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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Adrenomedullin stimulates proline-rich tyrosine kinase 2 in vascular smooth muscle cells.

A novel vasodilator peptide, adrenomedullin (AM) stimulates extracellular signal-regulated kinase (ERK) 1/2 via yet uncharacterized 120 kDa tyrosine kinase(s) in rat vascular smooth muscle cells (VSMC). In the present study, we have examined whether the AM-activated tyrosine kinase is proline-rich tyrosine kinase 2 (PYK2) associable with adapter proteins. AM rapidly (within 30 sec) and dose dependently increased tyrosine kinase activity, whose effect was enhanced in the presence of o-vanadate, a phosphatase inhibitor. A tyrosine kinase with an apparent molecular mass of 120 kDa corresponding to that of PYK2 was predominantly localized to the cytosolic fraction, whereas the tyrosine-phosphorylated 180-kDa protein was observed in the membrane fraction from EGF-treated cells, but not from AM-treated cells. AM induced rapid (within 30 sec) and transient phosphorylation of PYK2, but not focal adhesion kinase. AM caused autophosphorylation of tyrosine residue(s) of PYK2 and promoted its association with adaptor proteins (Shc/Grb2). AM rapidly (within 1 min) activated c-Src and enhanced its association with tyrosine-phosphorylated PYK2. These data suggest that AM stimulates PYK2 which, in turn, activates c-Src and induces recruitment of adaptor proteins (Shc/Grb2), thereby leading to activation of p21(ras)/ERK1/2 cascade in VSMC.

Adrenomedullin↗
PubMed2001

Transient QT interval prolongation with inverted T waves indicates myocardial salvage on dual radionuclide single-photon emission computed tomography in acute anterior myocardial infarction.

In patients with acute myocardial infarction (AMI), transient QT interval prolongation with a prominent negative T wave is frequently observed in cases of early spontaneous reperfusion and often indicates a good prognosis. Additionally, in nuclear cardiac imaging, technetium-99m/thallium-201 overlap on dual single-photon emission computed tomography (dual SPECT) in AMI patients indicates the presence of viable myocardium and early recanalization. To elucidate the clinical significance of this transient QT interval prolongation, 34 patients (64 +/- 8 years) admitted within 24h of the onset of anterior AMI were enrolled and classified into 2 groups according to the presence (group A, n=24) or absence (group B, n=10) of scintigraphic overlap on simultaneous dual SPECT imaging. The maximal QTc interval was 0.59 +/- 0.06 s in group A and 0.52 +/- 0.06 s in group B (p<0.01). The peak creatine kinase was lower in group A (2650 +/- 2160 IU/L) than in group B (3490 +/- 2060 IU/L). The left ventricular ejection fraction (LVEF) at discharge was 62 +/- 11% in group A and 49 +/- 14% in group B (p<0.01). The scintigraphic overlap group had a smaller infarct and better LVEF, which suggests that the QT interval prolongation that appears transiently in the acute phase of AMI indicates scintigraphically the presence of salvaged myocardium.

Aged↗
PubMed2001

Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure.

A 58-year-old man developed proteinuria and renal dysfunction following pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin was administered, and prednisolone pulse therapy and plasmapheresis were performed. Subsequently, serum creatinine was decreased. Eight months later, creatinine and CRP were again elevated, and MRSA was detected. Vancomycin was again administered and plasmapheresis was performed. However, renal function was not improved and continuous hemodialysis was initiated. This case indicates that complete eradication of MRSA is necessary to treat MRSA-associated glomerulonephritis, and if this is not attained, a permanent loss of renal function occurs.

Anti-Bacterial Agents↗
PubMed2001

IgA nephropathy with complement deficiency.

We treated a female patient suffering from immunoglobulin A (IgA) nephropathy and congenital deficiency of the ninth component of the complement system (C9). She was admitted with hematuria and proteinuria, and the C9 deficiency was diagnosed based on the low hemolytic activity of 50 % of the hemolytic unit of the complements (CH50) and the normal C3 level in the plasma. Renal biopsy revealed mild mesangial proliferation, and immunofluorescence examination revealed mild mesangial deposits of IgA and C3 with the same distribution. We discuss the pathogenesis of IgA nephropathy and the role of the complements in its progression.

Adult↗
PubMed2001

CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection.

