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Biomedical subjects

R Ganesan

Publications and source records attributed to R Ganesan.

At least 37 records · Page 2Linked to original sources

CD40 expression in bladder cancer.

The CD40 receptor is expressed in many immune cell types and is known to play a central role in both humoral and T-cell-mediated immunity, being a subject of intense research interest in recent years. It is also expressed on a variety of carcinomas and may therefore be of biological significance in the development and treatment of cancer. The expression of CD40 was examined immunohistochemically in a series of 131 bladder transitional cell carcinomas and the correlation with known prognostic markers and clinical outcome assessed. Seventy-eight per cent of the tumours were CD40-positive, with a highly significant association with both lower stage and lower grade (p<0.001). Ta and T1 tumours expressed CD40 in 89 per cent of specimens compared with 62 per cent seen in T2-T4 tumours and in contrast to normal urothelium, which was mainly CD40-negative. CD40 expression was not related to any other clinicopathological variable including Bcl-2 and p53 expression, nor was it an independent prognostic marker. The lack of the relationship with Bcl-2 staining which is normally seen in basal epidermal cells may indicate alternative or abnormal CD40-mediated cell differentiation mechanisms. The diffuse expression seen in Ta bladder tumours may account for its clinically less aggressive behaviour and is likely to be an important factor in the excellent clinical response seen to BCG immunotherapy. It also raises the possibility of the future development of CD40/CD40 ligand-based immunotherapy for bladder cancer.

Adult↗

A concurrent comparison of a WHO-recommended 30-cluster survey and a modified version of it under Indian conditions in the estimation of immunization coverages.

A concurrent comparison of the WHO 30-cluster sample survey method for estimating immunization coverages (DPT, Polio, BCG, Measles) and an Indian modification of (GOI) was undertaken in five districts in South India. The essential difference between the two methods is the manner in which the first household is selected in the chosen clusters. With the WHO method, it is chosen clusters. With the WHO method, it is chosen at random, whereas with the GOI method it is often close to the village centre. Estimates with the required degree of precision, i.e., 95% confidence limits of +/- 10 percentage points, were provided in 18 (90%) of 20 instances by the WHO method and in 19 (95%) by the GOI method, findings which are in accordance with expectation. The estimated coverages were, however, higher by the GOI method than by the WHO method in two districts, lower in one district, and in the remaining two districts there was no clear pattern. On the average, there was a suggestion that the GOI method yielded slightly higher coverages, but the differences were not statistically significant.

Health Surveys↗

A comparison of a 30-cluster survey method used in India and a purposive method in the estimation of immunization coverages in Tamil Nadu.

A 30-cluster survey method that is employed for estimating immunization coverages by the Government of India (GOI) was compared with a Purposive method, to investigate whether the likely omission of SC/ST and backward classes in the former would lead to the reporting of higher coverages. The essential difference between the two methods is in the manner in which the first household is selected in the chosen first stage sampling units (villages). With the GOI method, it is often close to the village centre, whereas with the Purposive method it is always in the periphery or in a pocket consisting of SC/ST or backward classes. A concurrent comparison of the two methods in three districts in Tamil Nadu showed no real differences in the coverage with DPT and BCG vaccines. However, the coverage was consistently higher by the GOI method in the case of the Polio vaccine (by 1.5%, 3.1% and 5.3% in the 3 districts), and the Measles vaccine (by 4.8%, 13.3% and 13.9%); the average difference was 3.3% for Polio vaccine (p = 0.08) and 7.3% for Measles vaccine (p = 0.01).

Analysis of Variance↗

The aversive and hypophagic effects of estradiol.

