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Biomedical subjects

N Rahman

Publications and source records attributed to N Rahman.

At least 19 recordsLinked to original sources
PubMed2006

ATM and breast cancer susceptibility.

ATM was originally identified by positional cloning as the gene that underlies the autosomal recessive condition ataxia-telangiectasia. The encoded protein plays a central role in the complex processes that repair DNA double-strand breaks. Nearly 20 years ago, epidemiological surveys of relatives of ataxia-telangiectasia cases suggested that female relatives were at modestly increased risk of breast cancer. Subsequently, many studies have tried to clarify the role of ATM in breast cancer susceptibility, but have produced inconclusive and/or inconsistent results. Recently, large epidemiological and molecular studies have finally provided conclusive evidence that ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2006

Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice.

BACKGROUND: Most Wilms tumours occur in otherwise healthy children, but a small proportion occur in children with genetic syndromes associated with increased risks of Wilms tumour. Surveillance for Wilms tumour has become widespread, despite a lack of clarity about which children are at increased risk of these tumours and limited evidence of the efficacy of screening or guidance as to how screening should be implemented. METHODS: The available literature was reviewed. RESULTS: The potential risks and benefits of Wilms tumour surveillance are finely balanced and there is no clear evidence that screening reduces mortality or morbidity. Prospective evidence-based data on the efficacy of Wilms tumour screening would be difficult and costly to generate and are unlikely to become available in the foreseeable future. CONCLUSIONS: The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3-4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.

Chromosome Disorders↗
PubMed2006

Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour.

Wilms tumour has been reported in association with over 50 different clinical conditions and several abnormal constitutional karyotypes. Conclusive evidence of an increased risk of Wilms tumour exists for only a minority of these conditions, including WT1 associated syndromes, familial Wilms tumour, and certain overgrowth conditions such as Beckwith-Wiedemann syndrome. In many reported conditions the rare co-occurrence of Wilms tumour is probably due to chance. However, for several conditions the available evidence cannot either confirm or exclude an increased risk, usually because of the rarity of the syndrome. In addition, emerging evidence suggests that an increased risk of Wilms tumour occurs only in a subset of individuals for some syndromes. The complex clinical and molecular heterogeneity of disorders associated with Wilms tumour, together with the apparent absence of functional links between most of the known predisposition genes, suggests that abrogation of a variety of pathways can promote Wilms tumorigenesis.

Chromosome Aberrations↗
PubMed2005

Laser bonded microjoints between titanium and polyimide for applications in medical implants.

Bioencapsulation of medical implant devices, and neural implant devices in particular, requires development of reliable hermetic joints between packaging materials that are often dissimilar. Titanium-polyimide is one of the biocompatible material systems, which are of interest to our research groups at Wayne State University and Fraunhofer USA. We have found processing conditions for successful joining of titanium with polyimide using near-infrared diode lasers or fiber lasers along transmission bonding lines with widths ranging from 200 to 300 microm. Laser powers of 2.2 and 3.8 W were used to create these joints. Laser-joined samples were tested in a microtester under tensile loading to determine joint strengths. In addition, finite element analysis (FEA) was conducted to understand the stress distribution within the bond area under tensile loading. The FEA model provides a full-field stress distribution in and around the joint that cause eventual failure. Results from the investigation provide an initial approach to characterize laser-fabricated microjoints between dissimilar materials that can be potentially used in optimization of bio-encapsulation design.

Equipment Failure Analysis↗
PubMed2005

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.

Abnormalities, Multiple↗
PubMed2005

Partial NSD1 deletions cause 5% of Sotos syndrome and are readily identifiable by multiplex ligation dependent probe amplification.

BACKGROUND: Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions. It is uncertain whether allelic or genetic heterogeneity underlies the residual cases and it has been proposed that other mechanisms, such as 11p15 defects, might be responsible for Sotos cases without NSD1 mutations or 5q35 microdeletions. OBJECTIVE: To develop a multiplex ligation dependent probe amplification (MLPA) assay to screen NSD1 for exonic deletions/duplications. METHODS: Analysis was undertaken of 18 classic Sotos syndrome cases in which NSD1 mutations and 5q35 microdeletions were excluded. Long range polymerase chain reaction (PCR) was used to characterise the mechanism of generation of the partial NSD1 deletions. RESULTS: Eight unique partial NSD1 deletions were identified: exons 1-2 (n = 4), exons 3-5, exons 9-13, exons 19-21, and exon 22. Using long range PCR six of the deletions were confirmed and the precise breakpoints in five cases characterised. This showed that three had arisen through Alu-Alu recombination and two from non-homologous end joining. CONCLUSIONS: MLPA is a robust, inexpensive, simple technique that reliably detects both 5q35 microdeletions and partial NSD1 deletions that together account for approximately 15% of Sotos syndrome.

Base Sequence↗
PubMed2005

Initial-rate method for the determination of pantoprazole in pharmaceutical formulations using 1-fluoro 2,4-dinitrobenzene.

