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Biomedical subjects

N Shah

Publications and source records attributed to N Shah.

At least 181 records · Page 10Linked to original sources
PubMed1994

Arthroscopic management of postoperative arthrofibrosis of the knee joint: indication, technique, and results.

From October 1987 through March 1991, 58 patients with postoperative joint stiffness underwent arthroscopic fibroarthrolysis. Forty-six knees in 46 patients were followed. The indication for arthroscopic management was decreased range of motion after surgery. Eighty-seven percent had been treated by arthrotomy. Thirteen percent had been managed by arthroscopic surgery. The indication for primary surgery was a torn anterior cruciate ligament in 74%. The mean interval between arthroscopic fibroarthrolysis and follow-up was 22.1 months. The average age was 32.7 years. A modified Blauth and Jäger score was used for classification of fibroarthrosis: grade I (mild 17.4%), grade II (moderate 63%), grade III (severe 15.2%), and grade IV (bad 4.3%). The gain in range of motion was evaluated by the Cauchoix index: the results were excellent in 54.5%, good in 21.7%, and fair and poor in 23.8%. Pain was evaluated according to a modification of the Lysholm score: 80.4% of the patients experienced a reduction in pain. The sports activity level in the Tegner activity scale increased from 2.3 to 4.8. Patient satisfaction was excellent or good in 56.5% (n = 26), fair in 39.1% (n = 18), and poor in 4.3% (n = 2). On the basis of our retrospective study, we feel that arthroscopic fibroarthrolysis is of benefit to the patients with postoperative joint stiffness even after a prolonged period.

Adult↗
PubMed1994

Demonstration by two-color flow cytometry that tyrosine kinase activity is required for down-modulation of the oncogenic neu receptor.

Expression of rat oncogenic neu receptor, p185T-neu (a growth factor receptor with constitutive tyrosine kinase activity), causes cells to become transformed. Treatment with anti-neu receptor monoclonal antibodies reverts the transformed phenotype by down-modulation of p185T-neu. Monoclonal antibody treatment of cells expressing normal neu receptor, p185C-neu (which lacks constitutive tyrosine kinase activity), does not result in down-modulation of p185C-neu. To understand further the role the biochemical activity of p185T-neu plays in transformation and endocytosis, we created a series of mutations in p185T-neu. We found that fibroblasts expressing the tyrosine kinase-defective mutants cannot form foci in culture, colonies in soft agar, or tumors in immunocompromised mice. To follow the antibody-induced endocytosis of neu receptors expressed in these transfectants, we developed a novel two-color flow cytometric assay and confirmed receptor localization by electron microscopy. Cells were treated with mAb7.16.4 over time. After 4 hr of antibody treatment, less than 50% of full-length p185T-neu and of mutant T691 remained on the cell surface, whereas internal expression of the neu receptors within these cells initially increased and then decreased to the original internal receptor level. In contrast, the level of kinase-deficient mutated neu receptors remaining on the cell surface initially decreased by 35%, but, after 4 hr of antibody treatment, the cell surface expression level returned to approximately the original level. Concurrently, fluctuations in expression levels were seen internally over time as well. These cell lines were also treated with gold-conjugated mAb7.16.4. Using electron microscopy, we consistently found the gold particles within multivesicular bodies of cell lines expressing full-length or mutated neu receptor. These data strongly suggest that the fate of the neu receptor, once internalized, is directed by its tyrosine kinase activity. When the kinase activity of the neu receptor is disrupted, the receptor is internalized but recycled to the cell surface, whereas neu receptors which have constitutive kinase activity are internalized and presumably degraded when engaged with anti-neu receptor mAb. Understanding the regulation of receptor endocytosis, degradation, and recycling will contribute to the development of novel therapeutic protocols to combat human malignancies, particularly those associated with the overexpression of the human homologue of the neu receptor, c-erbB2.

Animals↗
PubMed1994

Effects of acidosis and hypoxia on the response of isolated ferret cardiac muscle to inotropic agents.

