Biomedical subjects

Y Hirooka

Publications and source records attributed to Y Hirooka.

At least 73 records · Page 4Linked to original sources

PubMed1999

Cholinergic systems in the nucleus of the solitary tract of rats.

The pharmacological and physiological properties of excitatory amino acid and ACh systems in the nucleus of the solitary tract (NTS) were studied in slices of rat brain stem by extracellular and intracellular recordings from neurons activated by solitary tract (ST) stimulation. These neurons were characterized as having several long dendrites with multiple varicosities. Synaptic activation of the medial NTS (mNTS) neurons by ST stimulation was mediated by non-N-methyl-D-aspartate (NMDA) glutamate (Glu) receptors, because the excitation was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione but not by NMDA, nicotinic, or muscarinic antagonists. Identified mNTS neurons were excited by iontophoresis of both Glu and ACh. The most sensitive region of the cell was on the dendrites approximately 100 micrometer from the cell body for both putative neurotransmitters. Nicotinic and/or muscarinic excitatory ACh responses were detected on the mNTS neurons. Our observations suggest that both types of ACh receptors may contribute to the attenuation of the baroreceptor reflex, but the functional correlation of this receptor profile remains to be determined.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Nociceptin stimulates thyrotropin secretion in rats.

Effects of nociceptin on thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) secretion in rats were studied. Nociceptin (150 microgram/kg) was injected intravenously and rats were serially decapitated after the injection. The effects of nociceptin on TRH release from the hypothalamus and TSH release from the anterior pituitary in vitro were also investigated. TRH and thyroid hormones were measured by individual radioimmunoassays. TSH was determined by enzyme immunoassay. TRH contents in the hypothalamus decreased significantly after nociceptin injection, whereas plasma TRH concentrations showed no changes. Plasma TSH concentrations increased significantly in a dose-related manner. The TRH release from the hypothalamus was enhanced significantly in a dose-related manner with the addition of nociceptin. The TSH release from the anterior pituitary in vitro was not affected by the addition of nociceptin. The plasma thyroxine and 3,3',5-triiodothyronine levels did not change significantly after nociceptin administration. The inactivation of TRH by plasma or hypothalamus in vitro after nociceptin injection did not differ from that of controls. The findings suggest that nociceptin acts on the hypothalamus to stimulate TRH and TSH secretion.

Animals↗

PubMed1999

Endothelin-1 facilitates synaptic transmission in the nucleus tractus solitarii in normotensive rats but not in spontaneously hypertensive rats.

We previously demonstrated that endothelin-1 (ET-1) increases the neuronal activity of neurons in the nucleus tractus solitarii (NTS) and augments the response to glutamate (Glu), using in vitro brainstem slice preparations of normotensive Wistar-Kyoto (WKY) rats. This study was designed to determine whether the effects of ET-1 on neuronal activity and synaptic transmission in the NTS are altered in spontaneously hypertensive rats (SHR). Experiments were performed with WKY rats and age-matched SHR. We recorded the extracellular single unit of neuronal activity of NTS neurons in response to electrical stimulation of the solitary tracts using in vitro brainstem slice preparations. ET-1 or Glu was iontophoretically applied to the recording neurons. ET-1 increased the neuronal activity of NTS neurons in SHR as well as WKY. The magnitude of the increase in the neuronal activity evoked by Glu was augmented by application of ET-1 in WKY rats (6.1 +/- 0.6 to 11.1 +/- 1.7 spikes/s, p < 0.05) but not in SHR (5.6 +/- 0.5 to 5.6 +/- 0.6 spikes/s). These results indicate that ET-1 increases the neuronal activity of the NTS in both SHR and WKY. However, the increase in neuronal activity in response to Glu is augmented by ET-1 in WKY but not in SHR, suggesting that reflex control is impaired in SHR.

Animals↗

PubMed1999

Gene amplification as a common cause of inherited thyroxine-binding globulin excess: analysis of one familial and two sporadic cases.

