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Biomedical subjects

M A Salih

Publications and source records attributed to M A Salih.

At least 19 recordsLinked to original sources
PubMed2006

IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan.

Post-kala-azar dermal leishmanaisis (PKDL) in Sudan is associated with elevated interferon-gamma (IFN-gamma). To study interferon-gamma pathways in PKDL, we genotyped 80 trios from the Masalit ethnic group for polymorphisms at -470 ins/delTT, -270T/C, -56T/C and +95T/C in IFNGR1 and at -179G/A and +874T/A in IFNG. No associations occurred at IFNG. Global association with haplotypes comprising all four markers at IFNGR1 (chi(2)(10df)=21.97, P=0.015) was observed, associated with a significant (chi(2)(1df)=4.54, P=0.033) bias in transmission of the haplotype insTT T T T and less (chi(2)(1df)=5.59, P=0.018) than expected transmission of insTT C C C. When compared with data on malaria associations from Gambia, the results suggest a complex pattern of haplotypic variation at the IFNGR1 promoter locus associated with different infectious disease in African populations that reflect the complex roles of IFN-gamma in parasite killing versus inflammation and pathogenesis.

Genetic Predisposition to Disease↗
PubMed2000

Embryonal rhabdomyosarcoma and chromosomal breakage in a newborn infant with possible Dubowitz syndrome.

We report on a newborn girl with Dubowitz syndrome (DS) and embryonal rhabdomyosarcoma (ERMS), with multiple chromosomal breakage (MCB). The tumor was resected but recurred in a few months, resulting in the infant's death. Malignancy and chromosomal breakage have been reported previously in DS. However, ERMS has not been reported among the malignant tumors diagnosed in DS. To our knowledge, concurrence of DS, ERMS, and MCB has not been reported previously. This is the first observation of DS in the Arab ethnic group.

Abnormalities, Multiple↗
PubMed2000

Genetic refinement and physical mapping of the CMT4B gene on chromosome 11q22.

Charcot-Marie-Tooth disease type 4B (CMT4B) is a demyelinating autosomal recessive motor and sensory neuropathy characterized by focally folded myelin sheaths in the peripheral nerve. We recently mapped the CMT4B gene to a 5-cM interval on chromosome 11q22, using homozygosity mapping and haplotype sharing analysis on a large inbred pedigree. In the present study, we report the construction of a YAC-based transcript map across the 5-cM critical region, including 26 YACs, 35 STSs, and 52 ESTs. Furthermore, using 15 additional physically ordered microsatellite markers from the 11q22 region on the original inbred family, we were able to narrow the critical interval for the gene to 2 Mb, which is now flanked by markers D11S1757 and CHLC-GATA3B05. Finally, after computer analysis of the 33 ESTs assigned to the 2-Mb interval, we demonstrated that 21 different transcripts as well as 3 known genes might represent potential candidates for the disease.

Charcot-Marie-Tooth Disease↗
PubMed2000

Autosomal recessive hereditary neuropathy with focally folded myelin sheaths and linked to chromosome 11q23: a distinct and homogeneous entity.

We describe a six generation Saudi kindred, with a recessive hereditary motor and sensory neuropathy (HMSN). Four individuals were affected including two children (a boy and a girl) and a 23-year-old man. The fourth (a female) died at the age of 14 years. Onset of the disease was early (< 2 years) and the clinical and neurophysiological features were, generally, quite similar to those of an Italian family linked to chromosome 11q23. The peculiar pathologic pattern was irregular and redundant loops associated with folding of the myelin sheaths. The genetic study confirmed linkage to chromosome 11q23 and refined the location of the gene between D11S1311 and D11S917, a 3.3 cM region. These findings support the existence of a homogeneous and distinct entity within the form of HMSN associated with focally folded myelin sheaths.

Adult↗
PubMed2000

Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2.

A gene mutated in Charcot-Marie-Tooth disease type 4B (CMT4B), an autosomal recessive demyelinating neuropathy with myelin outfoldings, has been mapped on chromosome 11q22. Using a positional-cloning strategy, we identified in unrelated CMT4B patients mutations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosphatase (DSP).

