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Biomedical subjects

H Sheikh

Publications and source records attributed to H Sheikh.

At least 19 recordsLinked to original sources

Effects of chronic nerve cuff and intramuscular electrodes on rat triceps surae motor units.

In order to assess the long-term effects of implanted electrodes on motor unit properties, we studied triceps surae (TS) motor units in rats implanted for 3-10 months with a tibial nerve cuff electrode for H-reflex elicitation and intramuscular electrodes for recording TS electromyographic activity. Motor units with sag from implanted rats displayed greater tetanic force than those from unimplanted rats. Motor units without sag had shorter twitch contraction times. This disrupted the relationship between sag and contraction time that was always present in unimplanted rats. These differences were consistent with a small degree of muscle denervation and subsequent reinnervation. Further analyses ascribed this effect to the nerve cuff rather than to the intramuscular electrodes. Comparable changes in motor unit properties may occur in humans with implanted nerve cuffs.

Action Potentials↗

Operant conditioning of rat H-reflex affects motoneuron axonal conduction velocity.

This study assessed the effects of operant conditioning of the H-reflex on motoneuron axonal conduction velocity in the rat. After measurement of the control H-reflex size, rats were either exposed for at least 40 days to the HRup or HRdown conditioning mode, in which reward occurred only if the soleus H-reflex was greater than (HRup mode) or less than (HRdown mode) a criterion or continued under the control condition (HRcon mode) in which the H-reflex was simply measured. We then measured axonal conduction velocity of triceps surae motor units of HRup, HRdown, and HRcon rats by stimulating the axon in the ventral root and recording from the tibial nerve. Conduction velocity was 8% less in successful HRdown rats than in HRcon rats (P=0.02). Conduction velocity in HRup rats and unsuccessful HRdown rats was not significantly different from that in HRcon rats. Since recording bypassed the intra-spinal portion of the motoneuron, the change was clearly in the axon. This decrease was similar to the 6% decrease previously found in successful HRdown monkeys. Unsuccessful HRdown rats and monkeys did not show this decrease. This result suggests that the mechanism of HRdown conditioning is similar in rats and monkeys and provides further support for the hypothesis that HRdown conditioning decreases motoneuron excitability by producing a positive shift in firing threshold. While traditional theories of learning emphasize synaptic plasticity, neuronal plasticity may also contribute to operantly conditioned behavioral changes.

Action Potentials↗

Motor unit properties after operant conditioning of rat H-reflex.

Operant conditioning of the H-reflex produces plasticity at several sites in the spinal cord, including the motoneuron. This study assessed whether this spinal cord plasticity is accompanied by changes in motor unit contractile properties. Thirty-one adult male Sprague-Dawley rats implanted for chronic recording of triceps surae electromyographic activity and H-reflex elicitation were exposed for at least 40 days to HRup or HRdown training, in which reward occurred when the H-reflex was greater than (12 HRup rats) or less than (12 HRdown rats) a criterion value, or continued under the control mode in which the H-reflex was simply measured (7 HRcon rats). At the end of H-reflex data collection, rats were anesthetized and the contractile properties of 797 single triceps surae motor units activated by intraaxonal (or intramyelin) current injection were determined. Motor units were classified as S, FR, Fint, or FF on the basis of sag and fatigue properties. Maximum tetanic force and twitch contraction time were also measured. HRdown rats exhibited a significant increase in the fatigue index of fast-twitch motor units. This resulted in a significant decrease in the percentage of Fint motor units and a significant increase in that of FR motor units. HRup conditioning had no effect on fatigue index. Neither HRup nor HRdown conditioning affected maximum tetanic force or twitch contraction time. These data are consistent with the hypothesis that conditioning mode-specific change in motoneuron firing patterns causes activity-dependent change in muscle properties.

Action Potentials↗

The sensitivity of transesophageal pacing for screening in atrial tachycardias.

