[Acute renal failure. 3. Thrombotic microangiopathy].
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Biomedical subjects
Publications and source records attributed to Y Terada.
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Mitogen-activated protein (MAP) kinase kinase (MAPKK) is a recently characterized activator of MAP kinase (MAPK), and is considered to be regulated by a protooncogene product c-Raf-1. It is, however, unclear whether the signals originating from c-Raf-1 utilize this phosphorylation cascade to lead to oncogenesis. To clarify this point, we isolated rat MAPKK cDNAs, and identified two distinct cDNAs encoding MAPKK and a highly related kinase, both with molecular weights of approximately 45 kDa (MEK1 and MEK2). Genomic Southern blot analyses suggested that MAPKK may form a large gene family.
The lysozyme-hydroxyapatite interaction was studied by measuring individual hydrogen-deuterium (H-D) exchange rates of amide protons. The H-D exchange reaction was initiated by transferring the lysozyme adsorbed on hydroxyapatite powder from H2O into D2O. After various H-D exchange time periods (pH 7.0, 25 degrees C), the complex was dissociated and the remaining hydrogen label was determined by 2D NMR analysis. The H-D exchange rate of amide protons of residues 9, 11, 13, and 83 was slowed in the hydroxyapatite-lysozyme complex compared with free lysozyme. Residues 9, 11 and 13 positioned at the back of the active site would be the location of the binding site.
Recent studies revealed that angiotensin II (Ang II) interacts with two pharmacologically different subtypes of cell surface receptors. Type I Ang II (AT1) receptor is characterized by signal transduction mediated through G protein and phospholipase C. In this study, the micro-localization of mRNAs coding for AT1 receptor and angiotensinogen was carried out in the rat kidney, using an assay of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments along the nephron, glomeruli, vasa recta bundle, and arcuate arteries. Large signals for AT1 receptor were detected in the glomerulus, proximal convoluted tubule (PCT), proximal straight tubule (PST), cortical collecting duct, and vascular system. Small signals were also seen in medullary thick ascending limb, outer medullary collecting duct, and inner medullary collecting duct (IMCD). Angiotensinogen mRNA is expressed largely in PCT, PST, and a small amount in glomerulus and vasa recta. Our data demonstrate that Ang II could be produced locally in proximal tubule and vasa recta bundle, and that the AT1 receptor was widely distributed not only in the glomerulus and vessels but also in tubules from PCT to IMCD.
Endothelin (ET) is now known to be a family of three distinct peptides. Although many reports have studied the renal action of ET-1, comparatively little is known concerning ET-3. We previously reported that ET-1 mRNA is expressed in glomerulus (Glm) and inner medullary collecting duct (IMCD). In this study, microlocalization of mRNA coding ET-3 was carried out in the rat kidney using a reverse transcription and polymerase chain reaction (RT-PCR) assay of individual microdissected renal tubule segments along the nephron, Glm, vasa recta bundle, and arcuate arteries. Large signals for ET-3 PCR product were detected in proximal convoluted and straight tubules, cortical collecting duct, and outer medullary collecting duct. Glm, IMCD, and vasa recta bundle also expressed relatively large amounts of ET-3 mRNA. Small signals were found in medullary thick ascending limb, inner medullary thin limb, and arcuate artery. We detected ET-3 protein in tubule suspensions from cortex, outer medulla, and inner medulla of rat kidney. Furthermore, incubation with TGF-beta did not change ET-3 PCR signal, whereas ET-1 PCR signal was increased significantly by exposure to TGF-beta in Glm and IMCD. Thus, ET-3 and ET-1 are distributed differently along the nephron and are regulated in different manners. This suggests that ET-3 and ET-1 may affect kidney functions in different ways.
