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Biomedical subjects

D K Sharma

Publications and source records attributed to D K Sharma.

At least 37 records · Page 2Linked to original sources
PubMed1999

Differences between the trypanosomal and human GlcNAc-PI de-N-acetylases of glycosylphosphatidylinositol membrane anchor biosynthesis.

De-N-acetylation of N-acetylglucosaminyl-phosphatidylino-sitol (GlcNAc-PI) is the second step of glycosylphosphatidylino-sitol (GPI) membrane anchor biosynthesis in eukaryotes. This step is a prerequisite for the subsequent processing of glucosaminyl-phosphatidylinositol (GlcN-PI) that leads to mature GPI membrane anchor precursors, which are transferred to certain proteins in the endoplasmic reticulum. In this article, we used a direct de-N-acetylase assay, based on the release of [14C]acetate from synthetic GlcN[14C]Ac-PI and analogues thereof, and an indirect assay, based on the mannosylation of GlcNAc-PI analogues, to study the substrate specificities of the GlcNAc-PI de-N-acetylase activities of African trypanosomes and human (HeLa) cells. The HeLa enzyme was found to be more fastidious than the trypanosomal enzyme such that, unlike the trypanosomal enzyme, it was unable to act on a GlcNAc-PI analogue containing 2-O-octyl-d- myo -inositol or on the GlcNAc-PI diastereoisomer containing l- myo -inositol (GlcNAc-P(l)I). These results suggest thatselective inhibition of the trypanosomal de-N-acetylase may be possible and that this enzyme should be considered as a possible therapeutic target. The lack of strict stereospecificity of the trypanosomal de-N-acetylase for the d- myo -inositol component was also seen for the trypanosomal GPI alpha-manno-syltransferases when GlcNAc-P(l)I was added to the trypanosome cell-free system, but not when GlcN-P(l)I was used. In an attempt to rationalize these data, we modeled the structure and dynamics of d-GlcNAcalpha1-6d- myo -inositol-1-HPO4-( sn )-3-glycerol and its diastereoisomer d-GlcNAcalpha1-6l- myo -inositol-1-HPO4-( sn )-3-glycerol. These studies indicate that the latter compound visits two energy minima, one of which resembles the low-energy conformer of former compound. Thus, it is conceivable that the trypanosomal de-N-acetylase acts on GlcNAc-P(l)I when it occupies a GlcNAc-PI-likeconformation and that GlcN-P(l)I emerging from the de-N-acetylase may be channeled to the alpha-mannosyltransferases in this conformation.

Amidohydrolases↗
PubMed1998

Experience in adult population in dengue outbreak in Delhi.

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.

Adolescent↗
PubMed1997

Parasite and mammalian GPI biosynthetic pathways can be distinguished using synthetic substrate analogues.

Glycosylphosphatidylinositol (GPI) structures are attached to many cell surface glycoproteins in lower and higher eukaryotes. GPI structures are particularly abundant in trypanosomatid parasites where they can be found attached to complex phosphosaccharides, as well as to glycoproteins, and as mature surface glycolipids. The high density of GPI structures at all life-cycle stages of African trypanosomes and Leishmania suggests that the GPI biosynthetic pathway might be a reasonable target for the development of anti-parasite drugs. In this paper we show that synthetic analogues of early GPI intermediates having the 2-hydroxyl group of the D-myo-inositol residue methylated are recognized and mannosylated by the GPI biosynthetic pathways of Trypanosoma brucei and Leishmania major but not by that of human (HeLa) cells. These findings suggest that the discovery and development of specific inhibitors of parasite GPI biosynthesis are attainable goals. Moreover, they demonstrate that inositol acylation is required for mannosylation in the HeLa cell GPI biosynthetic pathway, whereas it is required for ethanolamine phosphate addition in the T.brucei GPI biosynthetic pathway.

Animals↗
PubMed1997

Substrate specificity of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol membrane anchor biosynthesis in African trypanosomes and human cells.

