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Biomedical subjects

Y Takatsu

Publications and source records attributed to Y Takatsu.

At least 19 recordsLinked to original sources
PubMed2004

Biochemical markers of myocyte injury in heart failure.

This review discusses the role of biochemical markers of myocyte injury in patients with chronic congestive heart failure. Heart specific assays have been developed for the measurement of cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart type fatty acid binding protein (H-FABP), and myosin light chain 1 (MLC-1). Concentrations of these biochemical markers increase in the absence of ischaemic events in the subset of patients with heart failure whose long term outcomes are most adverse. The markers are easy to measure serially and it is therefore easy to follow patients without inter-observer variability. The serial clinical use of these markers, separately or in combination, will sharpen our understanding of the state of heart failure.

Biomarkers↗
PubMed2003

Psycho-neuro-immunological treatment of hepatocellular carcinoma with major depression--a single case report.

A female patient, who was suffering major depression and advanced hepatocellular carcinoma (hepatoma), sought treatment in the Jozuka Mental Clinic. She was treated using a psycho-neuro-immunological approach. The treatments applied were psychotherapy, the antidepressant fluvoxamine, glycyrrhizinic acid and dehydroepiandrosterone (DHEA). Biochemical, endocrinological and immunological examinations were performed regularly. Improvement of liver function and reduction of alpha-fetoprotein were observed. The levels of DHEA, natural killer cell activity and cytokines (interleukines IL-2, IL-6, IL-12, interferon IFN-gamma) were normalised. Now, more than two and a half years after her admission, the patient is still well and symptom-free. While this may be a case of spontaneous regression, the results suggest that a psycho-neuro-immunological approach to treating the patient's depression and cancer was helpful for her recovery.

Antidepressive Agents↗
PubMed2001

Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.

Amino Acid Sequence↗
PubMed2001

Persistently increased serum concentrations of cardiac troponin t in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes.

BACKGROUND: The measurement of serum concentrations of cardiac troponin T (TnT) is a simple, useful method to detect myocyte injury that may be repeated multiple times to follow patients without interobserver variability. METHODS AND RESULTS: Multiple measurements of TnT with a second-generation assay were performed in 60 patients with dilated cardiomyopathy confirmed by coronary angiography and endomyocardial biopsy between April 1996 and December 1999. Three evolutionary patterns of TnT concentrations were identified. Thirty-three patients had concentrations of TnT <0.02 ng/mL throughout the follow-up period (group 1). The remaining 27 patients had high initial serum concentrations of TnT (>/=0.02 ng/mL). In 10 of these 27 patients, TnT decreased to <0.02 ng/mL during follow-up (group 2), whereas 17 had persistently high serum TnT concentrations despite being conventionally treated for chronic congestive heart failure (group 3). Although the initial echocardiographic left ventricular diastolic dimension (LVDd) and left ventricular ejection fraction (LVEF) were not significantly different among the 3 groups, follow-up echocardiography showed significantly decreased LVDd and increased LVEF in group 1 (each P:<0.01) and group 2 (each P:<0.05) compared with increased LVDd and decreased LVEF in group 3 (each P:<0.05). The cardiac event-free rate was significantly lower in group 3 than in groups 1 and 2 (each P:<0.001), and the survival rate was lower in group 3 than in group 1 (P:<0.05). CONCLUSIONS: Persistently increased TnT concentrations in dilated cardiomyopathy suggest ongoing subclinical myocyte degeneration associated with deterioration of the patients' clinical status.

Biopsy↗
PubMed2001

Estimation of the dissociation constants for functional groups on modified and unmodified silica gel supports from the relationship between electroosmotic flow velocity and pH.

Electroosmotic volume flow was directly observed in a simple instrument consisting of 1 cm long a home-made support, packed between two polyethylene frits in the polypropylene tube. Equations relating electroosmotic flow (EOF) velocity and pH for two functional groups on the surface of the solid materials were developed. With these equations, we can estimate the dissociation constants of two different kinds of functional groups on modified silica gel materials simultaneously. The dissociation constants of silanol groups, benzene sulfonic acid groups, and alkyl quaternary ammonium groups on the modified and unmodified silica gel supports were estimated. The estimated pK values of the silanol groups on the silica gel and modified silica gel surfaces are between 4.0 and 4.3. The estimated pK values of the benzene sulfonic acid groups and alkyl quaternary ammonium groups on the surface of the modified silica gel are 2.6 and 8.6, respectively.

