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Biomedical subjects

R Sud

Publications and source records attributed to R Sud.

11 recordsLinked to original sources
PubMed2005

An antidepressant mechanism of desipramine is to decrease tumor necrosis factor-alpha production culminating in increases in noradrenergic neurotransmission.

The monoamine theory of depression proposes decreased bioavailability of monoamines, such as norepinephrine (NE), as the underlying cause of depression. Thus, the antidepressant efficacy of NE-reuptake inhibitors such as desipramine is attributed to increases in synaptic concentrations of NE. The time difference between inhibition of reuptake and therapeutic efficacy, however, argues against this being the primary mechanism. If desipramine elicits its therapeutic efficacy by increasing NE release, in turn, increasing activation of the alpha(2)-adrenergic autoinhibitory receptor, then mimicking this increase with an exogenous agonist (clonidine) should support or even enhance the efficacy of the antidepressant. Intriguingly, simultaneous administration of clonidine with desipramine prevented the cellular and behavioral effects elicited by desipramine alone, in both acute and chronic administration paradigms. These results suggest the involvement of additional factor(s) in the mechanism of antidepressant action of this drug. Desipramine administration results in a virtual ablation of neuron-derived tumor necrosis factor-alpha (TNF), thus implicating an essential role of TNF in the therapeutic efficacy of this antidepressant. Additionally, following chronic administration of desipramine, TNF-regulation of NE release is transformed, from inhibition to facilitation. Here, we demonstrate that a transformation in TNF-regulation of NE release in the brain is a key element in the efficacy of this antidepressant. Interestingly, an increase in neurotransmission prior to the antidepressant's effect on TNF production prevents the efficacy of the antidepressant drug. Thus, the efficacy of desipramine is due to decreased levels of TNF in the brain induced by this drug, ultimately modifying noradrenergic neurotransmission.

Adrenergic alpha-Agonists↗
PubMed2001

Genetic alterations in gastric cancers from British patients.

Twenty-six gastric carcinoma and matching normal tissue DNAs, which had previously been analyzed for alterations of the APC (adenomatous polyposis coli) and MCC (mutated in colorectal cancer) genes were further investigated for the following genetic alterations: mutation and loss of heterozygosity (LOH) of the p53 gene, replication error (RER) and LOH at 12 microsatellite repeat loci, and mutation of the hMSH2 gene. In addition, 9 of the 26 gastric carcinomas were analyzed for genetic alterations using comparative genomic hybridization (CGH). Somatic mutations of the p53 gene were found to be frequent being detected in 31% of gastric carcinomas while LOH at the p53 locus was observed in 37.5% of informative cases. Loss of wild type p53 allele was detected in the majority (7 of 8) tumors found to be harboring a mutation. In the hMSH2 gene, an intronic 4 base pair insertion at 31 base pairs upstream of the beginning of exon 13 was detected in both tumor and normal tissue from one gastric carcinoma case. RER was detected in 11.5% of gastric carcinomas, at one or more microsatellite repeat loci. Of the 12 microsatellite repeat loci analyzed LOH was most frequently observed at D22S351 (30% informative cases) suggesting that a tumor suppressor gene on 22q may be important in gastric carcinogenesis. In support of this, CGH analysis carried out on 9 of the gastric carcinomas identified loss of chromosome 22 in 5 of these tumors.

Base Sequence↗
PubMed1996

Infrequent alterations of the APC and MCC genes in gastric cancers from British patients.

We examined 26 gastric carcinomas from British patients for mutations of the APC gene using a single-strand conformation polymorphism (SSCP) and heteroduplex assay in conjunction with the protein truncation test (PTT). In addition, we performed loss of heterozygosity (LOH) analysis of the APC and MCC genes. We detected an inactivating somatic mutation in one gastric tumour. LOH of APC was observed in one of 12 informative cases (8%) and of MCC in two of 20 cases (10%). We thus find that alteration of the APC and MCC genes are infrequent in gastric cancers from the British population. Tumour-suppressor genes on other chromosomes must play a more significant role in the development of these tumours.

Adenomatous Polyposis Coli Protein↗
PubMed1995

Biliary obstruction due to pancreatic insulinoma.

Pancreatic insulinomas are rare tumors and their association with polycystic disease of the liver is uncommon. We report here a patient with pancreatic insulinoma with hepatic metastasis and biliary obstruction presenting with neuroglycopenic symptoms and cholestasis on a background of polycystic liver disease.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1995

Rapid detection of rare variants and common polymorphisms in the APC gene by PCR-SSCP for presymptomatic diagnosis and showing allele loss.

During the course of screening the 5' half of exon 15 of the APC gene for germline and somatic mutations in two groups of patients, those with the inherited cancer prone syndrome adenomatous polyposis coli (APC) or with sporadic colorectal cancer, we have identified a number of intragenic changes that are not associated with the disease phenotype. Four of these changes are rare variants, each confined to one or two families and not detected in 50 additional unrelated people. Two common polymorphisms, at codon 1493 (exon 15I) and codon 1678 (exon 15J), were extensively investigated and found to be in almost complete linkage disequilibrium not only with each other but with a previously described polymorphism at codon 1960 (exon 15N). The rapid and sensitive single strand conformation assay used provides an efficient method for presymptomatic diagnosis using intragenic variants and was additionally used to show allele loss at the APC locus in sporadic colorectal carcinomas.

Adenomatous Polyposis Coli↗
PubMed1991

[Simple locomotion and during load carrying in pregnant women].

There have been few studies of the way women walk in pregnancy, though some of the causes of low back ache of which they complain have only been partially worked out. This is why this study has been carried out on ten women between the third and eighth month of pregnancy. The speed at which they walk and the parameters of the gait as well as the localization of the centre of gravity when keeping upright have been measured in these pregnant women as well as in twenty control women of the same age. The results show that the speed at which they walk whether with or without carrying a weight usually is identical at the beginning and the end of pregnancy. When walking normally the size of the steps taken are no larger in pregnant women than in the control patients (p less than 0.05). Though the results are not statistically significant the rhythm of the steps is faster as well as their being a reduction in the length of the steps between the third and eighth month of pregnancy. When carrying a weight the length of the steps does not change greatly with pregnancy (p less than 0.05) and it would seem therefore to be a good way of assessing the changes that locomotion undergoes in pregnancy. The fact that women do not walk faster or slower can give evidence that they adapt to the change in posture that happens in pregnancy and they make the best possible biomechanical use of the parameters of walking in order to economise total energy output of the organism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Exercise and pregnancy. Study of the change in heart rate in pregnancy when performing standardized moderate exercise].

The object of this study was to look at, on the one hand, the demands made on the pregnant woman's heart and, on the other hand, the effects on fetal heart rate resulting from moderate exercise with a definite rhythm performed by pregnant women. Ten primiparous pregnant women who had normal pregnancies took part in this study in the third and eighth months of the pregnancies. These women were compared with 20 control women who were not pregnant but whose mean age, height and weight were similar to those in the study before their pregnancies started. The maternal heart rate was monitored continuously and the fetal heart rate was recorded telemetrically when the women were carrying 5 kg in each hand with the arms held upright. We will discuss the results that were obtained in the 5 women who followed the course from the beginning to the end of the pregnancy for the sake of this study. The mean heart rate at rest was considerably higher in the pregnant women than in the controls at rest and standing. The heart rate was much higher during the exercise in the pregnant women than in the controls at rest and standing. The heart rate was much higher during the exercise in the pregnant women than in the controls. These changes in heart rate were essentially the same between the 3rd and the 8th month of the pregnancy. The fetal heart rate did not change significantly during nor after the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