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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 307 records · Page 17Linked to original sources
PubMed1995

Immunohistochemical localization of V2 vasopressin receptor along the nephron and functional role of luminal V2 receptor in terminal inner medullary collecting ducts.

We investigated immunohistochemical localization of V2 vasopressin receptor along the nephron using a specific polyclonal antibody. Staining was observed in some of thick ascending limbs and all of principal and inner medullary collecting duct (IMCD) cells. Not only basolateral but also luminal membrane was stained in collecting ducts, especially in terminal IMCD (tIMCD). To learn the functional role of luminal V2 receptor in tIMCD, we studied the luminal effects of arginine vasopressin (AVP) on osmotic water permeability (Pf), urea permeability (Pu), and cAMP accumulation using isolated perfused rat tIMCD. In the absence of bath AVP, luminal AVP caused a small increase in cAMP accumulation, Pf and Pu, confirming the presence of V2 receptor in the lumen of tIMCD. In contrast, luminal AVP inhibited Pf and Pu by 30-65% in the presence of bath AVP by decreasing cAMP accumulation via V1a or oxytocin receptors and by an unknown mechanism via V2 receptors in the luminal membrane of tIMCD. These data show that V2 receptors are localized not only in the basolateral membrane but also in the luminal membrane of the distal nephron. Luminal AVP acts as a negative feedback system upon the basolateral action of AVP in tIMCD.

Amino Acid Sequence↗
PubMed1995

Hormonal regulation of rat adrenomedullin gene in vasculature.

Adrenomedullin (AM), a novel vasodilatory peptide originally isolated from human pheochromocytoma, has subsequently been shown to be expressed in a variety of tissues, such as adrenal gland, lung, heart, kidney, and aorta. To determine whether vascular AM gene expression is under hormonal control, the effects of dexamethasone (DEX) and T3 on AM messenger RNA (mRNA) expression were tested in cultured rat vascular endothelial cells and smooth muscle cells (VSMCs) by Northern blot analysis using polymerase chain reaction-cloned rat AM complementary DNA as a probe. DEX dose and time dependently increased steady-state AM mRNA levels in both endothelial cells and VSMC. T3 modestly induced AM mRNA expression in both cells, whereas rT3, a biologically inactive isomer of T3, failed to affect AM mRNA expression. A glucocorticoid receptor antagonist (RU 38486) blocked DEX-induced AM mRNA expression in both cells, whereas neither estradiol nor testosterone affected AM mRNA expression. Actinomycin D abolished basal as well as stimulated AM mRNA expression by T3, whereas cycloheximide markedly increased steady state mRNA levels (superinduction). The approximate half-lives of basal and stimulated expression of AM mRNA by DEX in VSMC were within 1 h. In contrast, there was little, if any, decay in cycloheximide-induced AM mRNA expression over 6 h. Our study demonstrates that the AM gene expressed by vascular endothelial and smooth muscle cells is similarly regulated by glucocorticoid and possibly by thyroid hormone, and that superinduction of AM mRNA is most likely due to increased mRNA stability.

Adrenomedullin↗
PubMed1995

Presence and regulation of Raf-1-K (Kinase), MAPK-K, MAP-K, and S6-K in rat nephron segments.

