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Biomedical subjects

K Miyasaka

Publications and source records attributed to K Miyasaka.

At least 109 records · Page 6Linked to original sources
PubMed1999

Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats.

Whether cholecystokinin (CCK) has a direct action on duct cells and the role of CCK-A receptor in bicarbonate secretion were examined by comparing the results obtained from OLETF (CCK-A receptor-deficient rats) and control (LETO) rats. Rats were prepared with cannulae for draining bile and pancreatic juice separately, with two duodenal cannulae and an external jugular vein cannula. The experiments were conducted without anesthesia. The responses of bicarbonate secretion to intravenous infusion of CCK, acetyl-beta-methylcholine (Ach), and 2-deoxy-D-glucose (2DG), and to intraduodenal infusion of HCl and a liquid meal were examined. To examine the synergistic effect between CCK and secretin, the effect of CCK during a background secretin infusion was examined in LETO rats. CCK did not stimulate bicarbonate secretion in either strain, nor in LETO rats with secretin infusion. When gastric acid secretion was prevented by administration of omeprazole, Ach did not increase bicarbonate secretion, but 2DG did in both strains. Intraduodenal infusion of HCI and a liquid meal significantly increased bicarbonate secretion in both strains; however, the responses were much less in OLETF than LETO rats. In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants.

Animals↗
PubMed1999

Atropine-resistant secretion of a putative luminal CCK-releasing peptide in conscious rats.

The changes in levels of the newly discovered luminal CCK-releasing factor (LCRF) in the small intestinal lumen before and after bile-pancreatic juice diversion in conscious rats were examined by a specific RIA. Moreover, we also examined whether LCRF secretion was under cholinergic control. Anti-LCRF antiserum was raised in rabbits, and a sensitive RIA was established. The localization of LCRF was examined by immunohistochemistry. The luminal content of LCRF was significantly increased by bile-pancreatic juice diversion, during which luminal trypsin activity was eliminated. The increase in luminal LCRF content was not inhibited by intravenous infusion of atropine. The changes in plasma levels of CCK and pancreatic secretion were similar to those in luminal LCRF contents. LCRF immunostaining was observed in villus tip enterocytes of the small intestine and was most prominent in the duodenal portion. These results support our original hypothesis that LCRF may be released spontaneously into the small intestinal lumen from the villus tip enterocytes and its intraluminal degradation by proteases regulates CCK release. Furthermore, LCRF release was not subject to cholinergic regulation.

Animals↗
PubMed1999

Influence of increased abdominal pressure on steady-state cardiac performance.

The effect of steady-state increases in abdominal pressure (Pab) on cardiac performance was studied in seven acutely instrumented swine with pneumoperitoneum (PP). The animal was placed on volume-preset ventilation, and PP was created by air insufflation. Cardiac output (CO), right atrial (Pra), left atrial (Pla), pericardial (Ppe), and abdominal inferior vena cava pressures (Pivc) were measured while Pab was increased from baseline to 7.5, 15, and 30 mmHg (PP7.5, PP15, and PP30, respectively). Cardiac function curves of the right and left ventricle (RV and LV, respectively) were compared between baseline and PP30. CO presented biphasic changes, with an inital slight increase at PP7.5 followed by a fall at PP30. A significant discrepancy was observed between Pra and Pivc at PP15 and PP30, consistent with development of a "vascular waterfall." Transmural Pla (Pla - Ppe) showed parallel changes with CO, whereas transmural Pra (Pra - Ppe) exhibited a sustained increase. The RV cardiac-function curve was more depressed than was that of the LV at PP30; this suggests an increased RV afterload produced by the elevated airway pressure. These results support the hypothesis that our previously proposed concept of abdominal vascular zone conditions (M. Takata, R. A. Wise, and J. L. Robotham. J. Appl. Physiol. 69: 1961-1972, 1990) is also applicable to steady-state hemodynamic analyses. The abdominal zones appear to play an important role in determining CO, with increases in Pab, by modulating systemic venous return and the LV preload. Simultaneous measurements of Pra and Pivc may provide useful information in the hemodynamic care of patients with elevated Pab.

Abdomen↗
PubMed1999

Intratracheal anti-tumor necrosis factor-alpha antibody attenuates ventilator-induced lung injury in rabbits.