T4-binding globulin (TBG) is the major thyroid hormone transport protein in humans. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency and excess. A single nucleotide deletion or substitution in the TBG gene, located on Xq22, has been detected in partial and complete deficiencies. As for inherited TBG excess, the gene amplification has been recognized in two Japanese families recently. In this study, an additional three Japanese families, one familial (F-I) and two sporadic TBG excess (F-II, F-III), were analyzed. Serum TBG levels in hemizygous males were 73, 47 and 42 microg/ml, three- to two-fold the normal value. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The gene dosage of TBG was evaluated by coamplification with autosomal betaGlobin or X-chromosomal Duchenne Muscular Dystrophy (DMD) and subsequent quantitation by HPLC. The TBG/betaGlobin ratios of the affected male and female of F-I were 3.09- and 3.86-times, respectively, compared to that of the normal males. The TBG/DMD ratios were 2.93- and 2.09-times, respectively. These results are compatible with three copies of the TBG gene on the affected X-chromosome. Similarly, a twofold increase in gene dosage was demonstrated in the affected males of sporadic cases. Their mothers with normal TBG values had the same TBG gene dosage as normal females, suggesting that de novo gene duplication arose in gametes probably during meiosis. Amplification of the TBG gene was not recognized in these three families by in situ hybridization of prometaphase chromosomes. Though the mechanism remains unproved, gene amplification of TBG was considered to be a common cause for inherited TBG excess.

Female↗

PubMed1999

Expression of MAGE genes and survival in patients with hepatocellular carcinoma.

The human melanoma antigen (MAGE) gene family encode tumor-specific antigens recognized by autologous cytotoxic T lymphocytes. Some of these antigens may be potentially useful for cancer-specific immunotherapy. The expression of MAGE genes has been reported not only in melanoma but also in various other malignant tumors. However, little is known about the expression of these genes in human hepatocellular carcinoma (HCC). We therefore analyzed, by means of a reverse transcription-polymerase chain reaction (RT-PCR), the expression of MAGE-1, MAGE-2, and MAGE-3 genes in 60 tissue samples resected from HCCs. The MAGE-1, MAGE-2, and MAGE-3 genes were expressed in 18 (30.0%), 9 (15.0%), and 15 (25.0%), respectively, of the 60 tumor-tissue samples. Nineteen (31.7%) samples expressed at least one of the three MAGE genes, and 8 (13.3%) expressed all three genes. In contrast, none of the MAGE genes was expressed in any of the 60 adjacent non-tumorous liver samples. The age of patients was significantly older in at least one MAGE-positive group (MAGE-positive groups) than in the MAGE-negative ones (p<0.05). The tumor size was significantly larger in MAGE-positive groups than in the negative ones (p<0.05). The serum alpha-fetoprotein level was significantly lower in MAGE-positive groups than in negative ones (p<0.05). Patients with tumors expressing at least one MAGE gene showed a better recurrence-free survival rate than those with tumors showing no MAGE gene expression (p<0.05). These results indicated that the MAGE genes were exclusively expressed in cancerous tissues of a considerable proportion of patients affected by HCC, and that some of these patients might be potential candidates for tumor-specific immunotherapy using the MAGE encoded antigens.

Adult↗

PubMed1999

[Studies on recurrent breast cancer--clinicopathological factors and p53, p21Cip1/Waf1 and cyclin D1 protein expression].

Of patients radically operated on for breast cancer in our department, 46 patients who had recurrent breast cancer were clinicopathologically evaluated to clarify the prognostic factors of recurrent breast cancer. Furthermore, p53, p21 and cyclin D1 protein expression were studied immunohistochemically and their prognostic value was evaluated. The relapse-free interval was highly related to the survival rate after the recurrence. p53 overexpression was correlated with the progression of clinical stage and lymph node metastasis and negatively correlated with the expression of estrogen receptor. The p21 positive and p53 negative cases had a significantly better prognosis than the p21 negative and p53 positive cases. The combination of p53 and p21 protein expression seemed to have prognostic value in recurrent breast cancer.

Breast Neoplasms↗

PubMed1999

Distribution of calcium sensing receptor in rats: an immunohistochemical study.

