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Biomedical subjects

S Hakim

Publications and source records attributed to S Hakim.

At least 19 recordsLinked to original sources
PubMed2006

Tryptophan hydroxylase-2 gene polymorphisms in rhesus monkeys: association with hypothalamic-pituitary-adrenal axis function and in vitro gene expression.

Tryptophan hydroxylase-2 (TPH2) is a newly identified second form of TPH responsible for serotonin synthesis in the brain and has been increasingly implicated as a contributor to the etiology of various psychiatric disorders. In this study, we have identified the constellation of polymorphisms in rhesus monkey TPH2 and investigated genotype/phenotype association as well as gene expression effects of specific polymorphisms. Genomic DNA was obtained from 247 rhesus monkeys, among which 24 had been previously examined for plasma cortisol level, dexamethasone suppression, and combined dexmethasone/ACTH challenge. Polymorphisms in all exons, splicing junctions and approximately 2 kb of the 5'-flanking region (5'-FR) of TPH2 were identified by sequencing. We identified 17 single nucleotide polymorphisms (SNPs) including two that are predictive of amino-acid change (25Pro>His and 75Gly>Ser, respectively), two mononucleotide repeats, one dinucleotide repeat, and one 159-bp insertion polymorphism. The 3'-UTR polymorphisms were significantly associated with hypothalamic-pituitary-adrenal (HPA) axis activity, especially 2051A>C, which was strikingly correlated with plasma cortisol level in the morning only (F=10.203, P=0.001). Luciferase reporter gene assays showed that the 3'-UTR polymorphisms and haplotypes had a profound effect on in vitro gene expression. Accordingly, these investigations revealed that polymorphisms in 3'-UTR of rhesus monkey TPH2 modulate HPA axis function, presumably by affecting levels of TPH2 expression.

3' Untranslated Regions↗
PubMed2006

Chlamydia trachomatis infection & female infertility.

BACKGROUND & OBJECTIVES: Chlamydia trachomatis is a well recognized sexually transmitted pathogen. Besides its potential to produce genital tract infection, C. trachomatis is increasingly being associated with long-term complications like infertility. The present study was undertaken to assess the role of C. trachomatis in female infertility as such data are lacking. METHODS: Women of primary and secondary infertility (n=110) and 30 healthy term pregnant women as control group were enrolled in the study. Detailed clinical history of each patient was recorded. Hysterosalpingography was performed in all patients. Endocervical swabs were collected for culture on cycloheximide treated McCoy cell line and for antigen detection by ELISA. RESULTS: C. trachomatis was detected in 31 (28.1%) of the 110 infertile women while one (3.3%) in control group was positive for C. trachomatis (P<0.01). Cell culture alone identified 25 (22.72%) patients suffering from chlamydial infection while C. trachomatis antigen was detected by ELISA in 18 (16.37%) patients. The one control case was positive for Chlamydia antigen by ELISA and not by cell culture. Chlamydial positivity was seen in 20 of the 74 (27%) women with primary infertility and in 11 of the 36 (30.6%) with secondary infertility. Of the 58 asymptomatic women, 21(36.2%) had chlamydia infection while among the 52 symptomatic cases 10 (19.2%) were infected; 38 per cent women with chlamydial infection also had tubal occlusion. INTERPRETATION & CONCLUSION: A significantly high rate of C. trachomatis infection was found in infertile women and more so in asymptomatic females and in secondary infertility cases. Lack of symptoms make clinical diagnosis of chlamydial infection difficult. Screening of infertile women for C. trachomatis is therefore recommended so far early therapeutic interventions.

Antigens, Bacterial↗
PubMed2001

Normal-pressure hydrocephalus.

This article presents a brief history of normal-pressure hydrocephalus, its clinical presentation, and different theories on its pathophysiology. The different diagnostic tests, differential diagnosis, and its treatment are presented.

Brain↗
PubMed2000

Analysis of a 1-megabase deletion in 15q22-q23 in an autistic patient: identification of candidate genes for autism and of homologous DNA segments in 15q22-q23 and 15q11-q13.