Estradiol is known to reduce food intake in many species. Recent studies have also shown that estradiol can function as an unconditioned stimulus in taste aversion paradigms, suggesting that it induces nausea and malaise in rats and mice. The experiments reported here compared the hypophagic and aversive effects of estradiol. Using mice as subjects, the first investigation examined the taste aversion properties of the estradiol receptor antagonist MER-25, which is estrogenic with respect to feeding. MER-25 induced a strong taste aversion, contrary to a previous report. Second, progesterone, which counteracts the hypophagic effects of estradiol, did not disrupt the taste aversion induced by estradiol in mice. The third investigation used the Mongolian gerbil, a species in which estradiol increases food intake, in contrast to other species. Despite increasing food intake, estradiol induced a conditioned taste aversion in the gerbil similar to that seen in rats and mice. Taken together, these results indicate that the feeding and aversive effects of estrogen are mediated by different mechanisms.

Animals↗

New treatments for dementia. Myth, magic, and science.

Dementia could affect 778,000 Canadians by the year 2031. While current treatment is mainly supportive, a race to find new treatments for this dreaded disease takes varied approaches and currently accounts for 10% of drug company resources. Tacrine is the first drug licensed by the US Food and Drug Administration for use in Alzheimer's disease. New treatments raise several ethical issues and involve society's attitude toward death and dying.

Acetylcarnitine↗

Transposons in place of telomeric repeats at a Drosophila telomere.

We present the first isolation of the terminal DNA of an intact Drosophila telomere. It differs from those isolated from other eukaryotes by the lack of short tandem repeats at the terminus. The terminal 14.5 kb is composed of four tandem elements derived from two families of non-long terminal repeat retrotransposons and is subject to slow terminal loss. One of these transposon families, TART (telomere-associated retrotransposon), is described for the first time here. The other element, HeT-A, has previously been shown to transpose to broken chromosome ends. Our results provide key evidence that these elements also transpose to natural chromosome ends. We propose that the telomere-associated repetitive DNA is maintained by saltatory expansions, including terminal transpositions of specialized retrotransposons, which serve to balance terminal loss.

Animals↗

Investigation of anabolic steroids in two taste aversion paradigms.

The aversive effects of estradiol have been studied in two different taste aversion paradigms. A similar investigation was undertaken for the anabolic-androgenic steroids, nandralone and testosterone cypionate, using Rockland-Swiss mice. Experiments 1 and 2 used the brief exposure of a novel saccharin solution as the conditioned stimulus for taste aversion learning, and showed that anabolic steroids (1 mg) do not induce taste aversions. Instead, these hormones induced a small non-contingent increase in saccharin preference. Experiment 3 showed that daily nandralone administration (1 mg/day) had a greater anabolic effect than the same dose of testosterone cypionate. Experiment 4 paired the continuous exposure to a novel diet with daily nandralone injections, and showed that steroid treatment increased intake of the novel diet. When the novel diet was subsequently presented with the familiar diet in a two-choice preference test, there was no indication that an aversion was conditioned to the novel target diet. On the contrary, nandralone treatment significantly increased the preference for the novel diet. These experiments show that anabolic-androgenic steroids do not have aversive effects in mice, and that they may have positive consequences.

Anabolic Agents↗

Effect of morphine during pregnancy and lactation in mice.

The influence of pregnancy and lactation on morphine-induced hypothermia and hyperactivity was investigated in Rockland-Swiss mice. Pregnant mice were slower to recover from the hypothermic effect of morphine than nonpregnant controls. The greatest hypothermic response was seen in mice at day 18, the day before parturition. On the day after parturition, mice recovered faster from morphine-induced hypothermia than controls. During lactation, mice were again slower to recover from the morphine-induced hypothermia. Morphine-induced locomotor activity, however, was attenuated by both pregnancy and lactation. A further experiment compared the hypothermic effect of morphine in postpartum mice that were allowed to remain with pups and mice that were separated from pups. The enhanced hypothermia in the postpartum period was abolished by removing pups. This indicates that the altered response to morphine in the postpartum period was an effect of lactation rather than an aftereffect of pregnancy or parturition.

Animals↗

Conditioned taste aversion induced by estradiol pellets.

