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Biomedical subjects

A K Sharma

Publications and source records attributed to A K Sharma.

At least 145 records · Page 8Linked to original sources

Stroke like presentation of Creutzfeldt Jakob disease: an unusual variant.

Creutzfeldt-Jakob disease (CJD) is a degenerative process of the brain, induced by novel infectious agent or prion, and is usually characterized by a rapidly progressive dementia in association with myoclonus. However different patterns of disease presentation have been identified. The authors describe three probable cases of CJD. None of them had positive family history or any known modes of iatrogenic transmission. Interestingly, all the cases presented like a stroke. This is the first series of CJD cases from this part of country.

Adult↗

Lipid peroxide levels in chronic renal failure.

To determine presence of oxidant stress in chronic renal failure and to evaluate the efficacy of vitamin E in its amelioration, we studied 34 patients (Group I, age 32.4 +/- 11 years, M:F 3:1) and 10 healthy controls (Group II, age 27.4 +/- 5 years, M:F 4:1). The difference in baseline values of lipid peroxide (nmol/ml) was statistically significant (Group I 4.19 +/- 1.69, Group II 1.87 +/- 1.39, p = 0.004). Values of vitamin E (mg/l) were also significantly lower in Group I as compared to Group II (12.18 +/- 4.27 vs. 19.32 +/- 2.03, p = 0.003). Serum lipid peroxide values decreased significantly after supplementation with 400 mg/day of vitamin E for six weeks in Group I (4.19 +/- 1.69 to 3.21 +/- 1.13, p = 0.053) but not in Group II (1.87 +/- 1.39 to 1.03 +/- 0.87). Levels of vitamin E increased in both the groups (Group I: 12.18 +/- 4.27 to 16.01 +/- 5.13, Group II: 19.32 +/- 2.03 to 23.21 +/- 1.94, p < 0.005). No significant difference was observed in values of serum creatinine and urea before and after intervention.

Adult↗

A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome.

OBJECTIVES: This study was planned to assess the response of serratiopeptidase in patients with carpal tunnel syndrome (CTS). METHODS: Twenty patients with CTS were evaluated clinically. After baseline electrophysiological studies, these patients were given serratiopeptidase 10 mg twice daily with initial short course of nimesulide. Clinical and electrophysiological reassessment was done after 6 weeks. RESULTS: Mean age was 43.9 years with male to female ratio of 1:2.33. Sixty five percent cases showed significant clinical improvement which was supported by significant improvement in electrophysiological parameters. Recurrence was reported in four cases. No significant side effect was observed. CONCLUSIONS: Serratiopeptidase therapy may proved to be a useful alternative mode of conservative treatment. Larger study may be further helpful to establish the role of serratiopeptidase in CTS.

Adult↗

Role of members of the Wnt gene family in human hematopoiesis.

The hematopoietic system is derived from ventral mesoderm. A number of genes that are important in mesoderm development have been identified including members of the transforming growth factor-beta (TGF-beta) superfamily, the fibroblast growth factor (FGF) family, and the Wnt gene family. Because TGF-beta plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of the Wnt gene family, may play a role in hematopoiesis. Three members of the Wnt gene family (Wnt-5A, Wnt-2B, and Wnt-10B) were identified and cloned from human fetal bone stromal cells. These genes are expressed to varying levels in hematopoietic cell lines derived from T cells, B cells, myeloid cells, and erythroid cells; however, only Wnt-5A was expressed in CD34(+)Lin- primitive progenitor cells. The in vitro biological activity of these Wnt genes on CD34(+)Lin- hematopoietic progenitors was determined in a feeder cell coculture system and assayed by quantitating progenitor cell numbers, CD34(+) cell numbers, and numbers of differentiated cell types. The number of hematopoietic progenitor cells was markedly affected by exposure to stromal cell layers expressing Wnt genes with 10- to 20-fold higher numbers of mixed colony-forming units (CFU-MIX), 1.5- to 2. 6-fold higher numbers of CFU-granulocyte macrophage (CFU-GM), and greater than 10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared with the controls. Colony formation by cells expanded on the Wnt-expressing cocultures was similar for each of the three genes, indicating similar action on primitive progenitor cells; however, Wnt-10B showed differential activity on erythroid progenitors (BFU-E) compared with Wnt-5A and Wnt-2B. Cocultures containing Wnt-10B alone or in combination with all three Wnt genes had threefold to fourfold lower BFU-E colony numbers than the Wnt-5A- or Wnt-2B-expressing cocultures. The frequency of CD34(+) cells was higher in Wnt-expressing cocultures and cellular morphology indicated that coculture in the presence of Wnt genes resulted in higher numbers of less differentiated hematopoietic cells and fewer mature cells than controls. These data indicate that the gene products of the Wnt family function as hematopoietic growth factors, and that they may exhibit higher specificity for earlier progenitor cells.

