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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 397 records · Page 22Linked to original sources
PubMed1993

Alpha-smooth-muscle actin expression in normal and fibrotic human livers.

To determine the significance of the expression of alpha-smooth-muscle actin in the fibrotic human liver, normal and diseased livers were stained with anti-alpha-smooth-muscle-actin antibody by an immunoperoxidase method. Vitamin A-containing lipocytes were also identified by the modified Kupffer's gold chloride method. In the normal human liver, lipocytes as well as vascular smooth muscle cells expressed alpha-smooth-muscle actin. In alcoholic liver disease, there was an increase in the cells positive for alpha-smooth-muscle actin adjacent to the fibrotic areas, but the response of lipocytes to the gold chloride reaction diminished. In chronic hepatitis, the cells positive for alpha-smooth-muscle actin increased around the enlarged portal areas, and the response to the gold chloride reaction did not change appreciably. An increase in the cells positive for alpha-smooth-muscle actin was associated with the progression of hepatic fibrosis in the liver of patients with alcoholic liver disease and chronic hepatitis.

Actins↗
PubMed1993

Hepatocellular carcinoma producing universal type of alkaline phosphatase.

We report on a 54-year-old man with hepatocellular carcinoma (HCC) associated with a marked elevation of serum alkaline phosphatase (ALP) levels. Serum ALP was biochemically similar to that of universal (liver/bone/kidney) type. The noncarcinomatous area revealed typical micronodular cirrhosis due to excessive alcohol consumption. By histochemical staining, ALP activity was demonstrated diffusely within the cytoplasm of carcinoma cells. Immunohistochemical observation of the carcinoma cells excluded the intestinal or placental type of ALP. Tissue extracts from the carcinomatous area had much higher ALP activities than those from a noncarcinomatous area, which also showed characteristics of the universal type. The present HCC is the first reported to produce and excrete the universal type of ALP.

Alkaline Phosphatase↗
PubMed1993

Endothelin-1 is an autocrine/paracrine regulator of porcine granulosa cells.

We studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from porcine granulosa cells, and whether ET-1 acts directly on granulosa cells in an autocrine/paracrine fashion. The dilution curve of the conditioned medium from cultured porcine granulosa cells was parallel to a standard curve of ET-1 in RIA. Reverse-phase HPLC of the conditioned media from the granulosa cells revealed a major peak of ET-1-like immunoreactivity (ET-1-LI) coeluting with standard ET-1. ET-1-LI was released from cultured porcine granulosa cells as a function of time. Northern blot analysis demonstrated the expression of mRNA for prepro-ET-1 in the granulosa cells. We demonstrated the presence of ET-1 in the follicular fluid of porcine ovaries, and that the concentration of ET-1 in large follicles was higher than that in small-medium follicles. ET-1 dose-dependently stimulated cell growth and DNA synthesis in porcine granulosa cells. ET-1 inhibited the FSH- and hCG stimulated accumulation of progesterone in porcine granulosa cells in long-term incubation. These findings suggest that ET-1 produced by porcine granulosa cells may function as an autocrine/paracrine growth factor and modulator of steroidogenesis in ovarian granulosa cells.

Animals↗
PubMed1993

Characterization of vasopressin-mediated GSH efflux from Hep G2 cells: significance of protein kinase C.

Vasopressin stimulated GSH efflux from Hep G2 cells. The maximal effect was observed at 10nM. Pretreatment with pertussis toxin or cholera toxin for 18 hr increased GSH efflux. Vasopressin-mediated GSH efflux was observed even in the cells pretreated with those compounds. Dibutyryl-cAMP or dibutyryl-cGMP enhanced GSH efflux although an additive effect of vasopressin was not observed. Glucagon and a phorbol ester independently increased GSH efflux while both compounds decreased the effect of vasopressin. Staurosporine, an inhibitor of protein kinase C, inhibited vasopressin-mediated GSH efflux. The effect of vasopressin was observed even in the absence of extracellular Ca2+. Vasopressin stimulates GSH efflux from Hep G2 cells and protein kinase C-dependent pathway may play a significant role in vasopressin-mediated GSH efflux.