Transesophageal atrial pacing and recording performed in 128 patients for palpitations or tachycardia was retrospectively evaluated and compared to the same procedure in 77 routinely evaluated patients after a catheter ablation procedure. The sensitivity and specificity of the described protocol was 74 and 90% respectively. The procedure was well tolerated and a majority of patients could be completely evaluated according to the protocol. The outcome of the first time investigation influenced the subsequent choice of therapy in the studied population. The results suggest that transesophageal pacing is a valuable tool for evaluation of atrial tachycardias with specificity, sensitivity and tolerability comparable to other noninvasive methods used in cardiology.

Adult↗

Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor.

Endo180 was previously characterized as a novel, cell type specific, recycling transmembrane glycoprotein. This manuscript describes the isolation of a full length human Endo180 cDNA clone which was shown to encode a fourth member of a family of proteins comprising the macrophage mannose receptor, the phospholipase A(2) receptor and the DEC-205/MR6 receptor. This receptor family is unusual in that they contain 8-10 C-type lectin carbohydrate recognition domains in a single polypeptide backbone, however, only the macrophage mannose receptor had been shown to function as a lectin. Sequence analysis of Endo180 reveals that the second carbohydrate recognition domain has retained key conserved amino acids found in other functional C-type lectins. Furthermore, it is demonstrated that this protein displays Ca(2+)-dependent binding to N-acetylglucosamine but not mannose affinity columns. In order to characterize the physiological function of Endo180, a series of biochemical and morphological studies were undertaken. Endo180 is found to be predominantly expressed in vivo and in vitro on fibroblasts, endothelial cells and macrophages, and the distribution and post-translational processing in these cells is consistent with Endo180 functioning to internalize glycosylated ligands from the extracellular milieu for release in an endosomal compartment.

Amino Acid Sequence↗

Phycoerythrin 545: monomers, energy migration, bilin topography, and monomer/dimer equilibrium.

Phycoerythrin 545 was isolated having an alpha2beta2 (dimer) protein structure at pH 6.0 and 2 g/L protein concentration with eight bilin chromophores. Monomers (alphabeta) were produced by lowering the protein concentration to 0.15 g/L and the pH to 4.5. Dimer dissociation was monitored by dynamic light scattering and gel-filtration column chromatography. Monomers were stable and had bilin optical spectra different from the alpha2beta2 dimers, although they have very similar protein secondary structures. The optical spectra of phycoerythrin 545 showed four types of behavior with temperature: 10-20 degrees C, dimers; 40-50 degrees C, dimers/monomers; 60 degrees C, nearly fully disordered; 70 degrees C, disordered alpha and beta polypeptides. At 40 degrees C, the protein dissociated partially to monomer, which could be totally reversed to dimers at 20-25 degrees C. The visible circular dichroism difference spectrum for the protein dimers minus monomers exhibited positive and negative bands--such spectra may indicate exciton splitting between closely-spaced bilins. Circular dichroism also revealed a spectrum suggesting exciton coupling for the second excited state of the bilins. Ultrafast fluorescence using a two-photon method showed the fastest time for protein dimers to be 2. 4 ps and monomers had a 39-ps lifetime. Phycocyanin 645 was found to have a 550-fs lifetime.

Bile Pigments↗

Discrete domains within the hyaluronan receptor CD44 regulate membrane localization and cell migration.

CD44 is the principle transmembrane receptor for the extracellular matrix glycosaminoglycan, hyaluronan. This receptor: ligand interaction is required for many normal cellular processes including lymphocyte homing into inflammatory sites, assembly of a pericellular matrix during chondrogenesis, wound healing and tissue morphogenesis during development. In order to mediate these diverse events, CD44 expressing cells must be able to regulate, and respond to, interactions with hyaluronan. The mechanisms responsible have been subject to scrutiny over the past few years as it has become clear that their disruption can underlie the progression of both metastatic tumours and chronic inflammatory diseases. Here we describe recent data identifying discrete regions within the transmembrane and cytoplasmic domains of CD44 which regulate this important adhesion receptor.

Animals↗

Neural networks and blood cell identification.