Alternative Splicing↗
PubMed1999

Case of partial trisomy 2q3 with clinical manifestations of Marshall-Smith syndrome.

We describe a girl with physical anomalies, accelerated skeletal maturation, failure to thrive, and respiratory difficulties consistent with a diagnosis of Marshall-Smith syndrome (MSS). Chromosome analysis showed an inverted duplication of chromosome 2 [46,XX,inv dup(2)(q37q32) de novo] identified by G banding and confirmed by FISH. Several cases of trisomy 2q3 have been reported and established a syndrome, but the present case is the first to be associated with accelerated skeletal maturation and a clinical picture resembling MSS. This raises the possibility that the cause of MSS involves the q3 region of chromosome 2. Few reports of MSS include study of the karyotype, although the chromosomes were apparently normal in those cases where they have been examined. We suggest that karyotyping be undertaken with particular attention to the 2q3 region in patients with suspected MSS. It also would be prudent to assess bone age in all children with trisomy 2q.

Abnormalities, Multiple↗
PubMed1999

Growth hormone and the expression of mRNAs for matrix proteins and oncogenes in bone.

To examine the effects of growth hormone (GH) on the expression of the mRNAs of bone matrix proteins, three experiments were carried out with 3-month-old female Sprague-Dawley rats. In the first experiment rats were given a single subcutaneous injection of recombinant human GH (8 mg rhGH/kg b. wt.), sacrificed 15 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h later, and RNA isolated from cancellous bone from the distal femoral metaphysis. Growth hormone increased the level of type I collagen mRNA by 187, 417, and 509% over the control level at 15 min, 1 h and 2 h, respectively; the mRNA levels declined to 119 and 99% at 4 and 8 h, respectively, and then rose again to 351 and 423% over the control level at 16 and 24 h, respectively. Osteocalcin mRNA transcript increased by 89, 90, 325, 342, 361, and 407% over the control level at 15 min, 1 h, 2 h, 4 h, 8 h and 16 h, respectively, and fell to 66% at 24 h. The level of IGF-I mRNA increased by 45, 83, 120, 140, and 175% over the control level at 2, 4, 8, 16, and 24 h, respectively. In the second experiment, following the administration of rhGH (8 mg/kg b. wt.) bone osteocalcin mRNA increased by 127, 177, 361, and 413% over the control level at 30 min, 1 h, 2 h and 4 h, respectively; IGF-I mRNAs increased by 38, 33, 87, and 437 at 30 min, 1 h, 2 h and 4 h, respectively, but the levels did not become significant until 2 h; c-fos mRNA increased significantly at 30 min, and c-jun and c-myc mRNAs did not increase until 4 h. In the third experiment, animals were given a single injection of rhGH (8 mg/kg b. wt.) and the animals were bled at timed intervals and acid ethanol-extractable serum IGF-I determined. Serum IGF-I increased significantly only at 12 h following rhGH administration. Our data indicate that GH stimulates a rapid increase in the expression of mRNAs for the bone matrix proteins, type I collagen and osteocalcin, by a mechanism that appears to be independent of IGF-I, the early response oncogenes or an increase in osteoblast number.

Animals↗
PubMed1999

Sotos syndrome (cerebral gigantism): a clinical and radiological study of 14 cases from Saudi Arabia.

Fourteen children (of Arab ethnic origin) with Sotos syndrome are described. They were referred to King Khalid University Hospital, Riyadh between July 1992 and June 1997. Their phenotypic characteristics were compared with established diagnostic criteria. There was a male:female ratio of 1.3:1 and a high rate of consanguinity (36%) among parents. At birth, 54% were large and about one-third showed increased height and occipitofrontal head circumference (OFHC). The neonatal histories revealed respiratory and feeding problems in 21%, followed later by delayed motor milestones and speech development in 57%. During childhood, weight, height and OFHC increased further to > 97th centile in 71%, 71% and 93%, respectively. A seizure disorder affected 43%, and 75% had mental retardation (IQ < 70). A non-specific EEG abnormality was found in half of those with seizures. Cranial CT/MRI showed ventricular dilatation in 15% and one patient had corpus callosum dysgenesis. Abdominal ultrasound revealed hydronephrosis in two patients. Radiological cephalometric measurements showed relative prognathism in cases of Sotos syndrome compared with controls (p = 0.003). The study highlights the importance of considering Sotos syndrome in children who present with psychomotor delay.

