[Complications of gastrointestinal reflux diseases. 1. Mechanism for the etiology of Barrett esophagus].
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Barrett Esophagus↗
Biomedical subjects
K Nakao
Publications and source records attributed to K Nakao.
Outside-in signalling of fibronectin stimulates cardiomyocyte hypertrophy in cultured neonatal rat ventricular myocytes.
Cardiac hypertrophy involves the accumulation of extracellular matrix proteins, such as fibronectin, leading to increasing myocardial stiffness, ventricular dysfunction and heart failure. To better understand the possible role of extracellular matrix-evoked intracellular signalling in ventricular myocytes, we investigated the effect of fibronectin on myocyte hypertrophic responses using cell culture models. Cell size in myocytes cultured on fibronectin-coated dishes was three times larger than that grown on non-coated dishes. However, the number of cells on fibronectin-coated dishes was not changed throughout the experiment. Protein synthesis was significantly increased by fibronectin, as were synthesis of atrial and brain natriuretic peptides. Fibronectin also elicited actin reorganization, co-localization of beta 1 integrin and vinculin, formation of focal adhesions and tyrosine phosphorylation of focal adhesion kinase in myocytes. These fibronectin-mediated effects were inhibited in a dose-dependent manner by GRGDSP, a competitive antagonist of the fibronectin receptors; GRGDSP had no effect on cell number or viability. Blocking antibody for beta 1 and beta 3 integrin significantly suppressed fibronectin-induced secretion of natriuretic peptides. Myocyte hypertrophy was observed in myocyte-nonmyocyte co-culture that reflects more closely the myocyte environment in vivo. GRGDSP may also suppress the myocyte hypertrophic response in the co-culture. These findings demonstrate that the interaction of fibronectin and RGD-dependent integrins is involved in the hypertrophic responses of myocyte in vitro, and suggest that extracellular matrix proteins such as fibronectin are not merely passive adhesive molecules but are active participants in processes leading to myocyte hypertrophy.
Animals↗
Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes.
Growth factors and cytokines trigger survival signaling in a wide variety of cell systems, including cardiac myocytes. Participation of the phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway in survival signaling has already been described in some cell types, but its involvement in the survival of cardiac myocytes is as yet unknown. Recently, CT-1, an interleukin 6-related cytokine, was shown to have survival-promoting, anti-apoptotic effects on cultured cardiac myocytes. However, roles of PI3K-dependent pathways in this signaling have not been elucidated. In the present study, therefore, we examined the participation of the PI3K/Akt pathway in CT-1-induced, survival-promoting signaling in cultured ventricular myocytes. It was found that CT-1 phosphorylated and activated Akt, and the effect was blocked by the PI3K inhibitors LY294002 and wortmannin. CT-1 also phosphorylated the pro-apoptotic factor, BAD, and the BAD phosphorylation was inhibited by LY294002, suggesting that phosphorylation of BAD is one of the key events by which the PI3K/Akt pathway mediates CT-1-induced survival signaling. Further, CT-1 PI3K-dependently prolonged the survival of serum-starved ventricular myocytes by preventing apoptosis. In summary, our findings show that PI3K-dependent survival signals contribute to CT-1-mediated ventricular myocyte survival. In vivo, the death of ventricular myocytes leads to heart failure, and downregulation of survival signals and/or augmentation of pro-apoptotic signals are likely to be important components of disease processes. Thus, the extent to which CT-1 and the PI3K/Akt pathway mitigate such pathological processes, in vivo, is an important question for the future.
Animals↗
Molecular cloning and expression of a novel klotho-related protein.
Klotho protein is a novel beta-glucosidase-like protein produced predominantly in the kidney. The klotho mouse, which genetically lacks klotho gene expression, manifests various systemic phenotypes resembling aging. In the present study we succeeded in isolating a novel human protein structurally related to klotho protein. The protein possesses one beta-glucosidase-like domain and is 42% identical with klotho protein at the amino acid level. Unlike klotho protein, it possesses neither a signal sequence nor a transmembrane domain, suggesting that it is a cytosolic protein, and thus was termed cytosolic beta-glucosidase-like protein-1 (cBGL1). By Northern blot analysis cBGL1 mRNA was expressed most abundantly in the liver, followed by the small intestine, colon, spleen, and kidney. When klotho and cBGL1 gene expression was examined in renal cell carcinoma tissues, both klotho and cBGL1 mRNA levels in tumors were lower than those in nontumor regions, suggesting that renal epithelial cells may lose klotho and cBGL1 gene expression during the course of malignant transformation. In conclusion, we describe the primary structure and gene expression of a novel protein related to klotho protein.