OBJECTIVE: The aim was to study the effects of acidosis and hypoxia on the response of cardiac muscle to inotropic agents which (a) act predominantly by increasing intracellular [Ca2+] (raising extracellular [Ca2+], noradrenaline, isoprenaline) and (b) act partly (phenylephrine) or predominantly (EMD 57033) by increasing myofilament calcium sensitivity. METHODS: The experiments were performed on isometrically contracting, isolated ferret papillary muscles (n = 45). For each intervention dose-response curves were performed in control solution (pH 7.35), in hypercapnic acidosis (pH 6.85), and in hypoxia (produced by replacing O2 with N2 in the superfusing solution). In some experiments, the photoprotein aequorin was microinjected into superficial cells of the preparation in order to measure intracellular [Ca2+] as well as force. RESULTS: The results were broadly similar for both classes of inotropic agent. Acidosis caused a shift of the pCa-tension curve to the right (desensitisation of the myofilaments to calcium), but had no significant effect on maximum force. A sufficient inotropic stimulus supplied by either class of inotropic agent could completely reverse the negative inotropic effects of acidosis. The main difference between the two inotropic mechanisms was that the enhanced force produced by calcium sensitisers was associated with a reduction in calcium transient amplitude, while the other inotropes increased the amplitude. The main effect of hypoxia was to decrease maximum force. All the inotropes tested were relatively ineffective in reversing the force depression due to hypoxia. CONCLUSIONS: The negative inotropic effects of acidosis can be reversed by a sufficiently large inotropic stimulus. Since calcium transient amplitude is already increased in acidosis, the results suggest that calcium sensitisers are likely to be less arrhythmogenic in this situation. The relative ineffectiveness of the inotropes in hypoxia indicates that the main mechanisms causing reduced force in this situation lie downstream of the mechanisms of action of the inotropic agents tested.

Acidosis↗
PubMed1994

Risk factors for severe pneumonia in children in south Kerala: a hospital-based case-control study.

A case-control study was undertaken in 400 children under 5 years of age in South Kerala, India, to identify the risk factors for severe pneumonia. Cases were in-patients with severe pneumonia as ascertained by WHO criteria, while controls were out-patients with non-severe acute respiratory infections. Only four from many probable risk factors emerged as being significant, viz. young age, immunization, delayed weaning, and sharing of bedroom. The significant factors on univariate analysis were parental education, environmental pollution, discontinuation of breastfeeding in young infants, malnutrition, hypovitaminosis A, low birth weight, previous history of severe ARI, unresponsiveness to earlier treatment, and use of non-allopathic medicine. Correction of these factors can probably reduce mortality due to ARI.

Acute Disease↗
PubMed1994

Extraoral tooth eruption and transposition of teeth following trauma.

A six-year-old boy presented with extraoral eruption of a mandibular permanent canine and a loosely attached lateral incisor in the labial vestibule, 3 months following trauma to the chin. The trauma not only caused displacement of the permanent tooth buds, but also resulted in transposition of the lateral incisor and canine with subsequent ectopic eruption. The case is presented to demonstrate one of the infrequent complications of trauma involving the unerupted tooth buds of permanent teeth and its unusual clinical presentation.

Child↗
PubMed1994

A potential role for nitric oxide in myocardial stunning.

Nitric oxide (NO) production by the human heart has been demonstrated in patients undergoing cardiac surgery. Similar to what has been described in other species, a basal production of NO by the human heart is seen (126 +/- 42 pmol/min per gram). Following reperfusion, at the end of the procedure, the level of NO production increases significantly reaching concentrations of 1430 +/- 330 pmol/min per gram. Increased activity for the enzyme NO synthase (NOS) (8.0 +/- 1.2 pmol/mg prebypass vs 26.4 +/- 4.8 pmol/mg postbypass) coincides with changes in NO production and occurs at a time when myocardial stunning is clinically detectable. The significance of these findings is discussed and suggest a role for NO in the pathophysiology of myocardial stunning.

