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Biomedical subjects

S Muhammad

Publications and source records attributed to S Muhammad.

14 recordsLinked to original sources
PubMed2003

Contribution of proton-translocating proteins to the virulence of Salmonella enterica serovars Typhimurium, Gallinarum, and Dublin in chickens and mice.

We investigated the attenuating effects of a range of respiratory chain mutations in three Salmonella serovars which might be used in the development of live vaccines. We tested mutations in nuoG, cydA, cyoA, atpB, and atpH in three serovars of Salmonella enterica: Typhimurium, Dublin, and Gallinarum. All three serovars were assessed for attenuation in their relevant virulence assays of typhoid-like infections. Serovar Typhimurium was assessed in 1-day-old chickens and the mouse. Serovar Gallinarum 9 was assessed in 3-week-old chickens, and serovar Dublin was assessed in 6-week-old mice. Our data show variation in attenuation for the nuoG, cydA, and cyoA mutations within the different serovar-host combinations. However, mutations in atpB and atpH were highly attenuating for all three serovars in the various virulence assays. Further investigation of the mutations in the atp operon showed that the bacteria were less invasive in vivo, showing reduced in vitro survival within phagocytic cells and reduced acid tolerance. We present data showing that this reduced acid tolerance is due to an inability to adapt to conditions rather than a general sensitivity to reduced pH. The data support the targeting of respiratory components for the production of live vaccines and suggest that mutations in the atp operon provide suitable candidates for broad-spectrum attenuation of a range of Salmonella serovars.

Animals↗
PubMed2001

Rectal excision with coloanal anastomosis for superficial distal third rectal cancer: survival and local recurrence.

OBJECTIVE: Appropriate surgical treatment of distal third rectal cancer limited to bowel wall (i.e. T1 or T2) in medically operable patients is controversial. Transanal excision can deprive some patients of accurate pathological staging, prognosis and cure. In contrast abdominoperineal resection has considerable practical and psychosocial problems largely related to a permanent colostomy. We hypothesize that superficial distal rectal tumours can be effectively treated with rectal excision and coloanal anastomosis. SUBJECTS AND METHODS: Prospective oncological study of 80 patients with distal third superficial rectal carcinomas treated by complete rectal excision with coloananl anastomosis from December 1977 to January 1993 was carried out. The resected specimens were examined for depth of spread and number of histologically positive nodes. The actuarial local recurrence and survival rates for superficial node-negative and node-positive tumours were analysed independently. RESULTS: Seventy-eight patients had complete postoperative assessment. Thirty-one percent had received low-dose preoperative neo-adjuvant radiotherapy (3500 rads). Mean follow-up time in all patients was 70 months on average. The lymph node involvement rate for T1 and T2 tumours was 12.5 and 15.6%, respectively. The local recurrence rates for patients with (T1/T2) N0 and (T1/T2) N1 were 1.5 and 16.7%, respectively, and the five year actuarial survival rates were 96.6 and 90%, respectively. The overall local recurrence was 3.8% with five-year actuarial survival of 95.8%. CONCLUSIONS: Lymph node involvement in superficial tumours is not rare. Rectal excision with coloanal anastomosis results in a high cure rate especially for node-positive superficial tumours. This treatment strategy avoids the psychological trauma of colostomy following abdominoperineal resection and the potential risk of undertreatment by local excision.

Journal Article↗
PubMed2000

A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.

The yeast Sir2 protein, required for transcriptional silencing, has an NAD(+)-dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD(+)-dependent HDA activity that is eliminated in a yeast strain from which SIR2 and its four homologs have been deleted. This HDA activity is also displayed by purified yeast Sir2p and homologous Archaeal, eubacterial, and human proteins, and depends completely on NAD(+) in all species tested. The yeast NPT1 gene, encoding an important NAD(+) synthesis enzyme, is required for rDNA and telomeric silencing and contributes to silencing of the HM loci. Null mutants in this gene have significantly reduced intracellular NAD(+) concentrations and have phenotypes similar to sir2 null mutants. Surprisingly, yeast from which all five SIR2 homologs have been deleted have relatively normal bulk histone acetylation levels. The evolutionary conservation of this regulated activity suggests that the Sir2 protein family represents a set of effector proteins in an evolutionarily conserved signal transduction pathway that monitors cellular energy and redox states.

DNA, Ribosomal↗
PubMed2000

Partitioning of serpin-proteinase reactions between stable inhibition and substrate cleavage is regulated by the rate of serpin reactive center loop insertion into beta-sheet A.