Adolescent↗
PubMed1998

Moyamoya syndrome with unusual angiographic findings and protein C deficiency: review of the literature.

We describe the findings in a six-year-old female with typical clinical symptoms of Moyamoya phenomena, but with an unusual angiographic appearance. The vertebral artery showed segmented occlusion in the upper cervical region, with reconstitution via collateral circulation through muscular branches. The carotid circulation showed involvement of the external carotid artery (ECA) branches and marked narrowing of the internal carotid arteries (ICA) bilaterally, suggesting that this disease is systemic in nature.

Brain↗
PubMed1998

A novel form of familial congenital muscular dystrophy in two adolescents.

We report on two brothers (the product of first-degree consanguineous marriage; aged 15 and 12 years) who presented with severe hypotonia at birth, proximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elevated serum creatine kinase (CK) levels (300 and 824 IU/l; N < or = 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5%) without fibre-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial weakness and high-arched palate in both patients. The younger sibling also had ptosis but otherwise normal external ocular muscles. They showed symmetric proximal muscle weakness and wasting associated with calf-muscle hypertrophy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. Immunohistochemistry revealed normal expression of the dystrophin-glycoprotein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin), beta-, gamma-, and delta-sarcoglycan, laminin-alpha2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5%) were seen in the biopsy of the older patient, whereas immunohistochemistry showed normal expression of the DGC. Both cases also showed clear expression of integrin alpha7 at the muscle fibre surface and in the blood vessels. Three years later, they could still walk, but with difficulty, and the older brother showed enlargement of the tongue and echocardiographic features of left ventricular dilated cardiomyopathy.

Adolescent↗
PubMed1998

Whooping cough in Sudanese children.

The study describes the epidemiological and clinical features of whooping cough among eighty one Sudanese children (42 cases and 39 contacts aged below fifteen years) within 37 households who were under surveillance for a period of over six months. Using Khartoum Children's Emergency Hospital as the entry point, eleven patients were initially enrolled between July 1989 and August 1990 and led to the identification of another twenty six cases during home surveys. Subsequently, five of their contacts became secondary cases. The clinical criteria adopted by the Expanded Programme on Immunisation of the World Health Organization were used to identify the total of forty two cases included in the study. They were predominantly females (male: female ratio of 1:1.6), twenty (47.6%) were under five years of age and eight (19%) were infants. The attack rate was significantly higher among unimmunised infants (100%) compared to unimmunised children aged ten years and above (14.3%, p = 0.001). Half of the patients were from periurban areas, the majority (83.3%), were living in crowded households (room index > 5) and the primary immunisation rate was low (2.8%). Abnormal chest x-ray findings were detected in 26 (68.4%) patients and consisted mainly of bronchovascular thickening observed in 50%. During the follow-up period, a trend towards drop in patients' weight was observed. In four weeks, thirty (71.4%) children had a mean loss of 0.4 kg whereas eleven (26.2%) had static weight. A group of fifteen cases showed significant decrease in weight when compared to a control group of contacts that had been matched for age, sex and socio-economic status (p = 0.0001).

Age Distribution↗
PubMed1997

Effects of age and food restriction on calcium signaling in parotid acinar cells of Fischer 344 rats.