The objective of this project is to propose a method of identifying cells found in human blood and to classify them based upon their morphological features using neural networks. The project focuses on three major blood cell types, namely, erythrocytes, leukocytes and platelets. The data are collected using peripheral blood smears from clinical patients. The image acquisition requires 100x magnification on all the blood smears, the preprocessing involves the use of median and edge enhance filters; the feature extraction is done by performing the wavelet transform on the images. Finally classification of the blood cell types is done using ALOPEX and Back Propagation trained neural networks. The efficacy of both networks is then compared by comparing their outputs and number of iterations required to reach the final result.

Algorithms↗

Chronic invasive aspergillosis in apparently immunocompetent hosts.

Seventeen cases of invasive aspergillosis occurring since 1987 in apparently immunologically normal hosts have been reviewed: 9 of invasive sinus aspergillosis, 2 of isolated brain abscesses, 3 of pneumonia (1 in a patient who developed mediastinitis), 2 of lymph node aspergillosis, and 1 of osteomyelitis of the foot. Two of the 9 patients with sinus aspergillosis died; the rest were stable up to March 1993. They responded initially to combined surgical and medical therapy. Both patients with brain abscesses survived following surgery, but one had neurological sequelae. Both patients with pneumonia were well following therapy with amphotericin B; one also received itraconazole. The patient with mediastinitis died, but this disease was diagnosed late. The patients with lymph node involvement were lost to follow-up, as was the patient with osteomyelitis. Invasive aspergillosis may be common in Pakistan. Greater awareness would allow earlier diagnosis and therapy, thereby improving the outcome.

Adolescent↗

A di-hydrophobic Leu-Val motif regulates the basolateral localization of CD44 in polarized Madin-Darby canine kidney epithelial cells.

Both in vivo and in vitro the distribution of the resident plasma membrane adhesion protein, CD44, is restricted to the basolateral domain of polarized epithelial cells, suggesting a role in interepithelial interactions. To determine how this localization might be regulated a range of CD44 cytoplasmic domain mutations were generated and a minimal 5 amino acid sequence, His330-Leu-Val-Asn-Lys334, was identified which when deleted results in expression of CD44 on the apical microvillal membrane. Further mutagenesis throughout this regions pinpointed a critical di-hydrophobic motif, Leu331/Val332. The ability of wild type but not mutant CD44 cytoplasmic domains to redirect an apically targeted protein, placental alkaline phosphatase, to the basolateral plasma membrane demonstrates that this sequence can function as a dominant localization signal. This His330-Lys334 sequence is spatially separate from other CD44 regulatory elements and as discussed here, a comparison with known basolateral sorting sequences identified in other transmembrane proteins suggests that a distinct mechanism operates to retain resident plasma membrane proteins in their correct plasma membrane subdomains.

Amino Acid Sequence↗

CD44 exhibits a cell type dependent interaction with triton X-100 insoluble, lipid rich, plasma membrane domains.

CD44 is an abundant, widely expressed transmembrane glycoprotein which can act as a receptor for the extracellular matrix glycosaminoglycan, hyaluronan. Biochemical and morphological studies have demonstrated that in fibroblasts a significant of the CD44 population is resistant to Triton X-100 extraction and that the detergent insoluble protein is co-localized with components of the cortical cytoskeleton. Surprisingly, this distribution is not abrogated upon deletion of the CD44 cytoplasmic tail indicating that mechanisms other than a direct interaction with the cytoskeleton can regulate CD44. In this manuscript, the mechanisms underlying this detergent-insoluble association are further investigated. There was no evidence that the Triton X-100 insolubility of CD44 resulted from homotypic aggregation, an association with hyaluronan or from a direct, or indirect, association with the cytoskeleton. Instead, evidence is presented that the detergent insolubility of fibroblast CD44 at 4 degrees C results from an association of the CD44 transmembrane domain with Triton X-100 resistant, lipid rich, plasma membrane domains. The proportion of the CD44 found in these Triton X-100 insoluble structures is dependent upon cell type and cannot be altered by changing cell motility or extracellular matrix associations. These studies provide evidence for a novel mechanism regulating this adhesion protein in the plasma membrane.

Animals↗

Comparison of liver histology in chronic active hepatitis C and chronic active hepatitis B.