OBJECTIVE: To investigate the organ distribution of calcium sensing receptor (CaR) in rats by immunohistochemical method. METHODS: CaR was identified immunohistochemically in the rat tissues using specific anti-CaR antiserum raised in New Zealand white rabbits immunized with a conjugate of synthetic CaR peptide (186-204) with bovine serum albumin. Immunohistochemical analysis was performed by avidin-biotin complex method. RESULTS: CaR immunoreactivity was visualized in the central nervous system, anterior pituitary, gastric mucosa, small intestine and colon, Auerbach,s and Meissner,s gastric nervous branch, small intestine and colon, pancreas, adrenal medulla, kidney and testis. When using antiserum preincubated with synthetic CaR peptide (186-206) or kidney homogenates, no significant stain of kidney was detected. CONCLUSIONS: The findings suggest that CaR is widely distributed and that the method used is valuable in studying the distribution of caR in rat.

Amino Acid Sequence↗

PubMed1999

Distribution of thyrotropin releasing hormone receptor type 2 in rats: an immunohistochemical study.

OBJECTIVE: To investigate the organ distribution of thyrotropin releasing hormone receptor (TRHR) type 2 in rats by immunohistochemical method. METHODS: TRHR type 2 was identified immunohistochemically in the rat tissues using specific anti-TRHR antiserum raised in New Zealand white rabbits immunized with a conjugate of synthetic TRHR type 2 (5-23) with bovine serum albumin. Immunohistochemical analysis was performed by avidin-biotin complex method. RESULTS: TRHR type 2 immunoreactivity was visualized in the central nervous system, anterior pituitary, gastric mucosa, Auerbach's and Meissner's nervous branch of the stomach, small intestine and colon, retina amd testis. Significant stain was detected in neural perikarya, axons and dendrites. When using antiserum preincubated with synthetic TRHR type 2(5-23) or anterior pituitary homogenates, no significant stain of anterior pituitary was detected. CONCLUSIONS: These findings suggest that TRHR type 2 is widely distributed and that the method used is valuable in studying the distribution of TRHR type 2 in rats.

Animals↗

PubMed1998

Swimming stress that causes hyperglycemia increases in vivo release of noradrenaline, but not acetylcholine, from the hypothalamus of conscious rats.

The effects of acute swimming stress (10 min) on noradrenaline release from the medial basal hypothalamus (MBH; consisting of the ventromedial and dorsomedial hypothalamus) and acetylcholine release from the lateral hypothalamic area (LHA) were investigated in freely moving rats by using in vivo microdialysis techniques. Serum glucose, noradrenaline and adrenaline concentrations were also determined. Acute swimming stress produced significant hyperglycemia, with increases in serum noradrenaline and adrenaline concentrations. The release of noradrenaline from the MBH was significantly stimulated during the swimming stress. On the other hand, the swimming stress has no significant effect on the release of acetylcholine from the LHA. These findings support the idea that hypothalamic noradrenergic neurons play an important role in the sympathoadrenal hyperglycemic response to stressful stimuli. Moreover, it is suggested that hypothalamic cholinergic neurons are not involved in the responses of serum glucose, noradrenaline and adrenaline concentrations to swimming stress.