To evaluate the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of ventilator-induced lung injury, we 1) measured TNF-alpha production in the lung caused by conventional mechanical ventilation (CMV) and 2) evaluated the protective effect of anti-TNF-alpha antibody (Ab) in saline-lavaged rabbit lungs. After they received saline lung lavage, rabbits were intratracheally instilled with 1 mg/kg of polyclonal anti-TNF-alpha Ab in the high-dose group (n = 6), 0.2 mg/kg of anti-TNF-alpha Ab in the low-dose group (n = 6), serum IgG fraction in the Ab control group (n = 6), and saline in the saline control group (n = 7). Animals then underwent CMV for 4 h. Levels of TNF-alpha in lung lavage fluid were significantly higher after CMV than before in both control groups. Pretreatment with intratracheal instillation of high and low doses of anti-TNF-alpha Ab improved oxygenation and respiratory compliance, reduced the infiltration of leukocytes, and ameliorated pathological findings. CMV led to TNF-alpha production in the lungs, and intratracheal instillation of anti-TNF-alpha Ab attenuated CMV-induced lung injury in this model.

Acute-Phase Reaction↗
PubMed1999

A phase II study of concomitant chemoradiotherapy for laryngeal carcinoma using carboplatin.

PURPOSE: We conducted a phase II study of concomitant chemoradiotherapy with carboplatin for laryngeal carcinoma. MATERIALS AND METHODS: Sixty-four patients with stage II-IV (stage II, 36; III, 19; IV 9) laryngeal carcinoma were treated with concomitant administration of carboplatin (CBDCA) during radiotherapy (CRT group) between 1991 and 1994. There were 36 supraglottic, 25 glottic, and 3 subglottic carcinomas. Patients with stage II and stage III-IV received intravenous CBDCA of 100 mg/m2 and 120 mg/m2 once a week, respectively. Tumor response was assessed at 40 Gy in 16 fractions to select the patients suitable for total laryngectomy or radical radiotherapy of 65 Gy in 26 fractions in 6.5 weeks. The treatment results were compared with the historical control consisting of 56 patients consecutively treated from 1988 to 1990 without chemotherapy (RT group). The two studies were comparable with regard to patient characteristics, including age distribution, gender, tumor location, size, and clinical stage. RESULTS: The actuarial 5-year survival rate was 80.3% for the CRT group and 81.3% for the RT group. A favorable response (complete response or partial response) at 40 Gy was observed in 87.5% of the patients of the CRT group and in 62.5% of the patients of the RT group (chi2 = 7.566, p < 0.01). The actuarial 5-year larynx preservation rate for the CRT group (75%) was significantly higher than that for the RT group (57%) in patients with T2 supraglottic carcinoma (p < 0.05). There was no difference in the larynx preservation rate between the two treatment arms for any T stage of glottic carcinomas. CONCLUSION: CRT using carboplatin improved the tumor response at 40 Gy and consequently achieved a higher larynx preservation rate for T2 supraglottic carcinoma. A clinical randomized trial is indicated to certify the findings of this phase II study.

Antineoplastic Agents↗
PubMed1999

Mechanism of cholecystokinin-A- receptor antagonist on human pancreatic exocrine secretion. Localization of CCK-A receptor in the human duodenum.

Expressions of the cholecystokinin (CCK)-A and -B receptor genes in human duodenum, pancreas and gallbladder were examined by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. The autoradiographic study of CCK-A and -B receptors in the human duodenum and pancreas was examined in vitro. To determine the subtypes to CCK receptors in the pancreas or duodenum, we studied the abilities of CCK-A and -B receptor agonists (CCK-8 and gastrin) and antagonists (loxiglumide, L-364,718 and L-365,260) to inhibit binding of 125I-CCK-8. CCK-A receptor mRNA was not expressed in the human pancreas, but was expressed in the gallbladder and duodenum, although it was expressed in the pancreas by RT-PCR. CCK-B receptor mRNA was expressed in the pancreas, but not in gallbladder and duodenum. Using autoradiography, high concentrations of CCK-A receptors were detected in the duodenal mucosa, although in the pancreas only CCK-B receptors were detected by this method. These results suggest that localization of CCK-A receptor in human duodenum provides a biochemical and morphological basis for some physiological functions of CCK.

Autoradiography↗
PubMed1999

[Activity of a novel antitumor agent, TZT-1027].