OBJECTIVE: To study the histological features of chronic active hepatitis C (CAH-C) and to compare these with those of chronic active hepatitis B (CAH-B). METHODS: Thirty-two liver biopsy specimens from patients with chronic active hepatitis and presence of antibodies to hepatitis C on second generation enzyme immunoassay were studied and compared with those in 34 patients with CAH-B. Seventeen of the 32 CAH-C patients had fully developed or developing cirrhosis of liver whereas the remainder had only chronic active hepatitis. RESULTS: Among 32 patients with CAH-C, fatty change (20), Kupffer cell hyperplasia (30), sinusoidal lymphocytosis (27) lymphoid follicles aggregates in portal tracts (26) and bridging necrosis (16) were regular features. Focal necrosis, bile duct necrosis, cholestasis and ground glass cells were however seen much less often. On the other hand, in patients with CAH-B, fatty change (no patient), sinusoidal lymphocytosis (one patient) and lymphoid follicles/aggregates in portal tracts (one patient) were rare. Also, Kupffer cell hyperplasia (22 patients) was seen less commonly in patients with CAH-B as compared to CAH-C. Focal necrosis (34 patients), bile ductular proliferation (9 patients), cholestasis (17 patients) and ground glass cells (15 patients) were more prominent in CAH-B. CONCLUSION: Presence of certain histological features can help in distinguishing between CAH-C and CAH-B.

Adult↗

Peculiar histopathological features of giardiasis in distal duodenal biopsies.

Histological changes in 20 Giardia positive duodenal biopsies (Group A) were compared with 50, Giardia negative duodenal biopsies (Group B), taken during the same period. Stool examinations in Group B were negative for Giardia. Surface epithelium, villous and crypt architecture and cellular infiltrates were examined and compared between the groups. Atrophic changes in the villi were more common in Group A as compared to B(P < 0.0001). Intraepithelial neutrophil infiltration (P < 0.001), infiltration of the lamina propria with plasma cells (P < 0.5), and presence of eosinophils in the lamina propria (P < 0.001) were significant findings in group A. Some of the changes were related to the density of Giardia colonization e.g., the goblet cell depletion (P < 0.05) and the density of plasma cell infiltration in lamina propria (P < 0.01). Erosions and ulcerations were less commonly seen in group A. Thus we conclude that giardiasis manifests its peculiar features in the distal duodenal mucosa and a biopsy of this region is an important diagnostic tool for detection of this disease.

Adult↗

Disseminated bipolaris infection in an asthmatic patient: case report.

We present the case of a patient with a history of asthma who developed cough and hemoptysis that were unresponsive to antituberculous therapy. Chest roentgenography demonstrated right-sided collapse with consolidation and a pleural effusion. Bronchial biopsy revealed fungal hyphae, and cultures later yielded Bipolaris spicifera. In addition, weight loss and intractable hypotension in association with hyponatremia and elevated potassium levels suggested addisonian crisis, which was confirmed by measurement of serum ACTH and cortisol levels. Computed tomography of the abdomen revealed bilateral adrenal involvement. Tissue obtained on biopsy of the adrenal glands yielded B. spicifera. The patient responded to treatment with 2 g of iv amphotericin B; the adrenal masses and pneumonia resolved, and he remained well until last seen in July 1992. However, he requires replacement therapy with prednisone and fludrocortisone. On review of the available literature, we were unable to find a previously reported case.

Adrenal Gland Diseases↗

Microscopic colitis: a diagnosis to consider.

Microscopic colitis is a syndrome of chronic watery diarrhoea for which no cause can be identified other than the presence of diffuse, chronic inflammation in the lamina propria on colonic biopsy. Endoscopically and radiologically the colon appears normal. We studied case records of 215 patients presenting to our institution over a three year period with chronic diarrhoea. Nineteen patients were included in the study where two pathologists agreed on the presence of chronic inflammation on colonic biopsies. All patients had watery diarrhoea with urgency. Stool examination, laboratory indices, radiology of the large and small bowel and colonoscopy were normal in all patients. Patients did not respond to a variety of drugs. A significant improvement was noted in one patient given salazopyrin. In developing countries chronic diarrhoea is most often attributed to infection and treated with antibiotics. Microscopic colitis should be considered in the diagnosis of such patients.

Adult↗