De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol (GlcNAc-PI) is the second step of glycosylphosphatidylinositol (GPI) membrane anchor biosynthesis in eukaryotes. This step is a prerequisite for the subsequent mannosylation of glucosaminyl-phosphatidylinositol (GlcN-PI) which leads to mature GPI membrane anchor precursors, which are transferred to certain proteins in the endoplasmic reticulum. The substrate specificities of the GlcNAc-PI de-N-acetylase activities of African trypanosomes and human (HeLa) cells were studied with respect to the N-acyl groups (R) that could be removed from a series of GlcNR-PI substrates, where R=acetyl (Ac), propionyl (Pr), butyryl (Bu), isobutyryl (iBu), pentanoyl (Pen) or hexanoyl (Hex). The data show that the trypanosomal and HeLa enzymes had similar specificities and that the turnover of GlcNR-PIs by the trypanosomal enzyme was in the order GlcNAc-PI>GlcNPr-PI>>GlcNBu - PI approximately GlcNiBu - PI approximately GlcNPen - PI>>GlcNHex - PI. The trypanosome and HeLa de-N-acetylases were unable to de-N-acetylate mannosylated GlcNAc-PI intermediates, which explains why de-N-acetylation must precede mannosylation in the GPI biosynthetic pathway.

Amidohydrolases↗
PubMed1997

Early steps in glycosylphosphatidylinositol biosynthesis in Leishmania major.

A cell-free system based on washed Leishmania major membranes was labelled with GDP-[3H]Man in the presence of synthetic glucosaminyl-phosphatidylinositol (GlcN-PI) and N-acetylglucosaminyl-phosphatidylinositol (GlcNAc-PI). In both cases, the major radiolabelled products were Man alpha 1-4GlcN alpha 1-6myo-inositol1-HPO4- (sn-1, 2-dipalmitoylglycerol) and Man alpha 1-4GlcN alpha 1-6myo-inositol1-HPO4- (sn-1-palmitoyl-2-lyso-glycerol), to which an additional d-mannose residue was added when a chase with an excess of GDP-Man was performed. The L. major cell-free system can therefore be used to observe the actions of four enzymes, namely GlcNAc-PI de-N-acetylase, Dol-P-Man-GlcN-PI alpha 1-4-mannosyltransferase, a phospholipase A2-like activity and a second alpha-mannosyltransferase activity. The substrate specificities of the first two of these enzymes were studied using a series of substrate analogues. GlcNAc-PI de-N-acetylase was tested against a variety of N-acylated GlcN-PI substrates and was able to cleave N-acetyl and N-propyl groups but not larger groups such as N-butyl, N-isobutyl, N-pentyl and N-hexyl. The Dol-P-Man-GlcN-PI alpha1-4-mannosyltransferase activity required the amino group of the glucosamine residue and the d-configuration of the myo-inositol residue of the GlcN-PI acceptor substrate.

Amidohydrolases↗
PubMed1995

Incorporation of diaphyseal sequestra in chronic haematogenous osteomyelitis.

Seventeen patients with haematogenous osteomyelitis and long diaphyseal sequestra are reported. Treatment was incision and drainage with antibiotics for at least 6 to 8 weeks, the limb being protected in plaster for a long time. The sequestra became incorporated in every case. Sequestrectomy should only be undertaken when successive radiographs show no reduction in size of the sequestrum and an increase in the amount of the involucrum.

Adolescent↗
PubMed1995

An outbreak of bacillary haemoglobinuria in sheep in India.

An outbreak of bacillary haemoglobinuria was recorded in 60 out of 110 sheep in Ludhiana, Punjab, India. The condition was clinically characterised by fever, haemoglobinuria, constipation, weakness of hind quarters followed by recumbency, respiratory distress and death in 16 sheep. Haematological studies revealed moderate to severe degrees of anaemia associated with leucocytosis. Plasma gamma-glutamyl transferase, alkaline phosphatase and creatinine phosphokinase activities were significantly higher in haemoglobinuric sheep. Babesiosis and copper poisoning were ruled out on stained blood film examination and from blood mineral profiles, respectively. Post-mortem examination of affected sheep revealed no gross changes. Pure cultures of Clostridium haemolyticum isolated from heart blood, liver, kidney and spleen of freshly killed sheep confirmed the disease. Parenteral administration of procaine penicillin was effective in the treatment of affected sheep.

