Biomedical subjects

S Balasubramaniam

Publications and source records attributed to S Balasubramaniam.

At least 19 recordsLinked to original sources

PubMed2001

Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms.

This study presents the annotated genomic sequence and exon-intron organization of the human and mouse epidermal growth factor receptor (EGFR) genes located on chromosomes 7p11.2 and 11, respectively. We report that the EGFR gene spans nearly 200 kb and that the full-length 170-kDa EGFR is encoded by 28 exons. In addition, we have identified two human and two mouse alternative EGFR transcripts of 2.4-3.0 kb using both computational and experimental methods. The human 3.0-kb and mouse 2.8-kb EGFR mRNAs are predominantly expressed in placenta and liver, respectively, and both transcripts encode 110-kDa truncated receptor isoforms containing only the extracellular ligand-binding domain. We also have demonstrated that the aberrant 2.8-kb EGFR transcript produced by the human A431 carcinoma cell line is generated by splicing to a recombinant 3'-terminal exon located in EGFR intron 16, which apparently was formed as a result of a chromosomal translocation. Finally, we have shown that the human, mouse, rat, and chicken 1.8- to 3.0-kb alternative EGFR transcripts are generated by distinct splicing mechanisms and that each of these mRNAs contains unique 3' sequences that are not evolutionarily conserved. The presence of truncated receptor isoforms in diverse species suggests that these proteins may have important functional roles in regulating EGFR activity.

Alternative Splicing↗

PubMed2000

Heterotopic pregnancy presenting as an acute abdomen: a diagnostic masquerader.

Simultaneous intrauterine and extrauterine pregnancy is called heterotopic pregnancy. It is a rare complication of pregnancy, especially in the absence of predisposing factors. It is known to present with a variety of symptoms and signs often leading to a delay in establishing the correct diagnosis. We report the case of a 29-year-old woman, known to be 14 weeks pregnant, presenting with acute abdominal pain. The confirmation of a viable intrauterine pregnancy led to a general surgery consultation. A heterotopic ruptured right ectopic tubal pregnancy was found. Right salpingectomy was performed. The patient recovered uneventfully. The intrauterine pregnancy was not affected. This case illustrates the variable presentation of heterotopic pregnancy and the need for general surgeons to be suspicious of pregnancy related complications, even in the presence of a viable intrauterine pregnancy.

Abdomen, Acute↗

PubMed1999

Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) has a high mortality rate, which is due primarily to the fact that early clinical symptoms are vague and nonspecific; hence, this disease often goes undetected and untreated until in its advanced stages. Sensitive and reliable methods for detecting earlier stages of EOC are, therefore, urgently needed. Epidermal growth factor (EGF) is a ligand for EGF receptor (ErbB1); this receptor is the product of the c-erbB1 proto-oncogene. ErbB1 overexpression is common in human ovarian carcinoma-derived cell lines and tumors, in which overexpression is thought to play a critical role in tumor etiology and progression. Furthermore, ErbB1 overexpression is associated with disease recurrence and decreased patient survival. Recently, we have developed an acridinium-linked immunosorbent assay that detects a approximately 110-kDa soluble analogue of ErbB1, ie., sErbB1, in serum samples from healthy men and women (A. T. Baron, et al., J. Immunol. Methods, 219: 23-43, 1998). Here, we demonstrate that serum p110 sErbB1 levels are significantly lower in EOC patients with stage III or IV disease prior to (P < 0.0001) and shortly after (P < 0.0001) cytoreductive staging laparotomy than in healthy women of similar ages, whereas EGF levels are significantly higher than those of age-matched healthy women only in serum samples collected shortly after tumor debulking surgery (P < 0.0001). We observe that the preoperative serum sErbB1 concentration range of advanced stage EOC patients barely overlaps with the serum sErbB1 concentration range of healthy women. In addition, we show that serum sErbB1 and EGF levels changed temporally for some EOC patients who were surgically debulked of tumor and who provided a second serum sample during the course of combination chemotherapy. Finally, we observe a significant positive association between sErbB1 and EGF levels only in serum samples of EOC patients collected prior to cytoreductive surgery (correlation coefficient = 0.61968; P = 0.0027). These data suggest that epithelial ovarian tumors concomitantly affect serum sErbB1 and EGF levels. In conclusion, these data indicate that serum sErbB1 and EGF (postoperative only) levels are significantly different between EOC patients and healthy women and that altered and/or changing serum sErbB1 and EGF levels may provide important diagnostic and/or prognostic information useful for the management of patients with EOC.

