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Biomedical subjects

M Shah

Publications and source records attributed to M Shah.

At least 37 records · Page 2Linked to original sources
PubMed2003

High levels of fusidic acid-resistant Staphylococcus aureus in dermatology patients.

BACKGROUND: Antibiotic resistance is a significant problem both in hospitals and the community. Topical antibiotics are widely used for dermatological problems and this may be leading to the emergence of resistant bacteria. OBJECTIVE: To assess the level of fusidic acid-resistant Staphylococcus aureus inpatients with dermatological problems. METHODS: All microbiology samples over a 4-month period were tested for antibiotic sensitivities. Patients with cultures positive for S. aureus were studied. RESULTS: The study shows 50% of S. aureus isolates from dermatology patients were resistant to fusidic acid. This figure rose to 78% inpatients with atopic eczema. Of patients with fusidic acid-resistant S. aureus isolates, 96% had used a fusidic acid-containing preparation within the previous 6 months. The level of fusidic acid resistance in S. aureus samples cultured from nondermatology patients was only 9.6%, a level significantly below that for dermatology patients (P < 0.001). CONCLUSIONS: High levels of fusidic acid-resistant S. aureus are found in dermatology patients. Inappropriate use of topical antibiotics in dermatology patients leading to fusidic acid resistance may threaten the efficacy of systemic fusidic acid for the treatment of serious S. aureus infections. Education of health professionals and restriction of the use of fusidic acid is needed.

Administration, Topical↗
PubMed2002

Necrotising fasciitis in an infant with congenital insensitivity to pain syndrome.

We present a rare case of necrotising fasciitis in an infant with congenital insensitivity to pain syndrome. The aetiology, diagnosis and management of necrotising fasciitis in children are compared with those in adults. In contrast to adults, children affected by necrotising fasciitis are usually previously healthy and have no predisposing factors. Early diagnosis, intravenous antibiotics and aggressive surgical debridement are mandatory for an optimal outcome.

Amputation, Surgical↗
PubMed2002

Genetic susceptibility in Dupuytren's disease: lack of association of a novel transforming growth factor beta(2) polymorphism in Dupuytren's disease.

The genes involved in the pathogenesis of Dupuytren's disease have yet to be identified. In this study, we tested for an association between Dupuytren's disease (DD) and a novel insertion polymorphism within the 5'-untranslated region (5'-UTR), of the TGFbeta(2) gene. DNA samples from 179 DD patients and 187 ethnically matched controls were examined. There was no statistically significant difference in TGFbeta(2) allele frequency distributions between cases and controls for the TGFbeta(2) polymorphism.

Adult↗
PubMed2002

Simultaneous bilateral quadriceps tendon rupture while playing basketball.

Simultaneous bilateral quadriceps tendon rupture is an uncommon injury in healthy people and only a few cases have been reported in athletes. This is the first report of a patient with simultaneous bilateral quadriceps tendon rupture incurred while playing basketball. The injury was surgically repaired and the patient had a good functional outcome.

Adult↗
PubMed2002

Genetic susceptibility in Dupuytren's disease. TGF-beta1 polymorphisms and Dupuytren's disease.

Dupuytren's disease is a benign fibroproliferative disease of unknown aetiology. It is often familial and commonly affects Northern European Caucasian men, but genetic studies have yet to identify the relevant genes. Transforming growth factor beta one (TGF-beta1) is a multifunctional cytokine which plays a central role in wound healing and fibrosis. It stimulates the proliferation of fibroblasts and the deposition of extracellular matrix. Previous studies have implicated TGF-beta1 in Dupuytren's disease, suggesting that it may represent a candidate susceptibility gene for this condition. We have investigated the association of four common single nucleotide polymorphisms in TGF-beta1 with the risk of developing Dupuytren's disease. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-beta1 polymorphisms. DNA samples from 135 patients with Dupuytren's disease and 200 control subjects were examined. There was no statistically significant difference in TGF-beta1 genotype or allele frequency distributions between the patients and controls for the codons 10, 25, -509 and -800 polymorphisms. Our observations suggest that common TGF-beta1 polymorphisms are not associated with a risk of developing Dupuytren's disease. These data should be interpreted with caution since the lack of association was shown in only one series of patients with only known, common polymorphisms of TGF-beta1. To our knowledge, this is the first report of a case-control association study in Dupuytren's disease using single nucleotide polymorphisms in TGF-beta1.

Adult↗
PubMed2001

Correction of cross-linker sensitivity of Fanconi anemia group F cells by CD33-mediated protein transfer.

