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Biomedical subjects

P Kandasamy

Publications and source records attributed to P Kandasamy.

4 recordsLinked to original sources

Early results of a rotation flap to treat chronic anal fissures.

BACKGROUND: Treatment of anal fissures has changed dramatically in the past decade. This is primarily due to a better understanding of its pathophysiology and the implications of the various available options. Only a few anal fissures fail to respond to medical therapy. Sphincterotomy and anal dilatation have fallen out of favour due to the risk of incontinence. Island flaps have been proposed to address this, but 60-70% of the flap donor sites break down with complications. We propose using a rotation flap to overcome this problem. METHODS: A local rotation flap from perianal skin was used to fill the fissure defect in 14 patients who were followed up for a period of 6 months to determine fissure healing and incidence of donor site breakdown. RESULTS: Twelve patients had complete resolution of their symptoms. Of two patients who developed fissure recurrence, one also had dehiscence of the donor site. There were no donor site complications in the remaining patients. No patient suffered continence defects as a result of the surgery. CONCLUSION: Rotation flap is a simple, safe and appropriate modality for treating chronic anal fissures. Donor site problems are avoided using this approach. It should be the treatment of choice, particularly in patients who are at risk of incontinence.

Adult↗

Yeast desaturases.

The Saccharomyces OLE1 gene encodes the intrinsic membrane-bound Delta-9 fatty acid desaturase. OLE1 expression is regulated at the levels of transcription and mRNA stability by nutrient fatty acids and molecular oxygen. Its transcription is controlled through two distinct promoter elements, the fatty acid response element (FAR) region, and a downstream low-oxygen response element (LORE) that dramatically amplifies FAR-activated expression under hypoxic or cobalt-stimulated growth conditions. Transcription activation through both elements is repressed by unsaturated fatty acids. The half-life of the OLE1 mRNA is also dramatically reduced upon exposure to unsaturated fatty acids. OLE1 expression is governed by two homologous membrane-bound proteins, Spt23p and Mga2p, which activate OLE1 expression through N-terminal polypeptides that are released from the membrane through a ubiquitin-mediated mechanism that involves processing by the 23 S proteosome. Although proteolytic processing of Spt23p can be repressed by polyunsaturated fatty acids, Mga2p processing in normoxic cells appears to be regulated by a different mechanism. Mga2p is essential, however, for the induction of the high levels of expression that are triggered by hypoxia through the LORE promoter element. Surprisingly, Mga2p also plays a critical role in controlling OLE1 mRNA stability, suggesting that there may be a functional linkage between OLE1 transcription and the regulation of OLE1 mRNA stability.

Fatty Acid Desaturases↗

The membrane proteins, Spt23p and Mga2p, play distinct roles in the activation of Saccharomyces cerevisiae OLE1 gene expression. Fatty acid-mediated regulation of Mga2p activity is independent of its proteolytic processing into a soluble transcription activator.

The Saccharomyces OLE1 gene encodes the Delta-9 fatty acid desaturase, an enzyme that converts saturated fatty acyl-CoAs into cis-Delta-9 unsaturated fatty acids. OLE1 gene expression is regulated by unsaturated fatty acids, which repress transcription and destabilize the OLE1 mRNA. Expression of OLE1 is activated by N-terminal proteolytic fragments of two homologous endoplasmic reticulum membrane proteins, Spt23p and Mga2p. Disruption of either gene does not significantly affect cell growth or fatty acid metabolism; cells that contain null alleles of both genes, however, are unsaturated fatty acid auxotrophs. An analysis of spt23Delta and mga2Delta strains shows that Spt23p and Mga2p differentially activate and regulate OLE1 transcription. In glucose-grown cells, both genes activate transcription to similar levels of activity. Expressed alone, Mga2p induces high levels of OLE1 transcription in cells exposed to cobalt or grown in glycerol-containing medium. Spt23p expressed alone activates OLE1 transcription to levels similar to those in wild type cells. OLE1 expression is strongly repressed by unsaturated fatty acids in spt23Delta or mga2Delta cells, under all growth conditions. To test if OLE1 expression is controlled by fatty acids at the level of membrane proteolysis, soluble N-terminal fragments of Spt23p and Mga2p that lack their membrane-spanning regions (Deltatm) were expressed under the control of their native promoters in spt23Delta;mga2Delta cells. Under those conditions, Mga2pDeltatm acts as a powerful transcription activator that is strongly repressed by unsaturated fatty acids. By comparison, the Spt23pDeltatm polypeptide weakly activates transcription and shows little regulation by unsaturated fatty acids. Co-expression of the two soluble fragments results in activation to levels observed with the Mga2pDeltatm protein alone. The fatty acid repression of transcription under those conditions is attenuated by Spt23Deltatm, however, suggesting that the two proteins may interact to modulate OLE1 gene expression.

Base Sequence↗

Acute pancreatitis in north-eastern peninsular Malaysia: an unusual demographic and aetiological pattern.

A survey of 142 cases of acute pancreatitis was undertaken in two major hospitals serving the state of Kelantan in Malaysia. Females outnumbered males by a ratio of more than 3:1. The incidence among females peaked in the third decade of life. Twenty-one percent (23/109) of the females were pregnant. Ultrasonography revealed gallstones in only 9.4% (13/138). However, abnormalities of serum transaminases were found in 35% (35/100), suggesting that occult gallstones or microlithiasis may be the cause in a significant proportion of patients. Alcohol was virtually absent as an aetiological factor. There was a higher frequency of Ascaris infection in this group than a control hospital population (11/35 vs 33/242; p < 0.02) suggesting that ascariasis may be an important cause of acute pancreatitis in Kelantan. Only 8.4% fell into the category of severe pancreatitis. The overall mortality rate was 2.1%.

Acute Disease↗