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Biomedical subjects

H Nawata

Publications and source records attributed to H Nawata.

At least 163 records · Page 9Linked to original sources

Increased mRNA expression of a novel prostacyclin-stimulating factor in human colon cancer.

We recently cloned a prostacyclin (PGl2)-stimulating factor (PSF), which stimulates PGl2 production by cultured vascular endothelial cells. Immunohistochemistry and Northern blot analysis demonstrated that PSF was highly expressed in colon cancer sites compared with normal colon mucosa obtained from the same patient, as well as in cultured adenocarcinoma cell lines compared with cultured normal colon mucosal cell lines. Increased levels of the PSF protein were detected in the culture media of these adenocarcinoma cells compared with levels in the culture media of normal mucosal cells. These results suggest that PSF is closely associated with carcinogenesis of colon mucosa.

Adenocarcinoma↗

Complete response of early gastric cancer to uracil and tegafur.

A 74-year-old Japanese woman with early gastric cancer was successfully treated with uracil and tegafur (UFT). She was diagnosed by endoscopy (including endoscopic biopsy and endosonography) with an early gastric cancer, type IIa + IIc, on the greater curvature of the angulus. Surgical procedures or endoscopic therapy could not be performed because the patient had severe ischemic heart disease. Therefore, chemotherapy with UFT was administered at 300 mg/day for 15 months. Follow-up endoscopy, endosonography, and biopsy showed disappearance of the gastric cancer. To our knowledge, this is the first case report of the complete response of an early gastric cancer to UFT in the English-language literature.

Adenocarcinoma↗

Pretreatment staging of endoscopically early gastric cancer with a 15 MHz ultrasound catheter probe.

BACKGROUND: The usefulness of and problems associated with an ultrasound catheter probe in the pretreatment staging of endoscopically early gastric cancer remain unexplored. METHODS: Endoscopic ultrasonography using a 15 MHz catheter probe of 2.6 mm diameter was performed in a prospective study to determine the pretherapy staging of endoscopically early gastric cancer in 78 patients. The results of the ultrasound images were compared with the histologic findings of the specimens obtained by endoscopic mucosal resection or surgical resection. RESULTS: The accuracy of the catheter probe for depth of invasion of endoscopically early gastric cancers was 67% (52 of 78 patients). The accuracy in determining depth of invasion in relation to endoscopic type was significantly higher for the elevated type (91%) than for the depressed type of early cancer (56%) (p < 0.01). The staging accuracy classified by histologic type was significantly higher for differentiated (86%) than for undifferentiated (18%) cancer (p < 0.01). Staging accuracy decreased as tumor size increased. The accuracy, sensitivity, and specificity for nodal staging were 80%, 17%, and 90%, respectively. CONCLUSIONS: A 15 MHz ultrasound catheter probe is most useful for determining depth of invasion when the tumor is histologically differentiated and endoscopically of the small elevated type early gastric cancer, but it is unreliable in the diagnosis of metastatic lymph nodes.

Adenocarcinoma↗

Coronary sinus pacing initiates counterclockwise atrial flutter while pacing from the low lateral right atrium initiates clockwise atrial flutter. Analysis of episodes of direct initiation of atrial flutter.

