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Biomedical subjects

Y Hirooka

Publications and source records attributed to Y Hirooka.

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

Central suppressive effect of octreotide on the hyperglycemic response to 2-deoxy-D-glucose injection or cold-swim stress in awake rats: possible mediation role of hypothalamic noradrenergic drive.

Somatostatin (SRIH) and its analog have been reported to act within the central nervous system to suppress the hyperglycemic response to a variety of neural stimuli. On the other hand, the hyperglycemic response to 2-deoxy-D-glucose (2-DG) injection or cold-swim stress is well demonstrated to be closely associated with an increase in hypothalamic noradrenergic neuronal activity (NNA). To evaluate whether the suppression of the hypothalamic NNA response could be involved in the central mechanism whereby a SRIH analog inhibits the hyperglycemic response, octreotide, a clinically used long-acting octapeptide SRIH analog, was administered into the third cerebral ventricle of awake rats prior to the intraperitoneal injection of 2-DG or cold-swim stress. Hypothalamic noradrenaline (NA) and its neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were analyzed, and the ratio of DHPG to NA was used as an index of NNA. Intracerebroventricular (i.c.v.) pretreatment with octreotide suppressed the 2-DG-induced increase in hypothalamic NNA, accompanied by the inhibition of the serum glucose, NA and adrenaline responses. This suppressive effect of octreotide was dose-dependent. Similarly, i.c.v. pretreatment with octreotide prevented the hypothalamic NNA response to cold-swim stress, accompanied by a blockade of the increases in serum glucose, NA and adrenaline. A close relationship between hypothalamic NNA and serum glucose emerged from these studies. Intraperitoneal pretreatment with octreotide had no significant effect on the hyperglycemic or hypothalamic NNA response to 2-DG injection. These findings suggest that the inhibitory effect of octreotide on the hypothalamic NNA response to 2-DG injection or cold-swim stress is associated with the simultaneous suppression of the hyperglycemic response. Supporting the concept that hypothalamic NNA contributes to the modulation of blood glucose in stressful conditions, it is suggested that the suppression of the hypothalamic NNA response is, at least in part, involved in the central mechanism by which octreotide inhibits the hyperglycemic response to 2-DG injection or cold-swim stress.

Animals↗
PubMed2001

Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C: a pilot study.

The aim of the present study is to evaluate whether interferon alpha (IFNalpha) therapy can inhibit intrahepatic recurrence after the curative treatment of small HCC with underlying chronic hepatitis C. Forty patients were enrolled in this study. They had solitary, small HCC</=3 cm in diameter, underlying chronic hepatitis C, and were </=70 years old. Of the patients, 18 were treated with IFNalpha for 6 months after the treatment of HCC, and 22 patients who did not receive IFNalpha therapy were used as controls. Six (33%) patients in the IFN group showed sustained response. The incidence of local recurrence was not different in the IFN and non-IFN groups (6 vs. 9%). The cumulative incidences of distant recurrence in the non-IFN and IFN groups were 9 and 6% at 1 year, 27 and 11% at 2 years, 63 and 18% at 3 years, 76 and 28% at 4 years, and 82 and 28% at 5 years; they were significantly different (P<0.01). Six (27%) patients in the non-IFN group died from the progression of HCC, but all IFN-treated patients were alive (P<0.05). The pilot study demonstrates that IFNalpha therapy after the curative treatment of small HCC can inhibit intrahepatic recurrence in the remnant liver and improve the prognosis of hepatitis C virus-related HCC.

