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Biomedical subjects

S Hassan

Publications and source records attributed to S Hassan.

At least 19 recordsLinked to original sources

Transforming growth factor-beta 1 stimulates vascular smooth muscle cell L-proline transport by inducing system A amino acid transporter 2 (SAT2) gene expression.

Transforming growth factor-beta1 (TGF-beta 1) is a multifunctional cytokine that contributes to arterial remodelling by stimulating vascular smooth muscle cell (SMC) growth and collagen synthesis at sites of vascular injury. Since l-proline is essential for the synthesis of collagen, we examined whether TGF-beta 1 regulates the transcellular transport of l-proline by vascular SMCs. l-Proline uptake by vascular SMCs was primarily sodium-dependent, pH-sensitive, blocked by neutral amino acids and alpha-(methylamino)isobutyric acid, and exhibited trans-inhibition. Treatment of SMCs with TGF-beta 1 stimulated l-proline transport in a concentration- and time-dependent manner. The TGF-beta 1-mediated l-proline uptake was inhibited by cycloheximide or actinomycin D. Kinetic studies indicated that TGF-beta 1-induced l-proline transport was mediated by an increase in transport capacity independent of any changes in the affinity for l-proline. TGF-beta 1 stimulated the expression of system A amino acid transporter 2 (SAT2) mRNA in a time-dependent fashion that paralleled the increase in l-proline transport. Reverse transcriptase PCR failed to detect the presence of SAT1 or amino acid transporter 3 (ATA3) in either untreated or TGF-beta 1-treated SMCs. These results demonstrate that l-proline transport by vascular SMCs is mediated predominantly by the SAT and that TGF-beta 1 stimulates SMC l-proline uptake by inducing the expression of the SAT2 gene. The ability of TGF-beta 1 to induce SAT2 expression may function to provide SMCs with the necessary levels of l-proline required for collagen synthesis and cell growth.

Amino Acid Transport System A↗

Tegumental alterations in Schistosoma mansoni worms induced by treatment of infected mice with naproxen pre- and/or post-infection.

Schistosoma mansoni infected mice were treated with naproxen (CAS 22204-53-1) in a dose of 3-4 mg/kg body weight. Treatment was conducted for 7 days before and/or 28 days post infection. Adult worms, developed 7 weeks post infection, were studied by electron microscopy. In both groups, the dorsal surface of the male worms was much more affected by the drug than that of female ones. The most significant morphological degeneration was the change in the aspect and the form of tubercles. Moreover, shrinkage and loss of spines from the ventral surface were also observed. A small portion of the posterior end of female worms showed loss of spines. However, in the first group given naproxen 7 days before infection, the level and extent of changes increased particularly in male worms. There was pronounced oedema, swelling, wrinkling with constriction and collapse of sensory bulbs.

Animals↗

Endoscopic diagnosis of colonic tuberculosis.

BACKGROUND: GI tuberculosis is a diagnostic challenge, particularly in the absence of evidence of pulmonary infection. It may mimic many other abdominal diseases such as other infectious processes, tumors, and Crohn's disease. In the absence of positive laboratory and radiologic tests, the diagnosis is often established definitively by obtaining a surgical specimen. Colonoscopy, however, has been used successfully to diagnose the disease and thus avoid the morbidity and mortality associated with exploratory laparotomy. METHODS: An evaluation was conducted of colonoscopic features in 10 patients with colonic tuberculosis. OBSERVATIONS: In all cases there was ileocecal involvement; total colonic involvement was found in only 1 case. The colonoscopic appearance included the following: ulcerated lesions, sessile firm polyps, masses, and small diverticula, ranging from 3 to 5 mm in diameter. In 5 of our patients the diagnosis was confirmed bacteriologically, in 3 with endoscopic biopsy material, and in 2 by sputum examination. In all cases antituberculous therapy produced remarkable symptom and endoscopic improvement. CONCLUSION: This report highlights the importance of colonoscopy in the diagnosis of tuberculous involvement of the GI tract.

Adult↗

Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene.