In two experiments, ovariectomized rats were given a novel diet prior to the implantation of a fused pellet of estradiol (E2 pellet). In short-term (3 weeks) ovariectomized rats, the suppression of food intake induced by estrogen was not affected by the introduction of the novel diet. However, a sensitive two-choice preference test revealed that subjects implanted with the E2 pellet had a lesser preference for the novel diet than controls implanted with the vehicle pellet. In long-term (18 weeks) ovariectomized rats, implantation of the E2 pellet had a large effect on the consumption of the novel diet. Intake was reduced to less than 1 g in all subjects on Days 3-7 after E2 pellet implantation. A subsequent two-choice preference test indicated the presence of a strong aversion to the novel diet in the estradiol-treated rats relative to the controls. These experiments show that estradiol can induce conditioned taste aversions that have either no effect on intake or totally suppress food intake, depending upon postovariectomy time.

Animals↗

Comparison of morphine tolerance in body temperature and luteinizing hormone secretion.

Small doses of morphine induce a hyperthermic response that does not change with repeated injections, whereas higher doses induce a hypothermia that changes to hyperthermia with repeated treatment. Experiment 1 confirmed these results in ovariectomized rats, using 6 repeated injections of morphine at 5 or 30 mg/kg. Using the same treatment regimen. Experiment 2 showed that the low dose of morphine induced a transient suppression of LH levels followed by a hypersecretion, and that repeated injections did not affect this response. The high dose (30 mg/kg) of morphine initially induced a sustained suppression of LH. Following the sixth injection of the high dose, subjects showed an intact or exaggerated suppression of LH, but an accelerated recovery to control levels. Experiment 3 extended the phase of repeated treatment of the high dose to 12 days and replicated the results of Experiment 2.

Animals↗

The role of conditioned taste aversion in the suppression of food intake by estradiol.

In three experiments, ovariectomized rats were given a familiar or novel diet prior to treatment with a brain-enhanced estradiol-chemical delivery system (E2-CDS, 1 mg/kg). Experiment 1 showed that food intake was suppressed in subjects receiving either diet, but animals given a novel diet initially showed a profound anorexia which eventually recovered to the moderate suppression of animals given the familiar diet. In Experiment 2, rats showed an aversion to a novel diet paired with the E2-CDS in a two-choice preference test given on Day 2 after the injection, indicating that the initial large reduction in intake was mediated by a conditioned taste aversion. However, no aversion was observed seven days after the E2-CDS, suggesting that the residual intake suppression was mediated by unconditioned aversion or appetite suppression. Experiment 3 showed that lengthening the postovariectomy time resulted in a taste aversion that persisted for a longer duration.

Animals↗

Glucocorticoids potentiate the dipsogenic action of angiotensin II.

The effect of a short-term, acute treatment with a glucocorticoid, dexamethasone sodium phosphate, on the drinking induced by angiotensin II (AII) was investigated in a series of experiments. Initial studies indicated that a single injection of dexamethasone (700-750 micrograms/kg, i.p.) reduced food intake, body weight and water intake for up to 48 h, but had little effect on blood pressure when it was measured 6 h subsequent to the injection. The drinking elicited by peripherally administered AII (200 micrograms/kg, s.c.) was enhanced if the glucocorticoid (700 micrograms/kg, i.p.) was given 3 h or 6 h prior to the dipsogen. There was no effect of pretreatment with the steroid if the drinking test was delayed by 24 h. The subsequent experiment showed that the glucocorticoid effect on AII-stimulated drinking was dose dependent (100 micrograms-1600 micrograms/kg). The drinking stimulated by intracerebroventricular (i.c.v.) AII (2.5 ng) was enhanced in terms of volume and total duration by prior treatment with dexamethasone, but i.c.v. carbachol (200 ng)-induced drinking remained unaffected. The final study showed that binding of AII to its receptors in five different areas of the rat brain was not affected by prior treatment with dexamethasone.

