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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 253 records · Page 14Linked to original sources

Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis.

Human adrenomedullin (hAM), a potent vasodilatory peptide originally identified in pheochromocytoma, has been shown to be present in various human tissues and circulate in human plasma. We measured plasma concentrations of immunoreactive hAM in patients with sepsis who had been admitted to intensive care unit (ICU). Plasma hAM concentrations in 12 septic patients upon entering the ICU were extremely elevated (107 +/- 139 fmol/ml: mean +/- SD) compared to those of 16 age-matched normal subjects (7.9 +/- 3 fmol/mL). Among 10 patients with normal renal function, plasma hAM levels either decreased or increased during the hospital course; the former group survived and the latter group succumbed. Two patients with acute renal failure had markedly elevated plasma hAM levels during the early course, which declined rapidly during the recovery course. High performance liquid chromatography of plasma extracts from one patient with acute renal failure revealed a single major component of immunoreactive hAM coeluting with authentic hAM (1-52) during acute and recovery phase. Plasma hAM concentration showed positive correlations with heart rate, right atrial pressure, and serum creatinine concentration, but not with other hemodynamic variables. These data suggest that a marked increase in circulating hAM in sepsis may be caused by its decreased clearance and/or its enhanced synthesis by multiple organ dysfunction, and that increased endogenous hAM may be involved in the mechanism of cardiovascular abnormalities associated with sepsis.

Adrenomedullin↗

Angiotensin II activates endothelial constitutive nitric oxide synthase via AT1 receptors.

To determine whether angiotensin (ANG) II, a vasoconstrictor hormone, activates constitutive nitric oxide synthase (cNOS) in endothelial cells (ECs), we investigated the cellular mechanism by which ANG II induces nitric oxide (NO) formation in cultured bovine ECs. ANG II rapidly (within 1 min) and dose-dependently (10(-9)-10(-6) M) increased nitrate/nitrite (NOx) production. This effect of ANG II was abolished by a NOS inhibitor, NG-monomethyl-L-arginine. An ANG II type 1 (AT1) receptor antagonist (DuP 753), but not an ANG II type 2 (AT2) receptor antagonist (PD 123177), dose-dependently inhibited ANG II-induced NOx production. A Ca(2+)-channel blocker (barnidipine) failed to affect ANG II-induced NOx production, whereas an intracellular Ca2+ chelator (BAPTA) and a calmodulin inhibitor (W-7) abolished NOx production induced by ANG II. A protein kinase C (PKC) inhibitor (H-7) and down-regulation of endogenous PKC after pretreatment with phorbol ester decreased NOx production stimulated by ANG II. ANG II transiently stimulated inositol 1,4,5-trisphosphate (IP3) formation, and increased cytosolic free Ca2+ concentrations; these effects were blocked by DuP 753. Our data demonstrate that ANG II stimulates NO release by activation of Ca2+/calmodulin-dependent cNOS via AT1 receptors in bovine ECs.

Angiotensin II↗

Selective radiofrequency catheter ablation of the slow pathway for common and uncommon atrioventricular nodal reentrant tachycardia.

The utility of selective radiofrequency catheter ablation of the slow pathway for the treatment of common and uncommon atrioventricular nodal reentrant tachycardia (AVNRT) was studied in 110 consecutive patients, 94 with slow-fast form common AVNRT, and 11 and 5, respectively, with the fast-slow and slow-slow forms of uncommon AVNRT. Ablation sites were determined by mapping a late and spiky "slow pathway potential" in the posterior right atrial septum in common AVNRT, and also the earliest retrograde atrial activation over the retrograde slow pathway in uncommon AVNRT. AVNRT was successfully eliminated in all patients with a mean number of radiofrequency pulses of 2.9 +/- 3.0 and a mean total energy applied of 3536 +/- 2996 joules. There were no early or late complications, except for transient AV block for 15 sec immediately after energy application in one common AVNRT patient, and no recurrence of AVNRT in a mean follow-up period of 24 +/- 13 months. There were no significant differences between common and uncommon AVNRT in success rate, mean application number and total energy applied. However, the AVN physiology post-ablation was different. Slow pathway conduction was eliminated in only 32% of the patients post-ablation in common AVNRT, while it was elininated in 100% in uncommon AVNRT. Selective radiofrequency catheter ablation of the slow pathway can cure common and uncommon AVNRT effectively and safely. Common AVNRT can be eliminated irrespective of the persistence of slow pathway conduction, while uncommon AVNRT can be eliminated by the eradication of slow pathway conduction.

Adolescent↗

Role of thromboxane A2, endothelin-1 and endothelin-3 in rat nephrotoxic serum nephritis.

