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Biomedical subjects

G Ali

Publications and source records attributed to G Ali.

At least 19 recordsLinked to original sources
PubMed2006

Ectodermal dysplasia of hair and nail type: mapping of a novel locus to chromosome 17p12-q21.2.

BACKGROUND: Ectodermal dysplasias (EDs) describe a large and complex group of disorders characterized by abnormal development of the skin and appendages (hair, nails, teeth and sweat glands). Of the approximately 200 different EDs, about 30 have been studied at the molecular level. In an effort to understand the molecular bases of ED of hair and nail type, we studied a Pakistani consanguineous family with multiple affected individuals. OBJECTIVES: To localize the gene responsible for the autosomal recessive form of ED of hair and nail type. METHODS: Genotyping of nine members of the family, including five affected and four normal individuals was performed using microsatellite markers mapping to candidate regions, harbouring genes involved in related phenotypes. Five epithelial keratin genes located in the candidate region were sequenced to identify the pathogenic mutation. RESULTS: We mapped the disease locus to a 24.2-cM interval flanked by markers D17S839 and D17S1299 on chromosome 17p12-q21.2 (Z(max) = 4.4). DNA sequencing of five epithelial keratin candidate genes, present in the disease locus, did not reveal any pathogenic mutation in the affected individuals. CONCLUSIONS: The gene for ED of hair and nail type has been mapped to chromosome 17p12-q21.2 in a Pakistani consanguineous family. Failure to detect mutations in epithelial keratin genes suggests that the mutation may lie either in regulatory regions of one of the epithelial keratin genes or in another unknown gene, located in the linkage interval, with a possible role in the development of ectodermal appendages.

Chromosome Mapping↗
PubMed2006

The mapping of DFNB62, a new locus for autosomal recessive non-syndromic hearing impairment, to chromosome 12p13.2-p11.23.

Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common form of prelingual inherited hearing impairment (HI). Here is described the mapping of a novel ARNSHI locus in a consanguineous Pakistani family with profound congenital HI. Two-point and multipoint linkage analyses were performed for the genome scan and fine mapping markers. Haplotypes were constructed to determine the region of homozygosity. At theta = 0, the maximum two-point LOD score of 4.0 was obtained at marker AAC040. A maximum multipoint LOD score of 5.3 was derived at marker D12S320, with the three-unit support interval demarcated by D12S89 and D12S1042. The region of homozygosity is flanked by markers D12S358 and D12S1042, which corresponds to 22.4 cM according to the Rutgers combined linkage-physical map of the human genome and spans 15.0 Mb on the sequence-based physical map. A novel ARNSHI locus DFNB62 was mapped to chromosome 12p13.2-p11.23. DFNB62 represents the second ARNSHI locus to map to chromosome 12.

Chromosomes, Human, Pair 12↗
PubMed2006

A novel locus for alopecia with mental retardation syndrome (APMR2) maps to chromosome 3q26.2-q26.31.

Congenital alopecia may occur either alone or in association with ectodermal and other abnormalities. On the bases of such associations, several different syndromes featuring congenital alopecia can be distinguished. Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder, clinically characterized by total or partial hair loss and mental retardation. In the present study, a five-generation Pakistani family with multiple affected individuals with APMR was ascertained. Patients in this family exhibited typical features of APMR syndrome. The disease locus was mapped to chromosome 3q26.2-q26.31 by carrying out a genome scan followed by fine mapping. A maximum two-point logarithm of odds (LOD) score of 2.93 at theta=0.0 was obtained at markers D3S3053 and D3S2309. Multipoint linkage analysis resulted in a maximum LOD score of 4.57 with several markers, which supports the linkage. The disease locus was flanked by markers D3S1564 and D3S2427, which corresponds to 9.6-cM region according to the Rutgers combined linkage-physical map of the human genome (build 35) and contains 5.6 Mb. The linkage interval of the APMR locus identified here does not overlap with the one described previously; therefore, this locus has been designated as APMR2.

Alopecia↗
PubMed2006

Telomerase activity and hTERT mRNA expression in glial tumors.