Adult↗

Osteodysplastic primordial dwarfism type II with normal intellect but delayed central nervous system myelination.

We describe a 7-year-boy with severe prenatal and postnatal growth retardation, skeletal changes, normal intellect, and unusual facial appearance. The skeletal changes are suggestive of osteodysplastic primordial dwarfism type II (OPD II). He is the first patient of this kind from the Indian subcontinent and the 18th to be reported, based on a literature search (MEDLINE; 1982 to April 1997). He also represents the first case of OPD-II with normal intellect but delayed central nervous system myelination.

Brain↗

Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation.

Csk phosphorylates Src family protein tyrosine kinases on a tyrosine residue near their C-terminus and downregulates their activity. We previously observed that this regulation requires a stoichiometric ratio of Csk:Src in a time-independent manner. In this report we examined this unusual kinetic behavior and found it to be caused by Src autophosphorylation. First, pre-incubation of Src with ATP-Mg led to time-dependent autophosphorylation of Src, activation of its kinase activity and loss of its ability to be inactivated by Csk. However, the autophosphorylated Src can still be phosphorylated by Csk. The SH2 binding site for phospho-Tyr of this hyperactive and doubly phosphorylated form of Src is not accessible. Second, dephosphorylation of autophosphorylated Src by protein tyrosine phosphatase 1B allowed Src to be inactivated by Csk. Third, protein tyrosine phosphatase 1B preferentially dephosphorylates the Src autophosphorylation site and allows for Src regulation by Csk. Finally, Yes, another member of the Src family, was also only partially inactivated when a sub-stoichiometric amount of Csk was used. Mutation of the tyrosine autophosphorylation site of Yes to a phenylalanine resulted in a mutant Yes enzyme that can be fully inactivated by a sub-stoichiometric amount of Csk in a time-dependent manner. These results demonstrate that Csk phosphorylation inactivates Src and Yes only when they are not previously autophosphorylated and Src autophosphorylation can block the inactivation by Csk phosphorylation. This conclusion suggests a dynamic model for the regulation of the Src family protein tyrosine kinases, which is discussed in the context of previously reported observations on the regulation of Src family protein tyrosine kinases.

CSK Tyrosine-Protein Kinase↗

Modulation of lympho-proliferative responses of ovine peripheral blood mononuclear cells by Mycoplasma mycoides ssp. mycoides (LC type).

The present study was carried out to investigate the immunomodulating potential of M. mycoides ssp. mycoides (Mmm) (LC): a standard strain (Y-Goat, YG) and a local strain (M30) isolated from the pneumonic lung of a lamb during an outbreak of respiratory disease. The study was conducted in two parts to determine in vitro and in vivo aspects of the Mmm-induced modulation of cellular immune responses. In vitro experiments, using peripheral blood mononuclear cells (PBMC) of naive lambs, showed that live (Lv) or inactivated (Ina) antigens of Mmm (strains YG and M30) were not mitogenic for PBMC. Live antigens of both the strains, however, induced significant suppression of the PHA-driven lympho-proliferative (LP) responses. Suppression of LP responses by infectious Mmm (both strains) was restored in the presence of exogenous recombinant human interleukin-2 (rhIL-2). Following experimental inoculation of lambs with Mmm (YG), a significant reduction in non-specific LP responses was observed on days 6, 10 and 14 post inoculation (p.i.). There was a slow but significant rise in memory LP responses to Mmm strains (YG and M30). Specific subset depletion studies, using immunomagnetic cell separation (IMCS) technique, carried out on days 10 and 14 p.i., revealed that the OvCD4+ cell population was the main proliferating lymphocyte subset following an infection with Mmm (LC type).

