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Biomedical subjects

R Prasad

Publications and source records attributed to R Prasad.

At least 199 records · Page 11Linked to original sources
PubMed1993

A clinico-hematological profile of hemolytic-uremic syndrome.

Hemolytic uremic syndrome (HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and uremia. It is an important cause of acute renal failure (ARF) in children all over the world. The present study was carried out to assess the incidence, clinical presentation, hematological and biochemical profile of children presenting with HUS from 1987 to 1990. Out of the 100 cases who presented with ARF 22 had HUS. A majority of these children were males below 1 year of age, and had a prodromal phase of mainly gastrointestinal manifestations lasting for about a week. Anemia was a constant feature followed by bleeding diathesis, mainly melena and purpura. Neurological manifestations included altered sensorium, irritability, coma, hypertensive encephalopathy and convulsions. Renal problems mainly included oliguria, hypertension, hematuria and edema. Investigations revealed thrombocytopenia and microangiopathic hemolytic anemia in all cases. Evidence of disseminated intravascular coagulation (DIC) was observed in 3 cases as decreased fibrinogen levels, increased fibrinogen degradation products and deranged clotting studies. Blood biochemistry revealed azotemia in all cases, hyponatremia in 5 cases, hypernatremia in 3 cases and hyperkalemia in 12 cases. Stool culture showed the presence of Shigella in 8, E. coli in 6 and Klebsiella in 4 cases. Out of 22 cases of HUS, 15 were treated conservatively; of these 2 died. Both of these deaths were due to DIC 7 children were put on peritoneal dialysis; only 1 child died in this group. Factors affecting the outcome were duration of oliguria, levels of blood urea and presence of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

Pulmonary sarcoidosis and chronic cutaneous atypical mycobacter ulcer.

This interesting case of pulmonary sarcoidosis and Mycobacterium ulcerans ulcers raises many issues: 1. Our paucity of knowledge of deficient immune status in individuals; the multifarious presentation as recognisable ill health, its early detection, treatment and its prevention. In this present case the management of the immune status of the patient has not yet been fully addressed. The relationship between his pulmonary sarcoidosis as being an 'immune' response to the Mycobacterium ulcerans remains speculative; for example, did this patient have the Mycobacterium infection before he was diagnosed as having sarcoidosis? There is no evidence of this. With the history of repeated cellulitis associated with his business trips to Asia and the Middle East, the likelihood seems speculative--as would infection with Mycobacterium ulcerans contracted from swimming in pools and rivers. 2. As sarcoidosis is thought to have an association with Mycobacterium tuberculosis it is tempting to suggest that as, in this case, the Mycobacterium ulcerans is the caus-ative agent for his sarcoidosis. Additionally, should we be looking for sarcoidosis in every other case of Mycobacterium ulcerans infection? Other cases of Mycobacterium ulcerans could be assessed. 3. It is suggested that corticosteroids do pave the way for opportunistic infection as in this case. How often does this occur in 'usual practice' where patients are exposed to corticosteroids? Further comments are invited. 4. The question of sterility techniques in the home (daily dressings), the surgery, and at work as a food handler, is noted as a matter of concern. 5. The implications of the problem having any work-related association is also noted in passing.

Cellulitis↗
PubMed1992

The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene.

The ALL-1 gene located at human chromosome 11 band q23 is rearranged in acute leukemias with interstitial deletions or reciprocal translocations between this region and chromosomes 1, 4, 6, 9, 10, or 19. The gene spans approximately 100 kb of DNA and contains at least 21 exons. It encodes a protein of more than 3910 amino acids containing three regions with homology to sequences within the Drosophila trithorax gene, including cysteine-rich regions that can be folded into six zinc finger-like domains. The breakpoint cluster region within ALL-1 spans 8 kb and encompasses several small exons, most of which begin in the same phase of the open reading frame. The t(4;11) chromosome translocation results in two reciprocal fusion products coding for chimeric proteins derived from ALL-1 and from a gene on chromosome 4. This suggests that each 11q23 abnormality gives rise to a specific oncogenic fusion protein.

Amino Acid Sequence↗
PubMed1992

The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase.