We have identified a one megabase deletion in the 15q22-15q23 region in a patient with autism, developmental delay, and mild dysmorphism. Genes that map within the deletion region and genes that are interrupted or rearranged at the deletion breakpoints are candidate genes for autism. Fluroescence in situ hybridization studies in this patient revealed that part or all of the PML gene is absent from one chromosome 15 and a BAC clone containing the D15S124 gene locus hybridizes to only one chromosome 15. BAC clones containing the PTPN9, and SLP-1[hUNC24] genes showed markedly reduced hybridization in the 15q22-q23 region on one chromosome 15 in the patient. These BACs also hybridize to the 15q11-q13 region in close proximity to SNRPN and HERC2, and in this region there is equal intensity of signal on the normal and on the deleted chromosome. There are previous reports of deletions and duplications of the 15q11-q13 region in patients with autism. Our patient represents the first report of a 15q22-q23 deletion. Hybridization of the PTPN9 and Slp-1 Bac clones to the 15q11-q13 and the 15q22-q23 regions of chromosome 15 may be due to the presence of PTPN9 or SLP-1 gene sequences or to the presence of other gene sequences or to non-coding homologous DNA sequences. The PTPN9 gene encodes a non-receptor protein tyrosine phosphatase. The Slp-1 [hUNC24] gene is expressed mainly in the brain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:765-770, 2000.

Adult↗
PubMed1997

Ultrasound in the assessment of cranial bone thickness.

Preoperative knowledge of skull thickness before harvesting cranial bone grafts would be ideal to help minimize intracranial complications. Previous research has demonstrated regional variations in calvaria; however, accurate preoperative and intraoperative methods of skull thickness measurement are not available. The aim of this research represents the first attempt to examine the reliability of ultrasound to determine cranial bone thickness. Four previously studied calvarial sites were marked in 10 adult male cadaveric skulls. The individual points were insonified using an A-mode ultrasonic transducer operating in pulse-echo mode. The times of flight of the waves propagating in the bone samples were compared with caliper measurements. The mean difference in cranial bone thickness was 0.16 mm, with a standard deviation of 0.09 mm. Student's t-test failed to reveal any statistically significant differences between caliper and ultrasonic measurements (p = 0.569) and Pearson's correlation coefficient supported an extremely strong and positive relationship between the two modalities (r > 0.992). Multiple linear regression models predicted that calvarial thickness could be accurately predicted by ultrasound without consideration of cadaveric specimen or sampling point location (R2 = 0.988). The convergent values between ultrasonic and caliper measurements suggest that this modality can accurately and reliably determine skull thickness. A-mode ultrasound can have significant implications in guiding the harvest of in situ split cranial bone grafts, the placement of osseointegrated implants, skull anthropometrics, and related craniomaxillofacial applications.

Aged↗
PubMed1997

A radiation hybrid map of human chromosome 5 with integration of cytogenetic, genetic, and transcript maps.

One of the major goals of the human genome project is to establish a physical map of each human chromosome with a density of sequence-tagged site (STS) markers exceeding one every 100 kb. We report here the generation of a human chromosome 5-specific radiation hybrid (RH) map that includes 556 markers. Of these markers, 132 loci are ordered with a maximum likelihood ratio of >1000:1 compared with the next most likely order. An additional 113 loci were ordered relative to these backbone markers with a maximum likelihood ratio of >10:1 but <1000:1. Together, these 245 loci form an ordered framework map for the chromosome. Using this framework, >300 more markers were localized based on two-point analysis with the ordered set. On average, there are 50 markers in common with the RH map presented here and other chromosome 5 maps included in the current whole genome cytogenetic, genetic, and physical maps. The accuracy of all the maps is evident in that there are no more than two discrepancies between any one of them and these data. All of the maps encompassing chromosome 5 complement each other providing excellent STS coverage with >2200 loci combined. The chromosome 5-specific RH map contains 20% of these independent loci. In addition, our RH map contains STSs derived from clones suitable for fluorescent in situ hybridization, allowing alignment to the cytogenetic map. Together, these maps will assist in the assembly of sequence-ready contigs and will aid in the identification of disease loci on chromosome 5 by positional cloning and positional candidate approaches.

Centromere↗
PubMed1996

Outcome analysis of the modified Mathieu hypospadias repair: comparison of stented and unstented repairs.