A simple and selective kinetic spectrophotometric method for the determination of pantoprazole in pharmaceutical preparations is described. The procedure is based upon a kinetic investigation of the reaction of the drug with 1-fluoro-2,4-dinitrobenzene in DMSO at room temperature. The absorbance of the coloured product was measured at 420 nm. The plot of the logarithm of the initial rate of the reaction vs. the logarithm of molar concentration of pantoprazole is linear over the range 10-20 microg x ml(-1). The procedure retains its accuracy in the presence of a large excess of its degradate, sulfenic acid, which is prepared by degradating the pure drug in borate buffer of pH 8 at room temperature for seven days. The results are validated statistically and through recovery studies. The method has been successfully applied to the determination of pantoprazole in commercial tablets. Statistical comparison of the results with the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Nude mice as a model for gonadotropin-induced adrenocortical neoplasia.

Certain inbred mice (e.g., DBA/2J, CE) develop sex steroid producing adrenocortical tumors following gonadectomy. This adrenal response is thought to result from an unopposed increase in circulating gonadotropins and/or a decrease in factor(s) of gonadal origin. To differentiate between these two possibilities, we utilized the NU/J strain of nude mice, which are immunologically compromised and therefore permissive to xenografts. One group of female nude mice was gonadectomized, while another group of females received xenografts of CHO cells stably transfected with human chorionic gonadotropin (hCG). After 1-2 months, subcapsular adrenocortical neoplasms containing sex steroid-producing cells were observed in both groups. We conclude that high levels of circulating gonadotropins are sufficient to induce adrenocortical tumorigenesis, even in the presence of intact gonads.

Adrenal Cortex Neoplasms↗
PubMed2004

The prevalence of glaucoma in Bangladesh: a population based survey in Dhaka division.

BACKGROUND/AIM: Few studies have reported on the epidemiology and clinical characteristics of glaucoma in south Asia. This project aimed to determine the prevalence of glaucoma of Dhaka, Bangladesh. METHOD: A multistage, stratified, clustered sample was drawn from Dhaka Division, Bangladesh, using systematic sampling to identify individual subjects aged 35 years and older. Examination of all subjects included Snellen visual acuity, slit lamp examination (including gonioscopy and applanation tonometry) and a stereoscopic assessment of the vertical cup:disc ratio (CDR). In selected subjects, a threshold visual field examination was performed. Glaucoma was diagnosed on the basis of statistical abnormality of the vertical CDR combined with an abnormal visual field test, or in subjects with advanced glaucoma who could not complete field testing, a grossly abnormal CDR. If it was not possible to examine the optic discs and the subject was blind, glaucoma was diagnosed on the basis of a raised intraocular pressure. RESULTS: Of 3562 eligible subjects, 2347 were examined (66%). Among people aged 40 years and older, the prevalence of definite glaucoma was 2.1% (95% confidence interval: 1.5 to 2.9; 39 people). The prevalence of definite and probable glaucoma was 3.1% (95% CI: 2.4 to 4.0; 58 people) in subjects of the same age. Primary open angle glaucoma was the most common form of glaucoma, accounting for 75% of the total. Among cases of blindness not attributable to refractive error, 5% were caused by glaucoma. Glaucoma prevalence was higher in men than women, but did not show the typical increase with age. CONCLUSION: Glaucoma prevalence is relatively high in Bangladesh, although it accounts for only a small proportion of blindness in the community. It is estimated that there are approximately 586 000 people 40 years and older with definite or probable glaucoma in Bangladesh.

Adult↗
PubMed2004

A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO.

PURPOSE: To develop a simple scoring system for the likelihood of identifying a BRCA1 or BRCA2 mutation. METHODS: DNA samples from affected subjects from 422 non-Jewish families with a history of breast and/or ovarian cancer were screened for BRCA1 mutations and a subset of 318 was screened for BRCA2 by whole gene screening techniques. Using a combination of results from screening and the family history of mutation negative and positive kindreds, a simple scoring system (Manchester scoring system) was devised to predict pathogenic mutations and particularly to discriminate at the 10% likelihood level. A second separate dataset of 192 samples was subsequently used to test the model's predictive value. This was further validated on a third set of 258 samples and compared against existing models. RESULTS: The scoring system includes a cut-off at 10 points for each gene. This equates to >10% probability of a pathogenic mutation in BRCA1 and BRCA2 individually. The Manchester scoring system had the best trade-off between sensitivity and specificity at 10% prediction for the presence of mutations as shown by its highest C-statistic and was far superior to BRCAPRO. CONCLUSION: The scoring system is useful in identifying mutations particularly in BRCA2. The algorithm may need modifying to include pathological data when calculating whether to screen for BRCA1 mutations. It is considerably less time-consuming for clinicians than using computer models and if implemented routinely in clinical practice will aid in selecting families most suitable for DNA sampling for diagnostic testing.

Algorithms↗
PubMed2004

Galactocele in a male infant with congenital hypopituitarism.

Galactocele is an uncommon benign breast lesion usually occurring in young lactating women. It is a rare cause of breast enlargement in children. We report a galactocele in a male child with congenital hypopituitarism and propose an association between the two conditions.

Breast Cyst↗
PubMed2004

Kinetic spectrophotometric method for the determination of silymarin in pharmaceutical formulations using potassium permanganate as oxidant.