Human telomerase is a structurally complex ribonucleoprotein that is responsible for the maintenance of telomeric DNA at the ends of the chromosomes. The enzyme is proposed as having an important role in cell immortalization and oncogenesis. A limited number of studies have been performed on the telomerase system in brain tumors, and these studies are somewhat conflicting. The relative ineffectiveness of current therapies for malignant gliomas led to the need for novel targets for more promising approaches. In order to clarify the prognostic significance of telomerase expression in gliomas and to speculate on therapeutic implications, we examined telomerase activity by the telomeric repeat amplification protocol (TRAP) assay in 42 gliomas, (32 multiform glioblastomas, 4 anaplastic astrocytomas, 4 differentiated astrocytomas, 1 oligoastrocytoma and 1 oligosarcoma). Telomerase messenger expression (hTERT mRNA) was evaluated by reverse transcription-PCR analysis in the same group of tumors. High telomerase activity was detected in 21/42 gliomas (50%). The levels of telomerase in terms of its messenger level expression overlapped the activity; in fact, a significant association between telomerase activity and hTERT mRNA expression was found (chi2 test; p<0.0001). At univariate analysis, advanced age as well as high telomerase activity and hTERT mRNA levels were seen to be significant predictors of worse prognosis regarding both overall survival (p=0.007, p=0.007, p=0.04, respectively) and disease-free interval (p=0.008, p=0.008, p=0.04, respectively). All these variables maintained a significant independent prognostic role in multivariate analysis. Telomerase may represent an indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.

Aged↗
PubMed2005

Low prevalence of Connexin 26 (GJB2) variants in Pakistani families with autosomal recessive non-syndromic hearing impairment.

The Pakistani population has become an important resource for research on autosomal recessive non-syndromic hearing impairment (ARNSHI) due to the availability of large extended and highly consanguineous pedigrees. Here is presented the first report on the prevalence of gap junction beta-2 (GJB2) variants in Pakistan. One hundred and ninety-six unrelated Pakistani families with ARNSHI were recruited for a study on the genetics of NSHI. DNA sequencing of the GJB2 coding region was done on two affected individuals per family. Evolutionary conservation and predicted effect on the protein product were studied in order to hypothesize whether or not a variant was potentially deleterious. Homozygous putatively functional GJB2 variants were identified in 6.1% of families. None of the putatively functional GJB2 variants were observed in the compound heterozygous state. The six putatively causative variants noted were 231G > A(W77X), 71G > A(W24X), 167delT, 95G > A(R32H), 358-360delGAG(delE120), and 269T > C(L90P), with 231G > A(W77X) and 71G > A(W24X) being the most common. In addition, five benign polymorphisms, 380G > A(R127H), 457G > A(V153I), 493C > T(R165W), 79G > A(V27I), and 341 A > G(E114G), were identified within this population. In a few individuals, benign polymorphisms were observed to occur on the same haplotype, namely [457G > A(V153I); 493C > T(R165W)] and [79G > A(V27I); 341 A > G(E114G)]. The spectrum of GJB2 sequence variants in Pakistan may reflect shared origins of hearing impairment alleles within the Indian subcontinent. The high degree of consanguinity within Pakistan may have maintained the GJB2 prevalence at a much lower rate than within India and other populations.

Connexin 26↗
PubMed2001

Using manual handling equipment safely.

Information on patient equipment is essential for safety. Knowing the capabilities and limitations of equipment will minimise risk to the patient and operator.

Accidents, Occupational↗
PubMed2000

Ensuring the safe use of cotsides in patient settings.

Most serious incidents and deaths associated with the use of cotsides occur in primary care settings. Cotsides should only be used when all alternatives have been considered inappropriate. A full risk assessment should be conducted to minimise the risk of patient injury.

Accidental Falls↗
PubMed2000

Anhidrotic Ectodermal Dysplasia (Christ-Seimens-Touraine syndrome)--case report with a review.

Anhidrotic ectodermal dysplasia commonly transmitted as an x-linked recessive disorder is very rare. The complete syndrome occurs in males and females are carriers. Our patients comprised two sisters who had the complete syndrome. This is much rarer and is reported to be inherited as autosomal recessive disorder, there are only a few case reports of females presenting with a complete syndrome in the literature.