Acridines↗

PubMed1997

Pelvic ultrasound performed by emergency physicians for the detection of ectopic pregnancy in complicated first-trimester pregnancies.

STUDY OBJECTIVE: To determine the accuracy and application of pelvic ultrasound performed by emergency physicians in detecting ectopic pregnancy (EP) in complicated first-trimester pregnancies. METHODS: We studied consecutive pelvic ultrasounds performed in all women who presented with abdominal pain or vaginal bleeding during the first trimester of pregnancy over a 6-month period. Patients with clinical evidence of incomplete abortion were not included. We compared ultrasound results with subsequent ultrasound findings by the radiology department and correlated them with follow-up diagnoses and outcomes. RESULTS: Of the 136 eligible patients, a final diagnosis was rendered in 125; 11 were lost to follow-up. These ED ultrasound findings were recorded: established intrauterine pregnancy (IUP) with embryonic structures, 87 (70%); indeterminate scan revealing no distinct evidence of IUP or EP, 15 (12%); early intrauterine gestational sac of less than 6 weeks without embryonic structures, 12 (10%); EP, 8 (6%); blighted ovum, 2 (2%); and molar pregnancy, 1 (1%). The initial ED ultrasound determination was consistent with radiology department findings, final outcome, or both in 121 (96%) (95% confidence interval [CI], 91% to 97%). ED ultrasound accurately identified 87 pregnancies with intrauterine embryonic structures, including 5 patients with fetal demise (95% Cl, 97% to 100%). Diagnosis of pregnancy location in these 87 patients effectively ruled out EP, with a negative predictive value of 100%. The sensitivity and specificity of ED ultrasound in the detection of EP were 90% and 88%, respectively. CONCLUSION: Pelvic ultrasonography performed by emergency physicians can be used to rule out EP and make an accurate diagnosis in most patients with complicated first-trimester pregnancies during the initial ED visit. The remaining patients at risk can be identified and a diagnosis made by means of follow-up ultrasound and serial hCG determinations.

Adult↗

PubMed1996

What dose of vitamin E is required to reduce susceptibility of LDL to oxidation?

BACKGROUND: Oxidation modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Ingestion of vitamin E in high dosage has been shown to reduce the susceptibility of LDL to copper-induced oxidation, as assessed ex vivo. AIM: To determine a minimum dose of supplementary vitamin E which will significantly reduce the susceptibility of LDL to oxidation. METHODS: A single centre, double-blind, parallel placebo-controlled trial. Healthy volunteers (total n = 42) were randomised to receive placebo, 500, 1000 or 1500 IU/day of vitamin E (D-alpha-tocopherol) for a period of six weeks. Primary outcomes were change in lag time or oxidation rate to copper-induced LDL oxidation. Secondary outcomes were changes in plasma vitamin E levels and clinical tolerance. RESULTS: Lag time to LDL oxidation was significantly prolonged and oxidation rate significantly slowed at all dose levels of vitamin E, indicating a threshold effect from 500 IU/day. Compared to placebo, the median prolongation in lag time on 500 IU/day was 26%, on 1000 IU/day 24% and on 1500 IU/day 35%. The corresponding slowing in oxidation rates was 14%, 19% and 25% respectively. The per cent change in plasma vitamin E concentration was highly correlated with the change in lag time (r = 0.61, p < 0.001) and oxidation rate (r = 0.55, p < 0.001). Vitamin E was generally well tolerated. CONCLUSIONS: Vitamin E in a dose of 500 IU/day will significantly reduce the susceptibility of LDL to oxidation. Whether or not this treatment will consistently reduce the future incidence of coronary artery disease will only be answered by further clinical trials.

