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Biomedical subjects

S Sharif

Publications and source records attributed to S Sharif.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes.

We investigated the biological role of CC chemokines in the Th1-mediated pathogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1alpha (MIP-1alpha):MIP-1beta in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1alpha:MIP-1beta ratio was observed in nonobese diabetes-resistant (NOR) mice. IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1beta and monocyte chemotactic protein-1 (MCP-1): MIP-1alpha in the pancreas. Furthermore, NOD.MIP-1alpha-/- mice exhibited reduced destructive insulitis and were protected from diabetes. Neutralization of MIP-1alpha with specific Abs following transfer of diabetogenic T cells delayed the onset of diabetes in NOD.Scid recipients. These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1alpha, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes.

Adjuvants, Immunologic↗
PubMed2000

Transnasal penetrating brain injury with a ball-pen.

We report a case of a 44-year-old man with 1 day's history of epistaxis. He was an in-patient in a psychiatric ward with a history of depression. He had CSF rhinorrhoea, was confused and had no focal neurological deficits. A full length pencil was removed from his left nostril in the emergency department. CT of the brain revealed a tract, but also suggested another foreign body in the inter-hemispheric space. He had a para-sagittal craniotomy and a 14 cm ball-point pen was found lying between the two cerebral hemispheres. This was removed and the patient made an uneventful recovery. This is the first report of an attempted suicide by transnasal insertion of a ballpoint pen intracranially.

Adult↗
PubMed2000

Emergency room thoracotomy: a single surgeon's thirteen-year experience.

Our objectives were to elucidate the postoperative complications in patients who have had emergency room thoracotomy (ERT), to define anatomic and physiologic parameters that are compatible with survival and to document the evolution of management of these patients. A single surgeon's experience over a 13-year period was reviewed. All patients where he was the primary or supervising surgeon for the ERT were included. Data were analyzed for mechanism (penetrating/blunt), hospital where performed, survival to intensive care unit, survival to discharge, and postoperative complications. Among survivors, data were analyzed for the anatomic injuries and the patients' physiologic condition in the field and on arrival. There were a total of 102 patients; penetrating injury 94 (92 percent); blunt, 8 (8 percent). Ten patients (10 percent) reached the intensive care unit alive. Three of the ten (30 percent) died at 2 hours, 12 hours, and 7 days postoperatively. Seven patients survived to hospital discharge. All seven had penetrating chest injuries and were not in cardiac arrest when first examined by paramedics. Four of the seven survivors (57 percent) had major complications. Survival for the early period was 1.6 percent (1/62) and for the later period 15 percent (6/40); P < 0.05. During the study period, changes in patient management included 1) for penetrating torso injury, withholding ERT when survival was extremely unlikely; 2) increased use of blood- and fluid-warming measures; 3) elimination of aortic cross-clamping, instead judiciously using manual compression; 4) making the main purpose of ERT the relief of cardiac tamponade; and 5) immediately controlling any cardiac injury with a simple running suture on a large needle. We conclude the following: 1) The postoperative course after ERT carried significant mortality and morbidity. 2) Compatibility with survival required both the absence of cardiac arrest when initially evaluated in the field and the presence of penetrating chest injury. 3) Significant changes occurred in patient management during this 13-year period. Survival was higher in the latter part of this period.

Emergencies↗
PubMed1999

Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) with production traits in Canadian dairy cattle.

Associations of two alleles of the bovine major histocompatibility complex DRB3 gene (BoLA-DRB3) with lowered somatic cell score (SCS) and occurrence of disease (BoLA-DRB3.2* 16 and *23, respectively) have previously been documented. The objective of this study was to evaluate potential relationships between BoLA-DRB3 alleles with production traits, namely 305-day milk, milk fat and milk protein yield, in a population of Canadian dairy cattle (Holstein, n = 835 and Jersey, n = 66) over the course of two lactations. No significant associations were detected between BoLA alleles and production traits in Jerseys. In Holsteins, alleles *16 and *23 also did not show associations with production traits but allele *8 was significantly associated with increased 305-day milk, fat and protein yields in the previous lactation (the lactation prior to immunization with a gram negative core antigen vaccine), and with increased protein production in the subsequent (with reference to the time of immunization) lactation. Allele *22 was associated with decreased milk and protein yield in both previous and subsequent lactations. Therefore, it can be concluded that increasing or decreasing the frequency of BoLA alleles *16 and *23 to reduce SCS or increase resistance to mastitis in this population would not have adverse effects on production in this population, and that certain BoLA alleles (*8 and *22) are associated with altered production traits in Canadian Holsteins.