Adolescent↗
PubMed1998

[Vitamin B 12 deficiency: early diagnosis in ambulatory care medicine].

Many patients suffer from vitamin B12 deficiency and are thus exposed to irreversible sequelae if diagnosis occurs at a late stage. This prospective study undertaken by eight practitioners over a period of 12 months concerns early diagnosis. Blood vitamin B12 levels were measured in 152 patients presenting macrocytosis detected by systematic MCV analysis at the time of a blood test, a neuropathy or a recent cognitive, affective and behavioural problem, and were found to be lowered (< or = 175 pmol/l) in 54 patients of whom 43 had undergone vitamin B12 test treatment for 6 months. Haematological, neurological and psychiatric evaluation was carried out before and after treatment, and a diagnosis of deficiency was recorded in 24 patients based on unequivocal response to therapy. Improvement was greatest haematologically in 12 patients, neurologically in 6 patients and psychiatrically in 6 other patients, with 4 patients showing a combination of all modes. These 24 patients (mean age 69 years) suffered from numerous pathologies which were liable to complicate diagnosis in some of them: neurological (46%), psychiatric (37%), chronic alcoholism (33%), folic acid deficiency (29%), and diabetes (17%). The only diagnostic element used as a criterion of deficiency was an extremely low level of vitamin B12 (< or = 75 pmol/l). Marked macrocytosis or a combination of haematological and neuropsychiatric signs are strong indicators, but only improvement under treatment allowed a diagnosis to be made in the majority of patients. Macrocytosis was, however, not present in 6 of the 12 neuropsychiatric patients. The study thus identified a high proportion of patients with vitamin B12 deficiency who additionally presented, in equal proportions, both haematological and neuropsychiatric symptoms. Neither the clinical examination nor the vitamin B12 level in general permit early diagnosis based on a high probability index and long-term follow-up. Simpler methods for early diagnosis are therefore needed.

Aged↗
PubMed1997

Spectrum of neuropsychiatric complications in 791 cases of typhoid fever.

Over a 6-year period, we studied 791 patients with multidrug-resistant typhoid fever, of whom 665 individuals (84%) developed neuropsychiatric manifestations. These were: acute confusional state (73%); myelitis (6%); cerebellitis (1%); parkinsonism (1%); acute psychosis (0.6%); meningo-encephalitis (0.5%); encephalitis (0.25%); sensory motor polyneuropathy, polymyositis, acute schizophrenia and bizarre neurological syndromes (0.12% each). Severe parkinsonian rigidity and meningo-encephalitis are associated with significant morbidity but very low mortality (0.5%).

Adolescent↗
PubMed1995

Studies on the antimicrobial activity of honey.

Ten samples of crude and processed honey were used to determine antimicrobial activity against twenty five species of pathogenic and nonpathogenic bacteria, commonly encountered in human infections. The antifungal activity was checked against ten parasitic and saprophytic fungi. Most of the samples of honey used in the study showed broad spectrum antibacterial and promising antifungal activity.

Journal Article↗
PubMed1995

Seven-day viable analysis of some ophthalmic preparations with different concentrations of benzalkonium chloride.

The efficacy of zinc sulphate and boric acid ophthalmic preparations, containing benzalkonium chloride as preservative have been investigated against Gram-negative Escherichia coli and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. The viability of bacteria was checked after 7 days though they were completely suppressed after 24 hours of inoculation. Zinc sulphate increased the antimicrobial activity of benzalkonium chloride, whereas the boric acid or its combination with zinc sulphate reduced the same. The Pseudomonas aeruginosa was found to be viable against zinc sulphate, boric acid or its combination at a concentration of 0.01% to 0.005% of the preservative. Escherichia coil and Staphylococcus aureus also exhibited resistance but to a lesser extent than Pseudomonas aeruginosa. This viability may be dangerous in case of multidose ophthalmic preparations.

Bacteria↗
PubMed1995

Flexible sigmoidoscopy or colonoscopy for colorectal screening: a randomized trial of performance and acceptability.