Chromosomal region 11q23 is frequently rearranged in acute lymphocytic leukemias (ALLs) and in acute myeloid leukemias (AMLs), mostly in reciprocal exchanges with various translocation partners. The most common of these translocations is t(4;11)(q21;q23). It is present in approximately 10% of ALL patients, most frequently in very young children. We have recently cloned a region of chromosome 11, the ALL-1 locus, found to be rearranged in malignant cells from patients with the t(4;11), t(9;11), t(11;19), t(1;11), t(6;11), t(10;11), and del(11q23) chromosomal abnormalities. Here we report the cloning and characterization of chromosomal breakpoints from leukemic cells with t(4;11) aberrations. The breakpoints cluster in regions of 7-8 kilobases on both chromosomes 4 and 11. The presence of heptamer- and nonamer-like sequences at the sites of breakage suggests that the VDJ recombinase utilized for immunoglobulin gene rearrangement is also directly involved in these translocations. We also show that leukemic cells with t(4;11) express altered RNAs transcribed from the derivative chromosomes 11 and 4.

Acute Disease↗
PubMed1992

A strategy for increasing an in vivo flux by genetic manipulations. The tryptophan system of yeast.

Decreases in enzyme activity often have little effect on the flux carried by the pathway. Similarly, up-modulation of single genes, and hence of the dependent enzyme concentrations, is frequently found to be ineffective in increasing the flux in the pathway in which the enzyme occurs. This insensitivity to enzyme variation is demonstrated experimentally for five separate enzymes in the tryptophan synthesis system of yeast, first by down-modulation of the gene dose and secondly by increasing the dose using multi-copy vectors. Such a lack of response is discussed in terms of the concepts of metabolic control analysis. When these five enzymes, however, were simultaneously increased by a multi-copy vector carrying all five genes, a substantial elevation of the flux to tryptophan was observed. These findings revealed a new phenomenon, namely the more than additive effects on the flux of simultaneous elevations of several enzyme activities.

Down-Regulation↗
PubMed1992

Emerging role of lipids of Candida albicans, a pathogenic dimorphic yeast.

It is clear that C. albicans lipids have gained tremendous importance in recent years. In addition to being a barrier for entrance of various metabolites, it also provides the site of action for the synthesis of enzyme(s) involved in cell wall morphogenesis and antifungal action. While alterations in lipid composition during a yeast to mycelia transition have been observed, in most of the studies, lipid fluctuations reported could have been due to various environmental factors involved in the induction of morphogenesis [4,5]. A clear understanding of lipid biosynthesis and metabolic blocks due to antifungal action is likely to shed further light on selective interactions of antifungals. Despite the multifacet role of lipids in various functions of this pathogenic yeast, their exact involvement is poorly understood. The situation is little better with regard to ergosterol and its metabolism. Ergosterol is, indeed, important for anti-candidal activity and appears to be involved in the morphogenesis of C. albicans. The fluctuation in phospholipid composition have led to altered properties of plasma membrane namely, membrane fluidity, transport activities and drug sensitivity, which suggest that-a critical level of individual phospholipid is important for proper functioning of the plasma membrane. What the exact role is of individual phospholipid is far from clear. Many unanswered questions relating to the role of PI and sphingomyelin in signal transduction, involvement of phospholipases in the maintenance of phospholipid composition, and role of lipid transfer proteins in assembly and asymmetry of lipids are some aspects which merit further work.

Candida albicans↗
PubMed1992

An altered 11-kilobase transcript in leukemic cell lines with the t(4;11)(q21;q23) chromosome translocation.

The 11q23 chromosome band is frequently associated with chromosomal aberrations in human leukemias. We have previously cloned a DNA fragment derived from chromosome 11 which could be used as a probe to detect rearrangements in DNAs from the leukemic cells of patients with the t(4;11), t(9;11), and t(11;19) translocations. In this study we now show that the same probe detects DNA rearrangements in malignant cells from patients with the t(1;11), t(6;11), t(10;11), and del (11q23) chromosomal abnormalities. A second probe obtained from a region located centrometric to the breakpoint cluster detects major and minor transcripts of 12.5 and 11.5 kilobases, respectively, in all cell lines examined. The same probe identifies an altered 11-kilobase RNA in all three independent cell lines with the t(4;11)(q21;q23) chromosome translocation.

Chromosomes, Human, Pair 11↗
PubMed1992

Identification and partial characterization of a lipophosphoglycan from a pathogenic strain of Entamoeba histolytica.