Amino Acid Oxidoreductases↗
PubMed1994

The role of the sarcoplasmic reticulum in the response of isolated ferret cardiac muscle to beta-adrenergic stimulation.

beta-Adrenergic stimulation of cardiac muscle leads to an increase in the strength of contraction and an abbreviation of its time course. We have investigated the role of the sarcoplasmic reticulum in these changes by monitoring force and cytoplasmic [Ca2+] in ferret papillary muscles, and the Ca2+ current in isolated ferret myocytes, during the application of isoprenaline in the absence and presence of the sarcoplasmic reticulum inhibitor ryanodine (10(-6) mol/l). Isoprenaline (10(-6) mol/l) led to a marked increase in the size of both the twitch and Ca2+ transient, and a decrease in their duration. In the presence of ryanodine, application of isoprenaline had no significant effect on either the size or the time course of the twitch. However, the increase in the Ca2+ current in response to isoprenaline was the same in the absence and presence of ryanodine. Increasing bathing [Ca2+] led to a prolongation of both the twitch and the Ca2+ transient. In the presence of ryanodine, increasing bathing [Ca2+] still increased the size, but decreased the duration, of the twitch. These data provide direct evidence that both the inotropic and lusitropic effects of isoprenaline are mediated via the sarcoplasmic reticulum.

Animals↗
PubMed1994

Hepatic venular stenosis after orthotopic liver transplantation.

Fibrous stenosis of hepatic venules and other features of venous outflow obstruction, including zone 3 congestion and hemorrhage, are sometimes seen after orthotopic liver transplantation. similar changes associated with endothelial damage have recently been ascribed to azathioprine toxicity and may be forerunners of chronic rejection. Other potential causative agents such as viral hepatitis have yet to be considered. We reviewed 49 liver biopsy specimens from 21 consecutive patients after orthotopic liver transplantation, in whom full data including further follow-up biopsy samples were available. Hepatic venous stenosis was identified in seven patients who had received azathioprine and two additional patients in whom this change could not be ascribed to azathioprine. Stenosis was always associated with zone 3 hemorrhage and congestion and was first noted between 5 and 30 days after transplantation in all but two cases; in these two patients they were first noted after 72 and 133 days. Cellular rejection, including endotheliitis involving terminal hepatic venules, was found in five of the seven patients who had received azathioprine. Chronic (ductopenic) rejection was not seen during a follow-up period of between 97 and 540 days. In three of the nine patients with hepatic venular stenosis, zone 3 changes persisted, and in two of these azathioprine could not be held responsible. Of the 12 patients without hepatic venular stenosis, 10 had received azathioprine. Two of these 12 patients had peliosis-like foci but no other vascular abnormalities. Both also had moderate cellular rejection. Hepatic venular stenosis was found in 43% of patients after liver transplantation; this was usually associated with azathioprine administration and concomitant cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Functional effect of IL-7-enhanced CD19 expression on human B cell precursors.