Journal Article↗
PubMed2001

Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumors of the pancreas (IPMT) spread along the main pancreatic duct (MPD) or branch duct, or both. It is important to intraoperatively determine the extent of IPMT lesions in the MPD to perform a successful operation. METHODS: This study included 27 consecutive patients with IPMT who were referred for operation and who had undergone endoscopic ultrasonography, endoscopic retrograde pancreatography, and computed tomography as a diagnostic examination. Intraoperative ultrasonography with a 7.5-MHz annular array transducer and a 7. 5-MHz conventional transducer was performed. All patients underwent operation, and the pathology was confirmed. Endoscopic ultrasonography, endoscopic retrograde pancreatography, intraoperative conventional ultrasonography, and intraoperative annular array ultrasonography results were correlated with those from a pathologic examination of the resected specimens. The diagnostic accuracy of these 4 modalities in the detection of IPMT lesions in the MPD and the branch duct was confirmed. RESULTS: The diagnostic criterion of IPMT lesions by intraoperative annular array ultrasonography was the presence of echogenic masses with irregular margins in the MPD or branch duct, or both. An IPMT lesion in the MPD was found in 22 of the 27 patients. Intraoperative annular array ultrasonography detected 5 cases of IPMT lesions in the MPD that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. In 3 of 5 patients, pancreatic resection was extended to remove IPMT lesions. Intraoperative annular array ultrasonography detected 3 multifocal lesions that could not be detected by preoperative examinations. For the diagnosis of IPMT lesions in the MPD, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 86%, 100%, and 89%; the respective values were 50%, 100%, and 59% for endoscopic retrograde pancreatography; 59%, 100%, and 67% for endoscopic ultrasonography, and 32%, 100%, and 44% for intraoperative conventional ultrasonography. For the diagnosis of IPMT lesions in the branch duct, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 95%, 100%, and 96%. CONCLUSIONS: Intraoperative annular array ultrasonography is suitable for longitudinal scanning of the MPD, useful for accurate diagnosis of the extent of IPMT in the pancreas, and valuable for planning surgical strategy and successful operations for IPMT.

Adenocarcinoma, Mucinous↗
PubMed2001

Asymptomatic inflammatory bowel disease with special reference to ulcerative colitis in apparently healthy persons.

OBJECTIVE: We examined cases of asymptomatic inflammatory bowel diseases, particularly asymptomatic ulcerative colitis, which were found in apparently healthy Japanese persons who underwent general health screening. METHODS: Patients with positive immunological fecal occult blood test (IFOBT) among approximately 236,000 persons participating in the health screening program at the Aichi Prefectural Center for Health Care for the past 9 yr underwent total colonoscopy. In patients with ulcerative colitis, we investigated the sex and age distributions, extent of lesion, endoscopic activity, incidence rate, and clinical course. RESULTS: In all, 35 cases of inflammatory bowel disease were detected, and 274 cases of colorectal cancer (not discussed here) were detected in the same population. The 35 cases of inflammatory bowel disease consisted of 19 cases of ulcerative colitis (12 of asymptomatic and minimally symptomatic ulcerative colitis, and seven of symptomatic or with past history of ulcerative colitis); five of intestinal tuberculosis; two of Crohn's disease; two of amebic colitis; and seven of endoscopic colitis. The 12 patients with asymptomatic and minimally symptomatic ulcerative colitis consisted of 11 men and one woman aged 36-63 yr (mean 46.2 yr). We classified these cases into three grades of severity according to endoscopic findings: four cases were mild, eight moderate, and none severe. Of these 12 cases, three were found endoscopically because of positive IFOBT, although barium enema was normal. Anatomic types of colitis cases included three of total colitis, three left-sided colitis, two proctitis, and four right-sided or segmental colitis. In one case, the disease extended proximally during the course of observation. CONCLUSIONS: We found 35 cases of inflammatory bowel disease because of positive IFOBT performed as part of a general health screening. Of these, 19 cases were ulcerative colitis. These included many asymptomatic and minimally symptomatic cases, which could be very important in helping to elucidate the natural history of ulcerative colitis; thus, long-term follow up is necessary.

Adult↗
PubMed2001

Adenovirus-mediated gene transfer into the NTS in conscious rats. A new approach to examining the central control of cardiovascular regulation.