PURPOSE: We compared surgical outcomes of stented and unstented Mathieu repairs in boys with primary distal hypospadias, and evaluated the efficacy and safety of caudal analgesia relative to other forms of analgesia (penile block and epidural analgesia). MATERIALS AND METHODS: We retrospectively reviewed the records of 336 consecutive boys who underwent the modified Mathieu repair for primary distal hypospadias. A urethral stent was placed in 114 patients and nonstented repair was performed in 222. Adjunct caudal analgesia was given in 136 cases, a penile block in 158 and continuous epidural analgesia in 42. RESULTS: None of the unstented cases had urinary retention. Analysis of surgical outcomes revealed no difference in fistula formation between patients with and without stents (2.63 versus 2.70%, respectively, p > 0.999). Overall complication rates in the stented and unstented groups were not significantly different (2.63 versus 3.60%, respectively, p = 0.756). The fistula rate in patients who received adjunct caudal analgesia was no different than in those who received other forms of adjunct analgesia (2.21 versus 3.0%, respectively, p > 0.999). CONCLUSIONS: These data suggest that successful Mathieu hypospadias repair is independent of the use of a stent. Caudal analgesia, a penile block and epidural analgesia provided effective postoperative pain control with no difference in complication rates. To our knowledge our report represents the largest observational study reported to date comparing stented and unstented repairs. However, because of the small number of complications in each group, a much larger study is required to determine statistically significant differences among these groups.

Adolescent↗
PubMed1996

The attractiveness of a liquid bait to white-tailed deer in the Central Appalachian Mountains, Virginia, USA.

We determined the attractiveness of a bait composed of apple juice, apple odor, water, glycerin, and salt to captive white-tailed deer (Odocoileus virginianus) at the National Zoological Park Conservation and Research Center, Front Royal, Virginia, USA. Thirty-nine deer (three adult males, 20 adult females, eight male fawns, eight female fawns) were presented with the bait formulation in a 22-ha enclosure during January, February, and May 1994. Daily consumption, and the frequency of visits to bait dispensers and the frequency of drinking bouts were recorded. Overall consumption was greatest in May (P < 0.001). While adults and fawns visited bait dispensers equally often, fawns drank more frequently (P < 0.001).

Administration, Oral↗
PubMed1995

The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11.

The gene for the receptor for hyaluronan-mediated motility, RHAMM (designated hyaluronan-mediated motility receptor, HMMR (human) and Hmmr (mouse), for mapping purposes), was localized to human chromosome 5q33.2-qter by somatic cell and radiation hybrid analyses. Investigation of two interspecific backcrosses localized the mouse RHAMM (Hmmr) locus 18 cM from the centromere of mouse chromosome 11 within a region of synteny homology with human chromosome 5q23-q35 genes. The map position of the human RHAMM gene places it in a region comparatively rich in disease-associated genes, including those for low-frequency hearing loss, dominant limb-girdle muscular dystrophy, diastrophic dysplasia, Treacher Collins syndrome, and myeloid disorders associated with the 5q- syndrome. The RHAMM gene location and its ability to transform cells when overexpressed implicate RHAMM as a possible candidate gene in the pathogenesis of the recently described t(5;14)(q33-q34;q11) acute lymphoblastic leukemias.

Animals↗
PubMed1994

Grafting of cultured uroepithelium and bladder mucosa into de-epithelialized segments of colon in rabbits.

Urinary tract reconstruction using bowel can result in acid-base and electrolyte abnormalities. We tested the feasibility of grafting bladder mucosa and urothelial cells grown on a biodegradable polyglactin 910 scaffold onto de-epithelialized segments of bowel in the rabbit. A segment of de-epithelialized colon was either grafted with cultured urothelium on a collagen mesh scaffold (12 rabbits) or with free bladder mucosa (11 rabbits). In 10 rabbits that served as a control group another segment of bowel was isolated and de-epithelialized. No urothelial or bowel epithelial growth was present 4 weeks later in 10 of the isolated de-epithelialized colonic segments grafted with the cultured urothelium. In 2 segments a minute focus of epithelium staining positively for anticytokeratin antibodies AE1 and AE3 was seen but this could not be histologically differentiated as either urothelium or native colonic epithelium. All 7 surviving animals that underwent a bladder mucosal graft had viable urothelium at sacrifice 30 days postoperatively. In 2 of the 7 rabbits microscopic nests of colonic epithelium were also found underneath the urothelial layer. Of the 7 internal controls 6 had no evidence of bowel epithelial regrowth 4 weeks after de-epithelialization. This study demonstrated that a confluent layer of urothelial cells could be grown in culture using a scaffold of biodegradable mesh and rat tail collagen. We also showed that bladder mucosal grafts can be grown on de-epithelialized bowel segments. We were unable to graft successfully cultured urothelial cells onto a de-epithelialized bowel segment. Further improvement in understanding the role of the submucosal matrix in cell growth may lead to future success in covering large segments of de-epithelialized bowel with autologous urothelium.