To clarify the role of thromboxane A2 (TxA2), endothelin-1 (ET-1) and endothelin-3 (ET-3) in the progression of glomerular injury in accelerated nephrotoxic serum nephritis (NTN) in the rat, we studied the expression of ET-1 and ET-3 at the kidney by immunohistochemical method and examined the effect of a novel TxA2 receptor antagonist, S-1452. The S-1452-treated group showed significantly lowered 24-hr proteinuria and milder glomerular cell proliferation and lobulation than the non-treated group (NT group) on experimental day 10. There was no significant difference in the glomerular polymorphonuclear cell (PMN) exudation between the 2 groups. Immunofluorescent findings revealed that ET-1 and ET-3 were seen along the glomerular capillary wall and partly in the mesangial area in all rats of the NTN group. The degree and positive rate of ET-1 and ET-3 staining were significantly higher in the NTN group than in the S-1452 group. These findings suggest that TxA2 may be an important mediator in the development of NTN, and that TxA2 receptor antagonist may be useful for the reduction of glomerular injury in this type of nephritis. In addition, local production of ET may contribute to the development of this nephritis.

Animals↗

Large right ventricular myxoma in a 79-year-old male.

A 79-year-old male, admitted because of severe dyspnea on exertion, showed echocardiographic findings of a large tumor in the dilated right ventricle. The right ventricular outflow tract was nearly occluded by the tumor mass, and the mass was attached to the interventricular septum by a pedicle. The tumor removal operation was successful. The size of the tumor was 40 mm x 90 mm, and the weight 70 g. Microscopic findings showed typical myxomatous tissue with high cellularity, and no malignancy was observed. This is the oldest reported patient with right ventricular myxoma which was cured by operation.

Aged↗

[Renal disease and trace elements].

Correlation between renal disease and trace elements includes following two types; 1) Renal failure due to excess of trace element intake into the body, such as itai-itai disease or heavy metal intoxication. 2) Disturbances of trace elements in patients with chronic renal failure, such as aluminum dementia and aluminum-related bone disease. Itai-itai disease occurred by water pollution with cadmium. Cadmium causes Fanconi syndrome in the kidney and osteomalasia in person, especially in old women, who were living near the riverside. Recently, we have shown that an itai-itai disease model can be made using rats by long-term intravenous injection of cadmium chloride. In patients with chronic renal failure, aluminum dementia and aluminum related bone disease were reported. However, aluminum dementia has disappeared by using reverse osmosis system for making dialysate. Fluoride should be one of ions which must be paid attention, because excess of fluoride cause mottled tooth and osteosclerosis. It may be dangerous to add fluoride into tap water system for the purpose of preventing decayed tooth, because fluoride retention in the serum may occur in patients with chronic renal failure.

Animals↗

[Bronchial cyst in a patient with a high serum CA19-9 concentration that fluctuated with the cyst fluid volume].

A 44-year-old woman was found to have an abnormally high concentration of CA19-9 in serum. Five years later, she underwent a right upper lobectomy for an abnormal shadow on a chest roentgenogram, because it was thought to indicate a malignant tumor. A chest CT scan revealed a cyst with fluid in the right upper lobe. During the 5 years before the lobectomy, the serum CA19-9 concentration rose when the cyst fluid volume increased, and fell when the cyst fluid volume decreased. Before the operation, the serum CA19-9 concentration was very high and the cyst was swollen. The cyst wall was found to be lined with ciliated columnar epithelial cells and to contain hyaline cartilage and smooth muscle, which led to the diagnosis of bronchial cyst. The surface epithelium and cyst fluid were positively stained by a monoclonal antibody against CA19-9. The serum CA19-9 concentration decreased and was within the normal range 3 months after the operation.

Adult↗

Chloride transport across kidney epithelia through CLC chloride channels.

This review summarizes recent progress in elucidating the chloride-transporting mechanisms in kidney epithelia, focusing particularly on those which act through the newly identified chloride channels. A family of chloride channel proteins (ClC chloride channels) consisting of at least 9 members (ClC-1, 2, 3, 4, 5, 6, 7, K1 and K2) has recently been identified in mammals. Although all of these ClC channels, except for skeletal muscle-specific ClC-1, are expressed in the kidney, only ClC-K1 and K2 are kidney-specific ClC chloride channels, suggesting that they play an important role in the kidney. The functional properties and intrarenal localization of these chloride channels are summarized, and their involvement in certain tubular dysfunctions and physiological roles are discussed in this report.

Biological Transport↗

Increased plasma atrial natriuretic peptide and endothelin concentrations after surgery in patients with esophageal and gastric cancer.