The nucleus tractus solitarii (NTS) is an important site for the regulation of sympathetic nerve activity. It receives the signals through afferent fibers from arterial baroreceptors, chemoreceptors, cardiopulmonary receptors, and other visceral receptors. Many studies have examined the role of nitric oxide (NO) in the NTS in cardiovascular regulation. However, most of these studies were conducted in an acute state with anesthesia. We have developed a novel technique of endothelial nitric oxide synthase (eNOS) gene transfer into the NTS in vivo. Adenovirus vectors encoding either the beta-galactosidase gene (Ad beta gal) or the endothelial nitric oxide synthase gene (AdeNOS) gene were transfected into the NTS. In the Ad beta gal-treated rats, the local expression of beta-galactosidase was confirmed by X-Gal staining, and beta-galactosidase activity was quantified using a colorimetric assay. In the AdeNOS-treated rats, the local expression of eNOS protein was confirmed by immunohistochemistry, and eNOS production was measured by in vivo microdialysis. Blood pressure and heart rate were monitored by a radiotelemetry system in a conscious state. The expression of each gene was observed from day 5 to day 10 after the gene transfer. In the AdeNOS-treated rats, blood pressure and heart rate significantly decreased from day 5 to day 10, and then thereafter gradually recovered over time. Our method may be useful in examining the local effect of a particular substance produced by a specific gene in the brain on cardiovascular function.

Adenoviridae↗
PubMed2001

Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.

Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-D-aspartate (NMDA) receptors in the NTS facilitates the release of L-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO2- and NO3- (NO(x)) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NO(x) and Glu. L-NAME abolished the increases in the levels of NO(x) and Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.

Animals↗
PubMed2001

Endogenous angiotensin II in the NTS contributes to sympathetic activation in rats with aortocaval shunt.

Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.

Angiotensin II↗
PubMed2001

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Adult↗
PubMed2001

Role of nitric oxide in central sympathetic outflow.

The gaseous molecule nitric oxide (NO) plays an important role in cardiovascular homeostasis. It plays this role by its action on both the central and peripheral autonomic nervous systems. In this review, the central role of NO in the regulation of sympathetic outflow and subsequent cardiovascular control is examined. After a brief introduction concerning the location of NO synthase (NOS) containing neurons in the central nervous system (CNS), studies that demonstrate the central effect of NO by systemic administration of NO modulators will be presented. The central effects of NO as assessed by intracerebroventricular, intracisternal, or direct injection within the specific central areas is also discussed. Our studies demonstrating specific medullary and hypothalamic sites involved in sympathetic outflow are summarized. The review will be concluded with a discussion of the role of central NO mechanisms in the altered sympathetic outflow in disease states such as hypertension and heart failure.

Animals↗
PubMed2001

Stimulatory effect of endothelin-1 on neurons in the nucleus tractus solitarii is mediated by non-N-methyl-D-aspartate receptors.

We previously demonstrated that endothlin-1 (ET-1) augments and ETA receptor antagonist attenuates excitatory neuronal response to glutamate (Glu) in brainstem slices from normotensive rats. The aim of this study was to determine which type of Glu receptor is responsible for the stimulatory effects of ET-1 on neurons of the nucleus tractus solitarii (NTS). Single unit discharges were recorded extracellularly from rat brainstem slice preparations. Seven NTS neurons that were excited by solitary tract (ST) stimulation responded to iontophoretically applied ET-1 with neuronal activity. An N-methyl-D-aspartate (NMDA) receptor antagonist, non-NMDA, 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX), or DL-2-amino-5-phosphonovaleric acid (AP-5) was perfused over the slices with Kreb's-Ringer solution. The increase in neuronal activity evoked by iontophoretically applied ET-1 was nearly abolished by CNQX but not by AP-5. CNQX but not AP-5 decreased the basal spontaneous neuronal activity of NTS neurons. These results suggest that non-NMDA receptors play a role in mediating the stimulatory effect of ET-1 on neuronal activity in the NTS.

