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Biomedical subjects

Y Yazaki

Publications and source records attributed to Y Yazaki.

At least 163 records · Page 9Linked to original sources
PubMed1999

[Effects of the rational use of corticosteroids eye drops for the prevention of ocular toxicity in high-dose cytosine arabinoside therapy].

Although the use of corticosteroid (CS) eye drops of the use of eye washing by artificial tears was effective for the prevention of ocular toxicity such as keratitis and photophobia in the high-dose cytosine arabinoside (Ara-C) therapy, the toxicity was not prevented perfectly. We studied the effects of the rational use of CS eye drops, and the combined use of CS eye drops and eye washing by physiological saline in order to prevent the ocular toxicity. Before the study, the instillation of 0.1% sodium bethamethazone phosphate (BM) eye drops was carried out at 4-6 times per day during the high-dose Ara-C therapy, and continued for several days after the high-dose Ara-C therapy. However, the rational use of "eyelid closure" and "naso-lacrimal occlusion" after the instillation was not performed Consequently, the ocular toxicity was observed in 3 (19%) of 16 cases of the patients. When the instillation of BM eye drops at 4 times per day was carried out rationally according to the consultation of pharmacist during the high-dose Ara-C therapy and for additional 10 days after the therapy, no ocular toxicity was observed in all cases (0 of 6 cases). Furthermore, the combined use of eye washing by physiological saline and instillation of BM eye drops was effective for the decrease of the risk of ocular toxicity, because no ocular toxicity was observed in the high-dose Ara-C therapy (0 of 34 cases). Our procedure in this study would be effective for the prevention of ocular toxicity in the high-dose Ara-C therapy.

Adolescent↗
PubMed1999

Familial atrial septal defect and atrioventricular conduction disturbance associated with a point mutation in the cardiac homeobox gene CSX/NKX2-5 in a Japanese patient.

Atrial septal defect (ASD) is the most common form of congenital cardiac defect in humans. Recently, point mutations in the cardiac homeobox gene CSX/NKX2-5 have been reported to cause the autosomal dominant form of familial ASD. Notably, all the affected patients exhibit atrioventricular conduction disturbance and some of them died suddenly. The first case of familial ASD with a mutation of the CSX/NKX2-5 gene in a Japanese patient is reported here. Identification of CSX/NKX2-5 mutations in ASD patients would be very important because the existence of such mutations may predict sudden cardiac death.

Heart Block↗
PubMed1999

Evidence of cell-mediated cardiac myocyte injury involved in the heart failure of a patient with progressive systemic sclerosis.

A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 24%). Methylprednisolone, heparin, and diuretics were administered, without benefit. Anemia, thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart failure on the 14th hospital day. Immunohistochemical study of the myocardial tissue showed mild to moderate cell infiltration, mainly consisting of natural killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper cells. Perforin, a cytolytic factor, was expressed in the infiltrating CTLs and NK cells, indicating that these cells were activated killer cells. Furthermore, human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not to be expressed in cardiac myocytes under normal conditions, were moderately to strongly expressed in cardiac myocytes. There was no detectable level of enterovirus genomes in the polymerase chain reaction products from the myocardial tissue of this patient. These findings strongly suggest that the infiltrating killer cells recognized cardiac myocytes as target cells and directly damaged them by releasing perforin. Enhanced expression of these antigens may have played an important role in the activation and cytotoxicity of the infiltrating killer cells. Absence of enterovirus genomes in the myocardial tissue may suggest that this autoimmune process is primarily induced by PSS.

Antigens, CD↗
PubMed1999

Pulmonary embolism due to right ventricular thrombus in a case of Behcet's disease.

Right ventricular thrombus is a very rare manifestation of cardiovascular Behcet's disease. A 25-year-old man was admitted to hospital due to cough and fever of unknown origin. He experienced repetitive pulmonary embolism due to a right ventricular thrombus, which was surgically removed. A diagnosis of Behcet's disease was made based on his clinical course and the histological findings of the right ventricular wall and the skin lesion. He was quickly relieved of his symptoms after warfarinization and cyclosporine therapy.