Alleles↗
PubMed1999

Effect of simvastatin on proliferative nephritis and cell-cycle protein expression.

BACKGROUND: Mesangial cell proliferation is important in subsequent mesangial matrix expansion in glomerular injury. Therefore, the regulation of mesangial cell proliferation may be critical in the treatment of glomerulonephritis. Inhibition of 3-hydro-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibits the production of mevalonate and has been shown to suppress proliferation in many cell types, including mesangial cells in vitro. It is expected that HMG-CoA reductase inhibitor may suppress mesangial cell proliferation and subsequent progression of glomerulonephritis. Recently, the tight relationship between cell-cycle regulatory protein expression and mesangial cell proliferation in experimental glomerulonephritis was demonstrated. The aim of the present study is to examine the effect of simvastatin, one of the HMG-CoA reductase inhibitors, on the glomerular cell proliferation and on the expression of CDK2 or p27Kip1 in mesangial cells in experimental glomerulonephritis in vivo. METHODS: The effect of simvastatin on a rat mesangial proliferative glomerulonephritis induced by antithymocyte antibody (anti-Thy 1.1 GN) was studied. Administration of simvastatin or vehicle (for control GN) were started from two days before disease induction, and was continued to the day of nephrectomy. Nephrectomy was done at days 0, 2, 4, 7, 12 and 20 after disease induction. Immunohistochemistry for proliferating cells, macrophages, alpha-smooth muscle actin, type IV collagen and PDGF-B chain was performed, respectively, in addition to conventional periodic-acid Schiff staining. Double immunostaining for CDK2/OX-7 or p27Kip1/OX-7 was also done, respectively. RESULTS: There was no difference in the degree of the initial injuries between simvastatin-treated and control GN rats. The most pronounced feature of simvastatin-treated GN was the suppression of the early glomerular cell proliferation (about 70% of proliferation was suppressed at day 4). At day 4, alpha-smooth muscle actin expression was also decreased in simvastatin-treated GN rats. Inhibition of macrophage recruitment into glomeruli by simvastatin was also a prominent feature (about 30% decrease in the number of glomerular macrophages at day 2). Simvastatin significantly suppressed subsequent mesangial matrix expansion and type IV collagen accumulation in glomeruli. Although it might simply reflect the reduction in mesangial cells, glomerular PDGF-B chain expression was reduced. There was no significant difference in plasma lipids levels at day 2 and day 4. In vehicle-treated GN rats, the number of CDK2+/OX-7+ cells (CDK2-expressed mesangial cells) in glomeruli increased significantly from day 4 to day 7. Although simvastatin suppressed mesangial cell proliferation, the increase in the number of glomerular CDK2+/OX-7+ cells was also attenuated by simvastatin treatment. There was no difference in the number of p27Kip1+/OX-7+ cells (p27Kip1-expressed mesangial cells) in the glomerulus between vehicle-treated and simvastatin-treated GN rats. CONCLUSION: Simvastatin suppressed mesangial cell proliferation and subsequent matrix expansion, and macrophage infiltration into glomeruli in anti-Thy 1.1 GN rats. The antiproliferative effect of simvastatin in this model was also associated with the reduction of CDK2 expression in mesangial cells.

Animals↗
PubMed1999

Expression of bcl-2 and bax in glomerular disease.

