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Biomedical subjects

Z Ahmed

Publications and source records attributed to Z Ahmed.

At least 55 records · Page 3Linked to original sources
PubMed2000

Activation of platelet-activating factor (PAF) receptor stimulates nitric oxide (NO) release via protein kinase C-alpha in HEC-1B human endometrial epithelial cell line.

BACKGROUND: Impairment of the fertility in the platelet-activating factor (PAF) receptor transgenic female mice suggests changes in PAF functions can influence uterine receptivity. We hypothesized that vasodilatory actions of PAF in the uterus was exerted by PAF-mediated nitric oxide (NO) release via activation of isoenzyme-specific protein kinase C (PKC). MATERIALS AND METHODS: Inducible and endothelial NOS was shown by Reverse transcription polymerase chain reaction RT-PCR in cDNA synthesized from RNA extract of proliferative and secretory endometrium as well endometrial epithelial cell lines HEC-1B. The effect of WEB2170, N(G)-monomethyl-L-arginine (L-NMMA) and Ro31-8220 on PAF mediated NO release by HEC-1B cell was determined. PAF induced translocation of PKCalpha in HEC-1B cell and its antagonist effect by Ro 31-8220 was studied by Western immunoblot analysis. PKC isoenzyme regulated by PAF was determined in HEC-1B cell lysate by immunoprecipitation. RESULTS: PAF-evoked a rapid and concentration-dependent biphasic increase in total NO in human HEC-1B endometrial epithelial cell line [as measured by a Sievers NOA 280A NO Chemiluminescent Analyser.] This increase in NO release was attenuated by the PAF receptor antagonist, WEB2170. Inhibition of NO synthesis by N(G)-monomethyl-L-arginine produced marked dose-dependent attenuation of PAF-mediated NO release, indicating nitric oxide synthase (NOS) activation. PAF-mediated NO release was also inhibited by the PKC inhibitor Ro 31-8220 and by the removal of extracellular calcium, suggesting a dependency on PKC and calcium, respectively. RT-PCR analysis showed expression of inducible NOS and endothelial NOS in human endometrium, myometrium and HEC-1B cells. Western immunoblot analysis showed PKCalpha, betaII and iota were the principal isozymes present in the HEC-1B cell line and normal endometrium, suggesting that both HEC-1B cells and normal endometrium have similar PKC isozymes. PAF induced the translocation of both PKCalpha and PKCiota within the time frame of NO release. The translocation of PKCalpha, but not PKCiota, was susceptible to inhibition by Ro 31-8220 that also inhibited PAF-evoked NO release, suggesting that PKCalpha is the principal isozyme involved in this process and that eNOS may be a substrate for PKCalpha. Kinase assays performed using immunoprecipitated PKCalpha showed that PAF (1 nM) activated PKCalpha that was inhibited by co-incubation with Ro31-8220 and Ca(2+)-free medium. CONCLUSIONS: This study demonstrates that PAF-stimulated NO release via PKCalpha in epithelial cells might regulate endometrial functions such as implantation and menstruation.

Azepines↗
PubMed2000

Effectiveness of health education in promoting the use of iodized salt in Lotkoh, tehsil Chitral, Pakistan.

INTRODUCTION: We evaluated the effect of health education on the use of iodized salt in a remote region. METHODS: We randomly selected 31 villages in teh Lotkoh tehsil of district Chitral in the North West Frontier Province of Pakistan. We then randomly selected 7 households from each village and inteviewed the eldest women of the family. We also tested samples of salt for iodine concentration at the user's level. RESULTS: Eighty-five percent of families (184/217) used iodized salt exclusively. Among the samples population, the Aga Khan Health Services (AKHS) informed 67% about the importance of iodized salt. Shopkeepers and neighbors informed 25%. People informed by AKHS were more likely to know the volatile nature of iodine (76% vs 55%, p < 0.001) and the advantages of iodized salt (91% vs. 75%, p = 0.001) than persons informed by other sources. People who could name any single advantage of iodized salt were more likely to use iodized salt (97%) compared to those who could not name any advantages (62%) (p < 0.001) Iodine concentration in 78% (141/183) samples was acceptable (> or = 15 ppm). One specific brand of salt consistently had sufficient iodine concentration (91%) compared to all others (47%) (p < 0.001). CONCLUSION: Health education has been effective in promoting the use of iodized salt in these isolated rural communities. A joint effort by the government, local NGOs and the community can substitute the role of mass media in such areas. Regular evaluation of iodized salt brands should be considered.

Chi-Square Distribution↗
PubMed1999

APS, an adapter protein with a PH and SH2 domain, is a substrate for the insulin receptor kinase.