Adult↗
PubMed1999

Responses of blood pressure and catecholamine metabolism to high salt loading in endothelin-1 knockout mice.

The molecular mechanism responsible for salt sensitivity is poorly understood. Mice heterozygous for the null mutation of the endothelin-1 (ET-1) gene, Edn1, may be a potential tool for studying this mechanism, because they have elevated blood pressure and disturbances in central sympathetic nerve regulation. In the present study, we used this mouse model to examine the degree to which ET-1 contributes to the responses of blood pressure and catecholamine metabolism to high salt loading. Male Edn1+/- heterozygous mice and Edn1+/+ wild-type littermates were given either a high salt (8%) or a normal salt (0.7%) diet for 4 wk. During the normal diet, renal ET-1 levels in Edn1+/- mice were approximately 50% lower than ET-1 levels in wild-type mice, whereas the high salt diet decreased renal ET-1 levels by about 50% in both Edn1+/- and wild-type mice. The high salt diet significantly increased urinary sodium excretion and fractional excretion of sodium (FENa) but did not affect circulating plasma volume, serum electrolytes, creatinine clearance, or systemic blood pressure. In addition, urinary norepinephrine and normetanephrine excretion were significantly increased, indicating that salt loading can increase sympathetic nerve activity in normal mice. These responses to salt loading did not differ between Edn1+/- mice and their wild-type littermates. We conclude that physiological changes in ET-1 production do not affect the responses of blood pressure and catecholamine metabolism to salt loading, although the renal ET-1 content is decreased by salt loading.

Animals↗
PubMed1999

Hypertrophic responses of cardiomyocytes induced by endothelin-1 through the protein kinase C-dependent but Src and Ras-independent pathways.

We have previously shown that endothelin-1 (ET-1) modulates mechanical stretch-induced hypertrophic responses such as extracellular signal-regulated protein kinase (ERK) activation in cardiac myocytes. This study was undertaken to elucidate the ET-1-evoked signal transduction pathways leading to ERK activation. ET-1 was added to cultured cardiac myocytes of neonatal rats with or without a variety of inhibitors. ET-1 activated ERKs, which were followed by an increase in protein synthesis, and inhibition of protein kinase C activities by calphostin C completely suppressed the ET-1-induced ERK activation. We next examined whether tyrosine kinases or Ras are involved in ET-1-induced signaling pathways in cardiomyocytes. Pretreatment with a receptor tyrosine kinase inhibitor did not attenuate ET-1-induced activation of ERKs. Also, co-transfection of the dominant-negative mutant of Ras or active mutant of C-terminal Src kinase, a tyrosine kinase which inhibits Src family tyrosine kinases, with hemagglutinin-tagged ERK2 had no effects on ET-1-induced ERK2 activation. On the other hand, blockade of Raf-1 kinase function by overexpression of the dominant-negative mutant of Raf-1 kinase completely inhibited ET-1-induced ERK2 activation. These results suggest that protein kinase C and Raf-1 kinase, but not Src or Ras, are critical to ET-1-induced ERK activation in cardiac myocytes.

Amino Acids↗
PubMed1999

Lack of sex-specific effects on the association between angiotensin-converting enzyme gene polymorphism and hypertension in Japanese.