Bcl-2 may account in part for the maintenance of hypercellularity in human glomerular diseases through preventing cell death and by counteracting bax which may be expressed to regulate excessive proliferation. This process is associated with the effect of PDGF B-chain expression. Bax expression may be important in the cell loss leading to glomerulosclerosis and TGF-beta1 participates in this process by increasing bax expression. Thus, the balance of bcl-2/bax expression may be critical in the course of human glomerular diseases.

Animals↗
PubMed1998

Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle.

Potential associations were investigated between bovine leucocyte antigen (BoLA) alleles and occurrence of disease. Cows (Holstein n = 835; Jersey n = 66) were examined for polymorphisms of the second exon of the BoLA-DRB3 gene, using the polymerase chain reaction (PCR), followed by digestion of the amplified fragments with three restriction endonucleases. Disease occurrences were recorded for each cow throughout one lactation. Milk somatic cell count data were retrieved through the Dairy Herd Improvement records and converted to somatic cell score (SCS). There were no effects of BoLA alleles on SCS in Jersey cows, but BoLA-DRB3.2*16 was significantly associated (P < or = 0.05) with lower SCS in Holsteins. Since the number of Jerseys was relatively small and prevalence of diseases in this population was low, health records of Jerseys were not analyzed further. BoLA associations with occurrence of disease in Holsteins were investigated using a log-linear model. There was a significant (P < or = 0.05) association between BoLA-DRB3.2*23 and occurrence of severe mastitis, from which coliforms were the most commonly isolated bacteria. The BoLA allele *3 was associated with a lower risk of retained placenta (P < or = 0.05) and alleles *16 (P < or = 0.05) and *22 (P < or = 0.05) with a lower risk of cystic ovarian disease. Although more studies are required to confirm the present findings, it can be concluded that BoLA alleles may have potential usefulness as genetic markers of higher or lower risk of disease occurrence in cows.

Alleles↗
PubMed1998

Non-surgical treatment of meningioma: a case report and review.

A woman initially presented with a right hemiparesis and subsequently underwent subtotal resection of a left parietal meningioma arising from the lateral wall of the sagittal sinus. She again presented 18 months after surgery with a hemiparesis and repeat MRI showed tumour spreading into the sagittal and the transverse sinuses. She had a therapeutic abortion at 8 weeks gestation 3 weeks prior to her representation. Gestrinone, a synthetic steroid and an antiprogesterone was commenced. Two months later she stopped her medication and is asymptomatic at 16 months. A follow-up MRI revealed that the tumour had shrunk dramatically. This case is the first of its kind with tumour size reduction to less than 20%. We feel that the future of meningioma treatment will be multi-disciplinary and non-surgical options should be considered.

Adult↗
PubMed1998

Alteration in immune responsiveness during the peripartum period and its ramification on dairy cow and calf health.

Substantial evidence indicates that innate and acquired defense mechanisms are lowest from 3 wk precalving to 3 wk postcalving. This lowered responsiveness includes aspects of systemic and mammary gland immunity that may account, at least in part, for the increased incidence of peripartum disease. The physical and metabolic stresses of pregnancy, calving, and lactation may contribute to this decrease in host resistance and the subsequent increase in disease incidence. However, variation among cows in their host resistance mechanisms suggests that genotype and phenotype may possibly be used to identify cows that are able to mount beneficial immune responses over the periparturient period. Our own studies suggest that cows may be categorized as high or low responders based on the peripartum antibody responses to ovalbumin and Escherichia coli J5. Low responders were hyporesponsive to these test antigens and had a higher incidence of peripartum diseases, particularly mastitis. In many species, a functional link exists between the immune and endocrine systems, and, during periods of stress or physical injury, neuropeptides and neuroendocrine hormones function as immunomodulators. Initial investigations of peripartum cows reveal positive relationships between growth hormone kinetics and profiles of antibody response. Whether hormone fluctuations during the periparturient period are responsible for the alterations observed in immune responsiveness remains uncertain.

Animals↗
PubMed1997

"Tethered cord syndrome"--recent clinical experience.