Aged↗
Long-term role of nitric oxide in the enteric nervous system of the transplanted rat intestine.
We investigated the long-term changes of the nitric oxide (NO)-related neural component after syngeneic total small bowel transplantation in rats. In the present study, the NO-related neural component was examined using the electrophysiological and NADPH-diaphorase histochemical technique. The rats were divided into four groups: an untreated young adult control group, an untreated 2-year-old control group, a group killed 1 month after transplantation, and a group killed 2 years after transplantation. A superfusion apparatus was used to evaluate the response of jejunal strips to electrical transmural stimulation. In the presence of adrenergic and cholinergic blockade, the inhibitory effect of L-N(G)-nitro arginine (L-NNA; a nitric oxide synthesis inhibitor) on nonadrenergic, noncholinergic (NANC) relaxation was expressed as a L-NNA-sensitive component. The L-NNA-sensitive component accounted for 41.6 +/- 4.6% (mean +/- SE), 43.1 +/- 3.5%,54.6 +/- 4.1%, and 55.8 +/- 3.5% in the young control group, 2-year control group, 1-month transplant group, and 2-year transplant group, respectively, being significantly higher in the transplant groups (p < 0.05). The actual strength of the L-NNA-sensitive component was 0.24 +/- 0.03 (mean +/- SE), 0.26 +/- 0.02, 0.44 +/- 0.04, and 0.46 +/- 0.04 mg of tension per mg of wet weight, respectively, also being significantly higher in the transplant groups (p < 0.001). In addition, the percentage of NADPH-diaphorase-positive fibers was 24.1 +/- 1.1% (mean +/- SE), 25.5 +/- 1.4%, 31.0 +/- 1.6%, and 30.9 +/- 2.0%, respectively, being significantly higher in the transplant groups (p < 0.05). These results suggest that NO neurons in the intrinsic jejunal nervous system have an adaptive role in maintaining intestinal graft motility.
Animals↗
Prostaglandin E(2) (PGE(2)) induces the c-fos and c-jun expressions via the EP(1) subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells.
This study examined which subtype(s) of PGE receptors is involved in the induction of c-fos and c-jun by PGE(2) in MC3T3-E1 cells. We also investigated the possibility that the induction of these genes is involved in the growth and differentiation of this cell line. PGE(2) dose-dependently induced c-fos and c-jun mRNA expressions in MC3T3-E1 cells. Of the PGE analogs, 17-phenyl-omega-trinor PGE(2) (EP(1) agonist) and sulprostone (EP(1)/EP(3) agonist) were far more potent than butaprost (EP(2) agonist) and 11-deoxy PGE(1) (EP(2)/EP(4) agonist) in inducing c-fos and c-jun mRNA expressions. Since MC3T3-E1 cells do not express the EP(3) subtype, these results suggest that PGE(2) induces c-fos and c-jun mRNA expressions through the EP(1) subtype of its receptor. In order to study the functional relevance of these protooncogenes, we then studied the effect of inhibition of their synthesis by the use of antisense oligonucleotide. Alkaline phosphatase (ALP) suppression by 17-phenyl-omega-trinor PGE(2) was reversed by antisense oligonucleotide for either c-fos or c-jun. These results suggest that PGE(2), via the EP(1) subtype of the PGE receptor, negatively modulates the transition from proliferation to the matrix maturation stage through the induction of c-fos and c-jun. However, antisense oligonucleotide for c-fos or c-jun did not alter the prostaglandin G/H synthase-2 mRNA expression induced by EP(1). Thus, it is possible that c-fos and c-jun inductions do not account for all the EP(1)-mediated PGE(2) actions in MC3T3-E1 cells.
Alkaline Phosphatase↗
Spontaneous loss of hepatitis B surface antigen in chronic carriers, based on a long-term follow-up study in Goto Islands, Japan.