In a randomized clinical trail to assess acceptability, yields, costs, and unwanted effects of screening procedures, 232 subjects (137 with family history of colorectal carcinoma or adenoma, 95 without) were offered either flexible sigmoidoscopy or colonoscopy. Subjects with polyps found on sigmoidoscopy were followed up by colonoscopy. The two procedures were similar in compliance (65%) and yield (19% adenoma, 15% hyperplastic polyps). Polyps of either type were more common in those with a family history (prevalence: 41% compared with 24% without family history, p = 0.04). Costs per procedure were 60% lower for sigmoidoscopy, but follow-up colonoscopy reduced this cost advantage to 20% per subject. The subjects found the preparation for sigmoidoscopy easier, but the procedure more uncomfortable and embarrassing, as colonoscopy was performed under sedation. In this hospital-based study, colonoscopy was as acceptable to subjects, and only slightly more costly than sigmoidoscopy. Advantages of sigmoidoscopy would be greater for use outside hospitals and with less intensive follow up.

Aged↗
PubMed1994

Localization of the gene (OGDH) coding for the E1k component of the alpha-ketoglutarate dehydrogenase complex to chromosome 7p13-p11.2.

alpha-Ketoglutarate dehydrogenase (E1k), also designated oxoglutarate dehydrogenase (OGDH; EC 1.2.4.2), is a component of the enzyme complex that catalyzes the conversion of alpha-ketogluterate to succinyl coenzyme A, a critical step in the Krebs tricarboxylic acid cycle. Deficiencies in the activity of this enzyme complex have been observed in brain and peripheral cells of patients with Alzheimer's disease. This finding led us to localize the genes for the polypeptides that compose the alpha-ketoglutarate dehydrogenase complex (KDGHC). The E1k locus was mapped to chromosome 7p13-p11.2 using a pair of human/rodent somatic cell hybrid panels. A second related sequence, possibly a pseudogene, was identified and mapped to chromosome 10.

Base Sequence↗
PubMed1994

Pseudogene of dihydrolipoyl succinyltransferase (E2k) found by PCR amplification and direct sequencing of rodent-human cell hybrid DNAs.

Previous studies have indicated that the cDNA for the E2k component of the human alpha-ketoglutarate dehydrogenase complex (KGDHC) hybridized not only to a major locus on chromosome 14q24.3 in a region associated with familial Alzheimer's disease and with Joseph-Machado disease, but also to another locus on chromosome 1p31. We now report that PCR of genomic DNA and direct sequencing indicated that the chromosome 1 locus is an intronless pseudogene. PCR of genomic DNA amplified E2k fragments from mouse-human cell hybrids containing human chromosome 1 DNA but not from hybrids containing human chromosome 14 DNA. The resulting amplicons were of comparable sizes to those when the cDNA was used as template. The direct sequencing of these amplicons confirmed the lack of introns and indicated a frame shift, which led to the presence of four termination codons early in the coding region. PCR followed by direct sequencing of the amplicons appears to be a convenient method for identifying intronless pseudogenes.

Acyltransferases↗
PubMed1994

Isolation, characterization, and mapping of gene encoding dihydrolipoyl succinyltransferase (E2k) of human alpha-ketoglutarate dehydrogenase complex.

We have isolated and sequenced cDNAs representing the full-length (2987-bp) gene for dihydrolipoyl succinyltransferase (E2k component) of the human alpha-ketoglutarate dehydrogenase complex (KGDHC) from a human fetal brain cDNA library. The E2k cDNA was mapped to human chromosome 14 using a somatic cell hybrid panel, and more precisely to band 14q24.3 by in situ hybridization. This cDNA also cross-hybridized to an apparent E2k pseudogene on chromosome 1p31. Northern analysis revealed the E2k gene to be ubiquitously expressed in peripheral tissues and brain. Interestingly, chromosome 14q24.3 has recently been reported to contain gene defects for an early-onset form of familial Alzheimer's disease and for Machado-Joseph disease. Future studies will be necessary to determine whether the E2k gene plays a role in either of these two disorders.

Acyltransferases↗