APS (adapter protein with a PH and SH2 domain) is the newest member of a family of tyrosine kinase adapter proteins including SH2-B and Lnk. We previously identified SH2-B as an insulin-receptor-binding protein and substrate [Kotani, Wilden and Pillay (1998) Biochem J. 335, 103-109]. Here we show that APS interacts with the insulin receptor kinase activation loop through its SH2 domain and insulin stimulates the tyrosine-phosphorylation of APS. Furthermore, the phosphorylation of activation-loop tyrosine residues 1158 and 1162 are required for this interaction.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Prostaglandin E2 down-regulation of T cell IL-2 production is independent of IL-10 during gram-negative sepsis.

The present study ascertained the role of PGE2 in sepsis associated modulation of IL-2 and IL-10 production by T cells. Sepsis was induced in 225-250 g male rats (Sprague Dawley) by implanting fecal pellets containing Escherichia coli (100-150 CFU) and Bacteroides fragilis (10(4) CFU) into the abdominal cavity. Animals implanted with fecal pellets without the bacteria were designated as sterile. For the assessment of PGE2 role in sepsis, a group of septic and sterile rats were pretreated with indomethacin to inhibit endogenous PGE2 synthesis. Splenic T cells were obtained 48 h after septic or sterile implantations, and their IL-2 and IL-10 production was measured. A significant suppression in the levels of IL-2 production and mRNA expression was observed in T cells from septic rats compared with the T cells from sterile and control rats. IL-10 protein and mRNA expression was found to be significantly higher in septic rat T cell compared to sterile and control rat T cells. Although, treatment of animals with indomethacin significantly prevented the sepsis-related suppression of IL-2 production, such treatment of animals was associated with a further upregulation of IL-10 production. These data suggest that although PGE2 released during sepsis can cause T cell IL-2 down-regulation, it may not mediate the T cell IL-10 upregulation. The IL-2 down-regulation may not be an effect of IL-10 upregulation.

Animals↗
PubMed1999

Adhesion, alignment, and migration of cultured Schwann cells on ultrathin fibronectin fibres.

Individual fibres of fibronectin (Fn-fibres), an extracellular matrix cell adhesion glycoprotein, were produced from a purified solution of fibronectin. These fibres range from 0.5-7 microm in width and have been engineered to produce mats (Fn-mats) by using a unidirectional shear force to orientate the fibres. Fn-fibres have been shown to promote alignment by contact guidance of human dermal fibroblasts, neurites, macrophages, and epitenon fibroblasts. Fn-mats have been used to orientate and enhance the regeneration of peripheral nerve components. We investigated cell spreading, orientation, formation of focal contacts, and the speed of cell movement on individual Fn-fibres, glass-covered with poly-L-lysine and poly-L-lysine/laminin/Fn. Fibronectin fibres significantly promoted cell spreading and the speed of cell migration with alignment of focal contacts and F-actin filaments to the axis of the fibres. The study reveals the potential of Fn-fibres to guide and direct cellular behaviour by contact guidance. The increase in migration and other behaviour exhibited by Schwann cells on Fn-fibres justifies the use of Fn-mats for peripheral nerve repair and is clinically important in that atrophy of the target organ, which is the most common failure of nerve repair, may be minimised.

Actins↗
PubMed1999

Stabilization of fibronectin mats with micromolar concentrations of copper.

Fibronectin, a large extracellular matrix cell adhesion glycoprotein has diverse functions in wound repair including organization of matrix deposition and promotion of angiogenesis. We have previously shown that purified plasma fibronectin can be made into three-dimensional, fibrous materials, termed fibronectin mats (Fn-mat). The aim of this study was to examine means of increasing the stability of Fn-mats using a novel treatment with micromolar concentrations of copper ions which may be used to improve wound healing/nerve repair. Cytotoxicity of incorporated copper was determined using rat Schwann cells, rat tendon fibroblasts and human dermal fibroblasts. Dissolution of protein from the Fn-mat showed that treatment with the lowest concentration of copper used (1 microM) increased the stability of mats by 3-4 times at room temperature relative to control mats and twofold at 37 degrees C. Copper mediated increase in stability was dose dependent. Orientation of the Fn-fibres (within mats), monitored by scanning electron microscopy was retained with 1 microM copper but disappeared with higher concentrations. Schwann cells grew in culture with mats stabilized by 1 microM copper treatment without reduction in cell number but growth was inhibited at 10-200 microM Cu. All types of fibroblasts were unaffected by copper treatment upto 200 microM. Fn-mats can be successfully stabilized by this technique producing longer survival in vitro. The differential effects of copper on these cell types suggests that CuFn-mats may be used to select the type of cells which colonize these materials.

Animals↗
PubMed1999

Production of D-lyxose from D-glucose by microbial and enzymatic reactions.