Acetylcholine↗

PubMed1998

Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative pancreatoscopy with the ultrathin pancreatoscope for the main pancreatic lesions of mucin-producing tumors of the pancreas (MPT). DESIGN: Prospective diagnostic test study with a criterion standard of pathologic examination and masked comparison. SETTING: A university hospital. PATIENTS: Twenty-four consecutive patients with MPT referred for surgery in whom endoscopic retrograde pancreatography, endoscopic ultrasonography, and computed tomography had been performed as a diagnostic examination. All patients underwent surgery and the diagnosis was confirmed by pathologic examination. INTERVENTION: Intraoperative pancreatoscopy was performed with the ultrathin pancreatoscope. MAIN OUTCOME MEASURES: Findings of intraoperative pancreatoscopy, endoscopic retrograde pancreatography, and endoscopic ultrasonography were confirmed by pathologic examination of resected specimens. The diagnostic accuracy of these 3 modalities in detection of MPT lesions in the main pancreatic duct was compared. RESULTS: The diagnostic criterion of MPT lesions in the main pancreatic duct by intraoperative pancreatoscopy was a granular and papillary mural nodule. An MPT lesion in the main pancreatic duct was found in 17 of 24 cases. Intraoperative pancreatoscopy detected 10 cases of intraductal MPT lesions that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. Five of 10 cases were intraductal multicentric lesions. In 3 of these 5, additional pancreatic resection was performed. For diagnosis of MPT lesions, the sensitivity, specificity, and overall accuracy of intraoperative pancreatoscopy were all 100%; respective values were 43.8%, 100%, and 60.9% for endoscopic retrograde pancreatography and 47%, 100%, and 62.5% for endoscopic ultrasonography. CONCLUSIONS: Intraoperative pancreatoscopy is safe and effective in diagnosing the intrapancreatic duct extension and multicentric lesions of MPT. It provides important information for operative strategy and contributes to successful pancreatic surgery.

Adult↗

PubMed1998

Computerized nuclear morphometry of hepatocellular carcinoma and its relation to proliferative activity.

BACKGROUND AND OBJECTIVES: Nuclear profiles have been reported as useful prognostic predictor in various cancers. Data from computerized morphometries are objective and can be quickly derived using conventional microscopic analysis. However, it remains to be shown what types of pathological and biological factors influence the nuclear features. The aim of this study was to evaluate the correlation between the morphological nuclear features and clinicopathological parameters in patients with hepatocellular carcinoma (HCC). METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 76 patients with hepatocellular carcinoma who underwent hepatectomy at our hospital. In each case, 300 cancer nuclei were analyzed randomly on routine hematoxylin&eosin-stained slides through the use of a computer-assisted image analysis system that allowed us to trace the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patient survival, clinicopathologic status, and the proliferative activity of cancer cells. RESULTS: The mean nuclear area of poorly differentiated carcinoma was significantly larger than that of moderately and well differentiated carcinoma (P = 0.0003). Significant correlation was detected between the nuclear area of cancer cells and proliferative activity associated with proliferating cell nuclear antigen labeling index (PCNA LI) of cancer cells (r = 0.372, P = 0.0008). Moreover, blood vessel invasion of cancer cells or intrahepatic metastasis were more frequently detected in patients with large nuclear areas. Even though the nuclear area was not an independent prognostic factor in the multivariate analysis, the 5-year survival rate of the 35 patients who had tumors with large nuclear areas (>50 microm2, 25.9%) was significantly lower than that of the 36 patients who had tumors with small nuclear areas (< or =50 microm2, 63.3%, P = 0.001). CONCLUSIONS: The nuclear area of HCC correlates with cell differentiation and cell proliferative activity. Moreover, HCC with a large nuclear area has high potential for blood vessel invasion and intrahepatic metastasis. Thus, nuclear morphometry can be used as an useful morphological predictor for malignant potential in patients with HCC.

Adolescent↗

PubMed1998

Contrast-enhanced endoscopic ultrasonography in gallbladder diseases.

BACKGROUND: The purpose of this study was to investigate the usefulness of contrast-enhanced endoscopic ultrasonography in gallbladder diseases. METHODS: Subjects were 38 patients including 12 with adenocarcinoma, 2 adenosquamous carcinoma, 6 cholesterol polyp, 10 cholecystitis, and 8 adenomyomatosis. After endoscopic ultrasonography, sonicated albumin was intravenously injected and the enhanced effect on images of these lesions was determined. For malignancies we compared diagnostic accuracy (T factor, TNM classification) of endoscopic ultrasonography and contrast-enhanced endoscopic ultrasonography. Vascularity as shown by contrast-enhanced endoscopic ultrasonography and angiograms was compared. RESULTS: Enhancement was observed in 11 patients with adenocarcinoma but not of those with adenosquamous carcinoma or cholesterol polyp. Angiography provided hypervascular images for all cases of adenocarcinoma, but all other lesions were hypovascular. In one case of adenocarcinoma, 3 cases of adenomyomatosis, and 8 cases of cholecystitis, there was a discrepancy between contrast-enhanced endoscopic ultrasonography images and angiograms with regard to vascularity. The accuracy of depth of tumor invasion for endoscopic ultrasonography was 78.6% (11 of 14) versus 92.9% (13 of 14) for contrast-enhanced endoscopic ultrasonography. CONCLUSION: Contrast-enhanced endoscopic ultrasonography is useful in the diagnosis of gallbladder lesions.