A new simple and sensitive kinetic spectrophotometric method for the determination of silymarin in pure form and in pharmaceutical formulations is described. The method is based on the oxidation of the drug with potassium permanganate at pH 7.0 +/- 0.2. The reaction is followed spectrophotometrically by measuring the decrease in the absorbance at 530 nm. The calibration graph is linear in the range of 18-50 microg x m(-1). The method has been successfully applied to the determination of silymarin in pharmaceutical formulations. Statistical comparison of the results with the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.

Algorithms↗
PubMed2002

Congenital mesenterico-portal (Rex) shunt.

Congenital anomalies of the portal and umbilical-venous system are rare, with few reported cases. We describe a case where the native umbilical vein had acquired mesenteric venous outflow to bypass an in-utero portal-vein (PV) obstruction and restore normal venous return to the liver. This is analogous to the recently described Rex shunt procedure used in some cases of extrahepatic portal hypertension due to PV occlusion.

Hernia, Umbilical↗
PubMed2002

Clinical and genetic heterogeneity in peroneal muscular atrophy associated with vocal cord weakness.

BACKGROUND: The peroneal muscular atrophy syndrome is the most common inherited disorder of the peripheral nervous system and has extensive clinical and genetic heterogeneity. Cranial nerve involvement is rare, though there are distinct peroneal muscular atrophy syndromes in which vocal cord paralysis is a characteristic feature. Among these dHMN-VII and HMSN-IIC are clinically similar but are differentiated by sensory involvement in HMSN-IIC. The gene for dHMN-VII, designated DHMNVP, has been localised to chromosome 2q14, but the location of the gene for HMSN-IIC is currently unknown. It has been suggested that dHMN-VII and HMSN II-C are allelic disorders. OBJECTIVE: To assess the contribution of the dHMN-VII predisposition gene to peroneal muscular atrophy syndromes associated with vocal cord weakness. METHODS: Linkage analysis of microsatellite markers at chromosome 2q14 was undertaken on two families, one affected by HMSN-IIC and a second manifesting vocal cord paralysis and sensorineural deafness in addition to distal muscular atrophy. RESULTS: Two-point LOD scores at chromosome 2q14 markers encompassing the DHMNVP gene were negative in both families. CONCLUSIONS: These results suggest that at least one further gene predisposing to distal muscular weakness in association with vocal cord paralysis is likely to exist, and that dHMN-VII and HMSN-IIC are unlikely to be allelic disorders. Analyses of further HMSN-IIC families are required to confirm this.

Charcot-Marie-Tooth Disease↗
PubMed2001

Case of interstitial 12q deletion in association with Wilms tumor.

A 14-month-old boy presenting with Wilms tumor (WT) was found to have a small de novo deletion of the long arm of chromosome 12 (12q11-12q13.11). Microsatellite analysis of this region from constitutional DNA showed that the paternal allele was absent between the markers D12S331 and D12S1713 (inclusive). In the WT there was no evidence of loss of the maternal chromosome. Constitutional chromosome abnormalities can often point to the presence of genes that are important in disease, and the deletion of chromosome 12 in this patient may indicate a gene involved in WT. To determine whether a WT predisposition locus exists at 12q we examined the region in two familial Wilms tumor (FWT) pedigrees unlinked to the known FWT genes on chromosomes 17q (FWT1), 19q (FWT2), and 11p (WT1). In both families WT did not segregate with chromosome 12q markers located within the deletion boundaries.

Chromosome Deletion↗
PubMed2001

Structure of the 5' region of the Hst70 gene transcription unit: presence of an intron and multiple transcription initiation sites.

The rat Hst70 gene and its mouse counterpart Hsp70.2 belong to the family of Hsp70 heat shock genes and are specifically expressed in male germ cells. Previous studies regarding the structure of the 5' region of the transcription unit of these genes as well as localization of the 'cis' elements conferring their testis-specific expression gave contradictory results [Widlak, Markkula, Krawczyk, Kananen and Huhtaniemi (1995) Biochim. Biophys. Acta 1264, 191-200; Dix, Rosario-Herrle, Gotoh, Mori, Goulding, Barret and Eddy (1996) Dev. Biol. 174, 310-321]. In the present paper we solve these controversies and show that the 5' untranslated region (UTR) of the Hst70 gene contains an intron which is localized similar to that of the mouse Hsp70.2 gene. Reverse transcriptase-mediated PCR, Northern blotting and RNase protection analysis revealed that the transcription initiation of both genes starts at two main distant sites, and one of them is localized within the intron. As a result two populations of Hst70 gene transcripts with similar sizes but different 5' UTR structures can be detected in total testicular RNA. Functional analysis of the Hst70 gene promoter in transgenic mice and transient transfection assays proved that the DNA fragment of approx. 360 bp localized upstream of the ATG transcription start codon is the minimal promoter required for testis-specific expression of the HST70/chloramphenicol acetyltransferase transgene. These experiments also suggest that the expression of the gene may depend on 'cis' regulatory elements localized within exon 1 and the intron sequences.

5' Untranslated Regions↗