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Biomedical subjects

M Ahmad

Publications and source records attributed to M Ahmad.

At least 145 records · Page 8Linked to original sources
PubMed1998

Prenatal nicotine exposure modifies behavior of mice through early development.

Studies in humans and animal models (including rodents) have revealed lasting behavioral and cognitive impairments in offspring prenatally exposed to nicotine. Offspring of pregnant mouse dams prenatally subjected to 9-10 daily subcutaneous injections into the nape of the neck during pregnancy have been postnatally subjected to several developmental and behavioral tests to investigate the effects of prenatal nicotine exposure on those offspring at various stages of their life. The prenatal exposure to nicotine has resulted in significant reduced postnatal body weight gain, as well as in significant delay in eye opening, in the appearance of body hairs, and in sensory motor reflexes. However, motor activity was significantly stimulated in early adulthood of mouse pups prenatally exposed to nicotine, and such exposure proved to have long-lasting hyperactive effects on mice. Thus, exposure to nicotine during a critical prenatal period of brain development deduced from the present study in mice raises the alarm of the possible hazard of prenatal exposure to nicotine in humans. Hence, smoking by pregnant women might constitute a serious hazard to their in utero developing children.

Aging↗
PubMed1998

Supraventricular arrhythmia: a complication of 5-fluorouracil therapy.

5-Fluorouracil is an S-phase-specific, synthetic pyrimidine antimetabolite, which is used as a cytostatic agent for a variety of malignant lesions, either singly or in multidrug regimens. Gastrointestinal toxicity and myelosuppression are the most common adverse reactions, but, of late, clinical cardiotoxicity has been reported in both prospective and retrospective studies. We present our experience of clinical cardiotoxicity in five patients.

Adenocarcinoma↗
PubMed1998

The CRY1 blue light photoreceptor of Arabidopsis interacts with phytochrome A in vitro.

Plants have at least two major photosensory receptors: phytochrome (absorbing primarily red/far-red light) and cryptochrome (absorbing blue/UV-A light); considerable physiological and genetic evidence suggests some form of communication or functional dependence between the receptors. Here, we demonstrate in vitro, using purified recombinant photoreceptors, that Arabidopsis CRY1 and CRY2 (cryptochrome) are substrates for phosphorylation by a phytochrome A-associated kinase activity. Several mutations within the CRY1 C terminus lead to reduced phosphorylation by phytochrome preparations in vitro. Yeast two-hybrid interaction studies using expressed C-terminal fragments of CRY1 and phytochrome A from Arabidopsis confirm a direct physical interaction between both photoreceptors. In vivo labeling studies and specific mutant alleles of CRY1, which interfere with the function of phytochrome, suggest the possible relevance of these findings in vivo.

Alleles↗
PubMed1998

Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.

Activation of procaspase-9 by Apaf-1 in the cytochrome c/dATP-dependent pathway requires proteolytic cleavage to generate the mature caspase molecule. To elucidate the mechanism of activation of procaspase-9 by Apaf-1, we designed an in vitro Apaf-1-procaspase-9 activation system using recombinant components. Here, we show that deletion of the Apaf-1 WD-40 repeats makes Apaf-1 constitutively active and capable of processing procaspase-9 independent of cytochrome c an dATP. Apaf-1-mediated processing of procaspase-9 occurs at Asp-315 by an intrinsic autocatalytic activity of procaspase-9 itself. We provide evidence that Apaf-1 can form oligomers and may facilitate procaspase-9 autoactivation by oligomerizing its precursor molecules. Once activated, caspase-9 can initiate a caspase cascade involving the downstream executioners caspase-3, -6, and -7.

Adenosine Triphosphate↗
PubMed1998

Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse.