A twelve-year follow-up study was carried out with 98 consecutive patients operated on for pure mitral stenosis with open mitral commissurotomy (OMC) or valve replacement with porcine valves (MVR). Each patient had the extent of valve distortion diagnosed preoperatively by two-dimensional echocardiography as either grade I of the dome-formation type, grade II of the intermediate type, or grade III of the mass-formation type. Thirty grade I patients and 24 grade II patients underwent OMC and 44 grade III patients received MVR. The long-term survival and reoperation rates were significantly poorer with grade II than grade I patients and there was no statistical significance between grades II and III. However, the clinical conditions set by NYHA are significantly worse in grade II than in grade III. This can be clearly explained by the fact that the left atrial volume decreasing ratio (LAVDR) in the latest period, which was measured in patients with more than 7 years survival, remained nearly at the early postoperative value in grade III, while the LAVDR of grade II at the latest period grew worse and became insignificantly different from the preoperative values. This study clearly shows that when OMC is applied to grade II patients, frequent reoperations might be necessary because of poor hemodynamic conditions. Thus, it might be better to adopt MVR rather than OMC with grade II patients with moderately distorted mitral valves.
The effects of hyperosmolality on the production and mRNA expression of endothelin-1 (ET-1) in inner medullary collecting duct (IMCD) were examined in the present study. Osmolality in incubation media was changed from 290 to 490 or 690 mosmol/kgH2O by adding NaCl, urea, mannitol, or raffinose. A preliminary experiment was carried out using tubule suspension from the inner medulla. Hyperosmolality by NaCl stimulated ET-1 accumulation in rats (from 323.5 +/- 76.3 to 478.0 +/- 108.4 and 573.7 +/- 47.8 pg.mg protein-1 x 24 h-1 in 290, 490, and 690 mosmol/kgH2O, respectively) and rabbits. In contrast, hyperosmolality by urea markedly decreased ET-1 accumulation and hyperosmolality by mannitol showed no effect on it. We next examined whether hyperosmolality changes ET-1 mRNA. After incubation in isotonic or hypertonic solution for 6 h, ET-1 mRNA was determined using reverse transcription and polymerase chain reaction (PCR) in microdissected IMCD and glomerulus. Hyperosmolality by NaCl and raffinose significantly increased the PCR products of ET-1 mRNA in IMCD, whereas mannitol did not. The stimulatory effect of hyperosmolality by NaCl on ET-1 mRNA expression was not observed in glomerulus. Our data suggested a stimulatory effect of hyperosmolality on production and mRNA expression of ET-1 in IMCD but not in glomerulus.
Endothelin-1 (ET-1) is known as a vasoconstrictor peptide. However, recent reports suggested the effects on the transport of renal tubule. We previously reported that ET-1 inhibited arginine vasopressin (AVP)-dependent adenosine 3',5'-cyclic monophosphate in rat collecting ducts. Physiologically, ET-1 reversibly and significantly inhibited AVP-stimulated water permeability in inner medullary collecting duct (IMCD). We therefore investigated the effects on water and electrolyte transport in rat cortical collecting ducts (CCD), where Na and Cl are actively reabsorbed more than in IMCD. Pathogen-free male Sprague-Dawley rats weighing 80-120 g were used after treatment with deoxycorticosterone pivalate for 1-2 wk. Isolated CCD were microperfused in vitro. The Cl concentration was measured by a continuous-flow ultra-microcolorimeter, and the raffinose concentration was measured as a volume marker by a continuous-flow ultra-microfluorometer. In the presence of 10(-9) M AVP, 10(-8) M ET-1 significantly inhibited fluid absorption (nl.mm-1 x min-1) from 0.25 +/- 0.02 to 0.15 +/- 0.05 (mean +/- SE, n = 6, P < 0.01), Cl absorption (pmol.mm-1 x min-1) from 30. 6 +/- 2.8 to 14.9 +/- 4.0 (P < 0.01), and potential difference (mV) from -5.4 +/- 1.3 to -4.0 +/- 1.2 (P < 0.01). Similar results were obtained in the lower concentration of 10(-10) M AVP and 10(-10) M ET-1. As for the osmotic water permeability (microns/s), 10(-8) M ET-1 significantly inhibited this from 320.1 +/- 50.9 to 202.1 +/- 42.2 (n = 7, P < 0.01) in the presence of 10(-9) M AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
Recent studies have revealed that arginine vasopressin (AVP) has at least two types of receptors in the kidney: V1a receptor and V2 receptor. In this study, microlocalization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in the glomerulus, initial cortical collecting duct, cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct, and arcuate artery. Small but detectable signals were found in proximal convoluted and straight tubules, inner medullary thin limbs, and medullary thick ascending limbs. Large signals for V2 receptor mRNA were detected in the cortical collecting duct, outer medullary collecting duct, and inner medullary collecting duct. Small signals for V2 receptor were found in the inner medullary thick limbs, medullary thick ascending limbs, and initial cortical collecting duct. Next, we investigated V1a and V2 receptor mRNA regulation in the dehydrated state. During a 72-h water restriction state, the plasma AVP level increased and V2 receptor mRNA decreased in collecting ducts. In contrast, V1a receptor mRNA did not change significantly. Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state.