In this study, we characterized alpha-adrenergic (alpha AR) and muscarinic induced [Ca2+]i changes in individual parotid acinar cells from male Fischer 344 rats (6-24 month-old) fed ad libitum (AL) or 60% ad libitum intake (FR). Cells were prepared by collagenase/hyaluronidase digestion. [Ca2+]i was measured by video image, fluorescent microscopy in single acinar cells loaded with FURA2. Neither age nor food restriction altered the peak [Ca2+]i achieved in response to carbachol (100 microM). Similar results were obtained for epinephrine (Epi = 100 microM) stimulation in 6- and 12-month-old animals. However, the peak [Ca2+]i response to Epi declined between 12 and 18 months in both dietary groups (e.g., AL: 12 months = 387 +/- 21 nM, 18 months = 253 +/- 10 nM; FR: 12 months = 430 +/- 22 nM, 18 months = 325 +/- 14 nM). The decline in response to Epi seen with age was less in FR than in AL animals at 18 months, but not at 24 months. In addition, db cAMP reduced the carbachol-stimulated [Ca2+]i response to levels comparable to those observed with epinephrine. The results support the view that calcium mobilization in parotid acinar cells from male Fischer 344 rats in response to alpha AR, but not to muscarinic, stimulation is impaired with age. Food restriction may slow down, but does not prevent, the functional decline. Furthermore, cAMP appears to modulate the muscarinic response.

Aging↗
PubMed1997

Hemiconvulsion-hemiplegia-epilepsy syndrome. A clinical, electroencephalographic and neuroradiological study.

Six patients (4 boys and 2 girls) with hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome are described. They had prolonged seizures, lasting from 30 min to 12 h, at ages 1-4 years. These took the form of hemiconvulsion in three of the children and generalized tonic-clonic seizures in the others, being preceded by hemifacial twitching or head and eye deviation in two. They were followed by hemiplegia, which cleared with time in five patients, apart from subtle pyramidal tract signs. One child had spastic quadriparesis, choreiform movements, contracture deformities and severe mental retardation following repeated status epilepticus. Subsequent epilepsy developed in five patients and was satisfactorily controlled with carbamazepine and/or phenobarbitone. Cerebral hemiatrophy was documented in all patients by cranial computed tomography and/or magnetic resonance imaging. Single photon emission computed tomography (done in 4 patients) showed ipsilateral hypoperfusion (of the damaged hemisphere). Electroencephalography showed ipsilateral slowing and low voltage of background activity. Epileptiform discharges were found on the ipsilateral side in two cases and the contralateral side (the undamaged hemisphere) in one.

Atrophy↗
PubMed1997

AIDS and HIV infection in Sudanese children: a clinical and epidemiological study.

HIV surveillance and screening programs were established at Khartoum Teaching Hospital (KTH) following the first identified HIV case diagnosed in a hemophiliac boy in November 1987. As of December 1995, 15 cases of symptomatic HIV infection have been observed in Sudanese children (< or = 16 years) at KTH. An HIV seroprevalence rate of 35.7% was documented in a group of 28 patients (adults and children) with various congenital coagulation defects. The postulated mode of transmission was through contaminated factor concentrate. Screening of 52,000 volunteer male blood donors (March, 1987-1989) showed an HIV-seroprevalence rate of 0.05%. Selected groups, including 1118 children admitted to KTH during the period 1985-1995, were screened for HIV infection. These included aseptic meningitis/encephalitis group (n = 52), high-risk group (n = 523), children with various chronic and malignant diseases (n = 181), and chronic blood recipients (n = 330). A group of 32 displaced homeless children who survived on the streets were also included. Overall, an HIV seroprevalence rate of 1.2% was established. Among the 15 children with symptomatic HIV infection, tuberculosis accounted for the majority of admissions (33.3%) followed by admission for recurrent infections (20.0%). Of the 13 children with nonparental mode of HIV transmission, a vertical mode was documented in 61.5%. The pattern of HIV infection in Greater Khartoum is similar to that in North Africa and the Middle East. However, the geographic influence of high endemicity in neighboring sub-Saharan countries might change it in the future.

Adolescent↗
PubMed1997

Modulation by food restriction of intracellular calcium signaling in parotid acinar cells of aging Fischer 344 rats.