D-arabitol was first prepared from D-glucose using Candida famata R28. The reaction gave 5.0% D-arabitol from 10.0% D-glucose. D-arabitol was then almost completely converted to D-xylulose using Acetobacter aceti IFO 3281. Finally, D-lyxose was prepared from D-xylulose enzymatically using L-ribose isomerase from toluene-treated cells of Acinetobacter sp. strain DL-28. The isomerization reaction progressed steadily and the concentration of D-xylulose increased from 1.0 to 10.0%. About 70% of D-xylulose was converted to D-lyxose in all cases. Separation of residual D-xylulose from the reaction mixture is very difficult to achieve by column chromatography, but D-xylulose could be selectively degraded easily using Saccharomyces cerevisiae IFO 0841. The product was crystallized and was confirmed to be D-lyxose by HPLC, 13C-NMR spectra, IR spectra analysis, and optical rotation measurement.

Journal Article↗
PubMed1999

Biochemical preparation of L-ribose and L-arabinose from ribitol: a new approach.

L-ribose and L-arabinose were prepared biochemically from ribitol via a two-step reaction, by which the complete oxidation of ribitol to L-ribulose (approximately 98%) was achieved by the reaction of washed cells of Acetobacter aceti IFO 3281. The produced L-ribulose was then used as a substrate for the production of L-ribose and L-arabinose. The isomerization of L-ribulose to L-ribose and L-arabinose was carried out using L-ribose isomerase (L-RI) of Acinetobacter sp. strain DL-28 and L-arabinose isomerase (L-AI) of Mycobacterium smegmatis, respectively. At equilibrium, the ratio of L-ribose: L-ribulose was 70:30 and that of L-arabinose: L-ribulose was 90: 10. After a simple purification treatment, both pentoses could be crystallized without the use of column chromatography. The crystals were confirmed as L-ribose and L-arabinose by High-performance liquid chromatography (HPLC), Infrared (IR), Nuclear magnetic resonance (NMR) and optical rotation measurements.

Journal Article↗
PubMed1999

Nerve growth factor enhances peripheral nerve regeneration in non-human primates.

Fibronectin mat implants impregnated with NGF have been successfully used in rat nerve regeneration model. The aim of this study was to assess their action in a primate model. Mats were implanted into a 5 mm gap in a peripheral nerve in Macaca fascicularis monkeys, either alone (Fn) or in the presence of nerve growth factor (Fn + NGF). Four months postoperatively, the regenerated nerve was analysed by light microscopy, and target skin reinnervation was assessed by quantification of cutaneous nerve terminals immunostained with protein gene product (PGP) antibodies. The diameter of the regenerated nerve was similar in Fn + NGF grafts and nerve autografts, but significantly larger for plain Fn grafts with evidence of more connective tissue surrounding the axons. Myelinated fibres counts showed similarities in normal control nerve, nerve autograft and Fn + NGF graft groups. However, in nerve grafted with plain Fn mats the regenerating fibres were lower in number and showed a wider variability in diameter and myelination, resulting in a significantly smaller G-ratio (axonal diameter/myelinated fibre diameter). The amount of cutaneous reinnervation was lowest in Fn graft group, while comparable amounts of skin reinnervation were observed in the Fn + NGF and autograft groups. These results suggest that Fn-mats are a suitable conduit to promote peripheral nerve regeneration also in primate, and supplying NGF locally at the lesion site can further enhance nerve regrowth.

Animals↗
PubMed1999

PGE(2)-mediated inhibition of T cell p59(fyn) is independent of cAMP.

We recently observed that prostaglandin E(2) (PGE(2))-mediated suppression of T cell functions could result from an attenuation of p59(fyn) protein tyrosine kinase activity. The present study evaluated the effects of an adenylate cyclase agonist (forskolin) and antagonist (SQ-22536), as well as those of cAMP analogues (dibutyryl cAMP and 8-bromo- cAMP), on T cell p59(fyn) kinase activity. The study allowed us to assess whether PGE(2)-mediated activation of adenylate cyclase by itself or the elevation in intracellular cAMP levels is an integral event in the modulation of anti-CD3-linked p59(fyn) activation in T cells. The experiments were carried out with splenic T cells from male Sprague-Dawley rats. A 30-50% suppression in the autophosphorylation and the kinase activity of p59(fyn) in T cells incubated with PGE(2) or forskolin was observed. Pretreatment of T cells with SQ-22536 prevented significant PGE(2)-mediated inhibition of T cell p59(fyn) kinase activity. In contrast, no change in p59(fyn) autophosphorylation and kinase activity in T cells treated with cAMP analogues was observed. These data suggest that PGE(2)-mediated suppression of p59(fyn) autophosphorylation and kinase activity in T cells is dependent on the activation of adenylate cyclase and independent of the elevation in cAMP levels.

Adenine↗
PubMed1999

Percutaneous cuffed catheter insertion by nephrologists.