The density and distribution of substance P-like immunoreactive (SP-LI) and calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerve fibers in rat temporomandibular joint (TMJ) were investigated in whole-mount preparations and frozen sections by immunohistochemistry with the avidin-biotin-peroxidase complex method. Both types of immunoreactive nerves were observed primarily in the joint capsule, the peripheral articular disc, the synovial membrane, and the periosteum. The distribution of CGRP-LI nerves was similar to that of SP-LI nerves. The anterior portion of the joint capsule and disc was most densely innervated, followed by the posterior, lateral, and medial portions. In addition, CGRP-LI nerves were more numerous and more dense in immuno-intensity than SP-LI nerves. In the synovial membrane, many SP- and CGRP-LI nerves terminated in the subsynovial layer, but some branches extended into the superficial synovial lining layer close to the joint cavity. Immunolabeled nerves were prominently located in the disc attachment and peripheral portion of the disc, and occasional nerves were located in the dense collagenous disc band as an actual disc. However, no fibers were detected in the central disc band. Thus, most of the disc was not innervated by any nerves. The present study provides a morphological basis for the possible roles of neuropeptides in endocytosis by synoviocytes, regulation of blood flow in the synovial membrane, nociception mechanisms of the TMJ, and modulation of the inflammatory response in the TMJ.
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Urodilatin is found in the urine and is thought to be produced in the kidney. The effect of urodilatin on cGMP accumulation in the kidney was investigated. cGMP accumulation by urodilatin and atrial natriuretic peptide (ANP) were compared with tubule suspensions from renal cortex, outer medulla, inner medulla, and microdissected nephron segments. Urodilatin-stimulated cGMP accumulation was higher in tubule suspensions from the inner medulla than in those from the cortex and outer medulla. The highest accumulation stimulated by 10(-6) M urodilatin among nephron segments was observed in glomeruli and inner medullary collecting ducts (IMCD). Small accumulations were seen in proximal convoluted tubules and medullary thick ascending limbs. Urodilatin-stimulated cGMP accumulation was almost equal to that stimulated by the same concentrations of ANP in these nephron segments. Urodilatin (10(-8) M) did not stimulate cGMP accumulation in glomeruli, but it stimulated cGMP accumulation in IMCD by threefold. This pattern was quite similar to that with ANP. It was concluded that urodilatin has a similar ability to ANP in stimulating cGMP synthesis and that the main target sites are glomeruli and IMCD.