Animals↗

A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae.

Factor H (fH), a key alternative complement pathway regulator, is a cofactor for factor I-mediated cleavage of C3b. fH consists of 20 short consensus repeat (SCR) domains. Sialic acid binding domains have previously been localized to fH SCRs 6-10 and 13. To examine fH binding on a sialylated microbial surface, we grew Neisseria gonorrhoeae in the presence of 5'-cytidinemonophospho-N-acetylneuraminic acid, which sialylates lipooligosaccharide and converts to serum resistance gonococci previously sensitive to nonimmune serum killing. fH domains necessary for binding sialylated gonococci were determined by incubating organisms with recombinant human fH (rH) and nine mutant rH molecules (deletions spanning the entire fH molecule). rH and all mutant rH molecules that contained SCRs 16-20 bound to the sialylated strain; no mutant molecule bound to serum-sensitive nonsialylated organisms. Sialic acid was demonstrated to be the fH target by flow cytometry that showed a fourfold increase in fH binding that was reversed by neuraminidase-mediated cleavage of sialic acid off gonococci. Functional specificity of fH was confirmed by decreased total C3 binding and almost complete conversion to iC3b on sialylated gonococci. Sialic acid can therefore bind fH uniquely through SCRs 16-20. This blocks complement pathway activation for N. gonorrhoeae at the level of C3.

Antigens, Bacterial↗

Surgery for nonalcoholic chronic pancreatitis.

There are few reports on operations in patients with nonalcoholic pancreatitis. Between 1985 and 1995 we operated on 58 such patients, 38 of whom were male and 20 female with a mean age of 35 years (range 5-72 years). The indications for operation were pain (n = 49), biliary obstruction (n = 12), duodenal obstruction (n = 10), portal hypertension (n = 11), cysts (n = 14), and pancreatic ascites (n = 3). Thirty-four patients with a dilated pancreatic duct underwent pancreaticojejunostomy; cysts were drained internally in eight, and biliary and duodenal obstruction was bypassed. Ten patients also underwent surgery for portal hypertension. Four (7%) patients died during the postoperative period. Of the remaining 54 patients, 48 (89%) were followed up for a median period of 63 months (range 6 months to 10 years). Six died: four of pancreatic cancer, one of cerebrovascular accident, and one of malnutrition. Of the 34 surviving patients operated for pain, 30 (88%) felt better, of whom 24 (71%) had complete relief of pain; 14 (41%) recorded a weight gain. Pancreatic decompression results in immediate and lasting pain relief in most patients with nonalcoholic chronic pancreatitis.

Adolescent↗

Systemic juvenile rheumatoid arthritis complicated by two different renal lesions.

Systemic-onset juvenile rheumatoid arthritis (JRA) is a complex disease which affects many organ systems. Associated renal lesions are unusual, with the possible exception of amyloidosis. We describe a girl with systemic-onset JRA who developed first membranous nephropathy and then, 3.5 years later, a severe crescentic glomerulonephritis. The membranous lesion followed therapy with intravenous immune globulin, and the possibility that this intervention caused the renal disease must be considered. It appears that both of these lesions should be added to the list of possible complications of systemic-onset JRA.

Antirheumatic Agents↗

Pyogenic liver abscess in children--South Indian experiences.