Analysis of Variance↗

PubMed1996

'O' set connector system in CAPD.

51 CAPD patients (age 55.5 +/- 14.5 yrs, 35 male, 16 female) on CAPD using 'O' set were studied retrospectively during the period January 1993 to April 1995. Etiology of ESRD was Diabetic nephropathy-25(49%) and the other causes-26(51%). The total duration of observation on 'O' set was 553 patient months, the mean duration was 10.8 +/- 6.1 months. 24 patients (47%) developed total of 30 episodes of peritonitis. The incidence of peritonitis was 18.4 patient months per episode of peritonitis. The organisms responsible for peritonitis were Gram positive-6(20%), Gram negative-3(10%), Fungal-1(3.3%), Mycobacterial-1(3.3%), Eosinophilic-1(3.3%), Sterile-12(40%) and unknown-6(20%) 2 patients of bacterial peritonitis and a patient with tuberculous peritonitis died while rest of the patients responded favourably to antibiotics. 13(52%) diabetic patients and 11(42%) non-diabetic patients had peritonitis (p-NS) and the peritonitis rates in diabetics and non diabetics were 18.3 and 18.6 patient months per episode respectively (p-NS). Exit site infection was seen in 5 patients (10%) (Staph aureus-4, Enterococci-1) and all responded to antibiotic therapy. 7 patients had total of 10 episodes of symptomatic accidental intraperitoneal sodium hypochlorite instillation, none had any long term adverse effects. The 'O' set procedure was done by self in 10(20%) and by others in 41(80%) cases. The peritonitis rates when performed by self and others were 18.5 and 18.4 patient months per episode respectively (p-NS). The cost of being on CAPD using 'O' set, Y-bag and twin bag were Rs. 1,50,000, 2,10,000 and 3,72,000 per annum respectively and cost of maintenance haemodialysis was 1,36,800 per annum. The cost of CAPD using 'O' set was comparable to that of maintenance haemodialysis. The 'O' set connector system in CAPD is found to be safe, cost effective and efficient.

Adolescent↗

PubMed1995

Pregnancy terminating effect of Jatropha curcas in rats.

The fertility regulatory effect of the fruit of Jatropha curcas was investigated by oral administration of different extracts to pregnant rats for varying periods of time. Foetal resorption was observed with methanol, petroleum ether and dichloromethane extracts indicating the abortifacient properties of the fruit. The results also suggest that the interruption of pregnancy occurred at an early stage after implantation. This effect could be accomplished even when the extracts were given from the 6th to the 8th day of pregnancy. Loss of body weight during the dosing period, ranging from slight to severe was seen in the treated animals. Marked toxicity was observed with some extracts when given over a comparatively long period of about 10 days.

Abortifacient Agents↗

PubMed1995

On the effect of garlic on plasma lipids and lipoproteins in mild hypercholesterolaemia.

The ingestion of garlic has been reported to have many cardiovascular effects, including a reduction in plasma cholesterol concentration and the susceptibility of LDL to oxidation. A double-blind, placebo-controlled, randomised crossover study was conducted in subjects with mild to moderate hypercholesterolaemia who were subject to strict dietary supervision and assessment. After a baseline dietary period of 28 days, subjects took Kwai garlic powder tablets 300 mg three times daily or matching placebo for 12 weeks, followed by 28 days washout, followed by a 12 weeks crossover on the alternative preparation. In the analysis hypercholesterolaemia was defined as those subjects in the range 5.5-8.05 mmol/l. Three subjects were withdrawn, one allocated to garlic and complaining of garlic body odour, one using placebo having intercurrent health problems, and one with a baseline cholesterol below 5.5 mmol/l, yielding analysable results in 28 subjects. Comparing the period on garlic with that on placebo, there were no significant differences in plasma cholesterol, LDL cholesterol, HDL cholesterol, plasma triglycerides, lipoprotein(a) concentrations, or blood pressure. Mean LDL cholesterol concentration was 4.64 +/- 0.52 mmol/l on garlic and 4.60 +/- 0.59 mmol/l on placebo. There was no demonstrable effect of garlic on oxidisability of LDL, on the ratio of plasma lathosterol/cholesterol (a measure of cholesterol synthesis), nor on LDL receptor expression in lymphocytes. This study found no demonstrable effect of garlic ingestion on lipids and lipoproteins.