Studies have previously described the feasibility of receptor-mediated protein transfer in a cell culture model of Fanconi anemia (FA) group C. This study explores the versatility of this approach by using an antibody single-chain fusion protein to correct the phenotypic defect in FA group F cells. A 68.5-kd chimeric protein (His-M195FANCF) was expressed, consisting of a His tag, a single-chain antibody to the myeloid antigen CD33, and the FANCF protein, as well as a 43-kd His-FANCF fusion protein lacking the antibody motif, in Escherichia coli. The nickel-agarose-purified His-M195FANCF protein bound specifically to the surface of HeLa cells transfected with CD33 and internalized through vesicular structures. The fusion protein, but not CD33, sorted to the nucleus, consistent with the known nuclear localization of FANCF. No similar binding or internalization was observed with His-FANCF. Pretreatment of the transfected cells with chloroquine abolished nuclear accumulation, but there was little change with brefeldin A, indicating a minimal if any role for the Golgi apparatus in mediating transport from endosomes to the cytosol and the nucleus. The intracellular half-life of His-M195FANCF was approximately 160 minutes. Treatment of CD33-transfected FA group F lymphoblastoid cells with 0.1 mg/mL His-M195FANCF conferred resistance to mitomycin C. No similar protection was noted in CD33(-) parental cells or CD33(+) FA cells belonging to groups A and C. These results demonstrate that antibody-directed, receptor-mediated protein transfer is a versatile method for the delivery of biologically active proteins into hematopoietic cells.

Antigens, CD↗
PubMed2001

Real-time polymerase chain reaction analysis reveals an evolution of cytokine mRNA production in allograft acceptor mice.

BACKGROUND: The relative contribution of pro-inflammatory and anti-inflammatory cytokines in promoting the rejection or acceptance of experimental cardiac allografts remains controversial. We hypothesized that the posttransplantation induction of a new immune response to graft alloantigens at a distant delayed-type hypersensitivity (DTH) site would force the immune system to reveal its current disposition toward graft alloantigen as it initiates the new immune response. Thus, we should be able to monitor the evolution of the immunologic relationship between allograft recipients and their grafts at any time posttransplantation by challenging the recipient for DTH responses to donor alloantigen and evaluating the cytokine profiles displayed at the DTH site. METHODS: We have used the sensitive and quantitative technique of real-time polymerase chain reaction to evaluate the patterns of donor alloantigen-induced cytokine mRNA production for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10, and transforming growth factor (TGF)-beta. We evaluated cytokine mRNA expression in cardiac allografts and in donor alloantigen-challenged DTH sites in mice that have either accepted or rejected cardiac allografts. RESULTS: We observed the following. (1) Normal hearts and pinnae exhibited detectable baseline production of cytokine mRNAs: TGF-beta>IFN-gamma=IL-10>IL2->IL-4. (2) Both the accepted and rejecting cardiac allografts produced increased amounts of all cytokine mRNAs tested and displayed few quantitative differences in cytokine mRNA production. Notably, accepted allografts displayed enhanced IL-10 mRNA production on day 7 posttransplantation, but not on day 60 posttransplantation and reduced IFN-gamma mRNA production on day 60, but not day 7. (3) There was a high degree of variability in production levels among the various cytokine mRNAs, both for background levels and for allograft-stimulated levels. (4) Donor-reactive DTH sites of allograft rejector mice displayed a broad array of cytokine mRNAs, whereas the DTH sites of allograft acceptor mice displayed only IL-4 mRNA production. (5) Provision of exogenous TGF-beta or IL-10 at a DTH challenge site of allograft rejector mice caused a shift in the cytokine mRNA profile that minimized IFN-gamma and IL-2 mRNA production but spared IL-4, IL-10, and TGF-beta mRNA production. CONCLUSIONS: A broad array of cytokine mRNAs may be stockpiled for future use in cardiac allografts, regardless of whether the grafts will be accepted or rejected. This stockpile is continuously replenished for as long as the graft survives, thereby obscuring any changes in immune disposition of the graft recipient toward graft alloantigens. However, such changes can be revealed by challenge with donor alloantigens at a distant site (DTH challenge). In allograft acceptor mice, this disposition evolves from pro-inflammatory to anti-inflammatory.

Animals↗
PubMed2001

Adenovirus-mediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve.