PURPOSE: Eighteen cases of pyogenic liver abscess (PLA) admitted at JIPMER hospital, South India, over a 6-year period were analyzed to document the clinical profile and to evaluate the management of PLA among children. METHODS: Records of all these patients were reviewed for presenting signs and symptoms, any associated condition, investigative results, management, and follow-up findings. RESULTS: The overall incidence of PLA was 78.9 per 100,000 pediatric (under 12 years) admissions. One patient had aplastic anemia and was on long-term steroid therapy, whereas another had measles in recent past. Moderate to severe malnutrition was present in five (27.8%) and ascariasis in seven (38.9%) children. Common presentations were fever (100%), abdominal pain (76.9%), and tender hepatomegaly (83.3%). Ultrasonography results were positive in all cases. Fourteen patients (77.8%) had solitary liver abscess, and four had multiple abscesses. Organism was isolated in 11 cases (63.6%), and Staphylococcus aureus was the commonest isolate (66.7%). All patients received antibiotics. Twelve cases were managed conservatively with antibiotics alone, of these only two (16.7%) required drainage later on. Percutaneous aspiration was also undertaken in four additional (22.2%) cases and open drainage in two (11.1%), at presentation. The overall mortality rate was 11.1%. Time taken for complete resolution ranged from 10 days to 40 days. CONCLUSIONS: Any child presenting with fever, abdominal pain, and tender hepatomegaly should be subjected to ultrasound scan for early detection of PLA. S aureus is the commonest causative agent. Enterobacteriaceae contribute significantly during infancy. A combination of cloxacillin and gentamicin or a third generation cephalosporine and gentamicin, especially in infants, is a satisfactory initial coverage. Therapeutic drainage is not a must in all cases of PLA. When required, percutaneous needle aspiration is safe and effective. Resolution and significant reduction in mortality has been made possible by early detection and optimum antibiotics therapy.

Child↗

Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat.

An investigation was made of the effect of Momordica charantia fruit juice on the distribution and number of alpha, beta and delta cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods. The results indicated that there was a significant (Student's t-test, P < 0.004) increase in the number of beta cells in M. charantia-treated animals when compared with untreated diabetics, however, their number was still significantly less than that obtained for normal rats. There was also a significant (P < 0.006) increase in the number of delta cells in STZ-diabetic rats compared to non-diabetic rats. This increase in the number of delta cells was not affected by M. charantia treatment. The number of alpha cells did not change significantly in M. charantia-treated rats when compared with untreated diabetic rats. Our results suggest that oral feeding of M. charantia fruit juice may have a role in the renewal of beta cells in STZ-diabetic rats or alternately may permit the recovery of partially destroyed beta cells.

Animals↗

Burn mortality in Chandigarh zone: 25 years autopsy experience from a tertiary care hospital of India.

An analysis of autopsy records of burn victims revealed that most burn deaths occurred in the age group 21-40 years (67 per cent) with female preponderance (61 per cent) in all age groups except in the extreme age groups. 62 per cent of burn cases originated in urban areas. The majority of subjects (99 per cent females and 76 per cent males) died as a result of flame burns. Kerosene was the most common factor (76 per cent) in burn deaths. 11 per cent of deaths were due to the stove bursting and 27 per cent of victims died due to leakage of oil from the stove. 39 per cent of subjects sustained burns when their clothes caught fire. Scalds (3.3 per cent), electrical (4.7 per cent) and chemical (2.3 per cent) burns were more commonly seen in males, mainly sustained at their working place. Accidental burns were observed in 80 per cent of subjects followed by suicidal (16.2 per cent) and homicidal burn assaults (4.1 per cent). Peak incidence of burns in females was observed between 5.01 a.m. and 11 a.m. (38 per cent), which was the time of least incidence in males (10.3 per cent). The opposite trend was seen between 11.01 p.m. and 5 a.m. Among males, burn deaths were more common (85 per cent) in those who were living alone, away from their families; whereas in women the incidence of burn deaths was higher (74 per cent) in those living with their families. The majority of deaths due to burns occurred within one week (77 per cent) of the incident. Septicaemia was the major cause of death (55 per cent).

Accidents↗