Annual mass examination was performed between 1972 and 1997 in Tomie-town, Goto Islands, Japan, where hepatitis B virus (HBV) infection is very prevalent. In the present study, the incidence of spontaneous loss of hepatitis B surface antigen (HBsAg) in HBsAg carriers was determined in this area. Three thousand and nineteen inhabitants were tested for HBsAg two or more times in our annual surveys. Among them, 131 (4.3%) were defined as chronic HBsAg carriers based on the persistence of HBsAg for 1 or more years. These 131 subjects were followed for 12.2 +/- 7.6 years. During the follow-up period, spontaneous loss of HBsAg occurred in 38 (29%) of the 131 carriers, with a yearly incidence of 2.5%. This loss was seen more frequently in carriers aged 40 years or more on enrollment than in those aged less than 40 years during the same observation periods (P = 0.0141), irrespective of sex or the results of liver function tests. The values for liver function test results were similar before and after loss of HBsAg in these carriers. Stored serum samples were available for later analysis of HBV-DNA by polymerase chain reaction in 32 carriers with loss of HBsAg. The HBV-DNA sequence was detected in 26 (81%) and 2 of the 32 carriers (6%) before and after loss of HBsAg, respectively. These results indicate that spontaneous loss of HBsAg, largely attributable to clearance of viremia, occurs age-dependently in chronic carriers.
Adolescent↗
The synergistic effects of hyperthermia and anticancer drugs on induction of apoptosis.
We studied the synergistic effects of hyperthermia and anticancer drugs on induction of apoptosis in lung cancer cells (LK-2 and LU-65A) using in situ end-labeling of DNA, the DNA fragmentation assay, and transmission electron microscopy. A few apoptotic cells were detected only when both cell lines were heated at relatively high temperature (44 degrees C). Moderate numbers of apoptotic cells were observed when both cell lines were incubated with high concentrations (30 or 40 microM) of anticancer drug. Compared with hyperthermia or anticancer drug alone, the combined treatment induced many apoptotic cells in both cell lines, even in the cells treated with lower concentrations (6 or 8 microM) of anticancer drugs following mild hyperthermia (43 degrees C). In regard to kinetics of apoptotic cells induced by treatment, the maximum induction of apoptosis by the combined treatment was higher than that of hyperthermia or anticancer drug alone in both cell lines, although the time of the peak of apoptotic index differed among the three treatments. Therefore, "hyperthermo-chemotherapy" may reduce the required dosage of anticancer drug and decrease the temperature of hyperthermia on induction of apoptosis.
Antineoplastic Agents↗
Local control in differentiated thyroid carcinoma with extrathyroidal invasion.
BACKGROUND: The clinical significance of microscopically locoresional-residual differentiated thyroid carcinoma is still an unsolved problem. METHODS: Patients who underwent resectional management for advanced differentiated thyroid carcinoma were divided into complete (n = 58), microscopic (n = 37), macroscopic (n = 14), and distant (n = 22) groups. RESULTS: Postoperative recurrence was similar in the complete (28%) and microscopic (22%) groups and was significantly lower than that of the macroscopic (57%) and distant (67%) groups. Age, gender, lymph node metastasis, and the residual status (complete and microscopic versus macroscopic and distant) were independent risk factors for recurrence. Postoperative survival of the complete and microscopic groups groups was better than that of the macroscopic and distant groups. Age and the residual status were independent prognostic factors for overall and cause-specific survival. CONCLUSIONS: Postoperative recurrence and survival of patients with microscopic residual cancer were similar to those of patients with complete resection, and macroscopic residual cancer either in locoregional or distant loci was an ominous prognostic sign.
Adenocarcinoma, Follicular↗
Early stage primary malignant melanoma of the esophagus.
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Esophageal Neoplasms↗
Downregulation of leptin by free fatty acids in rat adipocytes: effects of triacsin C, palmitate, and 2-bromopalmitate.