We have previously demonstrated that IL-7 can sustain the growth of normal human B cell precursors (BCP) for several weeks on bone marrow-derived stromal cells. Flow cytometric analysis of BCP recovered from IL-7 supplemented cultures revealed two- to threefold higher levels of cell surface CD19, compared with BCP maintained without IL-7. Short term culture of BCP showed that IL-7 enhancement of CD19 was dose-dependent, with increases detected by day 1 and plateauing by days 3 to 4. IL-7 increased cell-surface CD19 on small lymphoid cells, and to a greater degree on lymphoblasts, whereas cell-surface CD10 was unchanged. The CD34+/CD19+ pro-B cell population showed a greater increase in cell-surface CD19 compared with pre-B and immature B cells. IL-1, IL-3, IL-4, IL-6, and stem-cell factor had no effect on CD19. The potential functional significance of IL-7-enhanced cell-surface CD19 was examined using a F(ab')2 fragment of anti-CD19. This reagent had no effect on [3H]TdR incorporation in BCP cultured in the absence or presence of IL-7 for 5 days, but homotypic adhesion of BCP was induced at a concentration as low as 1.0 ng/ml F(ab')2 anti-CD19. IL-7 enhanced the F(ab')2 anti-CD19 induced homotypic adhesion of BCP in a dose-dependent manner. Blocking antibody studies indicated that members of the beta 1 or beta 2 integrin families did not mediate anti-CD19-induced homotypic adhesion, even though the adhesion was completely ablated by 10 mM EDTA. The pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed comparable levels of cell-surface CD19, and exhibited comparable increases after IL-7 stimulation. However, their homotypic adhesion responses to anti-CD19 were different. NALM-6 cells exhibited a strong homotypic adhesion response to anti-CD19 that was EDTA-resistant, and beta 1/beta 2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA-sensitive and beta 1/beta 2 integrin independent. These collective results indicate that IL-7 not only acts as a growth factor for human BCP, but also regulates signal transduction through cell-surface CD19.

Antigens, CD↗
PubMed1993

Brefeldin A reversibly inhibits secretion in Saccharomyces cerevisiae.

Brefeldin A has proven to be a useful pharmacologic tool, which, when added to mammalian cells, results in a block in secretion as well as the structural disruption of specific intracellular organelles. In spite of our understanding of some of the biochemistry underlying the action of brefeldin A, the most proximal molecular target(s) of the drug remain elusive. In attempting to address this problem, a genetic approach will undoubtedly prove useful and complementary to the biochemical identification of such a site(s). As a result of the relatively resistant nature of wild-type Saccharomyces cerevisiae to brefeldin A, an approach utilizing yeast genetics has not been possible. We report the selective sensitivity of three drug-sensitive strains of S. cerevisiae (ise-1, ISE-2, and erg6) with enhanced membrane permeability allowing uptake of brefeldin A. Upon addition of the drug, growth is dramatically inhibited and invertase secretion is rapidly, specifically, and reversibly blocked at the level of the endoplasmic reticulum. In addition, only structural analogues of brefeldin A effective in mammalian cells are active in these yeast strains.

Antifungal Agents↗
PubMed1993

Genistein inhibits insulin-stimulated glucose transport and decreases immunocytochemical labeling of GLUT4 carboxyl-terminus without affecting translocation of GLUT4 in isolated rat adipocytes: additional evidence of GLUT4 activation by insulin.

A recent study from this laboratory (Abler et al., J. Biol. Chem. 267, 18172-18179, 1992) showed genistein blocked insulin-stimulated glucose oxidation without affecting receptor autophosphorylation or tyrosine kinase activity. The mechanism by which genistein inhibited insulin-stimulated glucose metabolism was investigated in the present study. Insulin caused a approximately 12-fold increase in 3-O-methyl-D-glucose (3OMG) uptake compared to that of control cells. Basal and insulin-stimulated 3OMG transport was inhibited 40-60% by genistein in a concentration-dependent manner (10-100 micrograms/ml). Genistein had no effect on insulin-stimulated GLUT4 translocation from low density microsomes to plasma membranes as determined by Western blotting. These results suggested that genistein inhibited glucose transport in adipocytes by decreasing the intrinsic activity, rather than the number, of the plasma membrane-associated glucose transporters. We also previously reported that insulin treatment of adipocytes resulted in the immunocytochemically visualized unmasking of the carboxyl-terminus of plasma membrane-associated GLUT4 and suggested the unmasking might be related to an insulin-induced increase in the intrinsic activity of the glucose transporter (Smith et al., Proc. Natl. Acad. Sci. USA 88, 6893-6897, 1991). In the present study, genistein decreased immunocytochemical labeling of plasma membrane-associated GLUT4 by approximately 50% in control and insulin-treated adipocytes by carboxyl-terminus antibodies but had no effect on labeling observed in an amino-terminus antibody. Since genistein did not affect the number of plasma membrane-associated GLUT4 transporters, this result supports the hypothesis that conformational changes in the glucose transporter, reflected by the ability of anti-carboxyl-terminus antibodies to bind to the transporter, may be an indication of the intrinsic activity of the plasma membrane-associated transporter. We therefore conclude that conformational changes in and activation of glucose transporters, in addition to insulin-stimulated GLUT4 translocation, play an important role in insulin-regulated glucose transport in adipocytes.

