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Biomedical subjects

J Prasad

Publications and source records attributed to J Prasad.

At least 37 records · Page 2Linked to original sources
PubMed1996

The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution.

Mammalian Clk/Sty is the prototype for a family of dual specificity kinases (termed LAMMER kinases) that have been conserved in evolution, but whose physiological substrates are unknown. In a yeast two-hybrid screen, the Clk/Sty kinase specifically interacted with RNA binding proteins, particularly members of the serine/arginine-rich (SR) family of splicing factors. Clk/Sty itself has an serine/arginine-rich non-catalytic N-terminal region which is important for its association with SR splicing factors. In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Tryptic phosphopeptide mapping demonstrated that the sites on ASF/SF2 phosphorylated in vitro overlap with those phosphorylated in vivo. Immunofluorescence studies showed that a catalytically inactive form of Clk/Sty co-localized with SR proteins in nuclear speckles. Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.

Amino Acid Sequence↗
PubMed1996

The management of left-sided large bowel obstruction: an audit.

BACKGROUND: The outcomes of patients admitted acutely to hospital with left-sided large bowel obstruction (LBO) were examined. METHODS: All patients admitted to the colorectal service (University Department of Surgery, Wellington School of Medicine) with LBO between 1975 and 1990 were reviewed. Sixty-four patients with left-sided LBO were identified. RESULTS: The most commonly found obstructing lesion was cancer. Two patients were not managed surgically. In 17.7% of patients there was development of postoperative respiratory complications and 16% developed wound problems following primary surgery. Fifty-nine patients survived their primary surgery and 45 had stomas. The stoma closure rate was 71.1% (32 of 45). The overall mortality rate for patients managed surgically was 6.5% (four of 62). The mortality rate for stoma formation was 4.3% (two of 47). The mortality rate for resection and then stoma closure was 3.2% (one of 32). CONCLUSIONS: This study has shown that a staged approach to the management of unselected patients with left-sided LBO is safe. Restoration of bowel continuity was achieved in 70% of patients.

Acute Disease↗
PubMed1996

Radioprotective effects of diltiazem on cytogenetic damage and survival in gamma ray exposed mice.

Diltiazem, a calcium ion channel blocker, already in use in cardiovascular therapeutics, has been observed to protect against bone marrow damage (cytogenetic damage, cell death) and mortality in whole body irradiated mice. The micronuclei fraction in bone marrow cells of whole body irradiated (60Co gamma rays, 2.0 Gy) mice was reduced from 2.24 +/- 0.23% to about 0.74 +/- 0.33% by preirradiation administration (-20 min) of 110 mg/kg body wt. diltiazem (ip). Endogenous colony forming unit counts in spleen of mice administered 110 mg/kg body wt. (-20 min) of diltiazem before 10 Gy whole body irradiation were 6 times more than untreated irradiated controls. Pretreatment with diltiazem accelerated the recovery of radiation induced weight loss also. Diltiazem (110 mg/kg body wt, -20 min) enhanced 30 day survival to about 95% and 85% after lethal whole body absorbed dose of 9 and 10 Gy respectively and also mitigated radiation induced life- span shortening. Post-irradiation (10 Gy) administration of diltiazem (+20 to 30 min) enhanced survival from about 2 to 15% only but was highly significant (P < 0.001). Possible modes of radioprotective action of diltiazem have been discussed.

Animals↗
PubMed1995

Histogranin, a modified histone H4 fragment endowed with N-methyl-D-aspartate antagonist and immunostimulatory activities.