The use of Dacron cuff double-lumen permanent catheters for hemodialysis has become more common in the dialysis unit as patients await for creation or maturation of a permanent hemoaccess for various reasons. Placement of these catheters is often done by surgeons. Nephrologists skilled in the placement of temporary central vein accesses can extend their skill to placement of cuff catheters with the current available peel-away insertion technique. Data are presented on the percutaneous placement of 77 Dacron cuff permanent catheters by 4 nephrologists in two medical centers in a nonoperating room setting with minimal complications.

Adult↗
PubMed1999

Trends in initiation of dialysis in an urban dialysis clinic in the United States: a long way from dialysis outcomes quality initiative guidelines.

The guidelines issued for peritoneal dialysis by the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) suggest initiation of dialysis at a glomerular filtration rate (GFR) of 10.5 mL/min/1.73 m2. We undertook this study to determine trends at a center in Philadelphia. Using the MDRD (Modification of Diet in Renal Disease) formula, we estimated the GFR (mL/min/1.73 m2) at the time of first dialysis for patients starting on dialysis at the center between 1994 and 1996. Data on 72 of the 86 new patients were available. Of the 72, 69 patients (96%) were black and 29 (40%) were diabetic. The estimated GFR at the time of dialysis initiation was 6.3 +/- 0.3 mL/min/1.73 m2. Only 3 patients (4%) had a GFR > 10.5; 25 patients (35%) had GFR < 5.0. Patients with a lower GFR had more severe acidosis (HCO3 15.8 +/- 0.5 mmol/L vs 19.5 +/- 0.9 mmol/L, p = 0.0023) and greater impairment in divalent ion metabolism (PO4: 7.6 +/- 0.2 mg/dL vs 5.6 +/- 0.3 mg/dL, p < 0.0001). Diabetic patients were initiated on dialysis at a higher level of GFR than non diabetic patients (7.2 +/- 0.3 mL/min/1.73 m2 vs 5.7 +/- 0.4 mL/min/1.73 m2, p = 0.0087). Even though diabetic patients had higher GFR and lower serum creatinine (8.6 +/- 0.5 mg/dL vs 11.8 +/- 0.9 mg/dL, p = 0.0021) than non diabetic patients, blood urea nitrogen (BUN) was similar in the two groups (89 +/- 3.7 mg/dL vs 96.8 +/- 5.8 mg/dL, p = 0.73). This difference may indicate that nondiabetic patients had a greater decline in protein intake. Finally, a trend towards initiation of dialysis at higher levels of renal function was seen with time (GFRs 5.5 +/- 0.4 mL/min/1.73 m2, 6.4 +/- 0.4 mL/min/1.73 m2, and 6.9 +/- 0.6 mL/min/1.73 m2 for 1994, 1995, and 1996 respectively; p = 0.058, 1994 vs 1996). The trend was stronger for diabetic patients (GFR 6.3 +/- 0.4 mL/min/1.73 m2 and 8.1 +/- 0.7 mL/min/1.73 m2 for 1994 and 1996 respectively; p = 0.06) than for non diabetic patients (GFR 5.1 +/- 0.5 mL/min/1.73 m2 and 6.2 +/- 0.7 mL/min/1.73 m2 for 1994 and 1996 respectively; p = 0.22). We conclude that initiation of dialysis is delayed in urban centers, particularly in non diabetic patients, and that the current practice is far below the DOQI recommendations.

Diabetes Mellitus↗
PubMed1998

Complications associated with different insertion techniques for Hickman catheters.

A dependable central venous access is an essential prerequisite for the delivery of care to the cancer patients. This has become easier since the introduction of indwelling central venous catheters. However, pancytopenia, often encountered in haematological malignancies, does influence the morbidity associated with these catheters. In this study the effects of two different placement techniques of Hickman catheters were evaluated. A total of 177 Hickman catheters were inserted in patients suffering from haematological malignancies. In 112 patients the catheters were placed percutaneously into subclavian veins without prior tunnelling; in the other 65 patients these were introduced, after having been tunnelled, into cephalic/external jugular veins by a cut-down technique. The catheters remained in use in each patient for between 18 and 253 days. Excessive bleeding and haematoma formation occurred in a significantly higher proportion of patients from the cut-down group (61% and 41%, respectively) compared to patients from the percutaneous group (8% and 0%, respectively). These in turn had a profound impact on the incidence of infective complications. Catheter exit site infection, tunnel infection and septicaemia were observed in 26%, 18%, and 41%, respectively, of the patients from the cut-down group, while in patients from the percutaneous group, skin exit site infection was noted only in 7% and septicaemia in 19% of patients. It was concluded that the placement technique of these catheters exerts a significant influence on the immediate as well as delayed complications. The results indicate that the insertion technique requiring minimal dissection is more beneficial. It is therefore recommended that percutaneous insertion without tunnelling should be the technique of choice for catheter placement.

Adolescent↗