Administration, Oral↗

PubMed1994

Coordinate diurnal regulation of hepatic acyl-coenzyme A: cholesterol acyltransferase and cellular levels of esterified cholesterol.

Hepatic ACAT, HMG-CoA reductase and both cellular free and esterified cholesterol were measured at 3 h intervals over a 24 h period in the rat. ACAT exhibited a characteristic low amplitude diurnal rhythm with maximum activity at the mid-light phase that was significantly higher than the minimum activity observed at the mid-dark phase. The cellular esterified cholesterol concentration showed a diurnal rhythm that closely paralleled the rhythm of ACAT activity. The cellular free cholesterol concentration was not significantly altered during the 24 h cycle. In rats fed cholesterol, the diurnal rhythm of ACAT was still maintained despite the increase in ACAT activity during the entire 24 h cycle suggesting that the ACAT rhythm is the result of changes in the level of ACAT protein expression. The results also indicate that the diurnal rhythms of ACAT and HMG-CoA reductase are generated by a process independent of the LDL receptor rhythm. All three rhythms are also independent of changes in the level of free cholesterol in the cell.

Animals↗

PubMed1994

Circadian rhythm in hepatic low-density-lipoprotein (LDL)-receptor expression and plasma LDL levels.

On the basis of studies in vivo and in vitro that involved the use of pharmacological amounts of drugs and hormones or excess cholesterol supplementation, the expression of the low-density lipoprotein (LDL) receptor appears to be tightly coupled to the regulation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity and to extracellular levels of LDL. The present study was undertaken to see how these three entities are regulated under normal physiological conditions over a 24 h period. The results show that, in the rat, hepatic LDL-receptor expression and plasma LDL levels exhibit diurnal periodicity, with a 2-3-fold difference between the peak and trough of each rhythm. Both rhythms showed high inverse correlation (r = -0.86, P < 0.01), plasma LDL levels being lowest at the onset of darkness when LDL-receptor expression was at its peak. The results also showed that the LDL-receptor protein in rat liver has a shorter half-life than that reported for cultured fibroblasts or HepG2 cells. The maximal expression of the LDL receptor occurred several hours before the peak activity of HMG-CoA reductase and appeared not to be influenced by cellular or membrane cholesterol levels during the 24 h cycle. Treatment with dexamethasone increased the LDL-receptor activity significantly at both the lowest and highest points of the rhythm, but the receptor rhythm was still maintained, suggesting that the signal for the circadian variation of the receptor expression is not mediated by adrenal hormones.

Animals↗

PubMed1993

The low-density lipoprotein receptor and cholesterol synthesis are affected differently by dietary cholesterol in the rat.

In the hamster and the rabbit, the low-density lipoprotein (LDL) receptor and cholesterol synthesis are coordinately downregulated by dietary cholesterol. In the rat, cholesterol synthesis is downregulated but LDL kinetic studies suggest that the LDL receptor is not. The aim of this study was to determine the effect of dietary cholesterol on the expression of the hepatic LDL receptor in the rat. Young (2 months) hooded and albino Wistar rats and older (9 months) Sprague-Dawley rats were used because of their reported different propensities to develop hypercholesterolaemia when fed cholesterol. Hepatic LDL receptor activity was measured using a dot blot assay with LDL-gold and LDL receptor mass was measured using an electroblot assay with a polyclonal antibody. Dietary cholesterol had no effect on the plasma cholesterol concentration in both strains of young Wistar rats but increased it in the older Sprague-Dawley rats. Cholesterol synthesis as measured with 3H2O or as indicated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity or the ratio of plasma lathosterol to cholesterol was effectively downregulated by dietary cholesterol (1% w/w) in all three strains. In contrast, dietary cholesterol increased both hepatic LDL receptor activity and mass in the young Wistar rats and had no effect on either receptor activity or mass in the older Sprague-Dawley rats. Increases in receptor activity occurred despite increases in hepatic cholesterol especially when cholic acid was added to the cholesterol diet. The effect was systemic because CL 277082, an inhibitor of intestinal cholesterol absorption, prevented the increase in LDL receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1992

Modulation of the low-density-lipoprotein-receptor-related protein and its relevance to chylomicron-remnant metabolism.