INTRODUCTION: Rapid atrial pacing in sinus rhythm may directly induce atrial flutter without provoking intervening atrial fibrillation, or initiate atrial flutter indirectly, by a conversion from an episode of transient atrial fibrillation provoked by rapid atrial pacing. The present study was performed to examine whether or not the direct induction of clockwise or counterclockwise atrial flutter was pacing-site (right or left atrium) dependent. METHODS AND RESULTS: We analyzed the mode of direct induction of atrial flutter by rapid atrial pacing. In 46 patients with a history of atrial flutter, rapid atrial pacing with 3 to 20 stimuli (cycle length = 500 - 170 ms) was performed in sinus rhythm to induce atrial flutter from 3 atrial sites, including the high right atrium, the low lateral right atrium, and the proximal coronary sinus, while recording multiple intracardiac electrograms of the atria. Direct induction of atrial flutter by rapid atrial pacing was a rare phenomenon and was documented only 22 times in 15 patients: 3, 11, and 8 times during stimulation, respectively, from the high right atrium, low lateral right atrium, and the proximal coronary sinus. Counterclockwise atrial flutter (12 times) was more frequently induced with stimulation from the proximal coronary sinus than from the low lateral right atrium (8 vs 1, P = .0001); clockwise atrial flutter (10 times) was induced exclusively from the low lateral right atrium (P = .0001 for low lateral right atrium vs proximal coronary sinus, P = .011 for low lateral right atrium vs high right atrium). CONCLUSIONS: Direct induction of either counterclockwise or clockwise atrial flutter was definitively pacing-site dependent; low lateral right atrial pacing induced clockwise, while proximal coronary sinus pacing induced counterclockwise atrial flutter. Anatomic correlation between the flutter circuit and the atrial pacing site may play an important role in the inducibility of counterclockwise or clockwise atrial flutter.

Adult↗

Subcutaneous or visceral adipose tissue expression of the PPARgamma gene is not altered in the fatty (fa/fa) Zucker rat.

We cloned 537 basepairs (bp) of rat partial peroxisome proliferator-activated receptor gamma2 (PPARgamma2) cDNA and examined the effect of fasting or obesity on the expression of two isoforms of rat PPARgamma, gamma1 and gamma2, in either subcutaneous or mesenteric adipose tissue specimens using an RNase A protection assay. In Wistar rats, expression of both isoforms was dramatically reduced after 48 hours of fasting in the two fat tissue specimens. In comparing genetically obese (fa/fa) Zucker rats and lean control rats, no significant difference was observed in expression of the two isoforms in either type of adipose tissue. From these findings, we conclude that the adipose tissue level of rat PPARgamma depends on nutritional deprivation but is not closely associated with either obesity or insulin resistance in obese Zucker rats.

Adipose Tissue↗

Inhibition of integrin signaling with Arg-Gly-Asp motifs in rat hepatic stellate cells.

BACKGROUND/AIMS: Activation of hepatic stellate cells plays a key role in liver fibrogenesis. Disruption of normal hepatic stellate cell-matrix interactions may contribute to this process. However, little is known about the molecular events leading from integrin-extracellular matrix interaction to hepatic stellate cell function. Therefore, we investigated the role of integrin signaling in tyrosine phosphorylation of focal adhesion kinase and cytoskeletal assembly in rat hepatic stellate cells using soluble Arg-Gly-Asp containing peptides. METHODS: Hepatic stellate cells were isolated from normal rat livers. Integrin alpha5beta1 expression in hepatic stellate cells was analyzed by immunoprecipitation and immunocytochemistry. The cytoskeletal assembly and tyrosine phosphorylation of focal adhesion kinase were determined by immunocytochemistry and immunoblotting. We also analyzed the effect of Arg-Gly-Asp containing peptides on the expression of smooth muscle alpha actin by immunocytochemistry and immunoblotting. RESULTS: We identified integrin alpha5beta1 in rat hepatic stellate cells. Stress fiber formation and cell shape were different when hepatic stellate cells were plated on various extracellular matrix components. Treatment of hepatic stellate cells with soluble Arg-Gly-Asp peptides diminished the adhesion-induced tyrosine phosphorylation of focal adhesion kinase and inhibited the formation of stress fibers. The peptides also reduced the expression of smooth muscle alpha actin. CONCLUSIONS: Our results demonstrate that adhesion to extracellular matrix induces tyrosine phosphorylation of focal adhesion kinase and promotes actin stress fiber formation and focal adhesion assembly in rat hepatic stellate cells, and that these events are disturbed by soluble Arg-Gly-Asp peptides.

Animals↗

Expression of an orphan nuclear receptor DAX-1 in human pituitary adenomas.