Although several studies of molecular genetics have investigated the relevance of the ACE gene to essential hypertension, the relationship remains controversial. Some studies have recently implicated sex-specificity of this candidate gene in hypertension genetics; that is, significant linkage and association were observed in men but not in women in Caucasian populations. In particular, a male-specific association was seen between the ACE insertion/deletion (I/D) polymorphism and hypertension. This could partially explain the negative results for such an association in a number of previous studies in which the subjects were not stratified according to sex. To determine whether the ACE I/D polymorphism is related to essential hypertension in Japanese subjects, we conducted a case-control study in 701 men (387 hypertensive and 314 normotensive subjects) and 542 women (324 hypertensive and 218 normotensive subjects). The genotype distribution (or allele frequencies) and hypertension status were compared between the case and control subjects with the chi2 test statistic. We found no significant association between I/D genotype and hypertension when men and women were analyzed separately or together. The results did not change appreciably when the case group of each sex was subdivided according to more stringent criteria. The odds ratio for D-allele vs. I-allele was estimated to be 0.90 (95% CI; 0.73-1.12) in men and 0.90 (95% CI; 0.70-1.16) in women. Taken together, our data do not support the existence of a sex-specific association between the ACE I/D polymorphism and essential hypertension in the Japanese population.

Aged↗
PubMed1999

The mechanism of insulin-induced signal transduction mediated by the insulin receptor substrate family.

Distinct from other growth factor receptors, insulin and insulin-like growth factor-I (IGF-I) receptors phosphorylate endogenous substrates on tyrosine residues which in turn associate with the SH2 domain-containing proteins transducing signals to downstream pathways. Among the cellular substrates of insulin and IGF-I receptors, insulin receptor substrate (IRS)-1 has been shown to play an important role in mediating the actions of these hormones. Recently, several proteins with similar structures and different tissue distributions were cloned as IRS-2, -3 and -4. To study the roles of these IRSs in mediating insulin actions, we analyzed liver, muscle and adipocytes, the major targets of insulin actions, from IRS-1 null mice which we previously generated, and showed that: 1) insulin-stimulated activation of PI 3-kinase, mitogen-activated protein kinase and glucose transport were impaired in muscles from IRS-1 null mice which was in contrast to the grossly normal signaling and actions in livers from these mice; 2) the difference in the degree of insulin resistance in these two major insulin targets appeared to depend on the amount of tyrosine phosphorylation of IRS-2 compensating for IRS-1 deficiency; 3) insulin-induced activation of PI 3-kinase, glucose transport and GLUT4 translocation were impaired but not abolished in adipocytes from these mice in which IRS-3 was the major tyrosine-phosphorylated protein activating PI 3-kinase and at least partially mediating some residual insulin actions in the absence of IRS-1. These data suggest that the members of the IRS family redundantly regulate insulin actions in each target organ in a distinct fashion.

Adipocytes↗
PubMed1999

A wide "gap" in retrograde conduction through a concealed accessory atrioventricular pathway depending on ventricular pacing sites.

We present a 57-year-old man with Wolff-Parkinson-White syndrome who exhibited a wide "gap" in retrograde conduction through a concealed atrioventricular accessory pathway. The appearance of the wide "gap" depended on the ventricular pacing sites. While ventricular extrastimuli at a basic cycle length of 600 msec from the right ventricular outflow tract consistently conducted to the atria, retrogradely through the accessory pathway, those from the right ventricular apex repeatedly revealed disappearance of the retrograde conduction at the wide coupling intervals from 550 to 380 msec. The mechanisms of this rare "gap"-like phenomenon are discussed in this paper.

Atrioventricular Node↗
PubMed1999

Embryonic smooth muscle myosin heavy chain SMemb is expressed in pressure-overloaded cardiac fibroblasts.