Hepatic levels of the low-density-lipoprotein (LDL)-receptor-related protein (LRP) and the LDL receptor were measured in rats subjected to treatments known to affect the expression of the LDL receptor. Propylthiouracil decreased both hepatic LRP and LDL receptor expression by 30-40%. Thyroxine treatment increased LDL receptor levels by 3-fold without altering LRP levels. In contrast, 17 alpha-ethinyloestradiol decreased LRP by 50%, whereas the LDL receptor was increased 5-fold. Plasma chylomicrons and their remnants were decreased to insignificant levels with this treatment. In rats fed with cholesterol there was a significant increase in these particles in plasma (1.21 +/- 0.4 versus 5.71 +/- 0.4 mg/dl), whereas the expression of LRP was unaltered. In Watanabe heritable hyperlipidaemic and cholesterol-fed rabbits, in which the LDL receptor expression is absent or decreased, the expression of LRP was not significantly different from that in normal rabbits. These results suggest that the expression of hepatic LRP can be modulated by changes in the hormonal status of the rat and that this modulation is not tightly co-ordinated with that of the LDL receptor. Moreover, LRP does not appear to have a significant role in chylomicron-remnant clearance, whereas the LDL receptor is actively involved in this process.

Animals↗

PubMed1992

Fish oil and oat bran in combination effectively lower plasma cholesterol in the rat.

Male rats were fed a semi-purified diet containing oat bran or wheat bran with or without a marine fish oil to investigate the effects of such combinations on lipid metabolism. Oat bran alone and wheat bran plus fish oil gave lower plasma cholesterol concentrations than wheat bran alone while oat bran plus fish oil gave the lowest. Oat bran increased plasma triacylglycerols compared with wheat bran but oat bran plus fish oil gave concentrations similar to those seen with wheat bran plus fish oil. Oat bran gave higher hepatic cholesterol synthesis rates and a higher activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase compared to wheat bran. The addition of fish oil to either bran diet decreased cholesterol synthesis but HMG CoA reductase activity was not reduced. Oat bran increased hepatic acyl coenzyme A:cholesterol acyl transferase (ACAT) activity and increased the ratio of esterified to unesterified cholesterol in hepatic microsomal membranes compared with wheat bran. Fish oil decreased hepatic LDL receptor activity and increased HDL binding activity when added to the wheat bran diet but these effects were not seen with oat bran. Oat bran also had no effect on hepatic lipoprotein receptor activity compared with wheat bran. These results show that fish oil and oat bran have complementary cholesterol lowering effects in the rat.

Animals↗

PubMed1991

High density lipoproteins, genetic polymorphism for apo A-I and coronary artery disease.

HDL cholesterol and apolipoprotein A-I are associated with the development of coronary artery disease (CAD). The presence of a PstI site polymorphism adjacent to the gene encoding apo A-I (known as P2) has also been shown to be associated with CAD but this relationship is controversial. A case control study was conducted in an Australian population to re-examine whether the rare P2 allele is associated with CAD. Data were derived from 159 cases of angiographically confirmed CAD and 99 healthy controls. The proportion of CAD cases carrying the P2 allele did not differ significantly from controls (11% versus 9%). In a multiple logistic regression model controlling for the effects of age, country of birth, hypertension and hypotensive drugs, body mass index and lipid variables, the P2 allele failed to predict significantly the presence of CAD (odds ratio 1.83; 95% confidence interval 0.65-5.19).

Alleles↗

PubMed1990

On the mechanism by which an ACAT inhibitor (CL 277,082) influences plasma lipoproteins in the rat.

