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Biomedical subjects

S Ahmad

Publications and source records attributed to S Ahmad.

At least 145 records · Page 8Linked to original sources
PubMed1999

Laboratory tests for heparin-induced thrombocytopenia: a multicenter study.

A multicenter clinical trial of the thrombin inhibitor argatroban (Novastan; Texas Biotechnology, Houston, TX; Smith-Kline Beecham Pharmaceuticals, Philadelphia, PA) was recently conducted in patients with heparin-induced thrombocytopenia (HIT) and HIT that had progressed to thrombosis (HITTS). In patients defined by the inclusion/exclusion criteria, the utility of three diagnostic HIT assays was investigated: the platelet aggregation assay, the serotonin release assay (SRA), and the enzyme-linked immunosorbent assay (ELISA) for the antibody to the heparin-platelet factor 4 (H-PF4) complex. Confirmation was made in 26%, 55%, and 64% of the patients, respectively (n = 199 patients; 512 to 606 samples; P < .001 platelet aggregation assay v SRA v ELISA). Patients who progressed to HITTS (n = 98) were more often confirmed than were HIT patients without associated thrombosis (n = 101) (P < .05). Confirmation by platelet aggregation assay and SRA results generally was associated with a higher antibody titer. However, a minimum critical titer could not be identified, because all patterns of positive and negative results by the platelet aggregation assay, SRA, and ELISA were observed, and clinically ill patients had a wide range of antibody titers. Over a 30-day period, the percentage of positive responses did not change. Although multiple testing over several days enhanced the chance of confirmation, this difference was not significant. Combined results of the three assays enhanced the positive response to 83% of the total population (P < .005). These data demonstrate that there is no direct correlation between the positive response of these assays, and that clinically positive HIT patients can be missed by all three assays. With these limitations, the combination of platelet aggregation assay, SRA, and ELISA testing with multiple samples offers the best chance of confirming a positive HIT patient. Caution is advised, however, in interpreting all assay results, as no assay is optimal.

Acute Disease↗
PubMed1998

Cloning and evaluation of the role of rat GALR-2, a novel subtype of galanin receptor, in the control of pain perception.

We have identified a novel subtype of galanin receptor (GALR-2) in rat dorsal root ganglia and spinal cord. The open reading frame of GALR-2 is 1116 nucleotides long, encoding a protein of 372 amino acids with a theoretical molecular mass of 40.7 kD. Membranes prepared from stable pools of 293 cells expressing GALR-2, but not wild-type 293 cells, demonstrated high affinity galanin binding sites. Rat galanin and galanin-related peptides M40, C7, M15, and galanin effectively competed for binding; peptide C7 demonstrated a lower affinity for rGALR-2, and all these peptides were agonists at rGALR-2 when assessed on a microphysiometer. Studies on the expression of GALR-2 in various tissues by Northern and in situ hybridization analyses suggest a low abundance but wide distribution of GALR-2 mRNA, including several discrete areas in brain and spinal cord and a high abundance in the dorsal root ganglia.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor.

A cDNA encoding a thyrotropin-releasing hormone (TRH) receptor expressed in the pituitary was previously cloned (De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) Biochem. J. 284, 891-899; De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) J. Biol. Chem. 267, 25703-25708; Duthie, S. M., Taylor, P. L., Anderson, J., Cook, J., and Eidne, K. A. (1993) Mol. Cell Endocrinol. 95, R11-R15). We now describe the isolation of a rat cDNA encoding a novel subtype of TRH receptor (termed TRHR2) displaying an overall homology of 50% to the pituitary TRH receptor. Introduction of TRHR2 cDNA in HEK-293 cells resulted in expression of high affinity TRH binding with a different pharmacological profile than the pituitary TRH receptor. De novo expressed receptors were functional and resulted in stimulation of calcium transient as assessed by fluorometric imaging plate reader analysis. The message for TRHR2 was exclusive to central nervous system tissues as judged by Northern blot analysis. Studies of the expression of TRHR-2 message by in situ hybridization revealed a pattern of expression remarkably distinct (present in spinothalamic tract, spinal cord dorsal horn) from that of the pituitary TRH receptor (present in hypothalamus, and ventral horn of the spinal cord, anterior pituitary). Therefore, we have identified a novel, pharmacologically distinct receptor for thyrotropin-releasing hormone that appears to be more restricted to the central nervous system particularly to the sensory neurons of spinothalamic tract and spinal cord dorsal horn, which may account for the sensory antinociceptive actions of TRH.

Amino Acid Sequence↗
PubMed1998

Differential translation of the alpha-1 isoforms of L-type calcium channel in rat brain and other tissues.