OBJECTIVES: An orphan nuclear receptor, DAX-1, is known to be involved in the development and differentiation of anterior pituitary cells. The present study aimed to examine 1) whether DAX-1 is expressed in human pituitary adenomas, and 2) if it is expressed, what types of adenoma express the factor. MATERIALS AND METHODS: Adenoma tissues examined included 18 clinically non-functioning adenomas, 14 GH-secreting adenomas and 7 PRL-secreting adenomas. The expression of the following genes were tested by reverse transcription-polymerase chain reaction (RT-PCR): DAX-1, Adrenal-4-binding protein/steroidogenic factor-1 (Ad4BP/SF-1), Pit-1, LH beta, FSH beta, gonadotrophin-releasing hormone receptor (GnRH-R), GH, PRL, and TSH beta, as well as beta-actin as a control. RESULTS: Eleven clinically non-functioning adenomas expressed DAX-1, 10 of which also expressed Ad4BP/SF-1. Nine out of the 11 DAX-1 expressing adenomas also expressed LH beta, FSH beta and GnRH-R as well, indicating that these adenomas possessed gonadotrophic properties. Nine clinically non-functioning adenomas expressed Pit-1 as well as GH, PRL and/or TSH beta, thus having somatomammotrophic or thyrotrophic properties, 3 of which overlapped with the above DAX-1-expressing adenomas. One non-functioning adenoma expressed Ad4BP/SF1 and FSH beta but not DAX-1, and another one expressed DAX-1 and Ad4BP/SF-1 with PRL. On the other hand, all GH-secreting and PRL-secreting adenomas expressed Pit-1 and GH and/or PRL, but neither DAX-1 nor Ad4BP/SF-1. CONCLUSIONS: The results shown here indicate that DAX-1 is expressed in the majority of human pituitary adenomas of gonadotrophic origin in parallel with Adrenal-4-binding protein/steroidogenic factor-1.

Adenoma↗

Low level of glucocorticoid receptor messenger ribonucleic acid in pituitary adenomas manifesting Cushing's disease with resistance to a high dose-dexamethasone suppression test.

OBJECTIVES: The overnight 8-mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of ACTH from the pituitary gland, from other kinds of Cushing's syndrome. However, a few patients with ACTH-producing pituitary adenoma show no suppression of plasma cortisol after the administration of 8 mg of dexamethasone. To clarify the relationship between the level of glucocorticoid receptor (GR) in the pituitary adenoma and the sensitivity to dexamethasone in Cushing's disease, we thus examined the levels of GR alpha and GR beta mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH-producing adenomas. MATERIALS: Total RNA was extracted from six pituitary adenomas and pituitary tissue adjacent to one of the adenomas, and the mRNA levels of GR alpha, GR beta, pro-opiomelanocortin (POMC) and beta-actin in these samples were sampled by quantitative RT-PCR. RESULTS: The GR alpha mRNA levels in the adenomas from the two patients who showed no response to the 8-mg dexamethasone suppression test were significantly lower than those in the adenomas of four patients who showed suppression. The GR beta mRNA level was much lower than that of GR alpha mRNA but not significantly different among the six adenomas. CONCLUSIONS: These results suggest strongly that decreased expression of GR alpha in pituitary adenomas may be the major reason for the marked insensitivity to the 8-mg dexamethasone suppression test observed in two patients with Cushing's disease.

Actins↗

Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding Ad4BP/SF-1 is independent of pituitary control.

Ad4BP/SF-1 is a transcription factor essential for the development of the adrenal gland and the gonads as well as for the maintenance of their functions through regulating tissue-specific gene transcription. In the whole body, hypothalamo-pituitary-gonadal and -adrenal axes are known to play prominent roles in mediating the function of the gonads and adrenal. In this study, the effects of the tropic peptide hormones secreted by the pituitary on the regulation of the rat Ftz-F1 (rFtz-F1) gene encoding Ad4BP/SF-1 were investigated. Immunochemical studies revealed that Ad4BP/SF-1 was expressed even in the adrenal cortex of hypophysectomized rats. Such persistent expression of Ad4BP/SF-1 was also observed in the testes and ovaries of the hypophysectomized animals. In contrast to Ad4BP/SF-1, the expressions of steroidogenic P450s were reduced significantly. The transcriptional activities of the endogenous and transfected rFtz-F1 genes were examined with Y-1 and I-10 cells derived from mouse adrenocortical and testicular Leydig cell tumors, respectively. Neither gene appeared to be activated significantly by cAMP, whereas both endogenous and exogenous CYP11A genes encoding P450(SCC) were activated. Taken together, these observations indicate that the expression of the rFtz-F1 gene is mainly regulated by a mechanism independent of the neuroendocrine axes.