Animals↗
PubMed1994

Use of biodegradable mesh as a transport for a cultured uroepithelial graft: an improved method using collagen gel.

OBJECTIVES: To create an improved delivery vehicle for cultured uroepithelial cells using biodegradable mesh and collagen gel. METHODS: Twenty uroepithelial grafts were prepared by seeding cultured urothelial cells onto previously prepared collagen gel-polyglactin mesh. As a control, cells were seeded onto 20 plain polyglactin mesh (without gel) squares in the same fashion. RESULTS: The presence of urothelial cells was confirmed in all cultures by immunohistochemistry testing with anticytokeratin antibody. After 5 to 7 days, a confluent monolayer of cells covered 90% to 100% of the surface of all 20 collagen gel-mesh grafts. A confluent monolayer of cells did not form on any control graft (plain mesh). After 3 weeks, the cells had formed a sporadic, multiple cell layer confluence over 10% to 50% of the control graft surface; however, the mesh became friable and fell apart. CONCLUSIONS: By combining collagen gel with a biodegradable mesh scaffold, we created a surgically implantable cultured uroepithelial graft. The production of the collagen gel-mesh vehicle is simple and inexpensive. With this technique, the use of cultured urothelium for reconstructive urologic surgery can be investigated in greater detail.

Animals↗
PubMed1993

Psoas abscess following intravesical bacillus Calmette-Guerin for bladder cancer: a case report.

An 87-year-old man with an abdominal aortic aneurysm received intravesical bacillus Calmette-Guerin therapy for transitional cell carcinoma of the bladder. He presented 9 months later with a psoas abscess that mimicked a contained retroperitoneal abdominal aortic aneurysm rupture. The abscess cultures yielded Mycobacterium bovis. Recent transurethral resection and high voiding pressures after instillations of bacillus Calmette-Guerin may have led to distant dissemination of the drug.

Administration, Intravesical↗
PubMed1991

A critical review of macro models for road accidents.

This paper presents a critical review of state-of-the-art macro models for road accidents. Such a review is meant to identify and establish the significance of policy and socioeconomic variables affecting the level of road accidents. The aim is to identify those variables associated with effective policies and interventions to enable decision makers to improve the level of road safety. The variables that appear to affect the number of fatalities or injuries are: vehicle miles travelled (VMT), vehicle population, income (in its various forms), percentage of young drivers, intervention policies such as speed limits, periodic vehicle inspection, and minimum alcohol-drinking age. Viewed critically, the state-of-the-art models being used to explain and predict road accidents are still deficient. One possible approach to correcting this deficiency draws from consumer utility theory, using analytical models built on a newly constructed theoretical framework. Success in estimating such models may improve predictions of road accidents, thus demonstrating the comparative cost effectiveness of alternative intervention policies.

Accident Prevention↗
PubMed1990

Verapamil as a hypotensive agent under general anaesthesia.

Thirty-six adult female patients undergoing abdominal hysterectomy under general anaesthesia were evaluated for the haemodynamic effects of IV verapamil in bolus dose of either 50 micrograms/kg (group A), 60 micrograms/kg (group B) or 75 micrograms/kg (group C). The result showed a dose dependent fall in the mean arterial pressure and increase in the P-R interval. The fall in heart rate was marginally more in group A and B as compared to group C.

Adult↗
PubMed1988

Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation.

We measured the neutrophil function of 6 patients with AIDS and Kaposi's sarcoma (KS); 22 patients with AIDS-related complex (ARC); and 28 healthy, heterosexual controls. Neutrophils from patients with ARC showed significantly less chemotaxis (P less than or equal to .025) than did those from patients with AIDS and KS or from controls. Serum from patients with AIDS and KS or with ARC significantly (P less than or equal to .05) inhibited chemotaxis of neutrophils from controls; heat treatment of the serum abolished this inhibitory effect. Bacterial killing by neutrophils from patients with AIDS and KS or with ARC was also significantly (P less than or equal to .05) less than for neutrophils from controls, as was neutrophil phagocytosis binding of Candida albicans (P less than or equal to .05). Expression of OKM1 antigen was increased in the patients studied. Enzyme degranulation, adherence, and aggregation were also examined. The defects found in neutrophil function are selective and may be important in the increased susceptibility of patients with human immunodeficiency virus infection to bacterial and fungal infections.

AIDS-Related Complex↗