Hydrogen-Ion Concentration↗
PubMed2001

Distribution of galanin-like peptide in the rat brain.

Galanin-like peptide (GALP) is a novel galanin-like peptide isolated from the porcine hypothalamus. To determine the distribution of GALP in the rat brain, we performed immunohistochemical studies using a monoclonal antibody toward the N-terminal sequence of GALP. GALP-immunoreactive neuronal cell bodies were observed only in the arcuate nucleus (Arc), which was further confirmed by in situ hybridization studies using digoxigenin-labeled antisense GALP riboprobe. Additional immunostained cells were found in the median eminence and infundibular stalk. The GALP neurons found in the Arc were further characterized by double label immunohistochemistry. More than 85% of the GALP neurons were immunostained with leptin receptor antibody. However, the GALP neurons and fibers found in the Arc were not labeled with alpha-MSH, somatostatin, neuropeptide Y, agouti-related protein, or galanin antibodies, indicating that GALP is found in neurons other than these known Arc neurons. Dense staining of GALP-containing fibers was found in the anterior parvicellular part of the paraventricular hypothalamic nucleus, in the ventral part of the lateral septal nucleus, and in the bed nucleus of the stria terminalis. Relatively dense staining was noted in the medial preoptic area (MPA), and weak staining was noted in the periventricular hypothalamic nucleus. Detailed double labeling studies in the paraventricular hypothalamic nucleus demonstrated that GALP-containing fibers converged in a more rostral direction than did agouti-related protein-containing fibers. Furthermore, GALP-immunoreactive fibers were in close apposition with GnRH-immunoreactive fibers in the MPA and bed nucleus of the stria terminalis, and about 6% of GnRH-positive neurons in the MPA showed close contact with the GALP-immunoreactive fibers. Our findings indicate that GALP neurons, as leptin-responsive neurons, may participate in the regulation of feeding behavior and/or reproductive functions.

Animals↗
PubMed2001

Stimulation effect of galanin-like peptide (GALP) on luteinizing hormone-releasing hormone-mediated luteinizing hormone (LH) secretion in male rats.

Galanin-like peptide (GALP) is a recently isolated hypothalamic peptide which has sequence homology to galanin and binds to galanin receptors with high affinity. It has been shown that GALP neurons are localized in the arcuate nucleus and that GALP-immunoreactive fibers are in close apposition with LHRH neurons in the medial preoptic area (MPA). In the present study, we found that intracerebroventricular (icv) administration of GALP increased the plasma LH level but did not change the levels of other hormones. Concomitantly, accumulation of c-Fos protein was dramatically increased in the nuclei of LHRH-positive cells in the MPA by icv GALP administration. Furthermore, the GALP-induced plasma LH response was completely abolished by pretreatment with Cetrorelix, a LHRH receptor antagonist. On the other hand, GALP did not affect the release of LH, FSH, TSH, ACTH, GH or PRL directly from dispersed rat pituitary cells in vitro. These results strongly suggest a role for GALP in the control of gonadotropin secretion through a hypothalamic mechanism involving the release of LHRH.

Animals↗
PubMed2000

TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development.

Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK superfamily and has been characterized as a component of the TGF-beta/bone morphogenetic protein signaling pathway. TAK1 function has been extensively studied in cultured cells, but its in vivo function is not fully understood. In this study, we isolated a Drosophila homolog of TAK1 (dTAK1) which contains an extensively conserved NH(2)-terminal kinase domain and a partially conserved COOH-terminal domain. To learn about possible endogenous roles of TAK1 during animal development, we generated transgenic flies which express dTAK1 or the mouse TAK1 (mTAK1) gene in the fly visual system. Ectopic activation of TAK1 signaling leads to a small eye phenotype, and genetic analysis reveals that this phenotype is a result of ectopically induced apoptosis. Genetic and biochemical analyses also indicate that the c-Jun amino-terminal kinase (JNK) signaling pathway is specifically activated by TAK1 signaling. Expression of a dominant negative form of dTAK during embryonic development resulted in various embryonic cuticle defects including dorsal open phenotypes. Our results strongly suggest that in Drosophila melanogaster, TAK1 functions as a MAPKKK in the JNK signaling pathway and participates in such diverse roles as control of cell shape and regulation of apoptosis.

Amino Acid Sequence↗
PubMed2000

Interferon treatment for dilated cardiomyopathy and striated myopathy associated with hepatitis C virus infection based on serial measurements of serum concentrations of cardiac troponin T.