Histogranin is a naturally-occurring pentadecapeptide with a structure 80% homologous with that a fragment-(86-100) of histone H4. First isolated from bovine adrenal medulla, the peptide was also shown to be present in the pituitary, brain, adrenal glands, blood plasma, lungs and spleen. At the subcellular level, histogranin is concentrated in secretory vesicles and it is released from perfused bovine adrenal glands 15-35 min after stimulation with carbamylcholine as opposed to catecholamines and [Leu5]enkephalin which are released immediately after stimulation. Rat brain membranes possess specific binding sites for [125I][Ser1]histogranin with characteristics of a receptor, namely high affinity, saturability, reversibility and sensitivity to heat and proteolytic enzyme treatments. Intracerebroventricular injections of synthetic histogranin (10-100 nmol) in mice protect them against N-methyl-D-aspartate (NMDA)-induced convulsions without affecting convulsions induced by (R,S)-alpha-amino-3-hydroxy -5-methyl-4-isoxazole-propionate (AMPA), kainate and bicuculline. The peptide also binds to specific sites on human peripheral blood mononuclear cells and it evokes the release of tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) from isolated rat macrophages in culture. Since the structure of histone H4 is considered as one of the most conservative, it is presumed that histogranin possesses its own precursor and that its gene is distinctly expressed.

Adjuvants, Immunologic↗
PubMed1995

Pilonidal disease.

All patients with pilonidal disease (abscess or sinus) managed surgically ('laying open') between 1975 and 1990 in the Colorectal Service, University Department of Surgery, Wellington School of Medicine were reviewed. A total of 323 operations (177 males, 146 females) were performed in 311 patients. Seven males and 5 females required two operations before satisfactory healing was achieved (recurrence rate 3.8%). Males were older than females (mean, 26.4 vs 21.5 years). One patient's wound bled following surgery and required immediate repacking. There were no other wound problems. One hundred and seventy-seven patients presented acutely with pilonidal abscess and 146 patients presented with pilonidal sinus. Patients with pilonidal abscess were younger than those with pilonidal sinus (male, 25.8 vs 26.9 years and female, 20.8 vs 23.5 years). There were proportionately more Maori patients who presented acutely. 'Laying open' under general anaesthesia seems to be a safe and successful method for managing pilonidal disease in all but the few patients in whom multiple operations have been performed previously or in those in whom healing has failed to occur. Based on our initial experience of 'day case' surgery the procedure could safely be done on an outpatient basis.

Abscess↗
PubMed1995

Hartmann's operation: a personal experience.

This paper documents a 15 year experience with Hartmann's operation in the Colorectal Service at the Wellington School of Medicine, New Zealand. There were 31 male and 30 female patients. The majority had either complicated diverticular disease (27) or rectal cancer (27). Fifty-six patients were discharged home and five patients died within 30 days of surgery (8.2%). Of the 27 patients with complicated diverticular disease 19 proceeded to stoma closure with no mortality. Of the 27 patients who had complicated colorectal cancer only 2 had their stoma closed. There were 41 patients in whom bowel continuity was restored following construction of a Hartmann's stoma. Thirty-nine anastomoses were hand-sewn and two anastomoses were stapled. One patient developed a major anastomotic leak and one patient died postoperatively. Hartmann's operation has a definite place in the management of patients with complicated diverticular disease and recto-sigmoid cancer. The operation can be performed and the stoma closed safely in the former group but is less likely to be followed by restoration of continuity in the latter group.

Aged↗
PubMed1995

Fissure in ano.

The present study documents a 15 year experience with anal dilatation in patients with fissure in ano. Patients who were unable to tolerate rectal examination were admitted urgently for anal dilatation. Patients in whom rectal examination and proctoscopy was possible were offered an anal dilator and were reviewed after 4 weeks. Patients who preferred not to use an anal dilator or who had not become asymptomatic were admitted for elective anal dilatation. Four finger anal dilatation was performed under general anaesthesia. Between 1975 and 1990 104 patients underwent 111 procedures. The male to female ratio was 1.3:1. Five patients were re-operated because of failure of resolution of symptoms. Three patients with anal fissures and Crohn's disease were successfully managed by anal dilatation. Nine patients had excision of a 'sentinel pile' in addition to anal dilatation. Ten patients were admitted acutely. One patient developed a perineal haematoma. Seventy-four procedures were performed as day cases. There was no mortality associated with the procedure. At the time of discharge from the clinic no patient complained of problems with continence. These results support our policy of gentle anal dilatation as first management choice in the treatment of anal fissure.

