiomegaly↗
PubMed1984

Global and regional wall motion and contractility of the left ventricle following cigarette smoking.

The hemodynamic and contractile effects of acute cigarette smoking were analyzed in 35 patients with normal cardiac and coronary function as well as with cardiac failure and with coronary artery disease. In normal patients (normal ventricular function, normal coronary arteriogram) cigarette smoking exhibited no contractile depressant effects. Moderate increase in global and in regional wall motion and contractility was found. Likewise, in patients with compensated hypertensive hypertrophy (normal ventriculogram, significant left ventricular hypertrophy, normal coronary arteriogram) cigarette smoking increased global and regional contraction function. In cardiac disease patients (dilatative cardiomyopathy, advanced coronary artery disease, decompensated hypertensive heart disease) cigarette smoking was associated with depression in the overall and regional contraction behavior of the left ventricular myocardium. In patients with coronary artery disease, cigarette smoking was accompanied by marked depression of the regional contraction pattern in hypokinetic, akinetic, and dyskinetic zones. Moreover, contractile depression also occurred in the non-ischemic zones, without pre-existing coronary artery stenoses. In conclusion, acute cigarette smoking may not cause contractile depressant effects in normal patients and patients with compensated hypertensive hypertrophy. However, in coronary patients, significant negative inotropic effects are present not only in the ischemic zones, but also in the non-ischemic myocardium.

Adult↗