BACKGROUND: Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (Ad(GV)VEGF(121.10)) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF(121.10). METHODS AND RESULTS: Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of Ad(GV)VEGF(121.10), in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with Ad(GV)VEGF(121.10). In response to acetylcholine (150 microg/min and 300 microg/min), there was a 0.9-fold (0.33+/-0.03 to 0.32+/-0.03 L/min) and 1.2-fold (0.33+/-0.03 to 0.490+/-0.02 L/min) change in flow before Ad(GV)VEGF(121.10) treatment. After Ad(GV)VEGF(121.10) treatment, flow increased 2.4-fold (0.310+/-0.04 to 0.730+/-0.10 L/min) and 2.3-fold (0.31+/-0.04 to 0.7+/-0.08 L/min), respectively (P<0.05 before Ad(GV)VEGF(121.10) treatment versus after Ad(GV)VEGF(121.10) for both doses). Infusion of nitroglycerin resulted in a 1.8-fold increase in flow before Ad(GV)VEGF(121.10) (0.33+/-0.03 to 0.58+/-0.06 L/min) compared with a 2.4-fold increase (0.31+/-0.04 to 0.73+/-0.09 L/min) after Ad(GV)VEGF(121.10) (P=NS before Ad(GV)VEGF(121.10) versus after Ad(GV)VEGF(121.10)). Lower-extremity flow reserve increased in all patients in response to at least 1 dose of acetylcholine. Peak walking times increased concomitant with improvement in endothelial function. CONCLUSIONS: Adenoviral gene transfer of VEGF(121.10) appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease.

Acetylcholine↗
PubMed2001

Social stress increases the susceptibility to endotoxic shock.

The influence of social disruption stress (SDR) on the susceptibility to endotoxic shock was investigated. SDR was found to increase the mortality of mice when they were challenged with the bacterial endotoxin lipopolysaccharide (LPS). Histological examination of SDR animals after LPS injection revealed widespread disseminated intravascular coagulation in the brain and lung, extensive meningitis in the brain, severe hemorrhage in the lung, necrosis in the liver, and lymphoid hyperplasia in the spleen, indicating inflammatory organ damage. In situ hybridization histochemical analysis showed that the expression of the glucocorticoid receptor mRNA was down-regulated in the brain and spleen of SDR animals while the ratio of expression of AVP/CRH-the two adrenocorticotropic hormone secretagogue, increased. After LPS injection, the expression of pro-inflammatory cytokines, IL-1beta and TNF-alpha, was found significantly higher in the lung, liver, spleen, and brain of the SDR mice as compared with the LPS-injected home cage control animals. Taken together, these results show that SDR stress increases the susceptibility to endotoxic shock and suggest that the development of glucocorticoid resistance and increased production of pro-inflammatory cytokines are the mechanisms for this behavior-induced susceptibility to endotoxic shock.

Animals↗
PubMed2001

Selective gene expression and activation-dependent regulation of vasoactive intestinal peptide receptor type 1 and type 2 in human T cells.

Vasoactive intestinal peptide (VIP) has potent antiproliferative and anti-inflammatory functions in the immune system. Two structurally distinct G-protein-associated receptors, VIP receptor type 1 (VPAC1) and VIP receptor type 2 (VPAC2), mediate the biological effects of VIP. The regulation of VIP receptor gene expression and the distribution of these receptors in different compartments of the human immune systems are unknown. This study reports, for the first time, a quantitative analysis of VPAC1 and VPAC2 mRNA expression in resting and activated T cells as well as in resting monocytes. Purified human peripheral blood CD4(+) T cells and CD8(+) T cells were stimulated via the TCR/CD3 receptor complex. Using the novel fluorometric-based kinetic (real-time) RT-PCR, we determined that VPAC1 is constitutively expressed in resting T cells and monocytes; the levels of expression were significantly higher in monocytes and CD4(+) T cells than in CD8(+) T cells. VPAC1 mRNA expression is significantly higher relative to VPAC2 in resting CD4(+) T cells and CD8(+) T cells. VPAC2 is expressed at very low levels in resting T cells but is not detectable in resting monocytes. In vitro stimulation of Th cells with soluble anti-CD3 plus PMA induced a T cell activation-dependent down-regulation of VPAC1. VPAC1 is down-regulated under conditions of optimal T cell stimulation. Our results suggest that selective VIP effects on T cell function may be mediated via selective expression of VPAC1 and VPAC2 on T cells and monocytes. Furthermore, down-regulation of VPAC1 in CD4(+) T cell subpopulations is highly correlated with T cell activation.

Adult↗
PubMed2001

Simple clinical variables are markers of the propensity for readmission in patients hospitalized with heart failure.