Mechanisms determining the chronicity or the pattern of clinical course of hepatitis C virus (HCV) infections have not been clarified. Recently, CD81 was reported to bind the E2 protein of HCV and was suggested to function as a cellular receptor for HCV. Accordingly, the hypothesis was examined that CD81 polymorphism, if it exists, might correlate with certain clinical courses of HCV infection. CD81 cDNA sequences were determined from peripheral blood mononuclear cells (PBMCs). Twenty-four Japanese subjects were enrolled initially as follows: patients with chronic hepatitis C without cirrhosis (n = 3), patients with cirrhosis (n = 3), patients with cirrhosis complicated by hepatocellular carcinoma (HCC) (n = 3), patients with persistent HCV viremia without ALT elevation (n = 3), those with positive anti-HCV antibodies without evidence of HCV viremia (n = 3), and healthy volunteers (n = 9). In all PBMCs samples analyzed, no polymorphism was found in the CD81 cDNA sequence. The sequence was different, however, from the one reported previously at three nucleotide positions: a transversion to thymine instead of cytosine at nt 1130, a deletion at nt 1206, and a guanine insertion at nt 71. Subsequently, CD81 cDNA sequences from PBMCs and HCC tissue were compared among the other 6 patients with chronic hepatitis C bearing HCC. A comparative study of the CD81 sequences from HCC and PBMCs revealed that various nucleotide mutations existed only in the HCC samples in 3 out of 6 patients. Several mutations in the 3' non-coding region of CD81 cDNA were observed exclusively in HCC tissue suggesting its possible role in hepatocarcinogenesis. Because of the absence of polymorphisms, however, CD81 is unlikely to affect the progression of chronic hepatitis C in terms of chronicity, hepatitis activity, or disease stage.

Adult↗
PubMed2001

Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations.

Liddle's syndrome is a rare form of hereditary hypertension caused by mutations of the epithelial sodium (Na(+)) channel (ENaC). Analysis of the diseased pedigrees indicates an autosomal dominant inheritance, and the identified mutations are heterozygotes of gain-of-function mutations. However, sporadic cases of Liddle's syndrome have been reported in the literature, including one recently reported case caused by a de novo mutation of ENaC. We identified two patients with Liddle's syndrome who did not have family histories of hypertension. Sequence analysis showed a mutation in each case (P616L in betaENaC and W576X in gammaENaC), both confirmed to be de novo mutations. These data indicate that Liddle's syndrome should be considered even in patients without a family history of hypertension.

Adult↗
PubMed2000

Isolation and characterization of the human CLC-5 chloride channel gene promoter.

The human CLC-5 chloride channel is expressed mainly in the kidney and its mutations cause Dent's disease (a familial renal tubular syndrome with hypercalciuria, tubular proteinuria, rickets, nephrocalcinosis, and eventual renal failure). To gain insight into the regulatory mechanism of CLC-5 expression, a genomic clone that contains the 5'-flanking region of the human CLC-5 gene was isolated and characterized. Two types of 5'-ends of cDNA were isolated by 5'-rapid amplification of cDNA ends, and one of them, approximately 2.1 kbp upstream of ATG-containing exon II, was first identified in human. The major promoter activity was detected in the 5'-flanking region of this newly identified exon Ia. The sequence of the proximal 5'-flanking region contained an activator protein (AP)-1-like site and cAMP-responsive element, but it lacked a TATA box, a GC-rich element, and an SP-1 site. Deletion analysis of the 5'-flanking region showed that the fragments containing the AP-1-like element (TGACTCC) positioned at -38 exhibited high promoter activities in CLC-5 expressing LLC-PK1 cells, but that further deletions not containing this AP-1-like element resulted in a great loss of luciferase activities. Gel-retardation analysis demonstrated the existence of a specific protein binding to this AP-1-like element in LLC-PK1 cells, which seemed to differ from an authentic AP-1. This study clarified the key element of the human CLCN5 promoter, and the mutation in this region could be the cause of Dent's disease.

Animals↗
PubMed2000

Functional characterization of a water channel of the nematode Caenorhabditis elegans.