The HLXB9 homeobox gene was recently identified as a locus for autosomal dominant Currarino syndrome, also known as hereditary sacral agenesis (HSA). This gene specifies a 403-amino acid protein containing a homeodomain preceded by a very highly conserved 82-amino acid domain of unknown function; the remainder of the protein is not well conserved. Here we report an extensive mutation survey that has identified mutations in the HLXB9 gene in 20 of 21 patients tested with familial Currarino syndrome. Mutations were also detected in two of seven sporadic Currarino syndrome patients; the remainder could be explained by undetected mosaicism for an HLXB9 mutation or by genetic heterogeneity in the sporadic patients. Of the mutations identified in the 22 index patients, 19 were intragenic and included 11 mutations that could lead to the introduction of a premature termination codon. The other eight mutations were missense mutations that were significantly clustered in the homeodomain, resulting, in each patient, in nonconservative substitution of a highly conserved amino acid. All of the intragenic mutations were associated with comparable phenotypes. The only genotype-phenotype correlation appeared to be the occurrence of developmental delay in the case of three patients with microdeletions. HLXB9 expression was analyzed during early human development in a period spanning Carnegie stages 12-21. Signal was detected in the basal plate of the spinal cord and hindbrain and in the pharynx, esophagus, stomach, and pancreas. Significant spatial and temporal expression differences were evident when compared with expression of the mouse Hlxb9 gene, which may partly explain the significant human-mouse differences in mutant phenotype.

Abnormalities, Multiple↗

Entomogenous fungi as promising biopesticides for tick control.

When ticks were sealed in nylon tetrapacks and infected with the entomogenous fungi, Beauveria bassiana and Metarizium anisopliae and maintained in potted grass in the field, the fungal oil formulations (10(9) conidia per ml) induced 100% mortality in larvae of Rhipicephalus appendiculatus and Amblyomma variegatum, whereas mortalities in nymphs varied between 80-100% and in adults 80-90%. The aqueous formulations (10(9) conidia per ml) induced mortalities of 40-50% and reductions in egg hatchability of 68% (B. bassiana) and 48% (M. anisopliae) when sprayed on Boophilus decoloratus engorging on cattle. The strains of B. bassiana and M. anisopliae isolated from naturally infected ticks were also found to induce high mortalities in both R. appendiculatus and A. variegatum in tetrapacks placed in potted grass. Both aqueous and oil-based formulations were found to be effective, although the latter induced higher mortalities. These fungal strains in aqueous formulation (10(8) conidia per ml) suppressed on-host populations of adult R. appendiculatus by 80% (B. bassiana) and 92% (M. anisopliae) when sprayed on tick-infested grass once per month for a period of 6 months. The feasibility of using entomogenous fungi for tick control in the field is discussed.

Animals↗

Recent advances in surgery for snoring-somnoplasty (radiofrequency palatoplasty) a pilot study: effectiveness and acceptability.

A prospective study was designed to investigate the effects of Somnoplasty (Radiofrequency palatoplasty) in patients with snoring. A group of 22 patients fulfilling the inclusion and exclusion criteria outlined underwent somnoplasty performed by a single surgeon. Every patient completed a standard questionnaire containing visual analogue scales at six weeks post operatively. The parameters assessed were post-operative pain, change in snoring score, effects on sleep of the patient and bed partner, speech and swallowing, alteration in weight, acceptance of the procedure and recommendation to friends and family. Results of improvement in snoring score were correlated to body mass index (BMI) kg/m2. We conclude that somnoplasty is an effective procedure in elimination of snoring and the success is closely linked to BMI. Best response is obtained in those with BMI < 25 and moderate response is obtained in those with BMI between 25-30. Obese (BMI > 30) patients are more likely to have a poor response. Morbidity associated with the procedure is minimal and patient acceptance is 100%. The long-term success of this procedure needs to be confirmed with further follow up.

Adult↗

The efficacy and safety of cefaclor in respiratory infections amongst Pakistani children.