Free fatty acid (FFA) has been reported to decrease leptin mRNA levels in 3T3-L1 adipocytes. When using this cell line, it is difficult to determine the protein levels because a very small amount of leptin is secreted into the medium. The effect of FFA on leptin secretion from adipocytes has not yet been determined. In addition, in vivo studies have failed to demonstrate a FFA-induced decrease in plasma leptin levels. To clarify the effect of FFA on leptin production, we investigated the leptin protein level in the medium and the mRNA level in primary cultured rat adipocytes treated with triacsin C, which is a potent inhibitor of acyl-coenzyme A (CoA) synthetase, palmitate, and 2-bromopalmitate. Triacsin C (0 to 5 x 10(-5) mol/L) decreased leptin concentrations in the culture medium in a dose-dependent manner. Leptin mRNA levels were decreased to 10% of the control in the presence of triacsin C. The concentration of triacsin C needed to suppress leptin production was similar to the Ki value (approximately 10(-5) mol/L) for inhibition of acyl-CoA synthetase. Both palmitate and 2-bromopalmitate decreased leptin concentra-tions but did not affect the triacsin C-induced decrease in leptin additively. In conclusion, both protein and mRNA levels of leptin were decreased by triacsin C and FFA in primary cultured rat adipocytes. Our findings suggest that FFA is involved in the regulation of leptin production in adipocytes.
Adipocytes↗
Current topics in pheochromocytoma.
Pheochromocytoma is the tumor that produces catecholamines and originates from chromaffin cells, which are differentiated from sympathoadrenal progenitor cells of neural crest under the influence of glucocorticoids. Genetic abnormalities of familial pheochromocytomas have elucidated oncogenic genetic bases of the tumor, including gene abnormalities of the RET proto-oncogene in multiple endocrine neoplasia type 2, VHL gene in von Hippel Lindau's disease or the NF1 gene in neurofibromatosis. Co-localization of various substances with catecholamines in the tumor, including neuropeptide Y, opioid peptides or adrenomedulOFF peptide elevating cAMP production, is recognized. The significance of these substances in modulating clinical features of pheochromocytomas is not fully understood.
Adrenal Gland Neoplasms↗
Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction.
Induction of the interferon (IFN)-alpha/beta gene transcription in virus-infected cells is an event central to innate immunity. Mice lacking the transcription factor IRF-3 are more vulnerable to virus infection. In embryonic fibroblasts, virus-induced IFN-alpha/beta gene expression levels are reduced and the spectrum of the IFN-alpha mRNA subspecies altered. Furthermore, cells additionally defective in IRF-7 expression totally fail to induce these genes in response to infections by any of the virus types tested. In these cells, a normal profile of IFN-alpha/beta mRNA induction can be achieved by coexpressing both IRF-3 and IRF-7. These results demonstrate the essential and distinct roles of thetwo factors, which together ensure the transcriptional efficiency and diversity of IFN-alpha/beta genes for the antiviral response.
Animals↗
Effects of levulinic acid on 5-aminolevulinic acid production in heterotrophic cultures of Chlorella regularis YA-603.
To investigate the effects of levulinic acid (LA) on extracellular 5-aminolevulinic acid (ALA) accumulation, a heterotrophic culture of Chlorella regularis YA-603 in basal medium containing 0 to 60 mM of LA was carried out. It was found that the extracellular and total ALA concentrations increased, while the chlorophyll (CHL) concentration was the same above initial LA concentrations of 30 mM, with an increasing initial LA concentration up to 50 mM. In the presence of an initial LA concentration of 60 mM, however, the specific growth rate decreased markedly. This suggested that excessive LA exerted a negative effect on ALA production because it also directly affected cellular growth. The relationship between the initial LA and total ALA concentrations mentioned above indicates that LA could promote the ALA-producing activity. Kinetic analysis revealed that an LA concentration of between 30 to 50 mM in the culture broth gave the maximum specific production rate of ALA ((q(ALA))max). When LA was added repeatedly to maintain this optimum range of LA concentration, (q(ALA))max could be maintained at a relatively high level for a longer period, and the maximum concentration of ALA reached 3.86 mM.
Journal Article↗
An empirical classification of social anxiety: performance, interpersonal and offensive.