A genome project for the species Caenorhabditis elegans has demonstrated the presence of eight cDNAs belonging to the major intrinsic protein (MIP) family. We previously characterized one of these cDNAs known as C01G6.1. C01G6.1 was confirmed to be a water channel and newly designated as AQP-CE1 [Am. J. Physiol. 275 (1998) C1459-C1464]. In this paper, we examined the function of another MIP protein encoded by F40F9.9. This cDNA encodes a 274-amino acid protein showing a high sequence identity with mammalian aquaporin-8 (AQP8) water channel (35%) and d-TIP (34%), an AQP of Arabidopsis. The expression of F40F9.9 in Xenopus oocytes increased the osmotic water permeability (P(f)) 10.4-fold, and the activation energy for P(f) from Arrhenius plot was 4.7 kcal/mol, suggesting that F40F9.9 is a water channel (AQP-CE2). AQP-CE2 was not permeable to glycerol or urea. Oocyte P(f) was reversibly inhibited by 58% after an incubation with 0.3 mM HgCl(2). To identify the mercury-sensitive site, four individual cysteine residues in AQP-CE2 (at positions 47, 132, 149, 259) were altered to serine by site-directed mutagenesis. Of these mutants, only C132S had a P(f) similar to that of the wild-type together with an acquired mercury resistance, suggesting that Cys-132 is the mercury-sensitive site. Similar results were obtained by the mutation of Cys-132 to alanine (C132A). Replacement of Cys-132 with tryptophan decreased P(f) by 64%, but P(f) was still 2.5 times higher than that of the control. Cys-132 is located in the transmembrane helix 3, close to the transition to the extracellular loop C. These results suggest that the transmembrane helix 3, including Cys-132, might participate in the aqueous pore formation, or, alternatively, that Cys-132 might contribute to the construction of the AQP protein.

Amino Acid Sequence↗
PubMed2000

Genetic changes in the interferon sensitivity determining region of hepatitis C virus during the natural course of chronic hepatitis C.

Amino acid mutations in the interferon sensitivity determining region (ISDR) are closely associated with the response to interferon in patients with hepatitis C virus genotype 1b (HCV-1b) infection. In this study, 36 patients chronically infected with HCV-1b, with no history of interferon therapy with respect to ISDR changes in HCV were studied. Two serum samples were obtained from each patient, with an average interval of 3.5 years, and predominant nucleotide and amino acid sequences of the ISDR at initial and subsequent time points were compared for each patient. Three of 12 patients with the wild type ISDR (no amino acid mutation in the ISDR compared to the consensus sequence) changed to the intermediate type (1 to 3 mutations) at later time points, whereas the other 9 still had the wild type. Similarly, 2 of 18 patients with the intermediate type changed to the wild type, whereas the other 16 patients continued to have the intermediate type. One of 6 patients with the mutant type (4 or more mutations) changed to the intermediate type, and the other 5 continued to have the mutant type. Although ISDR nucleotide changes/site/year were not significantly different among the 3 groups of patients, percentages of non-synonymous nucleotide changes were greater in the mutant type (63%) than the wild (9%) or the intermediate type (20%) (P < 0.05). These results show that mutations in the ISDR do not occur frequently, suggesting that interferon sensitivity does not change greatly during the natural course of the disease in each patient.

Aged↗
PubMed2000

Characteristics of hepatitis C viral genome associated with disease progression.

The clinical presentations of chronic hepatitis C are not uniform. Some patients show persistently high serum alanine transaminase (ALT) values and develop liver cirrhosis and hepatocellular carcinoma (HCC), whereas serum ALT values stay normal in other patients. The mechanism causing this diversity remains to be elucidated. The aim of this study was to identify genomic characteristics of hepatitis C virus (HCV) genotype 1b associated with disease progression. Full length sequences of HCV were determined in 14 patients who showed persistently normal serum ALT values (normal ALT group) and 13 cirrhotics with HCC (HCC group). Residues in which amino acid usage was different between these 2 groups were extracted, and Progression score was defined as the total number of residues with 7 amino acids, more frequently present in the HCC group than in the normal ALT group. In the validation of this Progression score in 9 patients with normal ALT and 25 with HCC, the score was significantly higher in the HCC group (3.1 +/- 1.1 vs. 2.0 +/- 0.9, P =.019). Finally, the correlation between the score and clinical markers related to disease progression was analyzed. In a total of 107 patients with chronic HCV infection, the Progression score was correlated significantly with platelet counts (r = -0.31, P =.0024) by multivariate analysis. In conclusion, high Progression scores were associated with the presence of HCC and low platelet counts. Sequences of the HCV-1b genome may be related to the progression of chronic hepatitis C.

Amino Acids↗
PubMed2000

Reference data of forearm bone mineral density in healthy Japanese male and female subjects in the second decade based on calendar age and puberty onset: Japanese Population Based Osteoporosis (JPOS) study.