2-Amino-5-phosphonovalerate↗
PubMed2001

Radioimmunoassay for somatostatin receptor type 2.

OBJECTIVE: To develop radioimmunoassay for somatostatin receptor type 2 (SSTR2) and search for its presence in certain rat tissues. METHODS: Anti-SSTR2 antiserum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic SSTR2 with bovine serum albumin. Radioiodination of SSTR2 was performed by chloramin T method followed by purification of radioiodinated material on Sephadex G-25 column. RESULTS: The obtained antibody did not crossreact with SSTR1, SSTR3, SSTR4, SSTR5, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The assay was performed with a double antibody system. SSTR2 was extracted from the tissues with acid acetone. The dilution curve of acid acetone-extracts of rat hypothalamus in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue SSTR2 was about 89 %, and the intra-assay and inter-assay variations were 4.9 % and 7.8 %, respectively. SSTR2 was found in the hypothalamus, cerebrum, cerebellum, pituitary, stomach and testis. CONCLUSIONS: These data suggest that this assay system is suitable for the estimation of SSTR2 in the tissues.

Acetone↗
PubMed2001

[Recent trends in studies of the etiology of hypertension: Central nervous system and autonomic nervous system].

Abnormality of autonomic nervous system is one of the important mechanisms in hypertension. Arterial baroreceptor reflex control of heart rate and sympathetic nerve activity is reset to higher level of blood pressure in hypertension. Abnormality of arterial baroreceptors has been studied as the mechanism of resetting in hypertension. However, recent studies have been focused on the role of central nervous system. Many factors in peripheral system also exist independently in the brain, such as the renin-angiotensin system, nitric oxide, endothelin-1. They contribute importantly to regulation of blood pressure. New approaches to examine the central control of cardiovascular regulation are now developing. Such methods will be useful in the study of the role of specific genes in the particular areas within the brain that regulate blood pressure.

Animals↗
PubMed2001

Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release.

In this study, we examine the role of NO located in the rostral ventrolateral medulla (RVLM) in the control of blood pressure and the activity of the sympathetic nervous system. To determine the effect of an increase in NO production in the RVLM on blood pressure in conscious rats, adenovirus vectors encoding either endothelial NO synthase (AdeNOS) or beta-galactosidase (Adbetagal) were transfected into the bilateral RVLM. The local expression of endothelial NO synthase (eNOS) protein in the RVLM was confirmed by immunohistochemical staining for the eNOS protein and by Western blot analysis. Mean arterial blood pressure (MAP) and heart rate, which were monitored using a radio-telemetry system, were significantly decreased in the AdeNOS-treated group from day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion was decreased on day 7 after the gene transfer in the AdeNOS-treated group. Microinjection of either N(G)-monomethyl-L-arginine (L-NMMA) or bicuculine, a gamma-amino butyric acid (GABA) receptor antagonist, into the RVLM at day 7 after the gene transfer increased MAP to significantly greater levels in the AdeNOS-treated group. However, microinjection of kynurenic acid into the RVLM on day 7 after the gene transfer did not alter MAP levels in either group. GABA and glutamate levels in the RVLM, when measured by in vivo microdialysis, were significantly increased in the AdeNOS-treated group. These results suggest that the increase in NO production caused by the overexpression of eNOS in the bilateral RVLM decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats. Furthermore, these responses may be mediated by an increased release of GABA in the RVLM.

Adenoviridae↗
PubMed2001

[Implication on thyroid function tests].

