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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 325 records · Page 18Linked to original sources
PubMed1999

Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation.

Hepatic tumors often recur in the liver after surgical resection. Postoperative radiotherapy (RT) could improve survival, but curative RT may induce delayed life-threatening radiation-induced liver damage. Because RT inhibits liver regeneration, we hypothesized that unirradiated, transplanted hepatocytes would proliferate preferentially in a partially resected and irradiated liver, providing metabolic support. We subjected F344 rats to hepatic RT and partial hepatectomy with/without a single intrasplenic, syngeneic hepatocyte transplantation. Hepatocyte transplantation ameliorated radiation-induced liver damage and improved survival of rats receiving RT after partial hepatectomy. We further demonstrated that transplanted hepatocytes extensively repopulate and function in a heavily irradiated rat liver.

Animals↗
PubMed1999

Benign parotid hypertrophy on +HIV patients: limited late failures after external radiation.

PURPOSE: Although 8-10 Gy of external radiation therapy for +HIV associated parotid hypertrophy has achieved high response rates, the responses were transient with only 1/12 of patients retaining cosmetic control at median follow-up procedures of 9.5 months. Retreatment for failures after 8-10 Gy has also been unsatisfactory. Having shown that 24 Gy of external radiation therapy for benign parotid hypertrophy produced more durable cosmetic control than 8-10 Gy, we now report on longer follow-up periods on a group of patients receiving 24 Gy. MATERIALS AND METHODS: Twenty +HIV patients with clinical and radiographic evidence of lymphoepithelial lesions of the parotid were treated with 24 Gy of external radiation therapy using daily 1.5 Gy fractions; parallel opposed technique and 6 MV photons were used in 19 patients, and unilateral electron treatment was performed for one patient. RESULTS: With a mean follow-up period of 24 months, the cosmetic control appears durable. We have had no late failures past 24 months. Two patients have complained of modest xerostomia. There was no correlation with size of the cyst and eventual cosmetic result. CONCLUSIONS: Twenty-four Gy produces durable parotid control for HIV associated lymphoepithelial lesions of the parotid glands in +HIV patients. Failures after 2 years are uncommon and the side effects have been tolerable.

Female↗
PubMed1999

Engagement of Gab1 and Gab2 in erythropoietin signaling.

Several signaling cascades are activated during engagement of the erythropoietin receptor to mediate the biological effects of erythropoietin. The members of the insulin receptor substrate (IRS) family of proteins play a central role in signaling for various growth factor receptors and cytokines by acting as docking proteins for the SH2 domains of signaling elements, linking cytokine receptors to diverse downstream pathways. In the present study we provide evidence that the recently cloned IRS-related proteins, Gab1 and Gab2, of the Gab family of proteins, are rapidly phosphorylated on tyrosine during erythropoietin treatment of erythropoietin-responsive cells and provide docking sites for the engagement of the SHP2 phosphatase and the p85 subunit of the phosphatidylinositol 3'-kinase. Furthermore, our data show that Gab1 is the primary IRS-related protein activated by erythropoietin in primary erythroid progenitor cells. In studies to identify the erythropoietin receptor domains required for activation of Gab proteins, we found that tyrosines 425 and 367 in the cytoplasmic domain of the erythropoietin receptor are required for the phosphorylation of Gab2. Taken together, our data demonstrate that Gab proteins are engaged in erythropoietin signaling to mediate downstream activation of the SHP2 and phosphatidylinositol 3'-kinase pathways and possibly participate in the generation of the erythropoietin-induced mitogenic responses.

Adaptor Proteins, Signal Transducing↗
PubMed1999

The Strength of Long-Range Forces across Thin Liquid Films.

We present experimental results on the instability of thin liquid polydimethylsiloxane films intercalated between a solid substrate and a liquid surrounding medium. The instability is induced by long-range van der Waals forces across the film. From the characteristic wavelength of the instability and from the apparent contact angle of the equilibrium structures, we deduce an effective Hamaker constant (A132) about 2-3 orders of magnitude higher than what is expected from calculations based on the individual Hamaker constants. With air as the surrounding medium, we obtain the expected values. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes.