The present authors recently suggested, on the basis of studies using polymerase chain reaction (PCR), that hepatitis C virus (HCV) infection is involved in the etiology or pathogenesis of cardiomyopathic disorders. They have also reported that the serum concentration of cardiac troponin T is an indicator of ongoing myocyte degeneration in patients with dilated cardiomyopathy (DCM) and hypothesized that its serial measurement may be a marker of therapeutic efficacy. This is the first case report of DCM and striated myopathy, associated with HCV infection, treated with interferon therapy guided by monitoring of serial serum concentrations of cardiac troponin T. Positive-plus strands of HCV RNA were found in the patient's myocardium, as well as plus and minus strands in the quadriceps muscle specimens. Serum levels of creatine kinase (CK), CK-MB and cardiac troponin T fell as serum HCV titers decreased during treatment with interferon, whereas conventional treatment of heart failure had no effect. Monitoring of serial serum concentrations of cardiac troponin T may allow the earlier diagnosis and treatment of patients with HCV-associated cardiomyopathy and improve their clinical course.

Antiviral Agents↗
PubMed1999

Suppression by ganglioside GD1A of migration capability, adhesion to vitronectin and metastatic potential of highly metastatic FBJ-LL cells.

Ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, has been shown to inhibit the serum-induced migration capability of highly metastatic FBJ-LL cells. In the present study, the capacity of FBJ-S1 cells to adhere to vitronectin was found to be about half that of FBJ-LL cells. Pre-treatment of FBJ-LL cells with GD1a decreased this capacity by 30% that of the control, whereas GM1-pre-treatment caused only a 10% decrease, indicating that GD1a specifically inhibits FBJ-LL cell adhesion to vitronectin. Since FBJ-LL cells contain almost no GD1a, transfectants capable of expressing GD1a to varying degrees were produced in this study by transfection of FBJ-LL cells with GM2/GD2-synthase cDNA. Decrease in the serum-induced migration capacity of these transfectants was accompanied by an increment in GD1a expression. Adhesion of the transfectants to vitronectin decreased by 30% as compared with mock-transfected cells. Within 4 to 5 weeks after GD1a-expressing transfectant and mock-transfected cells were transplanted into mice, metastatic nodules were observed in liver, lung, kidney and adrenal glands of mock-transplanted mice, but not in those with GD1a-expressing transfectants, indicating that GD1a suppresses the metastasis of FBJ-osteosarcoma cells, possibly by inhibiting cell migration and cell adhesion. The involvement of the ganglioside in the suppression of metastasis is clearly demonstrated in the present study.

Animals↗
PubMed1999

Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin.

Wnt/Wingless directs many cell fates during development. Wnt/Wingless signaling increases the amount of beta-catenin/Armadillo, which in turn activates gene transcription. Here the Drosophila protein D-Axin was shown to interact with Armadillo and D-APC. Mutation of d-axin resulted in the accumulation of cytoplasmic Armadillo and one of the Wingless target gene products, Distal-less. Ectopic expression of d-axin inhibited Wingless signaling. Hence, D-Axin negatively regulates Wingless signaling by down-regulating the level of Armadillo. These results establish the importance of the Axin family of proteins in Wnt/Wingless signaling in Drosophila.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Serial circulating concentrations of C-reactive protein, interleukin (IL)-4, and IL-6 in patients with acute left heart decompensation.

BACKGROUND: Interleukin (IL)-6 has recently been shown to have negative inotropic effects, and several studies have reported increases in circulating concentrations of this cytokine in patients with depressed left ventricular ejection fraction and chronic left heart failure. However, most previous clinical studies have measured cytokines in compensated chronic heart failure. HYPOTHESIS: The purpose of this study was to examine the temporal evolution of circulating concentrations of C-reactive protein (CRP) and cytokines in patients with cardiomyopathy and acute cardiac decompensation, free of infection and unstable angina. METHODS: The time course of circulating concentrations of CRP, an anti-inflammatory cytokine interleukin (IL)-4, and a proinflammatory cytokine IL-6 were studied in eight patients with cardiomyopathy and acute cardiac decompensation in the absence of infection or unstable angina. Control samples were obtained from eight age-matched asymptomatic subjects. RESULTS: Increased circulating concentrations of CRP (2.6 +/- 0.8 mg/dl), IL-4 (164.6 + 36.5 pg/ml), and IL-6 (17.1 +/- 5.1 pg/ml) were found in all eight patients during acute cardiac decompensation; these values decreased significantly with the resolution of symptoms of cardiac decompensation (0.5 +/- 0.1 mg/dl, 77.8 +/- 23.6 pg/ml, 2.3 +/- 0.1 pg/ml, respectively, p < 0.05 for both). There was a significant correlation between peak CRP and peak IL-6 (p < 0.05). CONCLUSIONS: In patients with acute left heart decompensation in the absence of infection or coronary events, CRP, IL-4, and IL-6 increased and returned toward normal levels as the symptoms of heart failure resolved. Since the changes in concentrations of CRP, IL-4, and IL-6 in patients with heart failure are dynamic, the distinction between compensated and decompensated state is important when discussing the significance of acute reactive proteins or cytokines in the pathogenesis of heart failure.