The serpin family of serine proteinase inhibitors is a mechanistically unique class of naturally occurring proteinase inhibitors that trap target enzymes as stable covalent acyl-enzyme complexes. This mechanism appears to require both cleavage of the serpin reactive center loop (RCL) by the proteinase and a significant conformational change in the serpin structure involving rapid insertion of the RCL into the center of an existing beta-sheet, serpin beta-sheet A. The present study demonstrates that partitioning between inhibitor and substrate modes of reaction can be altered by varying either the rates of RCL insertion or deacylation using a library of serpin RCL mutants substituted in the critical P(14) hinge residue and three different proteinases. We further correlate the changes in partitioning with the actual rates of RCL insertion for several of the variants upon reaction with the different proteinases as determined by fluorescence spectroscopy of specific RCL-labeled inhibitor mutants. These data demonstrate that the serpin mechanism follows a branched pathway, and that the formation of a stable inhibited complex is dependent upon both the rate of the RCL conformational change and the rate of enzyme deacylation.

Amino Acids↗
PubMed1998

Plasminogen activator inhibitor-1 contains a cryptic high affinity binding site for the low density lipoprotein receptor-related protein.

Much of the controversy surrounding the binding of plasminogen activator inhibitor-1 (PAI-1) to the low density lipoprotein receptor-related protein (LRP) may be due to the labile structure of PAI-1 and the distinct conformations that it can adopt. To examine this possibility and to test the hypothesis that PAI-1 contains a specific high affinity binding site for LRP, a sensitive and quantitative assay for PAI-1 binding to LRP was developed. This assay utilizes a unique PAI-1 mutant that was constructed with a hexapeptide tag at the NH2 terminus, which is recognized by the protein kinase, heart muscle kinase and can be specifically labeled with 32P. Our results show that only 32P-PAI-1 in complex with a proteinase binds LRP with high affinity and is efficiently endocytosed by cells, indicating that a high affinity site for LRP is generated on PAI-1 only when in complex with a proteinase. In addition, PAI-1 in complex with different proteinases is shown to cross-compete for LRP binding, demonstrating that the binding site is independent of the proteinase and therefore must reside on the PAI-1 portion of the complex. Finally, mutagenesis of PAI-1 results in loss of LRP binding, confirming that the high affinity binding site is located on PAI-1 and suggesting that the LRP binding site lays within a region of PAI-1 previously shown to contain the heparin binding domain.

Animals↗
PubMed1998

Is rectal intussusception a cause of idiopathic incontinence?

PURPOSE: The cause of rectal intussusception in patients primarily dominated by symptoms of anal incontinence has not been fully elucidated, especially for patients with idiopathic incontinence. METHODS: Between 1991 and 1996, 51 patients referred with a diagnosis of idiopathic incontinence were prospectively evaluated by standard questionnaire, clinical examination, defecography, and anal manometry. Fourteen female patients were identified with rectal intussusception and were treated by transabdominal rectopexy. Postoperatively, clinical assessment and anal manometry were performed at regular intervals. RESULTS: Continence was improved after rectopexy (P < 0.01). The postoperative increases in the anal resting pressure, maximum squeeze pressure, and maximum tolerated volume were not statistically significant. CONCLUSIONS: Rectopexy improved anal incontinence in patients with rectal intussusception. The cause of rectal intussusception in anal incontinence could not be explained by functional improvement of the internal anal sphincter tone or an increase in the maximum tolerated volume. Rectal intussusception may be a cause of idiopathic incontinence in patients; however, larger prospective studies are required to support this concept.

Aged↗
PubMed1998

[Surgical management of periocular basal cell carcinoma using frozen section control and immediate plastic reconstruction--indications and methods in 106 patients].