Endothelin-1 (ET-1) and human atrial natriuretic peptide (hANP) are known as vasoactive substances. In the present study, an attempt was made to evaluate the mode by which these substances are secreted in patients having severe surgical stress. Plasma ET-1 and hANP concentrations were measured in 15 patients with esophageal carcinoma who underwent subtotal esophagectomy via right-thoraco-ventrotomy (EC group) and 10 patients with gastric carcinoma who underwent total gastrectomy via ventrotomy (GC group). The volume of intraoperative hemorrhage was significantly larger and operation time was significantly longer in the EC group than in the GC group. Plasma ET-1 concentration in the EC group increased remarkably on the first operative day (1st POD), whereas that in the GC group did not. Plasma levels of hANP in both the EC and GC groups gradually increased until they peaked on the 2nd POD. The increment of plasma hANP secretion for the EC group was significantly higher than that for the GC group on the day of the operation, suggesting that ET-1 stimulated hANP in the EC group. Plasma hANP levels reached their peak values on the 2nd POD and returned to the preoperation level on the 5th POD, while PCWP did not change significantly after the surgery. Since this discrepancy between the postoperation patterns of PCWP and hANP cannot be explained by changes in the circulating blood volume, hANP secretion may be regulated by certain factors in addition to the left ventricular pressure experienced by patients receiving heavy operation stress, such as those in the EC group.

Atrial Natriuretic Factor↗

[Diseases caused by disorders of membrane transport: an overview].

Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis. Genes for transport proteins have been cloned one after the other in recent years, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. These diseases include Liddle's syndrome, long QT syndrome, hyperkalemic periodic paralysis, cystic fibrosis, myotonia congenita, nephrogenic diabetes inspidus, glucose/galactose malabsorption, cystinuria, and Wilson's disease. Gene mutations in several receptors, including vasopressin V2 receptor, dihydropyridine receptor, and Ca2+ -sensing receptor, also cause disorders of membrane transport, leading to diseases. Further advances in basic science are expected to provide us with a detailed understanding of the abnormality in the 3rd/4th structure of mutated transport proteins.

Carrier Proteins↗

Uptake of indium-111-anti-intercellular adhesion molecule-1 monoclonal antibody in the allografted rat lung during acute rejection.

BACKGROUND: Although many methods for detection and quantification of allograft rejection of the lung have been explored, only histologic diagnosis by lung biopsies has gained widespread acceptance. To examine whether indium-111-anti-intercellular adhesion molecule-1 monoclonal antibody imaging can noninvasively detect acute lung rejection, we measured the uptake of this radiopharmaceutical in lung tissue and with scintigraphy in orthotopically transplanted rat lungs. METHODS: The left lung transplant model was used with Lewis- to Wistar-King rat allografts and Lewis isograft controls. Lungs were harvested 2,3,4,5,6, and 7 days after transplantation. The transplanted and native lungs were removed 24 hours after injection of the radiotracer, weighed, and counted in a gamma well counter; uptake ratios of the transplanted or native lungs were then calculated, and scintigraphy was performed. RESULTS: Histologic rejection scores by the grading system of the International Society for Heart and Lung Transplantation at 2,3,4,5,6, and 7 in the allografts were 1.2 +/- 0.2, 2.3 +/- 0.6, 3.0 +/- 0.5, 3.7 +/- 0.4, and 4, and 4, respectively. The uptake ratios of the allografts 3,4, and 5 days after transplantation were significantly higher than the values of the respective isografts and correlated with histologic rejection grades. However, 6 days after transplantation, uptake ratios of allografts decreased and did not correlate with histologic grades. On days 3,4, and 5 after transplantation, the tracer uptake within the allografts was visualized by means of scintigraphy. CONCLUSIONS: We conclude that indium-111-anti-intercellular adhesion molecule-1 monoclonal antibody increased during mild to moderate acute lung rejection. An abnormal scintigram with this radiotracer suggests that lung biopsy should be performed to exclude lung rejection.

Animals↗

[Effects of nicorandil on coronary collateral circulation depend on the donor arteries].