Osteoporosis is a major public health problem in Japan. The second decade is an important period in which to attain a high peak bone mass. However, normal values of forearm bone mineral density (BMD) are not well known in children and adolescents. BMD at one-third of forearm length proximal to the ulnar end plate (BMD1/3) and the ultradistal forearm (BMDud) was measured using dual-energy X-ray absorptiometry (DXA) in 1207 (631 males, 576 females) Japanese subjects aged 9-18 years. Puberty onset was assessed by questionnaire, by obtaining the time that pubic hair appeared in males and the time that menstruation started in females. BMD1/3 and BMDud increased steadily with age in males. In relation to puberty development, these parameters also increased after puberty onset although the increase in BMD1/3 was not statistically significant after the fifth year from puberty onset and that of BMDud was not significant after the sixth year from puberty onset. BMD1/3 and BMDud increased with age and then plateaued in females. The increase in BMD1/3 was not statistically significant after 15-16 years of age and that of BMDud was not significant after 13-14 years of age. In relation to puberty development, the increase in BMD1/3 leveled out after the fourth year from puberty onset and that of BMDud also plateaued after the third year from puberty onset. We provide reference values of forearm BMD in Japanese children and adolescents by DXA according to calendar age and puberty development. Peak bone mass of the forearm may be in the late second decade in Japanese females.

Absorptiometry, Photon↗
PubMed2000

Expression of gap junction protein connexin 32 in chronic liver diseases.

BACKGROUND: Gap junctions contain intercellular channels through which contacting cells communicate directly. The expression of connexin 32, a major gap junction protein in the liver, during the progression of chronic liver diseases has not yet been clarified. METHODS: Immunohistochemical staining was performed using anti-connexin 32 antibody on 6 specimens of normal human liver, 7 of chronic viral hepatitis, and 7 of liver cirrhosis. RESULTS: The number of gap junction plaques in chronic viral hepatitis and liver cirrhosis was significantly smaller than that in normal liver (10350+/-2180 and 7550+/-3040 vs 22560+/-3700 spots/mm2, p<0.01). The number of gap junction plaques tended to be lower in liver cirrhosis than in chronic viral hepatitis. CONCLUSION: These results suggest that in chronic liver diseases impaired intercellular communication between hepatocytes occurs.

Chronic Disease↗
PubMed2000

Expression of C-C chemokines is associated with portal and periportal inflammation in the liver of patients with chronic hepatitis C.

Inflammation of the portal and periportal areas is a common feature of chronic hepatitis C. Antigen-presenting dendritic cells are located in the portal area, and infiltrating T cells are initially exposed to infected hepatocytes in the periportal area. Thus, these areas could be sites of the initial processes of the immune response in chronic hepatitis C. C-C chemokines (dendritic-cell-derived C-C chemokine [DC-CK1] and regulated upon activation, normal T-cell expressed and secreted [RANTES])-attracting T cells may play a role in the portal inflammatory changes. The relationship between the expression of these C-C chemokines, which attract T cells and the infiltration of T cells into the liver of patients with chronic hepatitis C, was examined by in situ hybridization and reverse transcription-polymerase chain reaction. T-cell activation was examined by immunostaining T-cell subsets. Specific signals were detected for DC-CK1 mRNA in mononuclear cells mainly in the portal area and for RANTES mRNA in the portal area and at sites of piecemeal necrosis in the liver of patients with chronic hepatitis C. Naive T cells were located mainly in the portal area, whereas active T cells were found mainly at sites of piecemeal necrosis in the periportal area. In addition, hepatic DC-CK1- and RANTES-mRNA levels were significantly correlated with serum alanine aminotransferase levels (p < 0.001). These results suggest that the local production of DC-CK1 and RANTES participates in immune responses by attracting naive and active T cells to the portal and periportal areas, respectively.

Actins↗
PubMed2000

Activated STAT1 suppresses proliferation of cultured rat mesangial cells.

BACKGROUND: JAK-STAT signaling has been shown to promote development and proliferation in lymphopoietic and hematopoietic lineages. We investigated the effect of activated STAT1 on mesangial cell proliferation. METHODS: Rat mesangial cells of primary culture (rMCs) were used in the following experiments: (1) Whole cell lysates were immunoblotted against JAK1 and JAK2. (2) Whole cell lysates and nuclear proteins were extracted from rMCs with or without treatment with interferon-gamma, and immunoblotting was performed against both STAT1 and tyrosine (701)-phosphorylated STAT1. (3) rMCs and rMCs electroporated with either wild-type STAT1, mutated STAT1, or antibody against STAT1 were incubated with interferon-gamma for 20 hours, followed by a further incubation with [3H]-thymidine for four hours. RESULTS: JAK1, JAK2, and STAT1 were detected in whole cell lysates, suggesting that JAK-STAT signaling could be activated by interferon-gamma (INF-gamma). Using an antibody specific for tyrosine-phosphorylated STAT1, we detected signal in the INF-gamma-treated nuclear extracts, which showed translocation of phosphorylated STAT1 to the nucleus. [3H]-thymidine incorporation in the presence of INF-gamma was significantly lower than that of control in a dose-dependent manner. The introduction of wild-type STAT1 enhanced the effect of interferon-gamma and decreased [3H]-thymidine incorporation, whereas tyrosine-mutated (Y701F) STAT1 and SH2 domain (R602T)-mutated STAT1 reversed INF-gamma-induced suppression of [3H]-thymidine incorporation. Electroinjected antibody against STAT1 increased [3H]-thymidine incorporation upon stimulation with INF-gamma. CONCLUSION: STAT1 activated by interferon-gamma suppresses mesangial cell proliferation.