This study empirically identified subtypes of social anxiety using a cluster analytic approach. From 87 out-patients with social phobia (taijin kyofusho) and 48 controls, social anxiety symptoms, social situations in which symptoms occur, and background information were evaluated. Factor analysis using the ratings of social anxiety symptoms identified four factors: socially inadequate feelings, performance anxiety, offensive fear, and tenacity. Four subtypes emerged from cluster analysis based on the factor scores and they were called performance anxiety type, offensive type, interpersonal anxiety type and mild type. Chi2 test and analysis of variance revealed the following: (i) the offensive type had the greatest symptom severity. Any situation could provoke symptoms, and interpersonal tense feelings became much stronger with persons of the same age; (ii) the interpersonal anxiety type was characterized by the fear of social interaction in daily life; and (iii) patients with the offensive type and the interpersonal anxiety type presented more difficulties than did those with the performance anxiety type on developmental and premorbid adjustment.
Adult↗
The influences of family environment on personality traits.
In order to clarify the influences of family environment on the development of personality traits, 150 children (104 males and 46 females, mean age 13.2 +/- 2.4 years) who had been interviewed at the Child Guidance Clinic in Osaka were investigated. From 13 behavioral characteristics (activity, talkativeness, sociability, social skills, rule-keeping, will, aggression, emotional control, imagination, anxiety, maturity, intelligence, and neuroticism), factor analysis identified three personality traits: extraversion, maturity, and intellect. The effects of family environment (maternal and paternal participation in child rearing before and after 4years of age, child-rearing style, parental relationship, sibling relationship, number of siblings, birth order, and socioeconomic status) on these personality traits were examined based on a structural equation model. The results found, first, that extraversion was negatively associated with overprotection/interference and with maternal participation in child rearing. Maturity correlated with high socioeconomic status, appropriate child-rearing style, and paternal participation in child rearing. Intellect was related to high socioeconomic status and maternal participation in child rearing. Second, path analysis with selected variables revealed that 8% of variance in extraversion, 14% in maturity, and 10% in intellect was due to family environment. Third, children with high introversion or high intellect had stronger influences from family environment than did those with high extraversion or low intellect.
Adolescent↗
Tau protein is a potential biological marker for normal pressure hydrocephalus.
A biological marker for normal pressure hydrocephalus (NPH) is beneficial for evaluation of its severity and of indications for shunt operation. Tau protein was initially considered as a biological marker in cerebrospinal fluid (CSF) from Alzheimer's patients. Recently, it has been demonstrated that degeneration in the brain causes elevation of tau in CSF. Therefore, the tau level in CSF from NPH patients was evaluated. Tau levels in CSF from NPH patients were significantly higher than that in controls. The tau levels were correlated with the severity of dementia, urinary incontinence, and gait disturbance in NPH. These results suggest that CSF tau may be useful as a biological marker for NPH to determine the level of neuronal degeneration.
Aged↗
Interaction on metabolic clearance between A-type and B-type natriuretic peptides in patients with heart failure.
A-type and B-type natriuretic peptides (ANP and BNP) are secreted into the systemic circulation via the coronary sinus. Plasma levels of ANP and BNP at the coronary sinus should directly determine the systemic circulating levels. However, the metabolic clearance of these hormones are dependent on similar systems, natriuretic peptide clearance receptor (NPR-C) and neutral endopeptidase 24.11 (NEP), suggesting a possible interaction between ANP and BNP on metabolic clearance. In this study, we examined the interaction on metabolic clearance in patients with heart failure. We obtained blood samples from the coronary sinus and aortic root in 100 patients with heart failure and 28 control subjects. The difference in ANP and BNP levels between the coronary sinus and the aortic root is reflected partly by the metabolic clearance in the pulmonary circulation. In this study, we examined the possible interaction on metabolic clearance between ANP and BNP using a statistical procedure. The ratio of the level of BNP to ANP (BNP/ANP) was significantly higher in the aortic root than in the coronary sinus at any stage of heart failure. We performed multiple regression analysis using ANP and BNP levels at the coronary sinus as independent variables (X1 and X2, respectively) and the ANP level at the aortic root as a dependent variable (Y). The analysis showed that both X1 and X2 were significant variables in the equation. On the other hand, we performed the same analysis using the BNP level at the aortic root as a dependent variable (Y). The analysis showed that only X2 was a significant variable in the equation. This study suggests that (1) the metabolic clearance in the pulmonary circulation is higher for ANP versus BNP and (2) the amount of ANP cleared in the pulmonary circulation depends on the amount of both ANP and BNP secreted from the heart, whereas the amount of BNP cleared in the pulmonary circulation is dependent solely on the amount of BNP secreted from the heart.
Aorta↗