We studied the antitumor activity of newly synthesized dolastatin 10 analogs. TZT-1027 showed remarkable activity and was selected for further development. TZT-1027 was found to inhibit the assembly of porcine brain microtubule proteins and to depolymerize the polymerized microtubule proteins. Therefore, its mechanism of antitumor activity seems to be at least partially ascribed to the inhibition of microtubule assembly. We further studied the binding site of TZT-1027 on tubulin. Scatchard analysis of 3H-TZT-1027 binding data suggested two binding sites including a high affinity site and a low affinity site. TZT-1027 affected the binding of vinblastine (VBL) on tubulin but its binding site isn't identical to the VBL binding site. TZT-1027 induced apoptosis within 24 h, not only in human leukemia cells such as HL-60, but also in solid tumors such as human prostate carcinoma cells DU145 and human mammary carcinoma cells MCF-7. TZT-1027 showed good antitumor activity against human xenografts (MX-1 and LX-1) without causing serious body weight reduction, which resulted in tumor regression. We examined the effect of TZT-1027 on the established tumor vasculature using the dye perfusion into tumor. TZT-1027 exhibited considerable antivascular activity in tumor sections in addition to excellent cytotoxic effect.

Animals↗
PubMed1999

Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats.

The entrainment function in the suprachiasmatic nucleus (SCN) of young non-diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats was studied. OLETF rats significantly needed more days for re-entrainment to a new light-dark cycle than control Long Evans Tokushima Otsuka (LETO) rats. We also assessed Fos expression in the SCN induced by dim light exposure. The number of Fos-immunoreactive cells was significantly decreased in 5- to 13-week-old OLETF rats compared with LETO rats. Moreover, the effect of glutamate on neuronal activity in the SCN of OLETF rats were investigated. In young non-diabetic OLETF rats, the phase delay in the SCN neuronal firing rhythm induced by 1 microM glutamate was significantly less than that in LETO rats. These results suggested that the entrainment function is reduced in OLETF rats before the onset of diabetes.

Animals↗
PubMed1999

Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats.

The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.

Allylglycine↗
PubMed1999

Functional prognosis after treatment of spinal dural arteriovenous fistulas.

Functional prognosis after treatment for spinal dural arteriovenous fistulas (SDAVFs) was retrospectively analyzed in 13 consecutive patients aged 38 to 73 years (mean 57 years) treated during the last 5 years. The duration of symptoms before diagnosis ranged from 3 to 72 months (mean 23 months). Neurological symptoms were examined before and 6 months after the treatment. Seven patients underwent embolization as the initial treatment. In four of six patients, N-butyl 2-cyanoacrylate (NBCA) embolization achieved complete obliteration of SDAVF. The other two patients with incomplete embolization and one embolized with polyvinyl alcohol particles underwent subsequent surgical treatment. Six patients were treated by direct surgery. Complete disappearance of SDAVF was confirmed in all nine patients treated surgically. Improvement of gait and micturition disturbance after the treatment was noted in six of 10 and three of six patients, respectively. Long duration of symptoms and high grade of neurological symptoms were associated with a poor functional outcome. NBCA embolization and surgery are curative treatments for SDAVF, but the functional prognosis is not always satisfactory. Embolization is the first choice of treatment for SDAVF because it is less invasive and relatively safe. However, when complete obliteration is not achieved, prompt surgery is recommended because a long duration of symptoms will result in a poor functional prognosis.

Adult↗
PubMed1999

Aggravation of brainstem symptoms caused by a large superior cerebellar artery aneurysm after embolization by Guglielmi detachable coils--case report.

An 81-year-old male presented with right oculomotor nerve paresis and left hemiparesis caused by a mass effect of a large superior cerebellar artery aneurysm. Endovascular treatment was performed using Guglielmi detachable coils. The patient subsequently suffered aggravation of the mass effect 3 weeks after the embolization. Bilateral vertebral artery occlusion was performed, which decreased the cerebral edema surrounding the aneurysm, but his neurological symptoms did not improve. Parent artery occlusion is recommended as the first choice of treatment for an unclippable large or giant aneurysm causing a mass effect on the brainstem.

Aged↗
PubMed1999

Results of the surgical treatment of perimedullary arteriovenous fistulas with special reference to embolization.

OBJECT: This retrospective study was performed to evaluate the results of surgical treatment and the use of preoperative embolization in managing patients with perimedullary arteriovenous fistulas (AVFs). METHODS: The authors studied 20 consecutive patients with perimedullary AVFs who underwent surgical treatment. Arteriovenous shunts were at the level of the cervical spine in five patients, the thoracic spine in 12, and the conus medullaris in three patients. Of the 20 AVFs, three were fed by the anterior spinal artery only, three by the posterior spinal artery, and 14 by both the anterior and posterior spinal arteries. Nine patients had varices that compressed the spinal cord. Eleven patients underwent surgery, and nine patients underwent surgery combined with adjuvant preoperative embolization. Preoperative embolization remarkably reduced blood flow through the AVFs and facilitated subsequent surgical procedures. Postoperative angiography revealed complete disappearance of the AVFs in 16 patients. However, small fistulas persisted in the other four patients, whose large lesions were fed by the anterior spinal artery. Postoperatively, neurological status was improved in 11 patients, unchanged in eight, and worse in one patient. CONCLUSIONS: Effective interruption of a spinal arteriovenous shunt was achieved by surgery in all cases, even when the anterior spinal artery was involved. For large and high-flow AVFs, embolization proved to be a useful adjunct to surgery.