L-Type voltage operated calcium channel plays an important role in the contraction-relaxation of muscle cells. The alpha-1 subunit of this pentameric protein performs catalytic functions. Multiple mRNA isoforms of this subunit are generated by alternative splicing. For example, an exon encoding 11 amino acids (aa) between the third and fourth transmembrane domains produces two mRNA isoforms in gastrointestinal (GI) tract. The corresponding exon in brain encodes 15 aa. Whether the alpha-1 mRNA isoforms are translated into the corresponding isozymes remain unknown. To address this issue and to characterize the exon in brain, isozymes specific anti-peptide polyclonal antibodies were raised. Both the antibodies reacted with a protein of Mr 180 kDa in the heart and GI-tract, while no reaction was obtained in the kidney or liver. Brain expressed the isoform containing the same exon encoding 11 amino acids present in GI-tract, but the corresponding isozymes were of Mr 145-150 kDa. These findings suggest a tissue-specific translation of the alpha-1 isozymes.

Alternative Splicing↗
PubMed1998

Increased toxicity of modified mosquitocidal binary toxins of Bacillus sphaericus expressed in Escherichia coli.

The binary mosquitocidal genes of 51-kDa and 42-kDa proteins isolated from Bacillus sphaericus 1593 have been expressed at moderate levels in Escherichia coli employing the pQE expression system. The expressed proteins are readily visible in Coomassie blue-stained protein gels. The recombinant E. coli cells expressing toxic proteins were toxic towards Culex larvae. During the assembly of crystals in B. sphaericus, the 42-kDa toxin is first cleaved at the N-terminal end by a specific B. sphaericus protease. To express the toxins in E. coli the B. sphaericus specific protease-recognition site was deleted at the N-terminal end of the 42-kDa toxin, thereby mimicking the structure of the toxin as present in the crystal. This modification resulted in a twofold increase in the toxicity of the E. coli cells expressing the modified 42-kDa toxin as a constituent of the binary toxin. Our results demonstrate the utility of this modification for heterologous expression of the binary toxin genes from B. sphaericus.

Animals↗
PubMed1998

How do I look with my minds eye: perspective taking in social phobic imagery.

This study explored perspective taking in social phobics' images of past anxiety-provoking social situations and non-social situations. For images of social situations, social phobics were significantly more likely than non-patient controls to take an observer perspective, viewing themselves as if from an external point of view. In contrast, social phobics and controls did not differ in the perspective taken in images of non-social situations, which were generally viewed from a field perspective (seeing the situation as if looking out through their own eyes). The clinical significance of these findings is briefly discussed.

Adult↗
PubMed1998

Streptozotocin-induced diabetes enhances protective effects of enalapril on nitric oxide-deficient stroke in stroke-prone rats.

Recently, we have shown that chronic administration of N-Nitro-L-Arginine Methyl Ester (L-NAME, an inhibitor of nitric oxide synthase) precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Enalapril maleate, an angiotensin converting enzyme inhibitor was shown to delay the onset of such stroke. In the present study, five groups of 4-week-old SHRSP were used. Three groups of SHRSP were made diabetic using streptozotocin (100 mg/kg i.p.). One week later, the SHRSP from groups I (non-diabetic) and III (diabetic) chronically received L-NAME (0.5 g/L) in saline as drinking water. Two SHRSP groups, II (non-diabetic) and IV (diabetic) received L-NAME (0.5 g/L) and enalapril maleate (20 mg/L) in saline as drinking water. Control SHRSP (group C; diabetic) received only saline to drink. SHRSP groups I and III developed stroke in 10+/-2 and 11+/-2 days, respectively. The average stroke-free period in groups II and IV was 19+/-2 and 28+/-2 days, respectively. Protective effect of streptozotocin-induced diabetes disappeared when SHRSP drinking L-NAME and enalapril, concurrently received subcutaneous injections of insulin (2 units daily per 100 g rat). Present data suggest that experimental diabetes delays the onset of L-NAME-induced stroke in SHRSP only in the absence of angiotensin converting enzyme activity. In addition, diabetes-induced enhancement of stroke-protective effect of enalapril appears to be independent of reduction in mean and systolic blood pressures.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Detection of antibodies to equine arteritis virus by enzyme linked immunosorbant assays utilizing G(L), M and N proteins expressed from recombinant baculoviruses.

Indirect enzyme linked immunosorbant assays (ELISAs) utilizing the three major structural proteins (M, N, and G(L)) of equine arteritis virus (EAV) expressed from recombinant baculoviruses were developed. A large panel of sera collected from uninfected horses, and from animals experimentally and naturally infected with EAV or vaccinated with the modified live virus vaccine against equine viral arteritis, were used to characterize the humoral immune response of horses to the three major EAV structural proteins. The data suggest that the M protein was the major target of the equine antibody response to EAV. The responses of individual animals varied and ELISAs that utilized individual EAV structural proteins were not reliable for detecting antibodies in all sera that contained neutralizing antibodies to EAV. An ELISA based on a cocktail of all three EAV structural proteins, however, was used successfully to detect antibodies in most equine sera that were positive in the standard serum neutralization assay following natural or experimental EAV infection (100% specificity, 92.3% sensitivity). In contrast, this ELISA did not reliably detect antibodies in the sera of vaccinated horses. EAV frequently causes a persistent infection in stallions and all sera from carrier stallions evaluated in this study had obvious reactivity with the N protein, whereas seropositive non-carrier stallions, mares and geldings did not respond consistently to the N protein.