Differentiated pancreatic beta cells are unique in their ability to secrete insulin in response to a rise in plasma glucose. We have proposed that the unique constellation of genes they express may be lost in diabetes due to the deleterious effect of chronic hyperglycemia. To test this hypothesis, Sprague-Dawley rats were submitted to a 85-95% pancreatectomy or sham pancreatectomy. One week later, the animals developed mild to severe chronic hyperglycemia that was stable for the next 3 weeks, without significant alteration of plasma nonesterified fatty acid levels. Expression of many genes important for glucose-induced insulin release decreased progressively with increasing hyperglycemia, in parallel with a reduction of several islet transcription factors involved in beta cell development and differentiation. In contrast, genes barely expressed in sham islets (lactate dehydrogenase A and hexokinase I) were markedly increased, in parallel with an increase in the transcription factor c-Myc, a potent stimulator of cell growth. These abnormalities were accompanied by beta cell hypertrophy. Changes in gene expression were fully developed 2 weeks after pancreatectomy. Correction of blood glucose by phlorizin for the next 2 weeks normalized islet gene expression and beta cell volume without affecting plasma nonesterified fatty acid levels, strongly suggesting that hyperglycemia triggers these abnormalities. In conclusion, chronic hyperglycemia leads to beta cell hypertrophy and loss of beta cell differentiation that is correlated with changes in c-Myc and other key transcription factors. A similar change in beta cell differentiation could contribute to the profound derangement of insulin secretion in human diabetes.

Animals↗
PubMed1999

Expression of saliva-binding epitopes of the Porphyromonas gingivalis FimA protein on the surface of Streptococcus gordonii.

Porphyromonas gingivalis, a gram-negative oral anaerobic bacterium, has been implicated in the onset and development of periodontitis. The P. gingivalis fimbriae which mediate bacterial adherence to host oral sites and induce host inflammatory responses have been suggested as a potential antigen candidate. for vaccine development. This study was undertaken to generate Streptococcus gordonii vectors expressing the major subunit protein (FimA) of P. gingivalis fimbriae for testing as a potential live vaccine against periodontitis. We report here the expression of the C-terminal saliva-binding epitopes of P. gingivalis FimA on the surface of S. gordonii and demonstrate that domains containing free cysteine residues are poorly expressed on the surface of S. gordonii.

Bacterial Proteins↗
PubMed1999

Prevention of cytotoxic effects of arsenic by short-term dietary supplementation with selenium in mice in vivo.

Interaction between selenium and arsenic has been used to protect against the genotoxic effects of sodium arsenite through dietary intervention by an equivalent amount (1/10 LD50) of sodium selenite. The two salts were administered by gavaging to laboratory bred Swiss albino mice sequentially and in combination. Cytogenetic endpoints, including chromosomal aberrations (CA) and damaged cells (DC) were recorded 24 h after exposure from chromosome spreads in bone marrow cells. Administration of sodium selenite 1 h before sodium arsenite reduced the clastogenic effects of the latter significantly. The protection was less when the salts were given together and negative when arsenite was given before selenite. Histological changes were recorded. Such reduction of arsenic toxicity through dietary intervention by selenium is of significance in protecting against the widespread toxicity observed in human populations exposed to arsenic through drinking water from contaminated deep tubewells in West Bengal and Bangladesh.

Administration, Oral↗
PubMed1999

Dynamics and Morphology of Holes in Dewetting of Thin Films.

The formation and growth of holes in apolar nonslipping Newtonian thin films subjected to long-range Lifshitz-van der Waals forces are investigated based directly on numerical solutions of the thin-film equation. The nonphysical divergences of the hydrodynamic model and of the van der Waals force at the three-phase contact line are removed by inclusion of the short-range Born repulsion. Three distinct regimes of the hole growth after its appearance are identified: (1) a short, unsteady phase in which the dynamic contact angle and velocity change rapidly, followed by (2) a long, quasi-steady phase with slow logarithmic changes, and finally (3) a hindered phase in which rims of the neighboring holes overlap and lead to formation of equilibrium drops. The cross section of the rim surrounding a growing hole is noncircular and asymmetric, with higher slopes near the contact line. A slight depression is created ahead of the moving rim, but the regions of the film away from the rim remain undisturbed. For very viscous (e.g., polymeric) liquids displaying small contact angles, a nonlinear regime of hole growth (radius ~ timeq, with the exponent q approximately 0.7-0.9) is obtained for realistic time scales. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Crystal structure of a heparin- and integrin-binding segment of human fibronectin.

The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals the primary heparin-binding site, a clump of positively charged residues in FN13, and a putative minor site approximately 60 A away in FN14. The IDAPS motif implicated in integrin alpha4beta1 binding is at the FN13-14 junction, rendering the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this observation reveal that both arginines of the PRARI sequence are important for alpha4beta1 binding to FN12-14. The PRARI motif may represent a new class of integrin-binding sites. The spatial organization of the binding sites suggests that heparin and integrin may bind in concert.

Amino Acid Sequence↗
PubMed1999

Vascularized bone flaps versus nonvascularized bone grafts for mandibular reconstruction: an outcome analysis of primary bony union and endosseous implant success.