PURPOSE: To evaluate the efficacy and safety of Cefaclor in respiratory tract infections amongst Pakistani children. PATIENTS AND METHODS: Multicenter, open label and non-comparative study was done to evaluate the response in terms of symptoms (In vivo) and bacterial cultures (In Vitro) to Cefaclor amongst children with respiratory tract infection between the ages 2 months to 12 years. Each patient was asked to visit the doctor on three occasions i.e., Day 0 (Initial evaluation prior to commencement of study), Day 4 (During therapy assessment and confirmation of compliance) and Day 10 (End of therapy assessment and compliance evaluation). Representative swab specimens (Throat swabs, Ear swabs or Sputum) were collected from the infected site on day 0 and day 10 for culture and sensitivity. Patients were also assessed by the evaluators on each visit in terms of clinical symptomatic response and information collected was documented on a prescribed data base form. RESULTS: A total of 160 patients were enrolled in the study, of whom 15 were lost to follow-up between the first and second visit and a further 38 were lost by the 3rd visit. Thus 107 patients completed the study as per protocol. Otitis media and Upper respiratory tract infection were the predominant ailments amongst the cases enrolled. One or more bacteria were isolated in 75 (46%) instances, the maximum number of isolates being from ear swabs of Otitis media patients. Beta haemolytic Streptococcus (group A,C,F,G) seen in 18 cases was the most common pathogen reported followed by Staphylococcus aureus, H. influenzae and Streptococcus pneumoniae in 13,12 and 11 cases respectively. Sensitivity of Cefaclor for bacteria commonly seen in the respiratory tract was greater than 90% in most of the cases. Evaluation of the 42 culture proven cases for patients who completed the study showed that Cefaclor had a 93% efficacy for indicated bacteria and 54% for non-indicated bacteria. In Vivo analysis of Cefaclor (i.e. on the basis of symptomatic response) showed that 96% cases had a symptomatic response by the second visit, which improved to 97% by the third visit. Only 15 non-serious adverse events were observed in 160 patients, none of the cases necessitated discontinuation of drug. Mild gastrointestinal symptom was the most common adverse event reported. CONCLUSION: Cefaclor was found to be a safe and efficacious drug in the treatment of bacterial respiratory tract infections amongst Pakistani children.

Bacterial Infections↗

The effect of magnesium sulfate on fetal heart rate parameters: A randomized, placebo-controlled trial.

OBJECTIVE: We sought to determine the effect of magnesium sulfate on fetal heart rate baseline value, variability, and acceleration-deceleration pattern. STUDY DESIGN: Normal, nonlaboring pregnant patients at >30 weeks' gestation were recruited. Baseline fetal heart rate monitoring for 1 hour was performed. After an 800-kcal meal, patients were randomized to receive either an intravenous loading dose of 6 g of magnesium sulfate in 100 mL of isotonic sodium chloride solution or 100 mL of isotonic sodium chloride solution alone. Subsequently, patients in the magnesium sulfate group received a 2-g/h intravenous infusion for 3 hours at a rate of 125 mL/h. Patients randomized to the sodium chloride solution group received a sodium chloride solution infusion at a similar rate (unlabeled intravenous bags). Maternal blood was drawn at 0, 1, and 3 hours for determination of total and ionized magnesium and calcium, electrolyte, and glucose levels. One hour of fetal heart rate monitoring was repeated at 1 and 3 hours of infusion. Tracings were interpreted without identifiers (of time or group) by using the National Institute of Child Health and Human Development fetal heart rate monitoring guidelines. RESULTS: Magnesium sulfate administration resulted in decreased fetal heart rate baseline values and variability in the third hour. The fetal heart rate baseline value was 134.4 +/- 6.3 versus 136.6 +/- 6.4 beats/min before infusion (P >.05), 134.4 +/- 7.1 versus 135.1 +/- 6. 6 beats/min in the first hour (P >.05), and 134.6 +/- 7.1 versus 132. 3 +/- 7.6 beats/min in the third hour (P <.05) in the sodium chloride solution group versus the magnesium sulfate group, respectively. Fetal heart rate variability (grades 1-5) was 2.75 +/- 0.33 versus 2.82 +/- 0.29 before infusion (P >.05), 2.81 +/- 0.30 versus 2.84 +/- 0.28 in the first hour (P >.05), and 2.71 +/- 0.52 versus 2.67 +/- 0.36 in the third hour in the sodium chloride solution group versus the magnesium sulfate group, respectively (P <. 05). Magnesium sulfate blocked the positive correlation between gestational age and number of accelerations found in control subjects. No significant decelerations were identified. CONCLUSIONS: Prolonged administration of magnesium sulfate was associated with decreased fetal heart rate baseline values and variability. Given the small magnitude of these changes, the clinical significance of these findings is questionable. Magnesium sulfate inhibition of the increasing number of accelerations with gestational age needs to be considered when fetal well-being is assessed.