The osteochondrodysplasias are a genetically heterogeneous group of disorders affecting skeletal development, linear growth and the maintenance of cartilage and bone. We have studied a large inbred Pakistani family with a distinct form of recessively inherited spondyloepimetaphyseal dysplasia (SEMD) and mapped a gene associated with this dwarfing condition to chromosome 10q23-24, a region syntenic with the locus for the brachymorphic mutation on mouse chromosome 19. We identified two orthologous genes, ATPSK2 and Atpsk2, encoding novel ATP sulfurylase/APS kinase orthologues in the respective regions of the human and mouse genomes. We characterized a nonsense mutation in ATPSK2 in the SEMD family and a missense mutation in the region of Atpsk2 encoding the APS kinase activity in the brachymorphic mouse. ATP sulfurylase/APS kinase catalyses the metabolic activation of inorganic sulfate to PAPS, the universal donor for post-translational protein sulfation in all cell types. The cartilage-specificity of the human and mouse phenotypes provides further evidence of the critical role of sulfate activation in the maturation of cartilage extracellular matrix molecules and the effect of defects in this process on the architecture of cartilage and skeletogenesis.

Amino Acid Sequence↗
PubMed1998

A gene for universal congenital alopecia maps to chromosome 8p21-22.

Complete or partial congenital absence of hair (congenital alopecia) may occur either in isolation or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal-recessive mode of inheritance (MIM 203655). As yet, no gene has been linked to isolated congenital alopecia, nor has linkage been established to a specific region of the genome. In an attempt to map the gene for the autosomal recessive form of the disorder, we have performed genetic linkage analysis on a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia). We have analyzed individuals of this family, using >175 microsatellite polymorphic markers of the human genome. A maximum LOD score of 7.90 at a recombination fraction of 0 has been obtained with locus D8S258. Haplotype analysis of recombination events localized the disease to a 15-cM region between marker loci D8S261 and D8S1771. We have thus mapped the gene for this hereditary form of isolated congenital alopecia to a locus on chromosome 8p21-22 (ALUNC [alopecia universalis congenitalis]). This will aid future identification of the responsible gene, which will be extremely useful for the understanding of the biochemistry of hair development.

Alopecia↗
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

Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia.

Complete or partial congenital absence of hair (congenital alopecia) may occur isolated or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal recessive mode of inheritance (MIM 203655). We have previously mapped the gene for autosomal recessive congenital alopecia in a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia) to a 15 cM region on chromosome 8p21-22. Here we report the cloning and characterization of the human homologue of the mouse hairless gene and show that it is located in the critical region on chromosome 8p21-22. Determining the exon-intron structure allowed detailed mutational analysis of DNA samples of patients with universal congenital alopecia. We detected a homozygous missense mutation in the Pakistani family and a homozygous splice donor mutation in a family from Oman. In addition, we show that the human hairless gene undergoes alternative splicing and that at least two isoforms generated by alternative usage of exon 17 are found in human tissues. Interestingly, the isoform containing exon 17 is the predominantly expressed isoform in all tissues but skin, where exclusive expression of the shorter isoform was observed. We speculate that this tissue-specific difference in the proportion of hairless transcripts lacking exon 17 sequences could contribute to the tissue-specific disease phenotype observed in individuals with isolated congenital alopecia.

Adult↗
PubMed1998

Chimeric proteins between cry1 and cry2 Arabidopsis blue light photoreceptors indicate overlapping functions and varying protein stability.

A blue light (cryptochrome) photoreceptor from Arabidopsis, cry1, has been identified recently and shown to mediate a number of blue light-dependent phenotypes. Similar to phytochrome, the cryptochrome photoreceptors are encoded by a gene family of homologous members with considerable amino acid sequence similarity within the N-terminal chromophore binding domain. The two members of the Arabidopsis cryptochrome gene family (CRY1 and CRY2) overlap in function, but their proteins differ in stability: cry2 is rapidly degraded under light fluences (green, blue, and UV) that activate the photoreceptor, but cry1 is not. Here, we demonstrate by overexpression in transgenic plants of cry1 and cry2 fusion constructs that their domains are functionally interchangeable. Hybrid receptor proteins mediate functions similar to cry1 and include inhibition of hypocotyl elongation and blue light-dependent anthocyanin accumulation; differences in activity appear to be correlated with differing protein stability. Because cry2 accumulates to high levels under low-light intensities, it may have greater significance in wild-type plants under conditions when light is limited.