Adenocarcinoma↗

PubMed1998

In vitro effects of endothelin-1 on somatostatin and thyrotropin-releasing hormone release from the rat stomach.

The effects of endothelin (ET) 1 on the release of somatostatin (SS) and thyrotropin-releasing hormone (TRH) from the rat stomach were studied in vitro. The rat stomach was incubated in medium 199 with 1.0 mg/ml of bacitracin (pH 7.4) for 20 min. The amounts of SS and TRH released into the medium were measured by individual radioimmunoassays. With the addition of ET-1, the release of SS from the rat stomach was inhibited significantly in a dose-related manner, whereas TRH released from the stomach was enhanced significantly. These effects of ET-1 on SS or TRH release were blocked by BQ-485, a blocker of ETA receptor. These findings suggest that ET-1 inhibits SS and stimulates TRH release from the rat stomach in vitro, and that these effects are mediate via ETA receptor.

Animals↗

PubMed1998

Thyrotropin-releasing hormone and somatostatin inhibit each others release in vitro in the rat retina.

The effect of thyrotropin-releasing hormone (TRH), somatostatin (SS) or octreotide, an analogue of SS, on release of TRH or SS from the rat retina was studied in vitro. The retina was incubated in medium 199 (pH 7.4) with 1.0 mg/ml of bacitracin (medium) for 20 min. The amount of TRH or SS release into the medium was measured by individual radioimmunoassays. The TRH release from the rat retina was inhibited significantly in a dose-related manner by the addition of SS or octreotide. The SS release from the retina was inhibited by TRH, and the inhibitory effect of TRH on SS release from the rat retina was blocked by the addition of anti-TRH receptor antiserum immunoglobulin fraction. The findings suggest an interaction between TRH and SS in the rat retina by which the addition of one inhibits the release of the other.

Animals↗

PubMed1998

Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has recently been reported to be useful in the diagnosis of submucosal tumors, but there are some cases in which the EUS diagnosis is questionable. We evaluated the diagnostic usefulness of endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNAB) in such cases. PATIENTS AND METHODS: From October 1993 to May 1997, EUS-FNAB was performed in 22 patients with upper gastrointestinal submucosal tumors who had also undergone EUS. We analyzed the capability of EUS-FNAB diagnosis compared to that of EUS imaging alone (presumptive diagnosis). RESULTS: Adequate specimens for histological diagnosis by EUS-FNAB were obtained in 18 of the 22 patients (82%). In 15 cases the final diagnosis was based on surgery. EUS-FNAB was correct in 14 of 15 lesions. In contrast, EUS alone suggested a correct diagnosis in only nine lesions. CONCLUSIONS: EUS-FNAB may be able to establish a histologic diagnosis, and whenever histology is deemed necessary EUS-FNAB would be an option. EUS-FNAB may increase the diagnostic capability of EUS in differentiating between submucosal tumors.

Adult↗

PubMed1998

Colour Doppler-guided spectral analysis of gall-bladder wall flow.