Renal nephron segments are heterogeneous, and receptors for endothelin (ET)-1, ET-3, Angiotensin II (AII), epidermal growth factor (EGF), and insulin-like growth factor I distribute differently along the nephron segments. Recently, growth factors and vasoactive substances are reported to stimulate mitogen-activated protein kinase (MAP-K). In this study, we showed that mRNA and proteins of MEK-K, Raf-1-K, MAPK-K, MAP-K (p42 and p44), and S6-K are expressed ubiquitously in intact nephron segment. We demonstrated that four tiers of a cascade composed of the Raf-1-K, MAP-K, MAP-K, and S6-K are stimulated by ET-1 and ET-3 in rat intact glomeruli (Glm) via primarily B-type ET receptors and PKC. The stimulatory effect of EGF and IGF-I to MAP-K activity is inhibited by a tyrosine kinase inhibitor in Glm. IGF-I significantly stimulates MAP-K activity and EGF and All moderately stimulate MAP-K activity in the proximal convoluted tubule (PCT). EGF significantly increased MAP-K cascades and ET-1 and ET-3 slightly increased MAP-K cascades in the medullary thick ascending limb (MTAL). EGF significantly stimulated MAP-K cascades, and ET-1 and ET-3 moderately stimulate MAP-K cascades in the outer medullary collecting duct (OMCD) and the inner medullary collecting duct (IMCD). MAPK-K and S6-K are similarly stimulated by these agonists in each segment. This study shows that MAP-K cascades are expressed in every nephron segment. ET-1, ET-3, All, EGF, and IGF-I stimulate MAP-K cascades heterogeneously along the nephron segment. It was concluded that MAP-K cascades play an important role in the regulation of renal function.

Animals↗
PubMed1995

Mechanisms of regulatory volume decrease in collecting duct cells.

The mechanisms of cell volume regulation upon osmotic cell swelling were examined in the inner stripe of the outer medullary collecting duct (OMCDi). Segments of OMCDi were dissected from rabbit kidney and perfused in vitro. Using an image processing system, the cross-sectional area of tubule cells was monitored as an index of the relative cell volume. In response to a decrease in extracellular osmolality (290 to 190 mOsm), the tubule cells swelled promptly and restored gradually their original cell volume by a mechanism termed regulatory volume decrease (RVD). The initial response of RVD (the rate of the decrease in cell volume during the first 10 min) was inhibited by 79% at a high concentration of basolateral K+ (50 mM). By contrast, the same concentration of luminal K+ did not affect the response. When basolateral Cl- was removed 30 min before the experiment, the initial response of RVD was decreased by 77%, whereas the response was not affected 30 min after removal of luminal Cl-. Addition of basolateral Ba2+ and basolateral anthracene-9-CO2H inhibited the response by 70 and 65%, respectively. RVD response was accompanied by a transient rise in intracellular Ca2+. The Ca2+ rise was abolished when intracellular Ca2+ was chelated by acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). In this condition, the initial RVD response was decreased by 68%. Our data suggest that the exit of basolateral K+ and Cl- via conductive pathways mainly mediates the RVD response in rabbit OMCDi cells, and that intracellular Ca2+ is involved in this response.

Animals↗
PubMed1995

[Exercise testing in cardiac patients].

Symptom-limited incremental exercise tests have been used, to estimate the severity of cardiovascular disease and the patients' daily activity. However, there is a considerable amount of interest in obtaining submaximal measurements of aerobic function rather than parameters requiring maximal exercise effort. We compared the parameters obtained during the incremental exercise with those during the 6 minutes of moderate constant work rate exercise. Peak oxygen uptake (VO2) and the anaerobic threshold were significantly decreased in patients with cardiovascular disease as compared to normal subjects. The slope of the increase in carbon dioxide output (VCO2) to the increase in VO2 (delta VCO2/delta VO2) above the anaerobic threshold was significantly increased and the slope of the increase in VO2 to the increase in work rate (delta VO2/delta WR) was significantly decreased in patients with cardiovascular disease. The anaerobic threshold was found to occur at the work rate above which left ventricular function decreased during exercise in these patients. The time constant of VO2 during and following recovery from 6 minutes of 50 watts of constant work rate exercise was significantly longer (the kinetics of VO2 were slower) in patients with cardiovascular disease than in normal subjects. The time constant of VO2 was significantly negatively correlated with peak VO2 and maximum work rate obtained during the incremental exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗
PubMed1995

Increased gene expression of water channel in cirrhotic rat kidneys.