Alkaloids↗
PubMed1993

Role of lipid peroxidation in acetaminophen-induced hepatotoxicity: comparison with carbon tetrachloride.

The effect of acetaminophen on lipid peroxidation in vivo and in vitro was studied in rat liver and the data were compared with those with carbon tetrachloride. Carbon tetrachloride increased diene conjugates in vivo and thiobarbituric acid reactive substance production in vitro in the liver microsomal incubation. These changes were further enhanced by ethanol that has previously been shown to increase carbon tetrachloride-induced hepatotoxicity. On the other hand, acetaminophen did not increase diene conjugates in vivo and inhibited thiobarbituric acid reactive substance production in vitro. These effects were minimally affected by ethanol which has previously been shown to inhibit acetaminophen-induced hepatotoxicity. Thus, lipid peroxidation may play a minimal role in acetaminophen-induced hepatotoxicity in contrast with carbon tetrachloride-induced hepatotoxicity.

Acetaminophen↗
PubMed1993

Detection of hepatitis C viral RNA in sporadic acute non-A, non-B hepatitis by polymerase chain reaction. Its usefulness for the early diagnosis of seronegative infection.

To determine the prevalence of hepatitis C viral infection in patients with sporadic non-A, non-B (NANB) acute hepatitis, hepatitis C viral RNA was studied in the plasma of 15 patients by reverse transcription-polymerase chain reaction assay. Plasma samples were sequentially obtained from 15 patients, and polymerase chain reaction was performed with two nested pairs of primers deduced from the 5'-non-coding region of hepatitis C viral sequences. Anti-C100 and anti-GOR antibodies were also measured with an enzyme-linked immunosorbent assay system. Plasma hepatitis C viral RNA was detected transiently in 7 of 15 patients (47%) at an early phase of the clinical course, while anti-C100 antibodies were detectable in only 2 (29%) of hepatitis C viral RNA-positive patients, and in 1 (13%) of the negative patients. Of 7 patients that were positive for plasma hepatitis C viral RNA, 4 (57%) had relapsing or protracted courses. In contrast, in all patients with undetectable hepatitis C viral RNA, hepatitis C viral RNA recovered and remained normal for at least 1 year. Thus, hepatitis C viral infection represents almost half the patients with acute sporadic NANB hepatitis, and detection of hepatitis C viral RNA in an early clinical phase is superior to anti-C100 measurement for diagnosing acute sporadic hepatitis C viral infection.

Adult↗
PubMed1993

Short-term effects of denopamine on anaerobic threshold and related parameters in patients with chronic heart failure: a double-blind crossover study.

BACKGROUND: The short-term effects of denopamine, an orally available beta-stimulant, on exercise capacity were studied in patients with chronic heart failure. METHODS AND RESULTS: Nineteen patients entered the study. Three patients had ischemic heart disease, 13 had dilated cardiomyopathy, and three had valvular disease; 16 patients were in New York Heart Association class II, and three patients were in New York Heart Association class III. Symptom-limited exercise testing (ramp protocol) on a bicycle ergometer with gas exchange analysis was conducted 1 hour after oral administration of either 20 mg denopamine or placebo. Drug administration sequence was randomly assigned in a double-blind crossover method, with 1 week between drugs. Peak VO2 was 20.4 +/- 3.2 and 21.2 +/- 3.1 ml/min/kg, respectively, for those administered the placebo and the drug, and anaerobic threshold was 13.1 +/- 2.1 and 14.0 +/- 2.0 ml/min/kg. There was a significant increase in peak VO2 (p < 0.05) and anaerobic threshold (p < 0.01) with denopamine, whereas no significant change was observed in peak work rate or exercise time. Denopamine increased heart rate in patients with atrial fibrillation but had little effect on heart rate in patients with sinus rhythm. CONCLUSION: Data obtained from gas exchange analysis are more sensitive and potentially more useful in the detection of short-term changes in exercise capacity than data obtained from either exercise time or peak work rate, indexes that are commonly used to assess drug therapy. Patients with mild-to-moderate heart failure with sinus rhythm, but not those with atrial fibrillation because of its frequent induction of tachycardia, may be good candidates for denopamine therapy.