Adolescent↗
PubMed1999

Multiple dural arteriovenous shunts in a 5-year-old boy.

We describe a rare case of multiple dural arteriovenous shunts (DAVSs) in a 5-year-old boy. MR imaging performed at 1 year of age showed only a dilated anterior part of the superior sagittal sinus; however, angiography at 5 years of age revealed an infantile-type DAVS there and two other DAVSs of the adult type. The pathophysiological evolution of DAVSs in children and their treatment strategies are discussed.

Angiography↗
PubMed1999

The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.

We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.

Animals↗
PubMed1999

Disruption of cholecystokinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth: a study in CCK-B receptor gene knockout mice.

Pancreatic exocrine function and bile secretion were examined in cholecystokinin (CCK)-B receptor gene-targeted mice and compared among different genotypes [i.e., CCK-B receptor gene: (+/+), wild-type; (+/-), heterozygous; and (-/-), homozygous deficient]. The histology and protein concentrations in the pancreas also were examined. Amylase release from the dispersed acini was examined in vitro by using the various doses of CCK-8, carbachol, and secretin. In vivo, the bile and pancreatic juice were collected, and the concentrations of amylase and bile acid were measured in anesthetized mice. The responses to CCK (100 pmol/kg) or acetyl-beta-methylcholine (500 nmol/kg) were examined. In vitro studies showed that the maximal effective concentrations of CCK-8 (10(-l0) M), carbachol (10(-5) M), and secretin (5 x 10(-7) M) were comparable for all genotypes. Fluid, amylase, and bile acid outputs in vivo also were comparable for all genotypes. Pancreatic wet weight and protein concentrations were not significantly different, and no abnormal findings were observed on histologic examination in any genotype. These results indicated that the CCK-B receptor has no role in pancreatic growth, exocrine secretion, or bile secretion in adult mice.

Aging↗
PubMed1999

[Evaluation of child-rearing environmental factors that affect the occurrence of sudden infant death syndrome: interview conducted by public health nurses].

PURPOSE: We examined the child-rearing environmental factors that affect the occurrence of sudden infant death syndrome (SIDS) by using a nation-wide survey. METHOD: Infants who died due to SIDS between January 1996 and June 1997 in Japan were identified from death certificates. Controls of the same sex, birthplace, and birth months as the corresponding SIDS were chosen from birth certificates. Interviews of both cases and controls were undergone in January and February 1998 by public health nurses. RESULTS: The following Child-rearing factors exhibited a significant relationship with the occurrence of SIDS: 1. Concerning the sleeping position, the prone position was associated with increased risk compared to the supine position, with an odds ratio of 3.02 (95% c.i. 2.07-4.65). 2. Regarding the feeding method, artificial feeding only demonstrated a higher risk than breast feeding only, with an odds ratio of 4.92 (95% c.i. 2.78-9.63). 3. With regard to smoking, infants with both parents who smoked exhibited a higher risk than infants where neither parents smoked, with an odds ratio of 3.50 (95% c.i. 1.74-8.32).

Child Rearing↗
PubMed1999

Molecular cloning and expression of rat antisecretory factor and its intracellular localization.

Antisecretory factor (AF) was identified as a pituitary protein that inhibits the intestinal fluid secretion induced by cholera toxin. One aim of this study was to elucidate whether AF is also synthesized in the intestine or if AF produced in the pituitary is transported to the intestinal tract for its function there. cDNA clones encoding a protein proposed to be AF were isolated from rat pituitary gland and intestinal mucosa cDNA libraries. The nucleotide sequences of clones isolated from the rat pituitary gland and intestinal mucosa were identical. The deduced amino acid sequence was highly homologous to the sequence for subunit 5a of the human 26S protease that exists abundantly in the cytosol and nucleus. The production of AF in the intestine was confirmed by Northern blot and immunoblot analyses. Immunocytochemical observations of cells transfected with the rat AF cDNA showed that the AF protein was localized in the cytoplasm. These findings suggest that the protein proposed to be AF may be a cytoplasmic protein, it exists in the intestine rather than being transported from the pituitary gland, and it may function in intestinal cells.

Amino Acid Sequence↗