In a consecutive cohort of patients hospitalized for decompensated heart failure, we found that chronic obstructive pulmonary disease and history of hospitalization for any cause in the preceding 6 months were the strongest correlates of early readmission. Based on these findings, we propose a simple risk stratification system to classify patients who are hospitalized for heart failure as low, medium, or high risk for early readmission.

Aged↗
PubMed2001

Design of a microfabricated magnetic cell separator.

A new magnetic separation idea utilizing several ideas from microfabrication and nanomagnetics is presented. The basic idea comes from our earlier work using asymmetry in obstacles and Brownian motion to effect separation of objetcs [10] by moving them in streams whose angle to the hydrodynamic average velocity is a function of the diffusion coefficient of the object. The device we propose here is not technically a Brownian ratchet device but uses the idea of force which acts at angle to the hydrodynamic flow. In our case, the force is generated by a magnetic field gradient which comes from an array of magnetized wires which lie at an angle 0 to a hydrodynamic field flow. The sum of the hydrodynamic force and the magnetic force create a new vector which as in the case of the Brownian ratchet moves the cell out of the main stream direction.

Animals↗
PubMed2001

A study of the influence of the hydrophobic core residues of yeast iso-2-cytochrome c on phosphate binding: a probe of the hydrophobic core-surface charge interactions.

To gain insight into the role of hydrophobic core-surface charge interactions in stabilizing cytochrome c, we investigated the influence of hydrophobic core residues on phosphate binding by mutating residues in yeast iso-2-cytochrome c to those corresponding to iso-l-cytochrome c in various combinations. Heat transition of ultraviolet CD was followed as a function of pH in the presence and absence of phosphate. Thermodynamic parameters were deduced. It was found that the I20V/V43A/M98L mutation in the hydrophobic core, whose locations are remote from the putative phosphate sites, modulates phosphate interactions. The modulation is pH dependent. The I20V/ M98L and V43A mutation effects are nonadditive. The results lead to a model analogous to that of Tsao, Evans, and Wennerstrom, where a domain associated with the ordered hydrophobic core is sensitive to the fields generated by the surface charges. Such an explanation would be in accord with the observed difference in thermal stability between iso-2 and horse cytochromes c.

Amino Acid Sequence↗
PubMed2001

AV.TK-mediated killing of subcutaneous tumors in situ results in effective immunization against established secondary intracranial tumor deposits.

Gene transfer vectors expressing herpes simplex thymidine kinase (HSVtk), in addition to direct killing of tumor cells, often have an associated local "bystander effect" mediated by metabolic coupling of tumor cells. A systemic antitumor effect mediated by the immune system, termed the distant bystander effect, has also been reported. We have observed the development of cytotoxic T-lymphocyte (CTL) populations and long-lasting antitumor immunity following treatment of subcutaneous tumors with an adenoviral vector expressing HSVtk (AV.TK) and ganciclovir (GCV) in rat glioma model. This vaccination effect seen with AV.TK/GCV treatment of subcutaneous tumor could even abrogate or retard growth of previously established secondary intracranial tumors.

Adenoviridae↗
PubMed2001

Classification of osteonecrosis of the femoral head. Reliability, reproducibility, and prognostic value.

The purpose of the current investigation was to determine interobserver and intraobserver reliability of the classification system of Steinberg et al for osteonecrosis of the femoral head. Sixty-five anteroposterior and lateral radiographs of hips were selected randomly from a pool of patients with confirmed osteonecrosis of the femoral head. Six fellowship-trained observers viewed the radiographs (Reading 1). The observers used six main stages of the classification excluding A, B, and C subgroups. The same observers viewed the radiographs 4 months later in reverse order (Reading 2). Reading 1 was used to calculate interobserver kappa values. Reading 2 was used to calculate intraobserver kappa values. Stage-specific kappa values for interobserver variation between all viewers were as follows: Stage I, k = 0.64; Stage II, k = 0.51; Stage III, k = 0.21; Stage IV, k = 0.49; Stage V, k = 0.36; and Stage VI, k = 0.80. Stage-specific kappa values for intraobserver variation between all viewers were as follows: Stage I, k = 0.74; Stage II, k = 0.60; Stage III, k = 0.46; Stage IV, k = 0.59; Stage V, k = 0.27; and Stage VI, k = 0.78. An average of 10 of 21 (48%) of these errors involved Stage III. An average of 6.3 of 21 (30%) intraobserver errors involved Stage V. The presence of the crescent sign in Stage III and joint space narrowing in Stage V markedly diminished the overall reliability of any four- to six-stage classification system. Based on the authors' experience and analysis of the current classifications of osteonecrosis of the femoral head, an easy and reproducible Pittsburgh classification system is proposed.

Female↗