Animals↗
PubMed1995

Giant staghorn ureteral calculus.

We are reporting a young female who presented with a history of right flank pain and urinary tract infection off and on. On investigation, she was found to have a giant fork-shaped ureteral calculus in a bifid ureter. Since her ipsilateral renal unit was nonfunctioning, nephroureterectomy was performed. Such a case of giant staghorn ureteral calculus in a bifid ureter has never been reported in the world literature.

Adult↗
PubMed1994

Psychiatric knowledge & orientation of non-psychiatrist doctors.

52 Non-psychiatrist doctors were evaluated in order to know their psychiatric orientation with the help of clinical case history along with questionnaire. Only one doctor subject could give all the diagnosis correctly on the basis of clinical stories; on the other hand all the doctors gave the diagnosis of epilepsy correctly. This reflects basic lack of understanding of psychiatry resulting from poor theoretical teaching and exposure at undergraduate level. Other characteristics of the sample and finding are discussed here.

Adult↗
PubMed1994

Socio-demographic pattern of drug and alcohol dependents.

The widespread abuse of drugs and Alcohol has become a human tragedy. Each year the abuse of Alcohol and Illicit drugs exact an enormous toll in deaths, decline in productivity, more crime and accidents and also increased expenditure in rehabilitation. The situation is likely to worsen and even may get out of hand if adequate measure are not taken to clearly identify the vulnerable group so as to provide them proper and maximal help. The present paper proposes to examine the sociodemographic correlates viz. Age, Sex group. Educational Status, Income Group, Marital Status and also possible causes of drug abuse of these patients. For this purpose patients of Dr. Vidya Sagar Hospital's drug-de-addition cum rehabilitation unit were statistically analysed. The findings have been discussed.

Adolescent↗
PubMed1994

Virulence & pathogenicity of Yersinia enterocolitica under different test systems.

Eight clinical isolates of Y. enterocolitica were tested for various pathogenicity and virulence markers. Seven of the eight strains gave positive results for Congo red magnesium oxalate (CRMOX) agar test and autoagglutination test at 37 degrees C. Seven strains bound crystal violet (CV) completely at 37 degrees C but not at 25 degrees C. One strain (Y1) bound CV partially. None of the strains showed pyrazinamidase activity indicating these strains to be virulent. Cells of all but one strains were aggregated by 1.8 M and 3.2M concentration of ammonium sulphate. A good correlation between these tests and virulence was observed.

Microbiological Techniques↗
PubMed1992

Rapid identification of viable bacterial spores using a fluorescence method.

A method has been devised to differentiate viable and nonviable bacterial spores. "Germination-like" changes are initiated in spores with performic acid and lysozyme. The germinated spores are stained with aqueous acridine orange, a fluorescent dye. Nonviable spores fluoresce lemon-green and viable spores orange-red. It is proposed that with the use of a membrane filter resistant to performic acid and lysozyme, the method may be used for spore enumeration in foods in about 4 hr compared to conventional plating methods, which usually require up to 72 hr.

Bacillus cereus↗
PubMed1992

Principles and practice of medical audit (medical care evaluation).

1. Medical audit is a philosophy in the field of medical science which has reached to an advanced stage of practice in Western World, but yet to reach and percolate into Indian medical community. 2. Of late, community is getting increasingly aware of its health rights, gradually community participation in health matters including quantum and quality of case, has started increasing. Thus community leaders have started demanding for quality of medical care and accountability of those, responsible for delivery of medical care at various levels. 3. Medical audit or Evaluation of medical care is an answer to ensure the quality of care. But there are misgivings and distrust about medical audit due to its terminology. 4. There is need to education the medical, nursing and paramedical staff regarding medical audit and its sole purpose of self education and improvement of patient care activity. The present paper spells out fundamentals of medical audit, its scope and limitations.

Community-Institutional Relations↗