Animals↗
PubMed2000

A jump in cycle length of orthodromic common atrial flutter during catheter ablation at the isthmus between the inferior vena cava and tricuspid annulus; evidence of dual isthmus conduction directed to dual septal exits.

INTRODUCTION: In orthodromic common atrial flutter (AFL), details of intraseptal propagation of the flutter (FL) wave exiting from the isthmus between the inferior vena cava and tricuspid annulus (IVC-TA isthmus) remain unknown. We hypothesized the existence of dual septal exits of the FL wave from the IVC-TA isthmus to both the anterior, coronary sinus ostium (CSO-TA) isthmus, and the posterior septal (IVC-CSO) isthmus, and that the IVC-TA isthmus might consist of dual muscle bundles directed to both septal isthmuses over the eustachian ridge; therefore, segmental ablation of the IVC-TA isthmus could change intraseptal FL wave propagation. METHODS AND RESULTS: To test the hypothesis, we investigated the influence of segmental ablation of the IVC-TA isthmus on intraseptal FL wave propagation. In seven of 40 (18%) consecutive patients, segmental ablation of the ventricular side of the IVC-TA isthmus during orthodromic common AFL led to sudden prolongation of the flutter cycle length (FCL) (from 266 +/- 33 ms to 291 +/- 45 ms) associated with changes in intraseptal activation sequences. They consisted of prolongation of the interval between the IVC-TA isthmus and the CSO (from 38 +/- 13 ms to 86 +/- 25 ms), shortening of the interval between the CSO and His (from 31 +/- 15 ms to 9 +/- 15 ms), and atrial electrogram polarity change at the His-bundle recording site. Morphological change in the FL wave was also seen on the 12-lead ECG. CONCLUSIONS: In some patients, segmental ablation of the IVC-TA isthmus can lead to a jump in FCL and changes in intraseptal activation sequences of FL waves due to anterior-to-posterior shifting of the septal exit. This indicates that the IVC-TA isthmus may contain dual circumferential muscle bundles as conduction pathways directed to dual septal exits both anterior and posterior to the CSO.

Atrial Flutter↗
PubMed2000

Intrahepatic mRNA expression of interferon-inducible antiviral genes in liver diseases: dsRNA-dependent protein kinase overexpression and RNase L inhibitor suppression in chronic hepatitis C.

As a part of the defense mechanism of the host to viral infection, interferons induce the transcription of several genes. These interferon-inducible genes contribute to the eradication of the viruses. Whereas some studies suggested the participation of a dsRNA-dependent protein kinase in the host reaction to hepatitis C virus infection, the involvement of other interferon-inducible genes has not been evaluated. Furthermore, there has been no analysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of interferon-inducible genes with a special concern to chronic hepatitis C. A total of 76 liver biopsy samples (28 with chronic hepatitis C, 10 with chronic hepatitis B, 9 with alcoholic liver disease, 14 with autoimmune hepatitis, 10 with primary biliary cirrhosis, and 5 of normal liver) were enrolled. The expression of the following genes was quantified by competitive reverse transcription-polymerase chain reaction and was compared according to the etiology; dsRNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase (2,5-AS), latent cellular endoribonuclease (RNase L), RNase L inhibitor, and MxA. As a result, PKR mRNA was significantly overexpressed in the liver of chronic hepatitis C compared with those of other etiologies (P =.0178), and it correlated significantly with serum alanine transaminase values (r =.51, P =.0054). Also, the expression of the RNase L inhibitor showed a significant reduction in chronic hepatitis C (P =.0184). The expressions of 2,5-AS, RNase L, and MxA were not different significantly irrespective to the etiology. In conclusion, hepatic overexpression of PKR and reduced expression of RNase L inhibitor seem to contribute to the anti-HCV mechanism characteristically.

ATP-Binding Cassette Transporters↗