Calcium↗

Growth inhibitory effects of somatostatin on human leukemia cell lines mediated by somatostatin receptor subtype 1.

Reverse transcription polymerase chain reaction analysis revealed that only somatostatin receptor (SSTR) 1 mRNA was expressed in Ball-1 B-, Jurkat T-, and HL60 leukemia cell lines. In contrast, human normal mononuclear cells expressed the mRNA of all five subtypes of SSTR, although the expression level of SSTR1 was the highest. A binding study, revealed that [125I]-somatostatin bound specifically to HL60 cells and this binding was inhibited concentration-dependently by unlabeled somatostatin (SS). A [3H]thymidine incorporation study showed that SS significantly and concentration-dependently inhibited HL60 and BALL-1 leukemia cell growth. Furthermore, this inhibition of leukemia cell growth was associated with reduces c-fos gene expression. These data indicate that leukemia cells express SSTR1 and SS reduce c-fos gene expression with resultant suppression of leukemia cell growth, possibly mediated by the SSTRI.

Cell Division↗

Patients view of the anaesthetist in a developing country.

OBJECTIVE: The objective of this study was to assess patients regarding their knowledge and perception of the anaesthetists' role in patient care in a developing country. SETTING: The audit was conducted at the Aga Khan University Hospital, Karachi. METHODS: Two hundred surgical and 102 medical out-patients were included in the audit prospectively who filled a detailed questionnaire. RESULTS: Fifty-six percent of the patients knew that anaesthetists were medically qualified but only 20% and 27% had an idea about their role in the intraoperative and immediate postoperative period. 14.6% were aware of the anaesthetists role outside the operating room. No difference was observed between the two groups of patients except that a higher percentage of surgical patients were interested in having more information regarding anaesthesia and wanted to choose their anaesthetist if the need arose. Gender difference was observed in answer to two questions only. A higher percentage of males know the role of anaesthetist in the recovery room whereas a greater number of females who had surgery before remembered their anaesthetist postoperatively. CONCLUSION: The results of this audit show a poor perception of the anaesthetists role both inside and outside the operating room. Although public knowledge surveys have been carried out in developed countries there is a pressing need to repeat these in developing countries since the image as perceived by public may have a direct bearing on the recruitment of young doctors into an already shortage specialty in these less affluent countries.

Anesthesia↗

Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats.

BACKGROUND & AIMS: Regenerating gene (Reg) has been isolated from rat regenerating pancreatic islets, and Reg protein is mitogenic to islet cells. We have recently shown that Reg gene and Reg protein are expressed in gastric enterochromaffin-like (ECL) cells. This study aimed to clarify whether gastrin enhances Reg protein production in ECL cells and whether Reg protein is mitogenic to gastric mucosal cells. METHODS: Reg gene expression in response to acute and chronic hypergastrinemia was investigated in rats. Immunohistochemical studies, Northern blotting, and in situ hybridization were performed to investigate the expression of Reg protein and Reg gene. The direct effect of gastrin on Reg gene expression was investigated using isolated ECL cells, and the trophic effect of Reg protein on cultured gastric epithelial cells was assessed by [3H]thymidine uptake. RESULTS: Both chronic hypergastrinemia and short-term gastrin administration stimulated Reg gene expression and Reg protein production in fundic mucosa. Reg gene expression was also augmented in isolated ECL cells after incubation with rat gastrin. Reg protein was mitogenic to cultured rat gastric epithelial cells. CONCLUSIONS: Gastrin stimulates the production of Reg protein in gastric ECL cells, which may be involved in the gastrin-induced gastric mucosal cell growth.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Selective tracheal suctioning to prevent meconium aspiration syndrome.