Thirty-three consecutive patients treated surgically for "tethered cord syndrome" over a 3-three year period were reviewed. The main presenting complaints were back and leg pain, progressive lower limb and spinal deformity, and neurological deficits. Untethering of the cord was achieved in 32 patients, in whom the filum terminale was divided in 17. There were no serious complications; one patient had a CSF leak which required surgical repair. The mean postoperative follow-up was 15 months and 20 of the patients reported improvement, the rest were unchanged. There was no neurological deterioration in any of the patients. Our series suggests that cord release in patients with "tethered cord syndrome" improves or arrests the progression of neurological deterioration.

Adolescent↗
PubMed1997

MK-801 administration during ethanol withdrawal in neonatal rat pups attenuates ethanol-induced behavioral deficits.

Alcohol exposure during development can produce central nervous system dysfunction, resulting in a wide range of behavioral alterations. The various mechanisms by which alcohol causes these behavioral changes, however, remain unknown. One mechanism that has been suggested is NMDA receptor-mediated excitotoxic cell death produced by ethanol withdrawal. The present study examined whether MK-801, an antagonist of the NMDA receptor that has been shown to protect against NMDA receptor-mediated excitotoxicity, could block alcohol's adverse effects on behavior. Sprague-Dawley rat pups were exposed to alcohol (6.0 g/kg) in a binge-like manner on postnatal day 6 using an artificial rearing procedure. Subjects then received an injection of MK-801 (0.1 mg/kg) or vehicle during withdrawal, 21 hr after ethanol exposure. At postnatal day 40, all subjects were tested on a serial spatial discrimination reversal task. Ethanol-exposed subjects were impaired in both discrimination and reversal learning, and committed a significantly greater number of perseverative-type errors, compared with controls. MK-801 administration during ethanol withdrawal significantly attenuated ethanol-induced deficits in reversal learning and increases in perseverative-type errors, whereas MK-801 exposure by itself had no significant effect on performance. Thus, exposure to MK-801 during ethanol withdrawal partially protected against alcohol-related disruptions in spatial reversal learning. These results support the suggestion that NMDA receptor-mediated excitotoxicity may be one mechanism by which alcohol induces behavioral teratogenicity.

Alcohol Withdrawal Delirium↗
PubMed1995

Total intraventricular migration of unisystem ventriculo-peritoneal shunt.

This is a report of an hydrocephalic adult, in whom a unishunt system migrated upwards into the ventricle despite using the appropriate clips (lock and slip). The shunt migration discovered 3 months following its insertion. Several mechanisms contributed to the migration; negative sucking intra-ventricular pressure, positive pushing intra-abdominal pressure, tortuous subcutaneous track and neck movements. It seams that lock and slip clips are not enough fixation. The best way of preventing such shunt migration is interposing a reservoir between the ventricular and peritoneal catheters.

Adult↗
PubMed1995

Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury.

The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration. We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and rat vascular smooth muscle cells in vivo. In vitro, cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BNDF, and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. In human coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role in regulating the response of vascular smooth muscle cells to injury.

Animals↗
PubMed1993

Detection of trisomy 18 and Y-derived sequences in fetal nucleated cells obtained by transcervical flushing.

A procedure which combines the collection of fetal cells by transcervical flushing and in situ hybridisation techniques on nuclei in interphase was used to detect trisomy 18 in a fetus at 12 weeks of gestation. Using a primed in situ labelling method, we could also detect Y-specific sequences in a small percentage of transcervically flushed cells obtained at 8-12 weeks from pregnant women with male fetuses. This approach seems to be suitable for prenatal diagnosis of major chromosomal abnormalities and other selected inherited disorders very early in gestation.

Adult↗
PubMed1993

Nutritional aspects of mammary carcinogenesis: a case-control study.