For the purpose of the present study to diagnose gall-bladder cancers, which cannot be detected or are only partly visible by conventional ultrasonography (US), we attempted differential diagnoses of 69 patients with gall-bladder diseases (12 with gall-bladder cancer, five with acute cholecystitis, 11 with chronic cholecystitis, 27 with cholesterol polyp and 14 with adenomyomatosis) using the evaluation of gall-bladder wall blood flow (GWBF). GWBF was evaluated by colour Doppler-guided spectral analysis (CDSA). Thirty-three healthy volunteers were selected as controls at random. Two parameters of GWBF, namely flow velocity and resistive index (RI), were compared between patients with gall-bladder diseases and healthy volunteers. GWBF could be ultrasonically evaluated in 92 (90%) of 102 subjects. All 12 patients with gall-bladder cancer had a significantly rapid blood flow value compared with other patients and healthy volunteers. There was no significant difference in RI among patients and healthy volunteers. When cut-off level of the flow velocity was set at 30 cm/s, gall-bladder cancer could be diagnosed by flow velocity with 100% sensitivity (12/12) and 96% specificity (50/52). Using the same cut-off level of the flow velocity, 17 patients were analysed prospectively. In four asymptomatic gall-bladder cancers and two acute cholecystitis cases with some symptoms, the flow velocity was over 30 cm/s. In two of four patients with gall-bladder cancer, only a part of the tumour was visualized on conventional abdominal US. In conclusion, CDSA was more useful for diagnosing gall-bladder lesions than the conventional abdominal US due to estimation of arterial flow velocity in the gall-bladder wall.

Blood Flow Velocity↗

PubMed1998

Intraductal ultrasonography for the diagnosis of proximal invasion in extrahepatic bile duct cancer.

Intraductal ultrasonography (IDUS) was performed on 22 patients with extrahepatic bile duct cancer, using the percutaneous transhepatic approach. Intraductal ultrasonography images of the proximal invasion of the bile duct cancer were defined. In addition, three patients were examined through the peroral approach, to try to diagnose whether or not the cancer invaded to the bifurcation of the hepatic duct. Intraductal ultrasonography images obtained through the percutaneous approach could be classified into three patterns, types 1, 2 and 3, according to the features of the interior surface of the bile duct and the thickness of the bile duct wall. Type 1 images, which did not show protrusions into the bile duct lumen and had a bile duct wall of even thickness, were not likely to show bile duct cancer. Type 2 images showed protrusions of the tumour into the bile duct lumen and the surfaces of the protrusions were irregular. Type 3 images showed single or multiple low echoic papillary masses in the bile duct. Using the peroral technique, we considered all three cases to be type 1 and could diagnose that cancer had not invaded to the bifurcation of the hepatic ducts. From the results of this study, we suggest that proximal invasion of extrahepatic bile duct cancer can be diagnosed using IDUS.

Bile Duct Neoplasms↗

PubMed1998

Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: a preliminary study.

OBJECTIVE: The purpose of this study was to clarify the usefulness of contrast-enhanced endoscopic ultrasonography in pancreatic diseases. METHODS: The subjects comprised 37 patients with pancreatic diseases: 11 with ductal cell carcinoma, 10 with mucin-producing tumor, five with pseudo-cyst, four with islet cell tumor, four with chronic pancreatitis, and three with serous cystadenoma. After endoscopic ultrasonography, Albunex (0.22 ml/kg) was injected intravenously at a rate of 1 ml/s into the right median vein, and observation was continued for 10 min. The presence or absence of enhancement of the lesion was determined in each disease. Because all the patients with ductal cell carcinoma, islet cell tumor, chronic pancreatitis, and serous cystadenoma, as well as five with mucin-producing tumor and three with pseudo-cyst, underwent angiography, vascularity was compared between angiographic images and those of contrast-enhanced ultrasonography. RESULTS: Enhancement of the lesion was observed in all patients with islet cell tumor and serous cystadenoma, in eight with mucin-producing tumor, and in three with chronic pancreatitis. However, no enhancement effect was observed in the patients with ductal cell carcinoma and those with pseudo-cyst. Comparison between the images of contrast-enhanced endoscopic ultrasonography and angiographic images showed three patients in whom angiograms were hypovascular, but enhancement effect was observed on ultrasonographic images. CONCLUSION: The combined evaluation of plain and enhanced images of endoscopic ultrasonography may be useful for the diagnosis of pancreatic diseases.

Adenocarcinoma, Mucinous↗