OBJECTIVE: To analyze the incidence and outcome of meconium aspiration syndrome (MAS) at Al-Yamamah Hospital, Riyadh, Saudi Arabia, where meconium-stained babies have intrapartum obstetrical cleansing of the upper airways, following which depressed/asphyxiated babies are intubated and vigorous babies are observed for 24 h. METHOD: The total live births, records of meconium-stained neonates who had intubations and of those observed, during a 6-year period were reviewed. RESULTS: During this period, there were 85562 live births. One in 325 births (0.27%) was complicated by MAS and the mortality rate was 7%. These figures concur with the reported incidence and mortality of MAS following routine combined obstetric-pediatric suction of airways at birth. Of the 265 cases of MAS that occurred during this period, 237 were in the intubated group and 28 in the observed group. The babies of the former group had severe disease compared with that of the latter. All mortality was from the intubated group. CONCLUSION: Adequate obstetrical cleansing of the upper airway in vigorous babies may obviate the need for endotracheal intubation; intubation of depressed babies following this treatment may be useful.

Asphyxia Neonatorum↗

Rat gastric mucosal cells express ICAM-1 and proinflammatory cytokines during indomethacin-induced mucosal injury.

Adhesion molecules and cytokines are known to be involved in the formation of acute gastric mucosal injury. However, it is not clear whether the gastric mucosal cells express these molecules and modulate the inflammation. To clarify whether gastric mucosal cells express intercellular adhesion molecule-1 (ICAM-1) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1-alpha (IL-1-alpha), and cytokine-induced neutrophil chemoattractant-2-beta (CINC-2-beta)) in the formation of gastric mucosal injury, we have used rat indomethacin-induced gastric mucosal lesions as an in vivo model. The gene expression of all cytokines and ICAM-1 increases at the early stages of indomethacin-induced gastritis (TNF-alpha and IL-1-alpha gene expression began to increase earlier than that of ICAM-1 and CINC-2-beta) and can mainly be detected in the gastric epithelial layer. To further identify the source of those molecules, the epithelial cells were separated into seven fractions according to their sizes by a counterflow elution. ICAM-1 and CINC-2-beta gene expressions are particularly enhanced in the middle-sized cell fractions that are rich in gastric mucous-producing cells. The effect of TNF-alpha or IL-1-alpha on the gene expression of ICAM-1 and cytokines was examined by using RGM-1 cells as a model for gastric mucosal cells. RGM-1 cells show an augmented ICAM-1 and proinflammatory cytokine expression in response to TNF-alpha or IL-1-alpha stimulation. Moreover, immunohistochemical staining also reveals an increase in ICAM-1 and CINC protein production in RGM-1 cells in response to TNF-alpha stimulation. We conclude that gastric mucosal cells express various cytokines and an adhesion molecule during the formation of acute gastric mucosal injury and that they may modulate the inflammation.

Animals↗

Expression of protooncogene c-kit and its ligand stem cell factor (SCF) in gastric carcinoma cell lines.

We examined 13 human gastric carcinoma cell lines for the expression of both c-kit and stem cell factor (SCF). Expression of mRNAs was detected by both Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR), and expression of translated proteins was detected by western blotting. Using RT-PCR we confirmed the expression of c-kit in five (ECC12, TMK1, MKN7, GCIY, and HGC27) cell lines. Northern blot analysis showed coexpression of both c-kit and SCF in ECC12 and expression of SCF in five other (MKN74, MKN1 OKAJIMA, KATOIII, and TMK1) cell lines. SCF stimulated both tyrosine phosphorylation of c-kit and growth of ECC12, whereas it did not stimulate those of GCIY. The sizes of c-kit transcript and protein in GCIY were slightly smaller than those of the reported ones, suggesting the presence of a biologically inactive truncated form of c-kit in GCIY. The present study suggests that c-kit/SCF system might play an important role in the carcinogenesis and tumor growth of ECC12 and that the truncated form of c-kit in GCIY might not be associated with malignant transformation.