An acidic glycoconjugate could be extracted from a delipidated residue fraction of [3H]galactose, [3H]mannose or [32P]orthophosphate metabolically labeled Entamoeba histolytica with water/ethanol/diethylether/pyridine/NH4OH (15:15:5:1:0.017). The radioactively labeled glycoconjugate comprised 50-55% of the total [3H]galactose label incorporated into macromolecules. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the radiolabeled glycoconjugate showed two diffuse smears centering around 110 kDa and 45 kDa. Similar profiles were observed for both [3H]galactose- and [32P]orthophosphate-labeled glycoconjugate. No such bands were visible in [35S]methionine-labeled material. The hydrophobic nature of this glycoconjugate was inferred from its chromatographic behavior on phenyl-Sepharose. The molecule was rendered hydrophilic after digestion with phosphatidylinositol-specific phospholipase C. It was also sensitive to deamination by nitrous acid. Mild acid hydrolysis led to its fragmentation into smaller molecules as revealed by Sepharose 4B chromatography. Paper chromatographic analysis of the depolymerized [3H]galactose- and [3H]mannose-labeled fragments revealed that each was sensitive to alkaline phosphatase. The major dephosphorylated fragment migrated as an apparent galactose and mannose containing disaccharide which migrated identically to the Gal beta 1-4Man disaccharide derived from the lipophosphoglycan of Leishmania donovani. The above data support the existence of a major acidic glycoconjugate in E. histolytica bearing striking structural similarities to the lipophosphoglycan of Leishmania.

Alkaline Phosphatase↗
PubMed1992

Recognition of Entamoeba histolytica lipophosphoglycan by a strain-specific monoclonal antibody and human immune sera.

Western blot analysis showed that the monoclonal antibody 2D7.10 recognized lipophosphoglycan (LPG) from Entamoeba histolytica HM-1:IMSS. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern of [3H]galactose-labeled LPG and Western blot analysis of total lysate of E. histolytica with 2D7.10 revealed patterns similar to that of LPG with 2D7.10. This antibody could also immunoprecipitate purified LPG from the strain HM-1:IMSS after biosynthetically labeling with [3H]galactose and [32P]orthophosphate. However, no immunoprecipitation was observed when 2D7.10 was incubated with [32P]orthophosphate-labeled purified LPG from strain 200:NIH. Sera from patients suffering from invasive amoebiasis also immunoprecipitated 32P-labeled, purified LPG and could immunostain this molecule in Western blots. The human immune sera recognized carbohydrate epitopes but not the associated polypeptides of LPG, as evidenced by sensitivity to periodate digestion, mild acid hydrolysis but not to pronase treatment. It was earlier shown that 2D7.10 binds a carbohydrate epitope in a subset of axenized pathogenic strains of E. histolytica and that this epitope undergoes changes when cultured along with bacteria. These observations suggest that the E. histolytica LPG contains a strain-specific, variable epitope and that LPG is immunogenic in human.

Animals↗
PubMed1992

Expression and characterization of the cloned Salmonella typhimurium enterotoxin.

Earlier, our laboratory reported the cloning of a chromosomally encoded cholera toxin (CT)-like enterotoxin gene from Salmonella typhimurium Q1 into pBR322. Cell lysates from the plasmid clone pC1, containing a 4.8 kb EcoR1 DNA fragment from Salmonella, caused elongation of Chinese hamster ovary (CHO) cells and this biologic activity was neutralized by anti-CT. However, this cloned gene product did not elicit fluid secretion in the rabbit intestinal loop (RIL) model, because of poor expression. We report here, subcloning of a 4.8 kb EcoRI and a 2.7 kb HindIII/Eco Rl fragment into a high expression T7 RNA polymerase/promoter system. Cell lysates from these clones elicited fluid secretion in the RIL model, caused firm induration in rabbit skin and elongated CHO cells. These biological activities were neutralized by anti-CT. SDS-PAGE and subsequent fluorographic analysis of Escherichia coli, harboring recombinant plasmids in a T7 expression system, revealed the presence of two prominent 35S-labeled polypeptides of 25 and 12 kDa, which were immunoprecipitated with anti-CT. The enterotoxin appeared to be 125 kDa in size, based on chromatography on a P-300 column, had a pl of 6.6 to 6.8, and was heat-labile (60 degrees C/5 min). Unlike cloned CT and heat-labile enterotoxin (LT-l), which were localized in the periplasm, the Salmonella enterotoxin was cytoplasmic in nature.