Left ventricular hypertrophy (LVH) is a secondary adaptation to increased external load. Various qualitative and quantitative changes in myocytes and extracellular components occur during the development of LVH. It has recently been demonstrated that alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblasts appear in the interstitium of the heart subjected to increased workload suggesting that cardiac fibroblasts as well as myocytes alter their phenotype in response to pressure overload. In the present study, to explore the load-induced response and phenotypic modulation of cardiac fibroblasts, the localization of embryonic smooth muscle myosin heavy chain (SMemb) and alpha-SMA in thoracic aorta-constricted rat hearts was investigated by immunohistochemistry, and the morphology of the SMemb-expressing cells was examined by electron microscopy. In addition, to clarify the mechanisms by which SMemb is induced in pressure-overloaded hearts, mRNA expression of SMemb in aorta-constricted rat hearts and in transforming growth factor-beta1 (TGF-beta1)-treated or mechanically-stretched cultured cardiac fibroblasts was investigated. Enhanced staining of SMemb and alpha-SMA was detected in the interstitial spindle-shaped cells in the fibrotic lesions of the pressure-overloaded left ventricles by immunohistochemistry. These cells were demonstrated by electron microscopy to have features specific for activated fibroblasts such as serrated nuclei or prominent rough endoplasmic reticulum. These cells also had characteristic features of myofibroblasts, i.e. irregularly arranged actin filaments and scattered dense bodies. Northern blot analysis revealed increased mRNA levels of SMemb both in aorta-constricted rat hearts and in cultured cardiac fibroblasts stimulated by TGF-beta1 or by mechanical stretch. These results suggest that SMemb may be a molecular marker both for the detection of activated cardiac fibroblasts that may play important roles in the remodeling of pressure-overloaded cardiac interstitium, and for the identification of the regu latory mechanisms that control the phenotypic modulation of cardiac fibroblasts in response to pressure overload.

Actins↗
PubMed1999

Early diagnosis of central nervous system aspergillosis with combination use of cerebral diffusion-weighted echo-planar magnetic resonance image and polymerase chain reaction of cerebrospinal fluid.

We treated a patient diagnosed as central nervous system (CNS) aspergillosis with the combined use of cerebral diffusion-weighted echo-planar magnetic resonance imaging (DWI) and polymerase chain reaction of the cerebrospinal fluid (CSF-PCR). DWI, a cutting-edge imaging modality to reveal the earliest changes of cerebral infarction, detected cerebral fungal embolization when the conventional computed tomographic scan and magnetic resonance imaging failed to reveal it. CSF-PCR demonstrated the presence of Aspergillus-specific DNA in the specimen, when the conventional examination and culture of CSF were nonspecific or negative. These diagnostic methods could be useful in the early diagnosis of CNS aspergillosis.

Aspergillosis↗
PubMed1999

Life-style related factors and idiopathic dilated cardiomyopathy--a case-control study using pooled controls.

A case-control study was conducted to investigate how basic habits of life including dietary habit, physical activity, cigarette smoking, and drinking, are involved in the development of idiopathic dilated cardiomyopathy (DCM). Collection of cases was entrusted to the clinical research group of DCM, and national pooled controls established by sex and age category by the epidemiological research group of intractable diseases were used to ensure representativeness of the controls. Fifty-eight cases of DCM which developed in and after January 1991 were collected, and 5,912 controls matched with the cases by residential area, sex, and age were selected. Analysis of the results of the study showed that items in the questionnaire suggestive of viral infection, such as "susceptibility to common cold" and "susceptibility to diarrhea", items concerning dietary habit, including "taking no breakfast", "ingestion of salty food", and "ingestion of fatty food", and such items as "cigarette smoking" and "lack of sleep" tended to be observed in the case group at significantly higher frequencies. Since viral infection has been suspected as a causative factor of DCM, further research of this area is thought to be of particular importance for determining the etiology of DCM.

Adult↗
PubMed1999

Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats.