Blotting, Northern↗

Development and validation of a visual acuity chart for Australian Aborigines and Torres Strait Islanders.

BACKGROUND: A new visual acuity chart was designed for use with Australia's indigenous population to overcome perceived inadequacies of conventional English letter charts for this group. This chart, which incorporates a black and white turtle icon, is described, and validation data are presented. METHODS: The chart is based on logarithm of the minimum angle of resolution (logMAR) principles and incorporates a turtle symbol modified from the design of an indigenous artist. The task is one of discrimination, with subjects being required to distinguish the split tail of the turtle from its head, which has the same overall shape and average luminance; the body of the turtle provides no directional cues which might assist in this judgment. The chart was validated in two ways: Experiment I. Performance was compared with the Bailey-Lovie and Konig bar charts in terms of unaided visual acuity data for 90 subjects (mean age: 38.3 +/- 20.3 years) and Experiment II. Data were obtained for 10 young subjects for these 3 charts and an Illiterate E chart, with refractive blur imposed with trial lenses over habitual distance corrections (spherical: +0.50, +1.00, +2.00, and +4.00 D; cylindrical: +1.00 and +2.00 D, axes 45, 90, and 180 degrees). To avoid cultural and literacy issues as possible sources of differences in performance between the charts in this validation study, subjects were selected from the wider Australian population rather than specifically from its indigenous segment. RESULTS: Experiment I: The Turtle chart performed most like the Konig Bar chart for this component of the validation exercise. Nonetheless, results for the Turtle chart correlated highly with those for the Bailey-Lovie chart as well as the Konig Bar chart, although there were subtle differences between charts in the rate of decline of visual acuity as visual performance decreased. Experiment II: The turtle chart behaved most like the Illiterate E chart with imposed spherical focusing errors, with the Bailey-Lovie chart showing a faster decline and the Konig Bar chart showing a slower decline in performance, with increasing defocus. All 4 charts showed similar directional biases with astigmatic defocus, being most affected by oblique (45 degrees) astigmatism. CONCLUSION: The Turtle chart met the criteria set for its validation as a visual acuity chart in that it gave comparable results to the other commonly used visual acuity charts, both in the case of unaided vision and when refractive blur was imposed.

Adolescent↗

Geranylgeranylacetone, an anti-ulcer drug, stimulates hexosamine production in a rat gastric mucosal cell line through binding to a specific cytosolic protein.

An anti-ulcer drug, geranylgeranylacetone (GGA), stimulates hexosamine production in a rat gastric mucosal cell line (RGM-1). The aim of this study was to elucidate the mechanism of this action. The role of protein kinase A, inositol phospholipid turnover and tyrosine kinase in the stimulatory action of GGA on hexosamine production in RGM-1 was determined by observing cAMP production, [3H]-inositol phosphate turnover and western blotting of tyrosine phosphorylation, respectively. Any trophic effect of GGA on RGM-1 was also checked by [3H]-thymidine incorporation. Our experiments showed that GGA has no effect on cAMP production, inositol phospholipid turnover, tyrosine phosphorylation or DNA synthesis in RGM-1. Finally, a [14C]-GGA competitive receptor binding assay was performed on RGM-1 and we found that [14C]-GGA specifically bound to RGM-1 cytosolic protein. Although retinoic acid (RA), another polyisoprenoid compound significantly stimulated hexosamine production in RGM-1, we confirmed that the [14C]-GGA binding site in RGM-1 is different from the RA binding site. In summary, GGA stimulates hexosamine production in RGM-1 and this action is probably mediated through its binding to a specific cytosolic protein in RGM-1.

Animals↗

Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan.

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.

Adult↗