Angiokeratoma circumscriptum of the oral cavity.
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Biomedical subjects
Publications and source records attributed to S Shanmugam.
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Five hundred pregnant women attending obstetrics OPD were screened for the presence of pruritus. The patients with other dermatological causes of pruritus (other than specific dermatosis of pregnancy) were excluded from the study. The selected patients were further subjected to routine laboratory investigations including liver function tests and IIBs Ag detection. The prevalence of pruritus in pregnancy was found to be 4.6% (23 cases). Ten patients were found to have specific dermatoses of pregnancy, including four cases of pruritus gravidarum and four of pruritic urticarial papules and papules of pregnancy. The prevalence of pruritus gravidarum was 0.8% of pregnancies. All the patients with pruritus gravidarum were primigravidae and had no clinical overlap with other specific dermatoses of pregnancy, jaundice, or intrahepatic cholestasis. One case of perinatal death was recorded among the pruritus gravidarum cases. This study has been helpful in determining the prevalence and severity of pruritus gravidarum in South India.
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Aside from the well known role of angiotensin II (Ang II) in blood pressure regulation and fluid homeostasis, accumulating evidence suggests that the octapeptide hormone also plays a role in growth and development. There are two major classes of Ang II receptors (AT1 and AT2) which mediate Ang II action. Both classes are members of the large superfamily of seven transmembrane domain spanning receptors. Fetal tissue express high levels of AT receptors. Throughout fetal and postpartum life, the AT1 and AT2 tissue distribution changes dramatically. The evolution of each receptor type is distinct and varies according to the organ. Thus, the different patterns of temporal expression of each receptor class could be related to various roles that Ang II may play during development.
Recent studies have shown that angiotensin II has a trophic action on the heart. The presence of two types of angiotensin II receptors, type 1 (AT1) and type 2 (AT2), has been reported in the rat heart. This in situ hybridization study describes the tissue and cell location of AT2 receptor mRNA in the developing rat cardiopulmonary system, from 15 days of gestation to adulthood. Expression of AT1A receptor mRNA was studied in parallel for direct comparison. The aortic arch and pulmonary artery expressed high levels of AT2 receptor mRNA from 15 days of gestation up until 15 days postpartum, whereas expression of this mRNA was observed only just before and after birth in the coronary arteries. AT2 receptor mRNA was not detected in any cardiac muscle of the fetus, neonate, or adult. The annulus of all four heart valves expressed AT2 mRNA from 21 days of gestation until 10 days postpartum, but no labeling was seen in the valve leaflets. The subendocardial atrial tissue showed a high level of AT2 receptor mRNA expression during the early postnatal period, but no expression was observed in the atrial myocytes from fetal stages to adulthood. The bronchi and trachea, but not the lung parenchyma, showed a high level of AT2 receptor mRNA expression starting from 17 days of gestation until 10 days postpartum. AT2 receptor mRNA expression in the cardiopulmonary system is therefore transient, developmentally regulated, and mostly located in vascular structures. By these three characteristics, its expression contrasts with that of AT1A, which is continuously expressed in the cardiac muscle to adulthood. This spatiotemporal pattern of expression of angiotensin II receptor mRNAs during development suggests a possible role for angiotensin II in organogenesis.
To study the distribution of the recently cloned angiotensin II type 2 (AT2) receptor in the rat fetus, a double stranded cDNA was generated by a new and recently described methodology requiring no cloning procedure. The cDNA obtained after reverse transcription (RT) and polymerase chain reaction (PCR) amplification corresponded to 500 base pairs of the gene coding sequence, and included the SP6 and T7 promoters at the 5' and 3' end, respectively. 35S-labeled cRNA sense and antisense probes were synthesized by in vitro transcription and used for in situ hybridization. From 13 to 19 days of gestation the AT2 receptor mRNA expression evolved and extended from a series of paired spots located para-axially, which were not identifiable at this level of observation, to a distribution in various mesenchymes (perichondrium, subepidermal layers), muscle cells (tongue, diaphragm, stomach), and classical target organs for Ang II (adrenal gland, kidney, aorta). During the first days after birth, the AT2 receptor mRNA decreased and remained detectable only in the adrenal gland and kidney. The distribution of the AT2 receptor mRNA appeared strikingly different from that of the AT1A receptor, which was studied in parallel for comparison.