BACKGROUND: Functional restoration following resection or traumatic injury to the mandible depends on the reliability of the bony reconstruction to heal primarily and support endosseous implants. Although vascularized bone flaps (VBF) and nonvascularized bone grafts (NVBG) are both widely used to reconstruct the mandible, indications for each remain ill-defined. The purpose of this study was to compare bone graft/flap healing and success of implant placement in patients reconstructed with VBF versus NVBG. METHODS: Over the past 10 years, 75 consecutive mandibular reconstructions were performed (26 free bone grafts, 49 vascularized bone flaps). Etiology of the defect, history of irradiation, bone defect size, number of operations, graft/flap success, and dental implant success rates were determined and compared. Bone graft/flap success was defined as complete bony union. Implant success was defined as complete osseointegration. Mean follow-up was 3 years. RESULTS: Free flaps were used primarily for malignant disease (78%, 38/49). Bone grafts were used primarily for benign disease (88%, 23/26). History of prior irradiation: 11% (3/26) NVBG versus 45% (22/49) VBF. Length of bony defect (mean): 8.1 cm NVBG versus 9.4 cm VBF. Successful bony union, any size defect: 69% (18/26) NVBG versus 96% (47/49) VBF (p < .0005); lateral defects only: 75% (15/20) NVBG versus 100% (17/17) VBF (p < .05). Number of operations to achieve bony union (mean), any size defect: 2.3 NVBG versus 1.1 VBF (p < .001); lateral defects only: 1.9 NVBG versus 1.0 VBF (p < .005). Twenty-two patients (29%) had a total of 104 endosseous implants placed (NVBG: 8 patients, 33 implants; VBF: 14 patients, 71 implants). Immediate implants placed: 0/33 NVBG versus 54% (38/71) VBF. Overall implant success: 82% (27/33) NVBG versus 99% (70/71) VBF (p < .0001). Implant success in VBF patients with a history of RT: 100% (15/15). CONCLUSIONS: Despite the fact that patients reconstructed with VBFs were older, had larger defects, and were treated primarily for malignant disease and therefore had a higher incidence of irradiation to the affected mandible than in patients treated with NVBGs, the incidence of bony union was higher, requiring fewer operations to achieve union, and the implant success rate was significantly greater than for NVBG patients. Results were similar when considering lateral defects only. Based on these results, VBFs are indicated in most cases of mandibular reconstruction; NVBGs are effective for short bone defects (<5-6 cm), in nonirradiated tissue, and/or in patients determined to be too medically compromised to tolerate the additional operative time required for a free-flap reconstruction.

Adolescent↗
PubMed1999

Protection against cytotoxic effects of arsenic by dietary supplementation with crude extract of Emblica officinalis fruit.

Dietary administration of a crude aqueous extract of Emblica officinalis Gaertn. fruit reduced significantly the cytotoxic effects of sodium arsenite administered orally. The crude extract (685 mg/kg bw) was given daily by gavaging to age and sex matched laboratory bread Swiss albino mice for 7 and 14 days, followed by a single dose of sodium arsenite (2.5 mg/kg bw = 1/10 of LD(50)). The animals were killed after 24 h and chromosome preparations made following a schedule of colchicine-fixative-air drying-Giemsa. The endpoints screened were chromosomal aberrations and damaged cells. The crude extract reduced arsenic damage bringing the cells almost to the normal level.

Animals↗
PubMed1999

Idazoxan potentiates rather than antagonizes some of the cognitive effects of clonidine.

Several investigations have revealed substantial influences of pharmacological manipulation of central noradrenergic activity upon performance in cognitive tests sensitive to frontal lobe dysfunction. They suggest a significant role for the noradrenergic coeruleo-cortical projection in cognitive function but conflicting findings and the complex pharmacology of adrenoceptor agents make it difficult to be precise about underlying mechanisms. In order to clarify these we have compared the effects of an alpha1/alpha2-adrenoceptor agonist, clonidine, an alpha2-adrenoceptor antagonist, idazoxan, and these agents in combination. Three groups of healthy volunteers were used to investigate the effects of these noradrenergic manipulations upon performance of tasks from the CANTAB test battery known to be sensitive to frontal lobe dysfunction. Previously reported effects of clonidine upon sustained visual attention and upon session-to-session improvement were replicated. Furthermore, idazoxan inhibited the hypotensive effect of clonidine. Idazoxan had no overall effect on performance of any of the tests but did inhibit session-to-session improvement in performance of a planning task, attentional set shifting and sustained visual attention. Rather than leading to the anticipated mutual antagonism of effects, combining clonidine and idazoxan led to a wider and more striking range of cognitive impairments. These results are discussed alongside findings which support a role for imidazoline (I1) receptors in blood pressure control, where clonidine and idazoxan are antagonistic, and evidence of less potent antagonism at somato-dendritic alpha2-adrenoceptors in the locus coeruleus.