The effects of nicorandil on coronary collateral circulation during exercise-induced ischemia were compared between the different donor arteries in 13 patients with effort angina, 7 with complete obstruction of the left anterior descending artery (LAD) with well-developed collateral vessels from the right coronary artery (RCA) (LAD group), and 6 with complete occlusion of the RCA (segment 2-3) with well-developed collateral vessels from the LAD (RCA group). Initial percentage thallium (%TI) uptake (thallium-201 single photon emission computed tomography) and washout rate were measured in the anterior, septal and posterior regions during ergometer exercise. The submaximal treadmill exercise test was also performed using a cardiopulmonary monitoring system to measure Vo2 at anaerobic threshold (AT). After the controls were obtained, nicorandil (15 mg/day) was administered for 4 weeks, during which ergometer exercise and treadmill exercise tests were carried out repeatedly. A significant improvement of initial %TI uptake on exercise was observed in the LAD group with nicorandil therapy, but no improvement was shown in the RCA group. The AT significantly increased after nicorandil treatment in the LAD group (13.9 +/- 0.38-->16.8 +/- 1.18 ml/min/kg), reflecting the improvement of cardiac function through the increased collateral flow. However, in the RCA group, it remained unchanged, suggesting no improvement of cardiac function. Nicorandil was effective to increase collateral flow from the RCA, but ineffective on that from the LAD. Nicorandil is an effective coronary dilator and is reported to affect both large and small coronary arteries. The effect on the collateral circulation is dependent on the donor artery supplying different areas. The vasodilator effect of nicorandil is mainly on the LAD, which is large enough to supply blood to a wider area of the heart, rather than the RCA.

Adult↗

Effect of alcohol drinking on gene expression of hepatic O6-methylguanine DNA methyltransferase in chronic liver diseases.

O6-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers methyl groups from O6-methylguanine to a cysteine acceptor in its own molecule, and restores DNA to its undamaged state. If left unrepaired, O6-methylguanine can pair with either a thymine or a cytosine, causing a C-G to T-A transition, which is considered to be one of the molecular mechanisms of both mutagenesis and carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively assessed by the competitive reverse transcription-polymerase chain reaction method in patients with chronic liver diseases with or without alcohol drinking. MGMT mRNA expression was 1.4 +/- 0.9 pg/micrograms RNA in control livers. Its expression in chronic hepatitis was 3.8 +/- 0.7 in alcoholics and 2.7 +/- 0.8 in nonalcoholics, which were not statistically different. MGMT mRNA expression in liver cirrhosis was significantly low, compared with that in chronic hepatitis, and 0.8 +/- 0.3 in alcoholics and 0.5 +/- 0.1 in nonalcoholics, which also were not significantly different. The present study shows that MGMT mRNA was not decreased in patients with chronic liver diseases with alcohol drinking, compared with those without alcohol drinking.

Alcohol Drinking↗

Molecular cloning of a novel serine/threonine kinase, MRK, possibly involved in cardiac development.

We have isolated a novel member of putative serine/threonine kinase from a rat heart cDNA library using polymerase chain reaction methods. The novel kinase is transcribed as 2.6 kb mRNA encoding for a protein of 629 amino acids with the C-terminal non-catalytic portion. Amino acids analysis revealed that the N-terminal catalytic domain is 87% identical to the male-germ cell associated kinase (MAK), a cdc2-related serine/threonine kinase found to promote meiosis during spermatogenesis. Therefore, we designated this novel kinase as the MAK-related kinase (MRK). MRK protein, with a molecular weight of 66 kD, was shown to phosphorylate itself and the exogenous substrates, histone H1 and myelin basic protein. In addition, phosphoamino acid analysis confirmed the serine/threonine-specific protein kinase activity of MRK. Although MRK was ubiquitous in adult rat tissues, the expression of MRK protein in embryos was restricted primarily to embryonic myocardium during early organogenesis. This finding suggests that MRK may be a participant in cardiac development.

Amino Acid Sequence↗

Detection of hepatitis C virus RNA in hepatocellular carcinoma by in situ hybridization.

BACKGROUND: Hepatocellular carcinoma frequently is associated with chronic hepatitis C virus (HCV) infection. The presence of HCV in hepatocellular carcinoma has been detected by reverse-transcription polymerase chain reaction of antigenomic HCV RNA, a tissue-specific replicative form of the virus. Now, however, this method of detecting the presence of HCV has been invalidated by reports of antigenomic RNA in the blood or in peripheral blood mononuclear cells. METHODS: In situ hybridization of HCV RNA was conducted with digoxigenin-labeled cDNA from the core region on surgical specimens of noncancerous and cancerous areas from 12 patients with chronic hepatitis C with or without cirrhosis associated with hepatocellular carcinoma. Several control experiments were also performed, including RNase digestion before hybridization, hybridization with the use of a negative control, and immunohistochemical staining of HCV-core protein. RESULTS: The in situ hybridization showed positive signals both in noncancerous and cancerous areas of the liver tissue in eight cases. Positive signals were confined to neoplastic cells and nonneoplastic hepatocytes. There were fewer HCV-positive cells in the cancerous area than in the surrounding noncancerous area. CONCLUSIONS: In situ detection of HCV presents direct evidence of HCV infection in the neoplastic cells of hepatocellular carcinoma and suggests that neoplastic cells may lose their affinity for HCV in the course of malignant transformation.

Carcinoma, Hepatocellular↗