Adrenergic beta-Agonists↗
PubMed1993

PCR localization of angiotensin II receptor and angiotensinogen mRNAs in rat kidney.

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.

Angiotensin II↗
PubMed1993

Expression of endothelin-3 mRNA along rat nephron segments using polymerase chain reaction.

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.

Animals↗
PubMed1993

Effects of dietary protein restriction on hemodynamics in chronic renal failure.

To elucidate the effect of protein and phosphorus restriction on hemodynamics in chronic renal failure, 14 patients were placed on a low-protein very-low-phosphorus diet (LPVLPD) and observed for metabolic and hemodynamic changes. For three weeks after initiation of the LPVLPD, the patients displayed a positive sodium balance in spite of dietary sodium restriction. During the fourth week, sodium balance decreased and approached zero. Sodium retention was accompanied by a significant decrease in plasma renin activity (P < 0.05) and mean blood pressure (P < 0.01), an increase in body weight (P < 0.05), a slight temporary decrease in hemoglobin (P < 0.05), hematocrit (P < 0.05) and total protein (P < 0.005), a negative nitrogen balance, and an increase in left ventricular ejection fraction (P < 0.01) and peak filling rate (P < 0.05). Serum creatinine concentration and endogenous creatinine clearance did not change during the experiment. These data indicate a role of dietary protein and phosphorus restriction in cardiac and fluid homeostasis in the pathophysiology of chronic renal failure.

Aged↗
PubMed1993

Atrial natriuretic peptide in the pericardial fluid of patients with heart disease.

1. The pericardial fluid of 20 open heart surgery patients with acquired heart disease was analysed for atrial natriuretic peptide by radioimmunoassay. 2. The concentration of atrial natriuretic peptide in the pericardial fluid was significantly higher than in the corresponding plasma (316.8 +/- 50.0 versus 121.7 +/- 29.1 pg/ml; P < 0.01) and was higher in patients with congestive heart failure than in those without heart failure (469.3 +/- 78.6 versus 181.8 +/- 26.7 pg/ml; P < 0.001). Pericardial and plasma atrial natriuretic peptide concentrations showed a significant positive correlation. Pericardial fluid and plasma samples were fractionated using both reverse-phase high-performance liquid chromatography and gel permeation chromatography. Each fraction was assayed for atrial natriuretic peptide by radioimmunoassay, revealing the presence of beta-atrial natriuretic peptide as well as alpha- and gamma-atrial natriuretic peptide. 3. The pericardial fluid concentration of cyclic GMP, the intracellular second messenger for atrial natriuretic peptide, was significantly higher in patients with congestive heart failure than in patients without heart failure.

Adult↗
PubMed1993

Heparin inhibits endothelin-1 and proto-oncogene c-fos gene expression in cultured bovine endothelial cells.

We studied the inhibitory effects of heparin, thrombin inhibitor, and protein kinase C (PKC) inhibitor on basal and thrombin-induced preproendothelin-1 (prepro-ET-1) and proto-oncogene c-fos mRNA expression in cultured bovine endothelial cells (ECs). Northern blot analysis using cDNA for bovine prepro-ET-1 as a probe showed that heparin lowered not only the basal but also the stimulated expression of prepro-ET-1 mRNA by thrombin. A selective thrombin inhibitor (argatroban) and a PKC inhibitor (staurosporine) also inhibited thrombin-induced but not basal prepro-ET-1 mRNA expression. Heparin similarly inhibited thrombin-induced c-fos proto-oncogene mRNA expression in ECs. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on prepro-ET-1 mRNA expression, possibly via a PKC-dependent pathway.