Angiotensin II↗

Effect of changing the unconditioned stimulus on appetitive blocking.

In four experiments we examined the effects of changing the unconditioned stimulus (US) on appetitive blocking. In Experiments 1A, 1B, and 2 we established that substituting food for water, or water for food, in the compound stage did not attenuate blocking relative to groups that received the same US throughout conditioning. Experiment 3 showed that satiation with the US used prior to compound conditioning with a different US does not affect blocking. Experiment 4 revealed that changing the location of US delivery, as well as the quality of the US, also leaves blocking unaffected. It is suggested that these results demonstrate that blocking occurs, provided that there is no change in the affective properties of the US.

Animals↗

Intravascular leiomyomatosis and benign metastasizing leiomyoma: an unusual case.

Benign metastasizing leiomyoma (BML) and intravascular leiomyomatosis (IVL) are rare variants of uterine leiomyomas. In our search of available literature, there have been only two reports of these conditions occurring in the same patient. We report a case of a 42-year-old female presenting with a left L4 nerve root lesion, left paravesical lesion, left ovarian cyst, multiple pulmonary metastases, and an intracaval lesion. Histology confirmed these to be leiomyomata strongly positive for estrogen receptors. Treatment included surgery, in two stages, to remove the L4 nerve root, left paravesical lesion, intracaval lesion, and a single pulmonary nodule. The remaining tumor was treated with a gonadotrophin-releasing hormone agonist, resulting in significant reductions in tumor size. It was concluded that the lesions in the lungs were an example of BML arising from the initial diagnosis of uterine leiomyoma, and the caval lesion was an IVL. Long-term follow-up is recommended, and familiarity with rare forms of benign smooth muscle uterine tumors is essential in avoiding misdiagnosis and overtreatment.

Adult↗

Significance of carotid restenosis following endarterectomy.

BACKGROUND AND PURPOSE: The clinical significance of restenosis after carotid endarterectomy as detected by duplex ultrasound has not been clearly established. To address this problem, we retrospectively evaluated the experience at two university-affiliated hospitals. METHODS: All charts of patients with carotid endarterectomies between June 1987 and April 1995 were reviewed. Inclusion required neurological assessment and postoperative duplex ultrasound. Exclusion was based on a known source of cardioembolic disease, or recent (<6 months) myocardial infarction. Primary clinical endpoints were ipsilateral transient ischemic attack (TIA) or ischemic stroke. Contributing vascular risk factors were also identified. The effect of restenosis on event-free survival was analyzed using life tables and Gehan-Wilcoxon rank sum tet. Logistic regression was used to identify independent risk factors for restenosis and vascular events. RESULTS: One hundred and eighty-seven patients were identified who underwent a total of 207 endarterectomies. Mean follow-up was 30.4 +/- 20.9 months during which a total of 64 vascular events, including 42 TIAs, 18 strokes, and 4 vascular deaths occurred. Of these 21 TIAs and 8 strokes were ipsilateral to the side of endarterectomy. Event rates were compared for patients with ipsilateral high- (>/=50%) and low-grade (<50%) restenosis. These two groups were comparable in terms of baseline risk factors. There was no significant difference in vascular event rates (for either ipsilateral events or events in any vascular territory) between the group with high- and low-grade restenosis. Nor was any such difference in event rates shown for patients who showed ipsilateral progression of carotid disease on serial ultrasound. However, patients operated for symptomatic carotid disease had a significantly higher risk of neurological events (p = 0.035). Logistic regression failed to disclose any other risk factors that were independently predictive of either restenosis or vascular events during follow-up. CONCLUSION: This study does not show a difference in vascular event rates for higher grades of carotid restenosis after carotid endarterectomy. Routine surveillance with carotid ultrasound does not appear to identify patients at higher risk for postoperative cerebrovascular events.

Carotid Artery, Internal↗