Adrenergic alpha-Agonists↗
PubMed1999

Covered exstrophy with incomplete duplication of the bladder.

A rare exstrophy variant in a 1(1/2)-year-old girl is reported. The child had a wide, scar-like lesion over the lower central abdomen with divarication of the recti and a spread symphysis pubis. The underlying bladder was divided into two unequal chambers by a complete sagittal septum with only the right chamber communicating with the single urethra and the left draining by a vesicocutaneous fistula. Both kidneys were normal. The clitoris was bifid and the anus anteriorly placed. Preliminary surgical management consisted of dissection of the bladder from its prevesical covering, excision of the sagittal septum, and cystocystostomy. Postoperatively, the child had normal urinary continence. The literature is reviewed with special reference to the various forms of duplicate exstrophy.

Abnormalities, Multiple↗
PubMed1999

Complete penoscrotal transposition and associated malformations.

Complete transposition of the penis and scrotum, or prepenile scrotum, is an uncommon congenital malformation. Concomitant genitourinary abnormalities, often life-threatening in nature, are frequently seen, and major malformations involving other organ systems may also be present. We report a newborn in whom complete penoscrotal transposition was accompanied by urethral atresia and radial dysgenesis.

Abnormalities, Multiple↗
PubMed1999

Survival and complications of cuffed catheters in children on chronic hemodialysis.

Central venous catheters are being increasingly used as hemodialysis vascular access. We evaluated catheter survival, outcome predictors, and complications in a total of 36 catheters used in 13 children and young adults undergoing chronic maintenance hemodialysis through catheter for a duration of 10.4+/-5.6 months. Reasons for catheter failure were: thrombosis 12 of 36 (33%), infection 6 of 36 (17%), and extrusion 2 of 36 (5.4%). Catheters were lost to infection and thrombosis at 1.1 and 2.2 episodes per 1,000 catheter days, respectively. Symptomatic infections, Gram-negative and polymicrobial sepsis increased the risk of catheter failure. Most of the thrombotic episodes occurred in patients with inherent thrombotic tendency. The survival of the 36 catheters was 62% at 1 year. The survival of 13 randomly chosen catheters, 1 from each patient, was 85% at 1 year. The time from insertion to first complication correlated significantly with the outcome (P<0.03). We conclude that central venous catheters are still associated with a high rate of failure and may be a regular access choice only in a selected patient population with no inherent thrombotic tendency and no other option available for long-term hemodialysis.

Adolescent↗
PubMed1999

A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis.

BACKGROUND & AIMS: The aim of this study was to determine if colchicine or methotrexate improves blood test results, symptoms, and/or liver histology in patients with primary biliary cirrhosis. METHODS: Patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase (ALP) levels were at least 2 times above normal and who were not yet candidates for liver transplantation received colchicine or methotrexate and were followed up for 2 years. RESULTS: In patients receiving colchicine (n = 43), mean pruritus score decreased from 1.63 to 1.12 (P = 0.04), ALP level from 494 to 355 U/L (P < 0.0001), and alanine aminotransferase (ALT) level from 79 to 61 U/L (P < 0.0001). In patients receiving methotrexate (n = 42), pruritus score decreased from 1.25 to 0.44 (P = 0.0001), ALP from 478 to 235 U/L (P < 0.0001), and ALT from 96 to 61 U/L (P = 0.0001). Methotrexate but not colchicine significantly improved liver histology (P = 0.005) and serum immunoglobulin G levels (P = 0.0002). Methotrexate improved most blood test results more than colchicine. Serum bilirubin levels increased slightly with each drug, and albumin levels decreased slightly. CONCLUSIONS: Both colchicine and methotrexate improved biochemical test results and symptoms in primary biliary cirrhosis, but the response to methotrexate was greater.

Alanine Transaminase↗
PubMed1999

Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance.

Growth of children during maintenance hemodialysis has been reported to be uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an intensive program of closely monitored energy and protein intake with dialysis urea clearances exceeding conventional recommendations. Twelve prepubertal or early pubertal children (aged 7 months to 14 years) were monitored for an average of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis. These children received an average of 90.6% and 155.9% of their recommended energy and protein nutritional intake, respectively. With a prescribed urea clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines. Over the course of dialysis treatment, the improvement in height SD score was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human growth hormone). Normal growth was achieved without overt obesity and was associated with normal pubertal growth spurt. These findings suggest that the combination of increased dialysis and adequate nutrition can promote normal growth in children treated with long-term hemodialysis.

Adolescent↗