PURPOSE: To review our first experiences with the surgical removal of basal cell carcinoma (BCC) utilizing frozen section control and immediate plastic reconstruction. PATIENTS AND METHODS: We analyzed the accuracy of clinical diagnosis, methods of surgical excision, plastic repair and recurrence rates in 162 consecutive patients who underwent surgical excision utilizing either frozen section (n = 106) or biomicroscopic control (n = 56) between January 1991 and June 1996. Specimens used for intraoperative frozen-section monitoring were also fixed, processed, and sectioned for permanent sections and served as postoperative controls for the frozen sections (n = 43). RESULTS: The accuracy of clinical diagnosis was 86% (n = 189). In 106 patients with BCC excised with frozen section control, there were no recurrences reported after a mean follow-up of 2.9 years. The mean surgical defect measured 55% of total eyelid length (range 10%-100%). The incidence of morphea pattern was 34%. Intraoperative re-excisions due to frozen sections positive for tumor were necessary in 31% of cases. Permanent postoperative sections of the tissue that had been used for intraoperative frozen sections confirmed in 97.5% of patients (n = 43) the preliminary findings made with frozen sections. In 56 patients with BCC excised with biomicroscopic control, three tumors recurred (5%) after a mean follow-up of 4.4 years. The mean surgical defect measured 42% of total eyelid length (range 16%-100%). The incidence of morphea type was 23%. CONCLUSION: Surgical removal utilizing frozen section control and immediate plastic repair appears to represent a reliable and effective option in the management of selected patients with periocular BCC.

Adult↗
PubMed1997

Prospective, randomized study comparing clinical results between small and large colonic J-pouch following coloanal anastomosis.

PURPOSE: Improved functional results can be obtained by construction of a colonic J-pouch after coloanal anastomosis. Variability in pouch size following coloanal anastomosis is prevalent in current literature. In this study, the authors compare clinical bowel function after complete rectal excision with coloanal anastomosis for patients with rectal carcinoma using either a small 6-cm or a large 10-cm colonic J-pouch anastomosis. The clinical outcome is assessed both at short-term and long-term follow-up. METHODS: Fifty-nine consecutive patients with rectal cancers 4 to 8 cm from the anal verge were recruited into the study. Patients were randomized intraoperatively to either a 6-cm J-pouch group or a 10-cm J-pouch group. Clinical assessments were performed prospectively at 3, 6, 12, and 24 months postoperatively, following colostomy closure. Clinical parameters such as frequency, urgency, continence, and laxative and enema use were assessed and compared between the two groups. RESULTS: There was no statistical differences in the mean defecation frequency, urgency, and fecal continence between the two groups at 3, 6, 12, and 24 months. In the first year, laxative and enema use between the two groups was negligible; however at two years, 30 percent of patients with a large reservoir compared with 10 percent of patients in the small-pouch group required laxative and/or enema for constipation and evacuation of bowels. CONCLUSION: Similar clinical results can be expected from patients with either small or large reservoirs at one year. However, with long-term follow-up, patients with a large reservoir are more likely to require medication for constipation and evacuation. To avoid these inconveniences a small reservoir is advocated for patients undergoing coloanal anastomosis.

Adenocarcinoma↗
PubMed1997

Synthesis of isomers of 18F-labelled amino acid radiopharmaceutical: position 2- and 3-L-18F-alpha-methyltyrosine using a separation and purification system.

To diagnose cancers with radiolabelled amino acid using positron emission tomography, we have constructed a separation and purification system for the production of L-18F-alpha-methyltyrosine (L-18FAmT). This system could provide radioprotection and consistent production of L-18FAmT. L-18FAmT was synthesized and purified and the efficiency of the system was examined. The radiochemical yield of L-18FAmT was 20.3 +/- 5.1% (n = 5) based on the radioactivity trapped in the reaction vessel. The radiochemical purity was greater than 99.4 +/- 0.3% (n = 5). The radiochemical stability in phosphate-buffered saline and human plasma was examined and little decomposition was observed by HPLC analysis. Our results indicate that the separation and purification system gave simple and quick synthesis of L-18FAmT with a large reduction in radiation exposure and consistent production of L-18FAmT.

Amino Acids↗
PubMed1994

Type II pseudohypoaldosteronism. Report of a case and review of the literature.

A 56-year-old white female presented with longstanding hyperkalemia, hyperchloremia, and hypertension. Renal function was normal. Plasma renin levels were low as were serum and urinary aldosterone. Plasma cortisol levels were normal. Fludrocortisone was ineffective in lowering serum potassium. Plasma renin and aldosterone levels responded appropriately to salt restriction and to postural changes. Plasma atrial natriuretic hormone (ANH) and urinary prostaglandins (PG) were normal. Salt loading resulted in suppression of renin and aldosterone levels and stimulation of plasma ANH and urinary PG but failed to increase potassium or chloride excretion. The persistent hyperkalemia, hyperchloremia, and suppressed renin-aldosterone axis were consistent with type II pseudohypoaldosteronism. Hydrochlorothiazide was effective in normalizing serum potassium levels and blood pressure. These studies exclude abnormalities in ANH and PG secretion in this disorder and are compatible with an abnormality in chloride reabsorption.

Aldosterone↗