In patients with liver cirrhosis, impaired water and sodium excretion has been incriminated in the pathogenesis of ascites formation. Increased reabsorption of water in the distal nephron has been shown to play an important role in water retention in cirrhotic rat kidneys. Recently, a complementary DNA (cDNA) for the vasopressin-regulated water channel (the aquaporin of the apical membrane of the kidney collecting duct [AQP-CD]) has been cloned. It is suggested that AQP-CD plays an important role in renal water handling. Therefore, in the present study, to investigate the pathogenic role of the water channel in water retention in liver cirrhosis, gene expression of AQP-CD in the kidney was evaluated in cirrhotic rats. Liver cirrhosis was induced by an intraperitoneal administration of carbon tetrachloride twice a week for 12 weeks in 14 rats. Messenger RNA expression of AQP-CD in whole kidney homogenates determined by Northern blot hybridization was significantly increased in cirrhotic rats (147%; P < .01) and dehydrated rats (206%; P < .0001) compared with control rats. Protein expression of AQP-CD in the homogenates of kidney medulla determined by Western blot analysis was significantly increased in cirrhotic rats (203%; P < .03) compared with control rats. Furthermore, mRNA expression of AQP-CD in the kidney showed a significant correlation with the volume of ascites in cirrhotic rats (r = .62, P < .02). No significant difference was observed in water intake, urinary volume, serum osmolality, serum sodium, and creatinine clearance between control and cirrhotic rats, suggesting that dehydration was unlikely in cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Diversity of quasispecies in various disease stages of chronic hepatitis C virus infection and its significance in interferon treatment.

Hepatitis C virus (HCV) populations in vivo exist as a mixture of heterogeneous viruses called quasispecies, which have variations in the hypervariable region (HRV). However, the relationship between the diversity of HVR quasispecies, the disease stage, or the interferon (IFN) responsiveness remains to be elucidated. To study these, serum samples were obtained from 42 patients with chronic hepatitis C virus infection; 24 with chronic active hepatitis (CAH) treated with IFN, 9 with cirrhosis, 9 with hepatocellular carcinoma (HCC). HCV quasispecies populations were separated by the single-strand conformation polymorphism (SSCP) method targeted to the HVR. The patients were classified into two groups; a single-band group (n = 12) in which HVR quasispecies was homogeneous and a multiple-band group (n = 30) in which HVR quasispecies was heterogeneous. Patients with multiple bands had significantly more advanced liver disease than those with a single-band group (P = .0082). The percentage of patients with single band were 41% in CAH, 22% in cirrhosis, and 0% in HCC. Multivariate analyses showed that viral diversity was independently related to the progression of liver disease and was not correlated with the duration of infection. We also found that in CAH, the patients who had multiple bands (n = 14) were more resistant to IFN therapy than those who had a single band (n = 10) (P = .002). These results indicate that the diversity of HCV quasispecies becomes more complex as the disease stage progresses and that CAH with more complex diversity shows less IFN effectiveness.

Aged↗
PubMed1995

[Biosynthesis of hormones in renal tubular and interstitial cells].

Renal tubular and interstitial cells produce various hormones. Renin is synthesized in juxtaglomerular cells which are derived from the media of the afferent arteriole. Endothelin-1 is formed in mesangial cells of glomeruli and inner medullary collecting duct. In contrast, endothelin-3 synthesis is observed in glomeruli and all the tubule segments. 1 alpha-hydroxylase is present in proximal tubule and catalyzes production of 1,25(OH)2D. PGE2 is synthesized in glomeruli, all the tubule segments, and interstitial cells. The major production sites of PGF2 alpha and 6-keto-PGF1 alpha are glomeruli and medullary collecting duct. Kallikreins are mainly produced in connecting tubule. The cells responsible for erythropoietin synthesis are thought to be interstitial cells which are localized around the proximal tubule.

Animals↗
PubMed1995

Intravenous calcitriol can increase bone mass in hemodialysis patients with osteitis fibrosa.