Insulin receptor substrate (IRS)-1 and IRS-2, which mediate phosphatidylinositol (PI) 3-kinase activation, play essential roles in insulin-induced translocation of GLUT4 and in glycogen synthesis. In this study, we investigated the process of PI 3-kinase activation via binding with IRS-1 and -2 in liver, muscle, and fat of high-fat-fed rats, a model of insulin-resistant diabetes. In the liver of high-fat-fed rats, insulin increased the PI 3-kinase regulatory subunit p85alpha and the PI 3-kinase activities associated with IRS-1 3.6- and 2.4-fold, and with IRS-2, 4.7- and 3.0-fold, respectively, compared with those in control rats. The tyrosine phosphorylation levels of IRS-1 and IRS-2 were not significantly altered, however. In contrast with the liver, tyrosine phosphorylation levels and associated PI 3-kinase proteins and activities were decreased in the muscle and adipose tissue of high-fat-fed rats. Thus, high-fat feeding appears to cause insulin resistance in the liver by a mechanism different from the impaired PI 3-kinase activation observed in muscle and adipose tissue. Taking into consideration that hepatic PI 3-kinase activation is severely impaired in obese diabetic models such as Zucker fatty rats, it is possible that the mechanism by which a high-fat diet causes insulin resistance is quite different from that associated with obesity and overeating due to abnormality in the leptin system. This is the first report to show increased PI 3-kinase activation by insulin in an insulin-resistant diabetic animal model. These findings may be important for understanding the mechanism of insulin resistance in human NIDDM, since a high-fat diet is considered to be one of the major factors exacerbating insulin insensitivity in humans.

Adipose Tissue↗
PubMed1999

No correlation of plasma cell 1 overexpression with insulin resistance in diabetic rats and 3T3-L1 adipocytes.

Membrane glycoprotein plasma cell 1 (PC-1) has been shown to be increased in type 2 diabetes and involved in insulin resistance through inhibiting the insulin receptor tyrosine kinase, which was demonstrated using cultured breast cancer cells. However, other reports have shown contradictory results in Chinese hamster ovary cells and in vitro kinase assay. Thus, we considered it necessary to investigate the effect of PC-1 using highly insulin-sensitive cells. Here, we used two of the following approaches: 1) investigating PC-1 expression levels in insulin-responsive tissues in rat models of diabetes and 2) overexpressing PC-1 in 3T3-L1 adipocytes. We found that PC-1 was highly expressed in insulin-responsive tissues, such as liver and adipose tissue, in normal rats. However, high-fat feeding or streptozotocin-induced diabetes did not change its expression levels in liver, adipose tissue, and skeletal muscle. Thus, PC-1 expression levels were not associated with high-fat-diet-induced insulin resistance or hyperglycemia. Although PC-1 was increased in adipose tissue in Zucker fatty rats (protein level, by 50%; mRNA level, by 90%), its expression levels in liver and skeletal muscle, tissues that are more responsible for whole body glucose metabolism than adipose tissue, did not significantly differ from those in normal rats. Next, we overexpressed PC-1 in 3T3-L1 adipocytes using an adenovirus transfection system. PC-1 expression was markedly increased to a level 16-fold greater than that in normal human adipose tissue, which is higher than the previously reported levels in diabetic patients. However, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1, activation of phosphatidylinositol 3-kinase, and glucose uptake were not affected by PC-1 overexpression. These results strongly suggest that increased PC-1 expression is not causally related to insulin resistance.

3T3 Cells↗
PubMed1999

Increased serum soluble Fas ligand associated with recurrent B-cell non-Hodgkin's lymphoma after autologous peripheral blood stem cell transplantation.

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.

Adult↗
PubMed1999

Long-term third chronic phase of chronic myelogenous leukemia maintained by interferon-alpha and methotrexate.

The prognosis of blast crisis (BC) of chronic myelogenous leukemia (CML) is extremely poor despite many efforts to induce remission with chemotherapy. We have recently treated a long-surviving CML patient who developed three separate episodes of BC. The administration of interferon-alpha (IFN-alpha) alone as maintenance therapy was incapable of preventing BC, which occurred twice in the first 2 years after the diagnosis of CML. Intensive chemotherapy using enocitabine, mitoxantrone, and etoposide was effective to induce hematological remission. Thereafter once per week oral administration of methotrexate (10-15 mg/week) was combined with IFN-alpha after the second BC. This treatment succeeded in obtaining a major cytogenetic response and keeping him in third chronic phase for 5 years until the last most recent third BC. We present here the rare clinical course of the patient, review the past literature, and discuss the efficacy of the combination of IFN-alpha and methotrexate in this disease.

Adult↗