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A A Ismail

Publications and source records attributed to A A Ismail.

185 records · Page 11Linked to original sources
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The role of interferon-alpha as a modulator of fluorouracil and leucovorin.

Several preclinical studies have demonstrated that interferon-alpha (IFN-alpha) may enhance the cytotoxicity of fluoropyrimidines in a greater-than-additive manner in a variety of human cancer cell lines. The underlying mechanism(s) have varied in different cancer cell lines, and include increased fluorouracil anabolism to fluorodeoxyuridine monophosphate, further inhibition of thymidylate synthase, stimulation of thymidine and uridine phosphorylase activities, greater DNA damage, and enhanced natural killer cell-mediated lysis of tumour targets. These preclinical studies stimulated clinical evaluation of IFN-alpha in combination with 5-fluorouracil (5-FU) with and without leucovorin (LV), and the initial clinical results appeared promising. We summarise preclinical research concerning the interaction of 5-FU and IFN-alpha. The rationale for combining 5-FU with IFN-alpha and LV is discussed, and we describe our clinical experience with the combination of 5-FU, LV and IFN-alpha-2a. The insights and unresolved questions concerning the clinical application of this combination are also discussed.

Antidotes↗
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Peptidyl substrates containing unnatural amino acid at the P'1 position are potent inhibitors of prohormone convertases.

In order to study further the importance of the P'1 residue upon the activity of human PC1 and human furin, two important members of subtilisin/kexin family of enzymes, we have prepared by solid-phase Fmoc or recently introduced FastMoc chemistry a series of 10 peptidyl substrate analogs. The structures of these analogs are based upon the core sequence of pro-mPC1(83-93) namely, D-Tyr-Lys-Glu-Arg-Ser-Lys-Arg-Xaa-Val-Gln-Lys-Asp, where D-Tyr replaces the native L-Tyr residue and Xaa, representing the P'1 position, corresponds to L-Ser or to nonproteinacous amino acids such as Tle, Sarc, MLeu, Aib, D-Tic or L-Tic. Two more analogs with L-Tic at P'1 position but with one amino acid less, namely P5 Glu or P'3 Gln, and one with a Cit residue in place of Arg at P1 site of the dodecapeptide were also obtained. These peptides were all fully characterized by a combination of MS, 1H-NMR and amino acid analysis. In contrast to the Ser analog, which is an excellent substrate for both hPC1 and hfurin, these analogs displayed moderate to strong inhibition of both hPC1 and hfurin activity in a reversible competitive manner. They all exhibited higher potency for hfurin than for hPC1, with an inhibition constant (Ki) ranging from 0.8 to 10 microM and from 1.0 to 170 microM, respectively. Incorporation of L-Tic yielded an analog with a two to four-fold increased inhibition of either enzymes when compared to its D-Tic counterpart, the effect being more pronounced for hPC1 than for hfurin. Comparison of these data with those for the corresponding N-terminal Fmoc protected peptides revealed that the highly hydrophobic N-terminal Fmoc function occupying the P8 position can contribute positively or negatively towards proteinase inhibition depending on the nature of the unnatural amino acid at P'1 and the enzyme used. Finally, none of the analogs was significantly cleaved by either enzyme. FTIR data on these analogs revealed some important structural differences between the substrate and inhibitor analogs, as there appears to be a conformational shift from a more beta-sheet-like structure for the substrates to a more alpha-helical-like structure for the inhibitors.

Amino Acid Sequence↗
PubMedDate not supplied

Laparoscopic cholecystectomy in patients with bilharzial portal hypertension.

OBJECTIVE: The purpose of this study was to evaluate the results of laparoscopic cholecystectomy in patients with bilharzial portal hypertension. METHODS: Patients who had gallstones and bilharzia had ultrasonographic assessment of peri-portal fibrosis, endoscopy, hemagglutination and rectal snip. Operating time, blood loss, hospital stay, time of return to work and operative mortality were recorded. Follow-up was two weeks, six weeks and six months after discharge. RESULTS: Twenty-five out of 450 patients, who had laparoscopic cholecystectomy, suffered from bilharzial portal hypertension. Ten patients had grade 1 varices, 10 had grade 2 varices, and 5 had grade 3 esophageal varices. All patients had varying degrees of peri-portal fibrosis as shown by ultrasound. Rectal snip showed schistosoma mansoni in 5 patients, and a hemagglutination test was positive in all. Two patients had conversion to open cholecystectomy. Mean operating time was 1 hour and 15 minutes. Average blood loss was 50 cc. Mean hospital stay for 23 patients was 48 hours. Average time of return to work was 2 weeks in 23 patients and 6 weeks in the 2 patients who had conversion. Twenty-two patients benefited from the operation. There was no mortality in this series. CONCLUSIONS: Laparoscopic cholecystectomy in patients with bilharzial portal hypertension is feasible and has low morbidity.

Adult↗
PubMedDate not supplied

Associations between dental treatment in the primary and permanent dentitions using insurance claims data.

PURPOSE: The purpose of this study was to assess the associations between dental treatment in the early primary dentition and later treatment in the primary and permanent teeth. METHODS: Delta Dental Plan of Michigan insurance claims data on 9,886 children who were born in 1990 and were covered by dental insurance from 1990-1998 were used. Risk ratios (RR), screening test measures of sensitivity (SN) and specificity (SP), and evidence-based dentistry research measures of Likelihood Ratio (LR) and Number Needed to Treat (NTT) were calculated. RESULTS: Primary anterior tooth treatment at ages 0-3 was weakly associated (RR = 1.43, 95% C.I. = 1.23, 1.65) with treatment of the permanent first molars at ages 6-8 and had SN, SP, LR, and NNT values of 7.4, 95.3, 1.57, and 12 respectively. Primary posterior tooth treatment at ages 4-8 was more strongly associated with future permanent first molar treatment with a RR of 2.44 (95% C.I. = 2.26, 2.64) and SN, SP, LR, and NNT values of 65.9, 61.7, 1.72, and 6. CONCLUSIONS: For this population, early childhood treatment in the primary anterior teeth was a weak predictor of future permanent first molar treatment. Primary posterior teeth treatment, while still not a strong predictor, was better than primary anterior teeth in predicting permanent tooth treatment. Caries treatment at ages 4-8 in the primary teeth was better than treatment at ages 0-3 in predicting permanent first molar treatment.

Age Factors↗