Adult↗
PubMed1994

Interaction of histogranin and related peptides with [3H]dextromethorphan binding sites in rat brain.

Histogranin (HN) and related peptides were tested for their ability to modulate the binding of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, [3H]dextromethorphan ([3H]DM), to rat brain membranes. HN, [Ser1]HN and the C-terminal fragment HN-(6-15) (0.1 nM-1 microM) potentiated (up to 1.6-fold) the binding of [3H]DM (5 nM) whereas the N-terminal fragment HN-(1-10) had no effect. The potentiation of [3H]DM binding by [Ser1]HN was blocked by NMDA (100 microM) and the NMDA receptor antagonist, CPP (1 microM) but not by the sigma (sigma) receptor ligand, (+)-pentazocine (0.1 microM) and the phencyclidine (PCP) receptor ligand, TCP (1 microM). Equilibrium binding experiments in presence of TCP (1 microM) to block PCP receptors indicated that [Ser1]HN (1 microM) causes a significant increase in the binding capacity (Bmax) of [3H]DM (from 2.46 to 3.46 pmol/mg protein) but no change in the apparent dissociation constant (Kd of 428 nM as compared with 487 nM). The results indicate that HN and related peptides specifically enhance the number of [3H]DM binding sites associated to the NMDA receptor complex.

Animals↗
PubMed1993

The calcium binding protein of Entamoeba histolytica: expression in Escherichia coli and immunochemical characterization.

The gene encoding calcium binding protein (CaBP) of Entamoeba histolytica is single-copy and transcribes a single class of mRNA. The coding region of the gene, amplified from a genomic clone of CaBP by polymerase chain reaction, was cloned into the Escherichia coli expression vector pET-3c. The expressed protein was 15 kD in size, which agreed with the predicted size from the open reading frame. The recombinant protein showed altered mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after binding calcium and was found to be resistant to boiling, a property shared by many calcium binding proteins. A polyclonal antibody raised against the recombinant CaBP recognized a 15 kD protein in lysates from E. histolytica pathogenic strain HM-1:IMSS. The amebic protein could compete with the recombinant protein in binding to the antibody. While the antibody recognized lysates from a number of E. histolytica strains, it failed to cross-react with other Entamoeba species, e.g., E. invadens and E. moshkovskii. Moreover, no homologue of the CaBP gene could be detected in these species by using a set of degenerate primers for amplification by polymerase chain reaction (PCR). Our data demonstrate that amebic CaBP can be expressed in E. coli and that this protein is detectable only in E. histolytica but not in other Entamoeba.

Animals↗
PubMed1992

Modulation of a surface antigen of Entamoeba histolytica in response to bacteria.

Changes in the cell surface of Entamoeba histolytica, a human intestinal parasite and the causative agent of amebic dysentery, were examined with a monoclonal antibody, 2D7.10, which selectively recognizes carbohydrate epitopes in some axenic amebic strains. While high-level expression of this epitope was observed in axenic amebae, it was either absent or present only in small amounts in xenic amebae. Furthermore, reassociation of the axenic amebae with intestinal flora resulted in loss of the 2D7.10 epitope. Our data suggest that surface antigens of E. histolytica can be modulated in response to bacteria and may provide an explanation for the observed influence of bacteria on amebic virulence.

Animals↗
PubMed1991

Fine needle aspiration of Sister Mary Joseph's nodule.

A case of Sister Mary Joseph's nodule (umbilical metastasis) is described from a primary adenocarcinoma of the transverse colon. Needle aspiration cytology made the diagnosis which was confirmed by immunocytochemical localization of CEA, B72.3, EMA, and cytokeratin in the tumour cells. Extensive mucus production in the tumour cells was demonstrated by alcian blue and mucicarmine stains.

Abdominal Neoplasms↗
PubMed1991

Lymphoid follicular hyperplasia--a distinctive feature of diversion colitis.

Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intestine following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Behçet's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease, with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined.

Adult↗
PubMed1987

Characterisation of ocular melanoma with cutaneous melanoma antibodies.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.

Antibodies, Monoclonal↗