Animals↗
PubMed1998

Antigenicity of deoxyadenosine 5'-monophosphate cross-linked with polyamine.

Deoxyadenosine 5'-monophosphate was cross-linked to spermine using glutaraldehyde as cross-linking reagent. The complex thus obtained was characterized by UV absorption spectroscopy, size-exclusion chromatography and CD. The complex had a molecular mass of around 10,200 Da. Antibodies were raised against this complex in rabbits and the titre obtained was found to be > 1:3200. The fine specificity of the raised antibodies was checked by competition ELISA. The complex also bound to naturally occurring anti-DNA autoantibodies, suggesting a possible role of the complex in the pathogenesis of systemic lupus erythematosus.

Animals↗
PubMed1998

Two psychological treatments for hypochondriasis. A randomised controlled trial.

BACKGROUND: Hypochondriasis is generally considered difficult to manage. This study aimed to assess the effectiveness of cognitive therapy and to compare it with an equally credible, alternative treatment. METHOD: Forty-eight patients with hypochondriasis were initially randomly assigned to either cognitive therapy, behavioural stress management or a no treatment waiting list control group. At the end of the waiting period, patients in the control group were randomly assigned to one of the two treatments. Assessments were at pre-, mid- and post-treatment or waiting list and at three-, six- and 12-month post-treatment follow-up. RESULTS: Comparisons with the waiting list group showed both treatments were effective. Comparisons between the treatments showed that cognitive therapy was more effective than behavioural stress management on measures of hypochondriasis, but not general mood disturbance at mid-treatment and at post-treatment. One year after treatment patients who had received either treatment remained significantly better than before treatment, and on almost all measures the two therapies did not differ from each other. CONCLUSIONS: Cognitive therapy is a specific treatment for hypochondriasis. Behavioural stress management is also effective but its specificity remains to be demonstrated.

Adult↗
PubMed1998

Hepatocellular carcinoma: analysis of 76 cases.

Hepatocellular carcinoma is one of the most common malignancies world wide. We present data on 76 patients admitted to the Shaikh Zayed Hospital. Mean age was 52.2 +/- 11.3 years. Eighty six percent were males and 14% females. Eighty-six percent patients had underlying cirrhosis documented on ultrasound examination. Seventy-five percent were positive for anti HCV, 10% for HBsAg positive, 10% for both HBsAg and anti HCV and 5% cases had negative viral serology. Main clinical features were abdominal pain, weight loss, jaundice, hepatomegaly and ascites. Forty-three percent patients were Child-Pugh class A, 30% class B and 13% class C and 14% were non cirrhotic. Mean alfa fetoprotein levels were 142 +/- 155 ng/ml (range 2.7 to 1470). Diagnosis of hepatocellular carcinoma was established in 60 patients by fine needle aspiration biopsy under ultrasound guidance. Two patients died after biopsy due to uncontrollable bleeding. Fifty-four percent patients had a solitary lesion and 46% had multifocal or diffuse lesions. The average size of lesion was 7.8 x 8.1 cm. Twenty-two patients received intralesional alcohol injection. Fifty-four percent of these with a tumor size greater than 8 cm died during follow up. The major cause of death was liver failure in 8 patients and fatal bleeding occurred in 4 patients. Hepatocellular carcinoma has a high prevalence in middle aged males with a strong association with anti HCV positive cirrhosis. Patients with a tumour size greater than 8 cm have a poor response to intralesional alcohol injection.

Abdominal Pain↗
PubMed1998

Population based data on urinary excretion of various metabolites in children of north western region of Pakistan.

Population based data on urinary excretion of various metabolites of pathological importance, Calcium, Magnesium, Sodium, Potassium, Oxalates, Citrates, Phosphates, Uric acid and urea have been collected from around three hundred children of the Quetta valley. The body weight was in the range of 11-50 kg and the age was in between 4-16 years. The urine excretion average was 987.5 +/- 452.5 ml per 24 hours. There was 11.5% incidence of hypercalciuria, 8.5% incidence of hyperuricosuria, 2.0% hyperphosphaturia, 2.5% hypomagnesuria, 3.5% hypocitraturia, 6.5% hypernatriuria, 43.5% hypokaliurea and 2.1% hyperoxaluria. Urea excretion average was 23.11 +/- 14.99 g per 24 hours. The study provided the basis for childhood reference pattern in urinary excretion of compounds related to various pathological conditions, in particular stone formation in this region.

Adolescent↗