The angiotensin II (ANG II) receptors have been pharmacologically classified into two major distinct types, designated AT1 and AT2. A high transient expression of AT2 receptors in the fetal tissues has been previously demonstrated. This study describes the cellular distribution of AT2 receptor mRNA in the developing rat kidney and adrenal gland by in situ hybridization with 35S-labeled cRNA probes. From day 12 of fetal life (F12) to day 15 postpartum (D15) AT2 mRNA was detected in the undifferentiated nephrogenic mesenchymal tissue but not in the immature and mature glomeruli and tubules of the kidney. No AT2 mRNA was observed in the kidney after D22. The adrenal gland also expressed AT2 receptor mRNA early during development from F12 but, unlike the kidney, continuously expressed the mRNA at high levels through to adulthood. The disappearance of AT2 mRNA in the kidney was synchronous with the completion of nephrogenesis and suggests that ANG II might act through this receptor as a differentiation/growth factor during nephron development. In the adrenal gland ANG II could act as a hormone and also as a differentiation/growth factor via the AT2 receptor.
The two subtypes (AT1A and AT1B) of the type 1 (AT1) angiotensin II receptor mRNA were localized by in situ hybridization in rat fetal tissues from day 11 to 19 of gestation and in the young rat from day 0 to 10 postpartum, by use of 35S-labeled cRNA probes. Both subtype mRNAs were present in the kidney and in the adrenal gland. Organs such as liver, lung, heart, and undifferentiated mesenchymes expressed only AT1A mRNA. In contrast to the adult, only AT1A subtype was expressed during fetal and postnatal periods in the pituitary gland. Large blood vessels (e.g., aorta and cerebral arteries) expressed exclusively AT1A mRNA during fetal stages. The expression of each subtype appears to be differentially regulated, in a tissue- and age-specific way. This spatotemporal regulation of AT1A and AT1B expression suggests that angiotensin II could act as a differentiation factor during organogenesis in addition to its classical role as a regulator of the cardiovascular system.
The localization of the two type 1 angiotensin II receptor subtype (AT1A and AT1B) messenger RNAs in the 19-day-old rat fetus was studied by in situ hybridization. AT1 receptor mRNAs were detected in target organs of the renin-angiotensin system such as the kidney, adrenal gland, liver, heart, large arteries, and pituitary gland. In addition, angiotensin II receptors were present in specialized mesenchymal cells surrounding the cartilage, in the pericardium, in the lung, and in the undifferentiated mesenchymal tissue. The AT1A subtype was predominant in all tissues and organs except the adrenal cortex and glomeruli in the kidney, which expressed both AT1A and AT1B mRNAs. The widespread distribution of AT1 receptors in tissues and organs involved in hydromineral equilibrium and blood pressure regulation shows that during fetal development angiotensin II may already act as a regulator of the cardiovascular system. An effect on cellular differentiation and/or proliferation via AT1 receptors is also suggested by their location in several mesenchymes.
The angiotensin II type 1 (AT1) receptor in murine species exists as two isoforms (AT1A and AT1B) encoded by two different genes. Both subtypes have a 9/10 homology in the coding sequence of their mRNA. We examined organs of adult rats (liver, pituitary gland, adrenal gland, kidney, heart, and lung) to study the differential expression of these two genes in target tissues for angiotensin II. AT1A and AT1B mRNAs were detected by in situ hybridization using specific riboprobes for the 3' noncoding region of the mRNAs that have the lowest homology (approximately 6/10). Only AT1A was expressed in the liver, heart, and lung, and only AT1B was expressed in the anterior pituitary, where most cells were positive. In the adrenal gland, AT1A mRNA was detected in the zona glomerulosa and medulla and AT1B in the glomerulosa. In the kidney, AT1A mRNA was the predominant isoform (mesangial and juxtaglomerular cells, proximal tubules, vasa recta, and interstitial cells), but AT1B was also detected in mesangial and juxtaglomerular cells and in the renal pelvis. The results of this in situ detection suggest a tissue-selective regulation of AT1A and AT1B mRNAs. This tissue specificity may constitute a prerequisite condition if the two angiotensin II receptor subtypes, which are pharmacologically similar, are to selectively modulate the various effects of angiotensin II in the different target tissues.
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