Intravenous calcitriol administration (IVC) suppressed parathyroid hormone (PTH) secretion and improved osteitis fibrosa (OF) in long-term hemodialysis (HD) patients, although it did not increase the mineralized bone area or the mineral apposition rate. We observed the long-term effects of IVC on OF in 8 HD patients. Bone biopsy of 7 patients revealed increased bone turnover and decreased bone mass. One microgram of calcitriol was given intravenously three times weekly after each HD session for 12 months. The dose was adjusted to maintain the serum corrected calcium level at < 11.5 mg/dl. Dual-energy X-ray bone absorptiometry (DEXA), 3rd lumbar vertebra bone density by quantitative computed tomography (QCT), and biochemical data were taken before IVC, and after 6 and 12 months of IVC. Seven HD patients were given 0.5 microgram/day 1 alpha-cholecalcitriol as controls. The serum corrected calcium levels were 9.9 +/- 0.3 (mean +/- SE) and 11.1 +/- 0.2 mg/dl at 0 and 12 months, respectively (p = 0.06). The serum phosphate levels were 6.2 +/- 0.7 and 6.6 +/- 0.6 mg/day at 0 and 12 months, respectively (p = 0.56). The serum intact PTH levels were 928 +/- 281 and 617 +/- 192 (p = 0.016) at 0 and 12 months, respectively. The bone mass of the 3rd lumbar vertebra measured by QCT was 195 +/- 17 and 218 +/- 186 g/cm3 at 0 and 12 months, respectively (p = 0.156). The bone mass of the trunk measured by DEXA was 660 +/- 44 and 706 +/- 32 g and 0 and 12 months, respectively (p = 0.156). These parameters did not change in controls. Sequential bone biopsy in 3 cases also supported these changes. We conclude that IVC not only suppresses bone turnover, but that it also restores decreased bone mass in HD patients with OF.

Adult↗
PubMed1995

Systemic hypotension and diuresis by L-arginine in cirrhotic patients with ascites: role of nitric oxide.

To investigate the role of nitric oxide in renal function and hemodynamics in cirrhotic patients with ascites, L-arginine (30 g in 300 mL of distilled water), a substrate for nitric oxide synthase, was infused into six cirrhotic patients with ascites, and the effects were compared with those of saline infusion. Healthy controls (n = 5) were also studied under the same conditions. In the patients, L-arginine infusion significantly decreased systolic and diastolic blood pressures while markedly increasing urinary flow and urinary sodium excretion; no significant changes were seen with saline infusion. In controls, only diastolic blood pressure was decreased by L-arginine infusion, whereas urinary flow and urinary sodium excretion were increased by both L-arginine and saline infusion. In both groups, a similar increase of plasma atrial natriuretic factor (ANF) was seen with L-arginine and saline infusions; endothelin and catecholamines were not affected by either infusion. In both groups, plasma levels of vasopressin were increased by L-arginine infusion. In the cirrhotic patients, urinary excretions of cyclic guanosine monophosphate (cGMP) and nitrates/nitrites (NOx) were significantly increased by L-arginine infusion, whereas no significant changes were seen with saline infusion. In controls, only the excretion of cGMP was increased by L-arginine infusion. In summary, L-arginine infusion induces diuresis and natriuresis accompanied by increased excretions of cGMP and NOx in cirrhotic patients with ascites. This differs from the response in controls, where the increase in urinary sodium excretion is not accompanied by an increase in markers of increased nitric oxide synthesis.

Adult↗
PubMed1995

Limited usage of T-cell receptor beta chains and sequences of the complementarity determining region 3 of lymphocytes infiltrating in the liver of autoimmune hepatitis.