Previous studies suggest that alpha 1-adrenergic (alpha 1-AR)-induced intracellular calcium ([Ca2+]i) mobilization in rat parotid acinar cells declines with age. In this study, we examined the effects of food restriction on alpha 1-AR and muscarinic-stimulated [Ca2+]i mobilization in parotid acinar cells during aging. [Ca2+]i levels in response to the alpha 1-AR agonist epinephrine and the muscarinic agonist carbachol were evaluated in Fura-2-loaded parotid acinar cells from ad libitum-fed (AL) and food-restricted (FR) Fischer 344 male rats at 4, 6, 14, and 24 months of age. [Ca2+]i responses to epinephrine and carbachol (10 microM) were significantly reduced (48% and 35%, respectively; p < .05) in cells from 24-month-old AL rats as compared to younger AL rats. In contrast, no significant reduction of epinephrine and carbachol responses was observed in 24-month-old FR animals. An age-related increase in basal [Ca2+]i (peak around 14 months; p < .02) was observed in both AL and FR rats. In addition, basal [Ca2+]i was higher in FR than in AL rats at 14 and 24 months of age (p < .02). These studies suggest that FR partially attenuates or delays age-related impairments in alpha 1-AR- and muscarinic-cholinergic signal transduction systems of parotid acinar cells. Basal [Ca2+]i also appears to be altered during aging and by FR.

Adrenergic Agonists↗
PubMed1997

Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha2-chain.

Congenital muscular dystrophy (CMD) is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive mode. The alpha2-chain of laminin-2 (previously called merosin) has been shown by immunohistochemical and genetic analyses to be implicated in the pathogenesis of the 'classic' form of CMD. In the 'merosin-deficient' subgroup, which represents about half of the cases, more definite evidence of the involvement of the laminin alpha2-chain has recently been reported with the identification of mutations in the gene encoding the alpha2-chain of laminin 2 (LAMA2) in CMD patients. Here we report on two siblings from a consanguineous family expressing an internally deleted laminin alpha2-chain as a result of a splice site mutation in the LAMA2 gene which causes the splicing of exon 25. The predicted protein lacks 63 amino acids in domain IVa which forms a globular structure on the short arm of the alpha2-chain. Interestingly, these patients appear mildly affected compared to others who completely lack this protein. This situation presents a striking analogy with Becker muscular dystrophy, where in-frame deletions in the dystrophin gene result in the expression of a semi-functional protein and lead to a mild phenotype.

Amino Acid Sequence↗
PubMed1996

Putative intestinal estrogen receptor: evidence for regional differences.

Previously we demonstrated that 17 beta-estradiol (E2) stimulates intestinal calcium absorption and enhances uptake of calcium by intestinal mucosal cells in vitro, and that the latter contains estrogen receptor (ER)-like proteins and mRNAs. The current study was undertaken to further characterize the putative intestinal ERs using RT-PCR analysis, Western blot analysis, Southern blot analysis, ligand binding assays and gel shift assays. RT-PCR analysis using primers directed at the terminal end of the A/B domain of the uterine ER confirmed our previous finding that intestinal ER mRNAs are present throughout the intestine, with the exception that the duodenum lacked the amplified region. Western blot analysis, using ER-715 antibody, detected the expected 68- to 70-kDa ER protein and additional 58-, 46- and 41-kDa proteins in the uterus and colon, while duodenal extract contained only a faint 46-kDa and strong 28-kDa protein bands. Southern blot analysis performed on enzyme-digested genomic DNAs demonstrated the presence of ER-like sequences in genomic DNA from the uterus, duodenum and colon. However, enzyme restriction maps of genomic DNAs from intestinal segments were different from the map for uterine genomic DNA digested with similar enzymes. In ligand binding assays, 125I-labeled E2 bound specifically to 46-kDa protein in duodenal, colonic and uterine extracts and the binding was competitively inhibited by excess cold E2. Gel mobility shift assays using 32P-labeled vitellogenin derived ERE demonstrated that jejunal, colonic and uterine ER protein contain the classical DNA binding domain. In addition, ERE bound in a specific fashion to sites in genomic DNAs from the uterus, colon and jejunum. In contrast, protein extracts and genomic DNAs from the duodenum failed to bind to 32P-labeled ERE and, consequently, appear to be devoid of the classical DNA binding domain. These findings establish the presence of ER-like proteins and genes in intestinal mucosal cells of rats and suggest that the duodenum contains a variant ER gene that encodes a variant ER protein.

Animals↗