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W Ahmad

Publications and source records attributed to W Ahmad.

At least 55 records · Page 3Linked to original sources
PubMed1998

A missense mutation in the zinc-finger domain of the human hairless gene underlies congenital atrichia in a family of Irish travellers.

Congenital atrichia is a rare, recessively inherited form of hair loss affecting both males and females and is characterized by a complete absence of hair follicles. Recently, a mutation in the human hairless gene was implicated in the pathogenesis of congenital atrichia. The human hairless gene encodes a putative single zinc-finger transcription-factor protein with restricted expression in brain and skin, which is believed to regulate catagen remodeling in the hair cycle. In this study, we report the identification of a missense mutation in the zinc-finger domain of the hairless gene in a large inbred family of Irish Travellers with congenital atrichia. The mutated arginine residue is conserved among human, mouse, and rat, suggesting that it is of significant importance to the function of the zinc-finger domain.

Alopecia↗
PubMed1998

Molecular and functional aspects of the hairless (hr) gene in laboratory rodents and humans.

For many years, hairless and rhino mouse mutants have provided a useful and extensively exploited model for studying different aspects of skin physiology, including skin aging, pharmacokinetic evaluation of drug activity and cutaneous absorption, skin carcinogenesis, and skin toxicology. Interestingly, however, hairless and rhino mice have rarely been studied for their primary cellular defect - hairlessness - and thus, the hairless gene itself and its physiological functions have been largely overlooked for decades. The recent identification of the human homolog of the hairless gene on human Chromosome 8p12 confirmed the clinical significance of the phenomenon of "hairlessness" in humans, which was predicted on the basis of similarities between hairless mice and a congenital hair disorder characterized by atrichia with papules. Mutations in the hairless gene of mice provide instructive models for further studies of hr gene function, and may facilitate insights into the pathophysiology of different human disorders associated with the disruption of hr gene activity. We provide an overview of current data on the structure and expression patterns of the hr gene, and of mutations at the hairless locus in mice and humans, including the genetic basis of different alleles, the pathology of hairlessness, reproductive and immunological defects, and susceptibility to dioxin toxicity. On the basis of our current understanding of hairlessness, we speculate on the putative functions of the hr gene product in skin physiology, and particularly, in hair follicle biology.

Alleles↗
PubMed1998

Molecular basis for the rhino Yurlovo (hr(rhY)) phenotype: severe skin abnormalities and female reproductive defects associated with an insertion in the hairless gene.

In 1989, mice bearing mutations at the hr (hairless) locus were first proposed as a model for the human hair growth disorder papular atrichia, since in both these mice and in corresponding patients, a complete hair loss develops due to disintegration of the normal follicle structure into dermal cysts and so-called utriculi. Recently, the human hairless gene was characterized, and pathogenetic mutations were found to be associated with a recessively inherited form atrichia with papular lesions; however, the functions of hr gene remain unclear. Allelic mutations in the murine hairless gene represent a potentially powerful tool to elucidate the role of the hairless gene protein product in hair follicle physiology. In 1980, several naked animals were discovered in a breeding colony of B10.R109/Y mice maintained in the Laboratory of Experimental Biological Models (L.E.B.M., Yurlovo, Moscow District, Russia). By cross breeding with hairless HRS/J hr/hr mice, this mutation was shown to be allelic with hairless. Here, we describe the molecular basis of the hr(rhY) mutation in mice, which consists of a 13 bp insertion in exon 16 of the hr gene. Histological evaluation of Yurlovo mouse skin revealed some differences as compared to the hairless and rhino mutations, with the formation of dermal megacysts being the most specific peculiarity of the Yurlovo mutation. These results, together with previous studies of hr(rhY)/hr(rhY) mutant mice, suggest that the rhino Yurlovo (hr(rhY)) mutation represents a third and potentially more severe variation of the hairless phenotype.

Animals↗
PubMed1998

Molecular basis of a novel rhino (hr(rhChr)) phenotype: a nonsense mutation in the mouse hairless gene.

The hairless and rhino mutations are autosomal recessive allelic mutations that map to mouse Chromosome 14. In general, the rhino phenotype is a more severe manifestation of the hairless phenotype. In both hairless and rhino mice, the hair begins shedding in a cephalocaudal pattern within 7 days after birth, and never regrows due to a series of irreversible cellular events. The hairless mutation closely resembles the human disease known as papular atrichia (MIM 209500). Recently, this disease was linked to Chromosome 8p12, the human homolog of hairless was cloned and mapped to the same locus, and mutations have been identified in several different families. In order to gain insight into the pathophysiology of disease in papular atrichia, we sought to utilize mouse mutations as in vivo model systems. In this study, we report the identification of a homozygous nonsense mutation in the coding region of the hr gene in a hairless mouse captured on a chicken farm in the Midwestern United States. To reflect the place of identification of this new mutation at the hr locus, we have designated this allele hr(rhChr) using the laboratory code Chr (Christiano).