Arabidopsis↗
PubMed1998

Combined solid-phase/solution synthesis of a 31-residue vasoactive intestinal peptide analog: general method for repetitive coupling of fragments without isolation and purification of intermediates.

A novel analog of vasoactive intestinal peptide (VIP) has been reported which exhibits high potency and enhanced duration of in vivo biological activity. This VIP analog, cyclo-(Lys21-Asp25)Ac[Glu8 Lys12 Nle17 Ala19, Asp25 Leu26,Lys27,28,Gly29,30,Thr31]-VIP, which also has a lactam bridge, has been reported to have relaxant effects that are significantly more potent than other beta-agonists such as salbutamol and salmeterol. Because it has potential use for the treatment of bronchial asthma in humans, various convergent syntheses were evaluated to enable the economic preparation of large quantities of this medium-sized hentriacontapeptide. From these studies we developed a combined solid-phase/solution synthesis which uses four protected fragments (each prepared by solid-phase synthesis with highly acid-labile resins) possessing Nalpha-9-fluorenylmethyloxycarbonyl and side-chain tert-butyl protection. Only equivalent amounts of each fragment were required to achieve near-quantitative coupling reactions using N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmeth anaminium hexafluorophosphate N-oxide/N-hydroxybenzotriazole. All reagents and side products were removed at each stage by simple extraction procedures. Final deprotection was carried out with 90% trifluoroacetic acid. Under these conditions only low levels of epimerization were observed (<2%). These diastereoisomers and other trace impurities were removed from the product in a single purification by preparative high-performance liquid chromatography. The procedure has been scaled up (10-g scale) and the final product obtained in an overall (nonoptimized) yield of 24%. This procedure for the repetitive coupling of fragments, without isolation of intermediates, may be generally applicable for the economic synthesis of other medium-sized and longer peptides.

Amino Acid Sequence↗
PubMed1998

Development of essential thrombocythemia in a patient treated with interferon alfa and pentostatin for hairy cell leukemia.

A patient is reported who developed essential thrombocythemia after successful treatment for hairy cell leukemia. He was initially treated with interferon alfa and subsequently relapsed within one year of treatment. His diagnosis was reconfirmed and then treated with Pentostatin. Six years after treatment he had a progressive increase in the platelet count and was diagnosed as essential thrombocythemia. Second cancers including various types of hematological malignancy have been reported in patients with hairy cell leukemia treated with chemotherapy or interferon alfa. These malignancies may represent either a new clonal disorder or a complication of drug treatment. This is the first report of a chronic myeloproliferative disorder following successful treatment of hairy cell leukemia.

Aged↗
PubMed1998

Hypomagnesemia and clinical implications in children and neonates.

The prevalence of hypomagnesemia was studied in neonates and children. The specimens were selected randomly from those submitted to the clinical chemical laboratory for blood test. A serum magnesium concentration less than 0.74 mmol/L was considered hypomagnesemic. A total serum magnesium determinations of 910 patients showed that 188 (21.7% prevalence rate) patients contained low serum magnesium levels. Frequently encountered hypomagnesemia was found among neonates with clinical conditions as diarrhea 41 (21.8%), premature births 24 (12.8%), neonatal hepatitis 20 (10.6%) and respiratory distress syndrome 5 (2.7%). In children the clinical conditions most frequently encountered with low serum magnesium were seizure 30 (16%), renal disease 26 (13.8%), metabolic acidosis 18 (9.6%), ideopathic apnea 14 (7.4%) and tachycardia 10 (5.3%). The statistical analysis of low serum magnesium values of patients in various clinical groups showed a significant difference (p < 0.0001) upon using homogeneity of variances but this was insignificant with the application of Kruskal-Wallis 1-Way ANOVA since Chi-square = 12.5748.

Child↗