From March 1986 to September 1991, the right gastroepiploic artery has been used for coronary artery bypass grafting in 200 patients (171 male and 29 female patients, mean age 58 years, range 6 to 80 years. They were followed up from 6 to 70 months with a mean of 27 months. There were 16 reoperations and 176 patients had triple vessel or left main disease. The gastroepiploic artery (182 in situ and 18 free grafts) was anastomosed to 11 anterior descending, 3 diagonal, 26 circumflex, and 160 right coronary arteries. The internal thoracic artery was concomitantly used in 192 patients. The mean number of distal anastomoses was 2.3 with arterial grafts and 3.3 including additional saphenous vein grafts. Postoperative angiography was performed in 152 patients within 6 months after the operation (mean 2 months) and after the operation second angiograms were done sequentially 1 to 5 years (mean 2 years) after the operation in 40 patients. There were 6 early and 4 late deaths. A new Q wave was noted in 4 patients. Duration of the operation and postoperative complications did not increase with the use of the gastroepiploic artery. Relief of angina was noted in 186 patients. Gastroepiploic artery graft patency was 95% (144/152) in the early postoperative period and 95% (38/40) in the late postoperative period. Percutaneous transluminal coronary angioplasty was done successfully through the in situ gastroepiploic artery graft for anastomotic stenosis in four cases. In stress myocardial scintiscans, performed sequentially preoperatively and in the immediate, 1-year, and 2-year postoperative periods in 11 patients, washout rate of the gastroepiploic artery-grafted area improved from 35% +/- 10% to 45% +/- 15% (p < 0.05) and was maintained to 43% +/- 6% and 48% +/- 9% at respective periods. In conclusion, the gastroepiploic artery is a suitable conduit for coronary artery bypass grafting in terms of low surgical risk, high patency rate, and excellent patient outcome.
This is a report of long-term follow-up of patients 70 years of age and older who underwent operations for ischemic heart diseases. (1) Two of them died in this follow-up period, one due to pneumonia seven months postoperatively, another due to lung cancer 20 months after operation. Actuarial survival rate was 96.8% at one year, 93.3% between two and five years. (2) Event-free rate was 80.6% at one year, 70.1% at two years, and 61.1% between three and five years. (2) Although 21 patients were classified in grade 0 (normal activity) of performance status, seven were classified between grade 2 and 4. We concluded that long-term results were good in surgical patients 70 years of age and older with ischemic heart disease.
Four patients underwent mitral valve re-replacement, and required tricuspid annuloplasty in two, through a right thoracotomy. There was no major postoperative morbidity and recovery was full and uneventful. The indications for selection of this approach were isolated mitral valve disease or combined tricuspid and mitral valve disease, severe adhesion between heart and sternum on CT scan, intact aortic valve and no severe reduction of respiratory function. We recommend right thoracotomy to approach atrioventricular valves in selected situations in patients for reoperations.
The antidiuretic hormone arginine vasopressin (AVP) receptors are G protein-coupled and have been divided into at least three types: V1a (vascular/hepatic) and V1b (anterior pituitary) receptors, which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+; and V2 (kidney) receptor, which is coupled to adenylate cyclase. Recently V1a and V2 receptor cDNAs were cloned. These cDNAs encode proteins with seven putative transmembrane domains and a similar structure to rhodopsin and other G protein-coupled receptors. Micro-localization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in glomerulus, cortical collecting duct (CCD), outer medullary collecting duct (OMCD), inner medullary collecting duct (IMCD), and arcuate artery. Large signals for V2 receptor PCR product were detected in CCD, OMCD, and IMCD. 72-hour dehydration caused decrease of V2 receptor mRNA, but no change in V1a receptor mRNA in rat IMCD. These data show that mRNA coding for the two AVP receptor subtypes are distributed differently along the nephron and renal vascular system, and that these mRNAs are regulated differently in response to the dehydrated state. Recently, two reports of a mutation in the vasopressin V2 receptor gene in a kindred with X-rinked nephrogenic diabetes insipidus are published. These studies demonstrated that point mutation of V2 receptor gene causes the nephrogenic diabetes insipidus. Understanding the nature of defective diabetes insipidus may ultimately lead to improved therapy.