Dietary factors are believed to play an important role in mammary carcinogenesis. International correlations, case-control and cohort studies have associated the incidence and mortality from breast cancer with high fat consumption in the form of meat, gravy and dairy products. Most of these studies have been conducted in the developed countries. Due to paucity of data from developing countries, we conducted a case-control study to evaluate the role of nutritional factors in mammary carcinogenesis. This prospective study was conducted in the oncology clinic at a university hospital. On a detailed questionnaire, information was collected from 80 patients with histologically proven breast cancer (cases) and 80 normal healthy subjects (controls). Information was collected on several patients characteristics as well as intake of 44 different food items. Special care was taken to exclude any recent changes in diet, induced in cases since learning the diagnosis of breast cancer. Interviews were conducted by the same interviewer and lasted approximately 20 minutes. Analysis of data reveal no significant difference in patients characteristics between cases and controls. Similarly, no significant difference was found in the intake of most dietary items including meat and dairy products. However, a significant difference was observed in the consumption of fish, vegetable and fruits (P = 0.05). We conclude that our study fails to support the fat-breast cancer hypothesis. It also suggests a potential role of other dietary items such as fish, vegetables and fruits in mammary carcinogenesis.

Adult↗
PubMed1993

Alterations in intracranial pressure and cerebral blood volume in endotoxemia.

Marked deterioration of neurologic function accompanies organ dysfunction in systemic sepsis. Although previous hypotheses have suggested that cerebral hypoperfusion, anoxia or progressive edema of the brain may be causative, the pathogenesis remains unknown. Patients with sepsis with stable or supported hemodynamics and adequate oxygenation may manifest confusion, stupor or coma. Recent evidence has demonstrated that the brain is the source of many classical mediators of inflammation after various forms of injury. These mediators, including the leukotrienes, have pronounced effect on cerebrovascular function. Endotoxin is known to stimulate the release of arachidonate from cell membranes, the rate limiting step in leukotriene synthesis. The current studies were performed to test the hypothesis that neurologic dysfunction associated with endotoxemia is characterized by alterations in cerebrovascular permeability or vasomotor function manifested by intracranial hypertension, or both. We studied the response of miniature swine to experimental endotoxemic shock and compared this response with hemorrhagic hypotension. We observed a dramatic elevation of intracranial pressure in swine subjected to endotoxemic shock, despite arterial hypotension. Moreover, estimation of cerebral blood volume (CBV) by reflectance infrared photoplethysmography demonstrated a dramatic increase in CBV, which corresponded to this elevation in intracranial pressure. However, cerebral cortical oxygen saturation was significantly reduced despite this net increase in CBV, indicative of an increase in the venous volume of the brain, while arterial volume remained the same or decreased from baseline levels. Oxygen extraction across the brain decreased during this same period compared with baseline and control values. These results demonstrate that endotoxemia is associated with the development of intracranial hypertension and an increase in CBV secondary to elevation of cerebrovascular venous volume coupled with reduced oxygen extraction across the brain. This evidence of cerebrovascular dysfunction probably represents blood flow maldistribution, similar to that seen in other organs with sepsis, suggesting a cause for altered neurologic function in systemic sepsis.

Animals↗
PubMed1990

TGF-alpha and TGF-beta expression during sodium-N-butyrate-induced differentiation of human keratinocytes: evidence for subpopulation-specific up-regulation of TGF-beta mRNA in suprabasal cells.

Sodium-N-butyrate (NaB) induces terminal differentiation and cornified envelope formation in cultured human keratinocytes. In the present study we explored the question of whether NaB-induced maturation could be mediated through changes in TGF-alpha and TGF-beta expression in normal keratinocytes. NaB induced a four-fold increase in TGF-beta mRNA transcript levels. This increase in TGF-beta mRNA abundance occurred only within the nonbasal keratinocyte subpopulation which maximally responds to NaB treatment by progression to cornified envelopes. Basal keratinocytes, which are relatively refractive to cornified envelope formation, did not show any increase in TGF-beta mRNA abundance after NaB treatment. By comparison, TGF-alpha mRNA transcript and extracellular TGF-alpha protein levels were unaffected by NaB treatment. A 50% decrease in EGF receptor binding was observed in NaB-treated keratinocyte cultures, rendering the cells less responsive to proliferation induction.

Butyrates↗