Alleles↗
PubMed1995

Lysosomal chitobiase (CTB) and the G-protein gamma 5 subunit (GNG5) genes co-localize to human chromosome 1p22.

Previously isolated human placental cDNA clones represent a fusion of specific RNA sequences encoded by two genes: lysosomal chitobiase (CTB) and G-protein gamma 5 subunit (GNG5, Fisher and Aronson, 1992a, 1992b). Both genes have now been mapped to 1p by PCR analysis of somatic cell hybrids and further refined to 1p22 by fluorescence in situ hybridization (FISH) using a YAC clone that contains both the chitobiase and gamma 5 genes.

Acetylglucosaminidase↗
PubMed1990

Directed mutagenesis of selected regions of a Bacillus thuringiensis entomocidal protein.

Comparison of the sequences of Bacillus thuringiensis entomocidal toxins of widely differing specificity reveals six conserved domains. The role of one of the most highly conserved domains (D1) located near the N-terminus has been investigated by site directed mutagenesis at two positions. Although preliminary results indicate that the capacity of the mutants to bind to putative receptors on the plasma membrane of susceptible cells was unaffected, toxicity in vivo was reduced by 70-80%. The role of the highly hydrophobic segment exposed at the N-terminus of the toxin after proteolytic activation was investigated by substituting two aspartate residues for phenylalanine and valine located adjacent to each other in the centre of this segment. The toxicity of the resulting mutant protein was only 40% of the unmutated toxin but again preliminary results suggest that binding to putative receptors was unaffected. These results suggest that regions close to the N-terminus of this and similar toxins may play an important role in the membrane insertion event which is believed to follow receptor recognition.

Animals↗
PubMed1989

Evidence for two different types of insecticidal P2 toxins with dual specificity in Bacillus thuringiensis subspecies.

Analysis of polypeptides in the crystalline delta-endotoxins from different Bacillus thuringiensis strains revealed two antigenically similar forms of the P2 protein which differed in molecular mass, peptide profile, and amino acid sequence. Purified preparations of the two forms displayed the characteristic dual toxicity of the P2 protein towards members of the orders Lepidoptera and Diptera in vivo but differed markedly in potency for the insects tested. Both species of the P2 protoxin, solubilized and activated by sequential proteolysis with insect gut extract and alpha-chymotrypsin, retained activity in vivo and in vitro, despite the removal of 144 residues from the N terminus. For the low-molecular-mass form, the dual insecticidal activity was reproducible in the in vitro assays.

Amino Acid Sequence↗
PubMed1989

A single nocte dose of famotidine in the treatment of duodenal ulcer.

Fifty three patients with duodenal ulcer were treated with 40 mg of famotidine at bed time. Repeat endoscopy showed healing rates of 69.8% and 83% at 4 and 6 weeks respectively. Seven patients were kept on a maintenance dose of 20 mg nocte for one year, of these one had a relapse despite taking the drug regularly. No appreciable side effects were observed with the drug (JPMA 39:104, 1989).

Adolescent↗
PubMed1988

Effect of anticalmodulin drugs on testosterone synthesis in hCG stimulated mouse Leydig cells.

The effect of three anticalmodulin drugs, prepared in this laboratory and a commercially available drug Mastoparan, was tested on the secretion (or synthesis) of testosterone in hCG stimulated Leydig cells. The results of the use of drugs RN-IV A, RN-IV B and RN-IV C indicated that hCG (10 ng/ml), DbcAMP (0.1 mM) and cholera toxin (2 micrograms/ml)-stimulated testosterone production was inhibited in Leydig cells in a dose dependent manner. In hCG stimulated cells, the ID50 for drug RN-IV A was 2 microM, for drug RN-IV B was 25 microM and for drug RN-IV C was 130 microM. Based on ID50 the most effective drug was RN-IV A. Maximum inhibition of testosterone production was obtained at a concentration of 20 microM for drug RN-IV A, 150 microM for drug RN-IV B and 200 microM for drug RN-IV C. Further extensive experiments with drug RN-IV B showed that (a) at 100 microM concentration the drug does not impair the binding of receptor with 125I hCG, (b) the cAMP accumulation was prevented in a dose dependent manner reaching a minimal of 1.1 pM at 50 microM, compared with 3.5 pM in hCG (10 ng/ml) stimulated cells. The drug RN-IV B at a concentration of 100 microM, which failed to prevent conversion of exogenous pregnenolone or progesterone to testosterone, otherwise caused complete inhibition of testosterone production in hCG stimulated cells. Mastoparan also inhibited testosterone production in hCG stimulated cells in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Leaks and obstruction after gastric resection.