Aged↗
PubMed1998

Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis.

OBJECTIVES: We investigated the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their genes in the hearts of patients with cardiac amyloidosis and those with isolated atrial amyloidosis. BACKGROUND: The expression of ANP and BNP is augmented in the ventricles of failing or hypertrophied hearts, or both. The expression of ANP and BNP in the ventricles of hearts with cardiac amyloidosis, which is hemodynamically similar to restrictive cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial amyloid. METHODS: We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hybridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiac amyloidosis. RESULTS: Four of the five right and all six left ventricular endomyocardial biopsy specimens obtained from six patients with cardiac amyloidosis were immunohistochemically positive for both ANP and BNP; none of the biopsy specimens from eight normal subjects were positive for ANP or BNP. All four of the right atria obtained at operation showed positive immunoreactions for both peptides. Electron microscopy identified specific secretory granules in ventricular myocytes of the patients with cardiac amyloidosis, but not in ventricular myocytes from the normal control subjects. Double immunocytochemical analysis revealed the co-localization of ANP and BNP in the same granules and that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas ventricular amyloid fibrils were negative for both peptides. Both ANP mRNA and BNP mRNA were expressed in the ventricles of the patients with cardiac amyloidosis but not in the normal ventricles. The autopsy study of four patients with cardiac amyloidosis revealed an almost transmural distribution of ANP and BNP, with predominance in the endocardial side. Plasma BNP levels in the patients were markedly elevated ([mean +/- SD] 1,165.1+/-561.2 pg/ml) compared with those in the control subjects (8.9+/-6.0 pg/ml, p < 0.05). CONCLUSIONS: Expression of ANP and BNP and their genes was augmented in the ventricular myocytes of the patients with cardiac amyloidosis. Both regional mechanical stress by amyloid deposits and hemodynamic stress by diastolic dysfunction may be responsible for the expression of the peptides in patients with cardiac amyloidosis.

Aged↗
PubMed1998

Luminal narrowing of coronary capillaries in human hypertrophic hearts: an ultrastructural morphometrical study using endomyocardial biopsy specimens.

BACKGROUND: Abnormal microcirculation has been suggested in hearts with pathological conditions, particularly in hypertrophic hearts, even in the presence of normal epicardial coronary arteries. However, the morphology of coronary capillaries has not been well investigated in those hearts. METHODS: Ultrastructural morphometry of the capillaries in 47 endomyocardial biopsy specimens taken from 30 patients was performed. PATIENTS: Six patients had hypertrophic cardiomyopathy with dilated cardiomyopathy-like features (DCM-like HCM), six had HCM, six had DCM, five had postmyocarditis, and seven were normal subjects. RESULTS: The short axial diameters of capillaries were similar among the groups. Abnormal stenosis of more than 90% luminal narrowing was found in 31% of capillaries of the DCM-like HCM group, 16% of the HCM group, 13% of the DCM group, 11% of the postmyocarditis group, and 2% of the normal subjects. Mean (SD) stenosis of the lumen was most severe in DCM-like HCM (78(8)%), and more severe in HCM (67(9)%), DCM (66(8)%), and postmyocarditis (68(4)%) than normal subjects (56(8)%). The mean cross sectional areas of capillaries were similar among the groups; however, the endothelial cellular area was significantly (p < 0.05) greater in DCM-like HCM (24.2 (8.2) microns2) than in normal subjects (14.7 (1.8) microns2), indicating that capillary narrowing was due to the increased volume of capillary endothelial cells. The endothelial cells of the stenosed capillaries showed severely oedematous changes of the cytoplasm wholely or partially, but the cytoplasmic organelles and nuclei appeared intact. CONCLUSION: Narrowing of the coronary capillaries may be of pathophysiological significance in microcirculatory abnormality in hypertrophic hearts, particularly in patients with DCM-like HCM.

Adult↗