Animals↗
PubMed1992

Transport of acidic amino acids in Candida albicans.

In Candida albicans ATCC 10261, two kinetically different amino acid transport systems with a high (S1) and a low (S2) affinity for aspartic acid (asp) and glutamic acid (glu) were identified. The S1 for the two acidic amino acids was characterized by low Kt values while Kt values of S2 were 30 to 40 times higher. Based on competitive studies of both systems, S1 was found to be specific and common to both asp and glu while S2 was relatively less specific. The S1 and S2 systems were also different in their sensitivity to respiratory inhibitors, mercurials and a K+ channel blocker. Both systems, however, showed maximum transport rates during the mid-exponential growth phase.

Aspartic Acid↗
PubMed1992

Comparative study of omeprazole and famotidine in the treatment of duodenal ulcer.

In a double blind, multicenter, parallel group clinical trial in patients with symptomatic duodenal ulcers, 129 patients were randomized to receive either omeprazole 20 mg once daily (n = 65) or famotidine 40 mg once daily (n = 64) for 2 weeks, and if the ulcers were not healed, for a total of 4 weeks. Seventy four percent of these receiving omeprazole had healed ulcers after 2 weeks compared with 34.3% of those receiving famotidine (p < 0.001). At 4 weeks, the respective figures were 97.3% and 77.6% (p < 0.001). After 2 weeks of treatment, only 11.1% and 29.8% of omeprazole and famotidine treated patients respectively had day time pain (p < 0.02). Diary cards (successfully completed by 2/3rd of patients) showed that omeprazole treated patients required smaller amounts of antacids (p = ns). Over the first two weeks, ulcer healing rate was similar in smokers and non- smokers. No significant side effects were reported in either group. Omeprazole 20 mg/day provides more rapid relief of symptoms and heals a greater proportion of duodenal ulcers at 2 and 4 weeks than famotidine 40 mg/day.

Adolescent↗
PubMed1992

Detection of beta-endorphin in human blood. A study of performance characteristics of different radiometric systems.

beta-Endorphin, an opioid peptide that contains 31-amino acids derived from proopiomelanocortin, has been implicated in a variety of disorders. To understand its role in pathophysiological states, its levels have been determined in body fluids, particularly in serum or plasma, with the use of commercially available radiometric assay kits. Because the circulating levels of this endogenous opioid peptide are small and antibodies can cross-react with chemically related peptides to different degrees and give rise to faulty interpretation of the data, the performance characteristics of the available radioimmunoassay kits for beta-endorphin from the Immuno Nuclear Corporation, Stillwater, Minn, the New England Nuclear Corporation, Boston, Mass, and the Nichols Institute, San Juan Capistrano, Calif, were evaluated. In overall performance, the Nichols kit was found to be the most reliable in this laboratory, even though the sensitivity of the Immuno Nuclear kit was better at lower concentrations of beta-endorphin. Serum was better than plasma in terms of recovery of beta-endorphin. When collected on ice, no significant loss in beta-endorphin immunoreactivity was observed at 1 hour. The use of edetic acid (EDTA), siliconized edetic acid, and aprotinin (Trasylol)-added siliconized edetic acid tubes was not helpful in improving the performance of the assay. The optimal condition to collect the specimen was to use glass tubes, place the glass tubes on ice immediately, separate the serum, and freeze the sample within 1 hour of collection.

Anemia, Sickle Cell↗
PubMed1991

Cloning and sequence analysis of hydrogenase regulatory genes (hydHG) from Salmonella typhimurium.

The nucleotide sequence of the hydHG operon, comprised of chromosomal genes that regulate labile hydrogenase activity in Salmonella typhimurium, was compared with the reported hydHG sequence of Escherichia coli. Nucleotide sequence analysis of a 4.8 kb EcoRI fragment of Salmonella chromosomal DNA revealed that one of the open reading frames (ORF) encoded a protein of 441 amino acid residues. This large ORF was identified on a 2.7 kb Eco RI/HindIII fragment and coded for the complete hydG gene. The carboxy-terminus (626 bp) of the hydH gene also was present immediately upstream of hydG. Expression of the Salmonella hydG gene in a T7 promoter/polymerase system revealed the presence of a unique 45 kDa protein band. The incomplete hydH gene was not expressed. It is proposed that the labile hydrogenase activity in S. typhimurium may be regulated by the multiple component system.

Amino Acid Sequence↗