Postoperative gastric retention may be minimized by avoiding the use of the Billroth I reconstruction when a large duodenal ulcer must be retained. Postoperative gastric retention is more likely to remit with conservative therapy if the procedure was a Billroth I reconstruction with a vagotomy. In other instances where there is difficulty in gastric emptying, a mechanical cause should be strongly suspected. The optimum duration of a conservative trial with suction for postoperative gastric retention may be debatable, and contrast radiography or endoscopy may be helpful; however, patience and suction are not long-term substitutes for a needed operation.

Adult↗
PubMed1982

Applications of choledochoduodenostomy in biliary tract obstruction.

Forty-three patients each underwent choledochoduodenostomy for distal biliary obstruction. The results were satisfactory for those patients with benign obstructions. Choledochoduodenostomy was complicated by recurrent biliary obstruction in five of 19 patients with obstructing neoplasms, and is generally a poor choice in those circumstances. Choledochoduodenostomy is a useful procedure for patients with benign distal biliary tract obstructions, particularly when dealing with elderly, poor-risk patients.

Adenocarcinoma↗
PubMed1981

A prospective study of carotid endarterectomy with and without shunt.

The extent of cerebral protection necessary during carotid endarterectomy for ischemia is controversial. In 147 carotid endarterectomies, carotid backflow was estimated and, in later years, these clinical impressions were correlated with stump pressure. These estimates or values, modified particularly in early years by the extent of contralateral disease and (inversely) of ipsilateral occlusion, were used to determine the need for a shunt at the time of carotid clamping. Only 32 shunts were used, 12 because of poor back bleeding and 20 because of stump pressure below 50 mmHg. The patients who received shunts had no mortality or neurologic deficits. In 30 patients excluded by adequate stump pressure there was only a single minor and temporary monoparesis. In 85 patients excluded by apparently good back bleeding, there were two deaths (one due to stroke), a permanent 10 per cent neurologic deficit, and two postoperative thromboses salvageable by reoperation. Routine shunting would probably have prevented only the temporary monoparesis and the 10 per cent neurologic deficit. Meticulous technique and selective use of a shunt should give satisfactory results.

Adult↗
PubMed1980

Pseudoaneurysms and related complications of aortic bypass grafts.

During a recent five-year period 14 patients had pseudoaneurysms as late complications of aortic bifurcation grafts. Severe atherosclerosis had been present at the time of the aortic grafts, and subsequent progression of arterial disease appeared to be the usual cause of the pseudoaneurysms which occurred from two to 14 years later. Nineteen of the 23 pseudoaneurysms in the 14 patients were in the groin. Excision and interposition graft usually worked well. Eleven patients had early benefit. Two early failures were due to infection. The long-term results correlated with success in obtaining adequate arterial outflow. Rupture of pseudoaneurysms, concomitant thrombosis, other complications, and diagnostic errors also caused operative problems and influenced results.

Adult↗
PubMed1979

Results of corrective surgery for alkaline reflux gastritis.

Reflux alkaline gastritis and esophagitis have been incriminated as a source of symptoms in achlorhydric patients afer operation for duodenal ulcer. Documentation of such pathologic findings has increased due to widespread use of fiberoptic endoscopy. As reported in the literature, results of remedial operations have ranged from encouraging to excellent, and evaluations have been uniformly laudatory. Correlation of the extent of symptoms and of pathologic findings has been difficult, and our results have not been as good as those reported in the literature. During a six-year period, the diagnosis of bile reflux gastritis in 13 patients was based on a characteristic symptom complex, endoscopic appearance, and histopathologic confirmation. Either a Roux-en-Y gastrojejunostomy or a Tanner-Roux 19 was the corrective procedure. There was complete relief of symptoms in five patients (38%) and partial relief in four, but no apparent relief in four others. In at least three of the patients, chronic gastritis and/or esophagitis have persisted and have not improved despite biliary diversion. Tabulation of the results of 13 remedial operations for reflux alkaline gastritis disclosed that copmlete relief of symptoms was achieved in 50% of those who had the Roux-en-Y and in 20% of those who had the Tanner 19 procedure. Based on our findings, we recommend a cautious approach to the surgical management of alkaline gastritis.

Adult↗