Adrenal Cortex↗

Big endothelin analogues with inhibitory activity on endothelin-converting enzyme-1.

Big endothelin-1 (big ET-1) is converted into an active form, ET-1, by endothelin-converting enzyme-1 (ECE-1). To assess the mechanism of substrate recognition by ECE-1, we examined the effects of variously substituted analogues of big ET-1 on ECE-1 activity, using solubilized membranes prepared from human ECE-1-expressed CHO-K1 cells. Among the big ET-1 analogues tested, [21Phe]big ET-1[18-34] and [31Ala]big ET-1[18-34] exhibited significant inhibition of ECE-1. A kinetic analysis revealed [21Phe]big ET-1[18-34] to be a competitive inhibitor (Ki = 21 microM) and [31Ala]big ET-1[18-34] to be a noncompetitive inhibitor (Ki = 36 microM). These results suggested that ECE-1 recognizes big ET-1 at the P1 position and the C-terminal region in a different manner and that modification of these regions can produce ECE-1 inhibitors.

Animals↗

Atypical form of the fourth criterion for transient entrainment.

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory pathways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.

Adolescent↗

Nonfluoroscopic guidance for catheter placement into the coronary sinus under direct vision using a balloon-tipped cardioscope.

The right atrial posterior septum, including the coronary sinus (CS) ostium, is an important landmark in radiofrequency catheter ablation therapy for supraventricular tachycardia or atrial flutter. The anatomical findings around the CS ostium would be useful to determine a target site or line during catheter ablation. The aim of the study was to test the ability of the imaging catheter to identify structures in the posterior septal area of the right atrium and to evaluate the feasibility of guidance for catheter placement in the CS using a cardioscope that we recently developed. In 12 anesthetized dogs, the cardioscope, consisting of a deflectable 7 Fr fiberoptic endoscope with an inflatable and transparent balloon, was introduced into the right atrium via the femoral vein. The cardioscope was manipulated to observe the right atrial posterior septum. A deflectable electrode catheter was inserted via the jugular vein and positioned in the CS under cardioscopic guidance. In 10 of 12 dogs, the right atrial posterior septum, including the CS ostium, and the tendon of Todaro could be anatomically identified by cardioscopy. It was possible to position an electrode catheter in the CS in all 10 dogs under direct vision without fluoroscopy. But the CS ostium could not be detected in the remaining two dogs, although the cardioscope was placed at as many sites as possible. No complication occurred. The balloon-tipped cardioscope appears to be useful in observing the right atrialposterior septum and in guiding an electrode catheter into the CS.

Animals↗

Liver failure caused by hepatic angiodysplasia in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia is a systemic vascular disease with autosomal dominant inheritance that results in telangiectasia, arteriovenous malformations, and hemangiomas. The liver is one of the organs commonly affected in hereditary hemorrhagic telangiectasia, and hepatic lesions consist of angiodysplasia and fibrosis. A patient with hereditary hemorrhagic telangiectasia and significant impairment of synthetic liver function is reported. Dynamic computed tomography revealed marked enlargement of the common hepatic and intrahepatic arteries, heterogeneous parenchymography, and early opacification of the hepatic veins consistent with telangiectasias and arteriovenous shunting. Overall, the liver was predominantly occupied by vascular structures and scarce residual hepatic parenchyma. Other causes of liver dysfunction, such as viral hepatitis and alcohol abuse, were excluded. In general, hepatic fibrovascular dysplasia seen in hereditary hemorrhagic telangiectasia usually results in only mild liver dysfunction; however, this case shows that hepatic involvement may rarely result in hepatic failure.

Aged↗