3-O-Methylglucose↗
PubMed1993

Management of patent saphenous vein grafts during reoperative coronary artery bypass grafting.

A patient was referred for coronary artery bypass reoperation. After a left internal mammary artery was grafted to the left anterior descending coronary artery, the diseased but patent old saphenous vein graft was ligated. This resulted in severe myocardial failure, which was corrected only after restoration of flow through the old vein graft. We suggest the decision to ligate or replace an old vein graft should be individualized to avoid the risk of myocardial ischemia.

Cardiac Output, Low↗
PubMed1993

Survival from localized breast cancer. Variability across trials and registries.

Age-specific (< 50, 50-69 years) 10-year survival proportions in four European trials for node-negative, Stage I and II breast cancer patients differ significantly. These patients, identified as having the same stage as localized-breast cancer patients in the End Results Registry of the U.S. National Cancer Institute, had pooled survival proportions for the two age groups (0.713, 0.579) close to those of the registry (0.713, 0.607).

Adult↗
PubMed1993

A novel thiadiazinone derivative fully reverses acidosis-induced depression of force in cardiac muscle by a calcium-sensitizing effect.

1. We examined the effects of the novel thiadiazinone derivative EMD 57033 on developed force and intracellular [Ca2+] in cardiac muscle during control conditions (pH 7.35) and in acidosis (pH 6.8). 2. In the control solution, application of EMD 57033 fully activated the muscle. Acidosis reduced developed force to 18% of maximum, but application of EMD 57033 in acid solution was able to fully reverse this effect and restore force to its previous maximum. 3. During the positive inotropic effect in acidosis, the Ca2+ transients declined to 62% of their initial amplitude, whereas force increased to 557%. 4. These observations suggest that EMD 57033 increases force by a Ca(2+)-sensitizing action in intact cardiac muscle. Since EMD 57033 is able to fully reverse the effects of acidosis on force without increasing the amplitude of the Ca2+ transients, this compound and others with similar mechanisms of action appear to hold particular promise for heart failure therapy.

Acidosis↗
PubMed1993

Mouse preimplantation embryos exhibit receptor-mediated binding and transcytosis of maternal insulin-like growth factor I.

High-resolution microscopy in conjunction with colloidal gold-labeled insulin-like growth factor I (IGF-I) has been used to provide evidence that the IGF-I receptor is first detected in 8-cell-stage mouse embryos, confirming the results of previous reverse transcriptase polymerase chain reaction (RT-PCR) studies. Specificity for the IGF-I receptor was demonstrated by displacement with unlabeled IGF-I and dual-labeling experiments with colloidal gold-labeled or unlabeled insulin. Labeled IGF-I ligand is internalized by means of receptor-mediated endocytosis following its concentration in coated pits, and it can be visualized within cytoplasmic organelles. Immunocytochemical analyses at the blastocyst stage, using gold-labeled antibodies to the receptor, confirmed the expression of IGF-I receptors on all cells of the embryo. Similar studies with antibodies directed against the ligand demonstrated that IGF-I internalized by the embryo in vivo is maternally derived. Approximately 40% of blastocysts showed apical plasma membrane binding of gold-labeled ligand ("responders"), while approximately 60% did not demonstrate binding ("nonresponders"); however, both classes of embryo expressed receptors on basolateral membranes of trophectoderm cells and on the surface of inner masses. Functional studies show that incubating embryos in physiological levels of IGF-I (40 ng/ml) results in increased numbers of cells in the inner cell mass (p < 0.05), but not the trophectoderm, as compared to controls.

Animals↗