Alkaloids↗
PubMed1993

Endothelin subtype B receptors are coupled to adenylate cyclase via inhibitory G protein in cultured bovine endothelial cells.

We studied whether endothelin (ET) isopeptides have any effects on adenylate cyclase activity in cultured bovine endothelial cells (ECs). Both ET-1 and ET-3 dose-dependently inhibited cAMP formation stimulated by forskolin and isoproterenol, although the inhibitory effect of ET-1 was less potent than that of ET-3. In contrast, ET-1 and ET-3 almost equipotently inhibited forskolin-stimulated cAMP formation in bovine EC pretreated with phosphoramidon, a putative ET-1 converting-enzyme inhibitor. These data suggest that endothelial ETB receptors are functionally coupled to adenylate cyclase, possibly via Gi protein.

Adenylyl Cyclases↗
PubMed1993

Detection of hepatitis C virus RNA in the liver by in situ hybridization.

To examine HCV infection histologically, we attempted non-radioactive in situ hybridization of HCV-RNA in the liver. We amplified cDNA probe (360 base pairs) by PCR using the primers deduced from the core region of the HCV genome. The probe was labelled with digoxigenin by PCR and used for in situ hybridization on paraformaldehyde-fixed frozen liver sections. The hybrids were visualized immunohistochemically with alkaline-phosphatase-conjugated anti-digoxigenin and alkaline-phosphatase substrates. HCV-RNA-cDNA hybrids were detected in 21 of 24 patients with positive serum HCV markers, whereas there were no positive signals in the liver of 12 cases without HCV infection. The signal intensity of HCV-RNA-cDNA hybrids was abolished after RNase treatment. Various other specificity experiments also verified specific hybridization of HCV-RNA-cDNA. HCV-RNA was visualized in liver cells and most of them were regarded as hepatocytes from their characteristic features. The infected hepatocytes were frequently associated with mononuclear cell infiltration. Hepatocytes positive for HCV-RNA were sometimes binuclear and distributed in various patterns among cases tested. The present in situ hybridization of HCV RNA is highly sensitive and specific and the results suggest the host immune response to HCV-infected cells.

Hepacivirus↗
PubMed1993

Role of hepatic vitamin A and lipocyte distribution in experimental hepatic fibrosis.

Lipocytes are the major site of hepatic vitamin A storage, and they have been demonstrated to lose their vitamin A content in the process of hepatic fibrosis. To investigate the relationship between hepatic vitamin A content and the degree of hepatic fibrosis, we measured levels of retinyl palmitate and retinol in the CCl4-induced fibrotic liver using high-performance liquid chromatography. We estimated hepatic collagen content using a spectrophotometric analysis with sirius red, and also by measuring hydroxyproline levels. Lipocytes were detected by an immunoperoxidase method with anti-desmin antibody, and were counted morphometrically through a Texture Analyzing System. A significant negative correlation was observed between the level of retinyl palmitate and collagen content (r = -0.64) as well as the hydroxyproline level (r = -0.69) in the CCl4-induced fibrotic liver. In the process of fibrosis, hepatic retinol levels were elevated in association with a decrease in retinyl palmitate. In particular in the early stage of fibrosis, lipocytes increased remarkably in number in fibrotic areas in spite of a decrease in total hepatic vitamin A. The present study suggests that an increase in hepatic retinol as well as a decrease in retinyl palmitate may facilitate the process of hepatic fibrosis produced by lipocytes.

Animals↗
PubMed1993

Effect of hyperosmolality on production and mRNA expression of ET-1 in inner medullary collecting duct.

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.

Animals↗
PubMed1993

Effects of ET-1 on water and chloride transport in cortical collecting ducts of the rat.

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)

Animals↗