CL 277,082 is an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT). The effects of this drug on lipoprotein metabolism have been examined in cholesterol-fed rats. An optimal dose of drug incorporated into the diet (0.1% w/w) for 7 days reduced plasma cholesterol by 48% and plasma triglycerides by 72%. The decrease in plasma cholesterol was due to a reduction in triglyceride-rich lipoproteins and in HDL cholesterol. There was a significant 72% reduction in intestinal ACAT activity, accompanied by a 41% reduction in hepatic cholesterol content. There was a smaller 21% reduction in hepatic ACAT activity. Hepatic HMG-CoA reductase activity increased 3-fold. HDL binding activity by liver membranes was not altered significantly. The decrease in plasma cholesterol with this ACAT inhibitor is most likely due to decreased absorption of dietary cholesterol resulting from inhibition of intestinal ACAT.

Analysis of Variance↗

PubMed1990

Effects of an ethyl ester preparation of fish oils (Himega) on lipids and lipoproteins in hyperlipidaemia.

Clinical trials were conducted to assess the utility of HimegaR in the management of hyperlipidaemia. Himega is an ethyl ester concentrate from fish oil containing at least 50% n-3 fatty acid and minimal cholesterol. In Study 1, 13 subjects with primary hypertriglyceridaemia consumed Himega or a triglyceride-based fish oil in a randomised, double-blind crossover study for 12 weeks. Nine subjects took 2 g/day of n-3 fatty acid but four subjects with marked hypertriglyceridaemia took 4 g/day. Plasma triglycerides were reduced by approximately 50% with either product. There was a very similar effect on all lipid and lipoprotein parameters, including an 18% increase in LDL cholesterol and 23% increase in serum apolipoprotein B. In Study 2, nine subjects with primary hypercholesterolaemia took 2 g/day of n-3 fatty acid (Himega) or placebo (olive oil) in a randomised, double-blind crossover study for nine weeks. Plasma cholesterol was reduced by 6%, without significant change in LDL cholesterol. Fish oils in the form of ethyl esters or triglyceride are assimilated to a similar degree and lead to equivalent triglyceride-lowering in hypertriglyceridaemia, while simultaneously increasing LDL particle numbers. Himega does not reduce LDL levels in hypercholesteraemia, despite being a product with minimal cholesterol content.

Adult↗

PubMed1990

The effects of adrenergic blockade on lipoproteins using the rat as an experimental model.

Adrenergic blocking drugs are known to have adverse effects on lipids and lipoproteins in man, although the mechanisms underlying these effects are unclear. In order to see whether the rat might be a suitable model to explore this issue, adrenergic blockers having differing properties with respect to receptor interaction were administered to rats orally over seven days, followed by measurement of plasma lipids and lipoproteins. Total plasma cholesterol was not significantly influenced by any of the drugs used, while triglycerides were reduced by 20% and 31% respectively with pindolol and prazosin. With respect to changes in HDL cholesterol, it was found that: (a) HDL cholesterol was significantly reduced by 8% during combined beta 1, beta 2 blockade with propranolol; (b) HDL cholesterol was not significantly changed during selective beta 1 blockade using atenolol, or during combined beta 1, beta 2 blockade and partial beta 2 stimulation using pindolol; and (c) HDL cholesterol was significantly increased during combined beta 1 blockade and beta 2 stimulation using celiprolol by 12%, or during alpha 1 blockade with prazosin by 8%. It appears that beta 2 receptor exposure or stimulation may be one of the key points in the interaction between adrenergic blockade and lipoprotein metabolism.

Adrenergic beta-Antagonists↗

PubMed1988

Toxic shock syndrome due to an infected human bite.

We report a case of nonmenstrual toxic shock syndrome. A 21-year-old man presented with severe pain in the right hand after an altercation in which he sustained a bite from a person. Physical examination revealed a small abscess on the right proximal interphalangeal joint with edema in the fourth and fifth digits and tenderness of the flexor sheath. The patient was hypotensive with diffuse macular erythematous skin. He responded to surgical drainage and antibiotics.

Adult↗