We tried to investigate the present problems, concerning the reference individual and interval in thyroid function tests and find the solutions for them. We are now using healthy adults for the reference individual and interval. Recently, we found the sex-difference and age-related changes for reference individual and interval in free T3 measurement. We raised the questions on whether there are any sex-differences and/or age-related changes or not. Surprisingly, there were almost no detailed data about them especially in Japan. Therefore, we examined the Europe data, and found out some kind of sex-differences and age-related changes. We propose the following examinations using many Japanese population in order to provide a precise and proper reference individual and interval: 1. Whether there are any sex-difference in thyroid function tests? 2. Whether there are age-related change in thyroid function tests, for instance, simply dividing population into the immature, adult and the aged?

Adult↗
PubMed2000

Urine levels of CD46 (membrane cofactor protein) are increased in patients with glomerular diseases.

Soluble membrane cofactor protein (MCP, CD46) has not been detected by conventional ELISA in human urine. Here, we established a highly sensitive assay method for determination of urinary MCP (uMCP) using monoclonal antibody-coated paramagnetic beads. This method enabled us to detect less than 0.05 ng/ml of purified membrane and recombinant soluble MCP, a sensitivity 10-fold higher than that of conventional ELISA. In normal subjects, the levels of uMCP were <0. 05 ng/ml. The levels of uMCP were elevated in patients with IgA nephropathy and more prominently in patients with rapidly progressive glomerulonephritis. The levels of uMCP were correlated significantly with those of serum MCP (sMCP) and N-acetyl-beta-glucosaminidase and nonsignificantly with those of beta(2)-microglobulin, total urine protein, or serum creatinine. The properties of uMCP were inconsistent with those of the reported sMCP, since uMCP showed three bands on SDS-PAGE/immunoblotting with molecular mass profiles different from those of sMCP. uMCP exhibited factor I cofactor activity for cleavage of C3b comparable to that of sMCP. The origin of uMCP, however, remains to be determined. These results, taken together with the parameter correlation profiles, suggested that uMCP is secreted or produced secondary to tubular or glomerular damage. The physiological role and clinical significance of uMCP are now within the scope of our investigation by establishment of this assay.

Acetylglucosaminidase↗
PubMed2000

Transpapillary biopsy in gallbladder disease.

BACKGROUND: Endoscopic biopsy is routine in gastrointestinal disease; similarly, histopathologic diagnosis is desirable in gallbladder disease. In this study we examined the clinical usefulness and the problems associated with transpapillary gallbladder biopsy. METHODS: Transpapillary gallbladder biopsy was attempted in 9 patients with gallbladder disease. After inserting a catheter sheath into the gallbladder using a guidewire via the transpapillary route without sphincterotomy, we inserted a biopsy forceps into the lumen of the sheath up to the gallbladder lumen and obtained specimens. RESULTS: We could obtain sufficient specimens for histopathologic diagnosis in 8 of 9 cases (88.9%). Of the 8 successful cases, targeted specimens were obtained in 7 (87.5%). Diagnostic accuracy with respect to malignant versus benign disease was 100% (2 of 2) and 83.3% (5 of 6), respectively. There were no complications. CONCLUSION: Transpapillary gallbladder biopsy is a clinically useful technique because it facilitates histopathologic diagnosis and therefore guides the choice of therapy.

Biopsy↗
PubMed2000

Radioimmunoassay for orexin A.

A radioimmunoassay for orexin A has been developed. Anti-orexin A antiserum was raised in New Zealand white rabbits immunized with a conjugate of synthetic orexin A with bovine serum albumin. This antibody did not crossreact with orexin B, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. Radioiodination of orexin A was performed with the chloramin T method, followed by purification of radioiodinated material on Sephadex G-25 column. Orexin A was extracted from tissues using acid-acetone. The assay was performed with a double antibody system. The dilution curve of acid-acetone-extracts of rat hypothalamus in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue orexin A was about 80%,and the intra-assay and inter-assay variations were 5.2% and 7.8%, respectively. Orexin A was found in the hypothalamus, cerebrum and testis. These data suggest that this assay system is suitable for the measurement of tissue orexin A and that orexin A is found in the central nervous system and testis.

Animals↗