To study the role of antigen-specific T lymphocytes in the pathogenesis of autoimmune hepatitis, messenger RNA of T-cell receptors (TCR) was analyzed in liver biopsy specimens from four patients with autoimmune hepatitis. Using the TCR beta-chain variable region family specific oligonucleotides, a remarkable bias for the usage of beta-chain variable region 3 was detected in all four patients. Therefore, nucleotide and amino acid sequences of the complementarity-determining region 3 rearranged to the beta-chain variable region 3, which is a putative contact site for peptide fragments from antigens bound in the groove of the human leukocyte antigen molecule, was further analyzed in randomly selected 10 clones from each patient. An Asp-Arg-Pro motif in the complementarity-determining region 3 was identified in three of four patients with human leukocyte antigen DR4, and this motif was always rearranged to the beta-chain junctional region 1.2. From these results, beta-chain variable region 3+, Asp-Arg-Pro+, beta-chain junctional region 1.2+ T-cell clones may be among the responsible lymphocytes involved in the liver damage in autoimmune hepatitis, especially in patients with human leukocyte antigen DR4. Thus, an analysis of the complementarity-determining region 3 may give us an important clue to clarify characteristics of target antigens included in autoimmune hepatitis.

Adult↗
PubMed1995

Effects of verapamil on hepatic glutathione in the rat.

Effects of verapamil, an calcium channel blocker, on hepatic glutathione were studied in vivo in the rat and in the perfused rat liver. An injection of verapamil at a dose of 15 mg/kg body weight but not at 5 mg/kg significantly decreased hepatic glutathione contents in both fed and fasted animals 6 h after the injection. The administration of verapamil at a dose of 10 mg/kg twice a day for a week brought a significant decrease in hepatic glutathione contents and a significant increase in plasma glutathione levels. In the perfused rat liver, sinusoidal glutathione efflux was significantly increased when verapamil was added to the perfusion medium in a concentration of 20 microM. These data indicate that verapamil increases glutathione efflux from the liver and that calcium mobilization may be concerned in glutathione efflux in vivo.

Animals↗
PubMed1995

Effects of one-year cadmium exposure on livers and kidneys and their relation to glutathione levels.

To study the effects of a long-term cadmium exposure on livers and kidneys, rats were administered cadmium chloride (0.228 mg Cd/kg, 3 days/week ip), for one year. Significant accumulation of cadmium was observed in livers (183 +/- 40 micrograms/g liver) and kidneys (92 +/- 17 micrograms/g kidney). Serum urea nitrogen and creatinine levels were significantly elevated in the cadmium-treated rats, while liver function tests were minimally affected. Histological observations showed interstitial fibrosis with minimal cell necrosis and inflammatory cell infiltration in livers, and apparent degeneration of proximal tubules and infiltration of inflammatory cells in parenchyma of kidneys. Lipid peroxidation in livers and kidneys, as assessed by thiobarbituric acid reactive substances, revealed no differences between the cadmium-treated rats and the controls. Glutathione contents were significantly increased in the cadmium treated rats both in livers (p < 0.001), and in kidneys (p < 0.001) compared with the controls. Increased glutathione levels in livers may contribute, in part, to the prevention of serious hepatotoxicity during chronic cadmium exposure, while nephrotoxicity due to cadmium may not be prevented by glutathione.

Animals↗
PubMed1995

[A case of alveolar soft part sarcoma found by pulmonary metastasis].

A 34-year-old housewife presented to a hospital because of dry cough. Her chest radiograph showed bilateral multiple nodular lesions. Smaller but similar lesions had been seen on the chest radiograph 2 years earlier. Because the tissue taken during a trans bronchial biopsy was non-diagnostic, open lung biopsy was done and the diagnosis was pulmonary metastasis of alveolar soft part sarcoma. The primary tumor was found in her left calf by MRI. Malignant tumors are important for differential diagnosis of slow-growing multiple pulmonary nodules, and in some cases MRI is useful for finding the primary site.

Adult↗
PubMed1995

Aeromonas sobria infection with severe muscle degeneration in a patient with alcoholic liver cirrhosis.

A 56-yr-old male who had been followed for alcoholic liver disease was admitted for abdominal pain and a high fever. Gastrointestinal endoscopy revealed bleeding esophageal varices that were treated by endoscopic sclerotherapy. Blood culture on admission was positive for Aeromonas sobria. Then skin bullas and ulcers and severe muscle degeneration developed. The patient died despite extensive treatment with antibiotics. A. sobria infection in patients with liver cirrhosis is rare.

Aeromonas↗