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Biomedical subjects

K Miyasaka

Publications and source records attributed to K Miyasaka.

At least 73 records · Page 4Linked to original sources

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer.

BACKGROUND: This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. METHODS: Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm2, number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. RESULTS: Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, alpha/beta = 10(BED10) > or =65 Gy, dose per fraction > or =3.0 Gy, field area > or =42 cm2, fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. CONCLUSIONS: Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment.

Aged↗

The diurnal rhythm of energy expenditure differs between obese and glucose-intolerant rats and streptozotocin-induced diabetic rats.

Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of noninsulin-dependent diabetes mellitus (NIDDM) with mild obesity. Changes in carcass composition and in the daily profile of energy expenditure were examined before and after manifestation of diabetes (8 and 24 wk, respectively), and compared with the normal control Long Evans Tokushima (LETO) rats and streptozotocin (STZ)-induced diabetic LETO rats. OLETF rats had greater body weights than LETO rats and significantly greater absolute and relative fat weights. A diurnal rhythm of energy expenditure associated with two peaks was observed in LETO rats, but the two peaks were not apparent in OLETF rats at 24 wk of age. A diurnal rhythm associated with one peak was observed in STZ-induced diabetic LETO rats. Energy derived from fat constituted this peak; the pattern of the daily energy expenditure was significantly different from that of either nontreated LETO or OLETF rats at 24 wk of age. NIDDM in OLETF rats at 24 wk of age has only a small role in modification of the diurnal rhythm of energy expenditure, whereas STZ-induced diabetes significantly affected the rhythm.

Animals↗

Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats.

The basal exocrine secretion of the pancreas is maintained at a constant level in conscious rats. We examined the changes in basal secretion with respect to the effect of various time periods of pancreatic duct occlusion (PDL). Male Wistar rats were prepared with cannulae that separately drained bile and pancreatic juice as well as with a duodenal cannula. Rats were placed in restraint cages, and experiments were conducted without anesthesia 4 days after the operation. Cholecystokinin (CCK) release was artificially prevented by the continuous infusion of bile with trypsin into the duodenal lumen throughout the experimental period to avoid the modification of pancreatic response by CCK. After 2-h basal collection, a pancreatic secretion was interrupted for 0.5-4 h, and then the collection of pancreatic juice was initiated again for an additional 2-4.5 h. The pancreatic secretion after the reopening of the 0.5-to 3-h PDL was comparable to basal secretion levels. However, protein secretion was significantly inhibited after the removal of 4-h PDL. Both vagotomy and capsaicin treatment abolished this inhibition, and the protein secretion after 1-h PDL in vagotomized rats increased 1.5-fold high compared with the basal value. These observations indicate that protein secretion was ceased during PDL via vagal nerve, and this may be a self-protective mechanism.

Afferent Pathways↗

Oral administration of a synthetic trypsin inhibitor increases pancreatic duct function in CCK-A receptor-deficient rats.

The effects of oral administration of a synthetic trypsin inhibitor on bicarbonate secretion were examined in cholecystokinin A (CCK-A) receptor-deficient (OLETF) rats and compared with Wistar rats. Rats were fed chow containing 0.1% trypsin inhibitor for 7 days. Rats were prepared with cannulae draining bile and pancreatic juice separately and with duodenal and extrajugular vein cannulae after 3-day trypsin inhibitor ingestion. Then the animals were maintained in Bollman cages, and the experiments were conducted 4 days after surgery. After 1.5 h of basal secretion with bile-pancreatic juice return, bile-pancreatic juice was diverted for 2 h. The responses of bicarbonate secretion to bile-pancreatic juice diversion were significantly enhanced in rats treated with trypsin inhibitor compared with those given a control diet, whereas responses of fluid and protein secretion were not affected in OLETF rats. The response of protein secretion, but not those of fluid or bicarbonate secretion, was enhanced in Wistar rats by treatment with trypsin inhibitor. Carbonic anhydrase II gene expression was increased by 7-day treatment with trypsin inhibitor only in OLETF rats, and not in Wistar rats.

Allylglycine↗

Induction of acute pancreatitis by cerulein in human IL-6 gene transgenic mice.

Whether acute pancreatitis induced by cerulein was aggravated in human interleukin 6 (IL-6) transgenic mice and whether a specific anti-IL-6 receptor antibody improved pancreatitis were investigated. To induce acute pancreatitis, cerulein (50 microg/kg, seven injections) with or without 1 mg/kg lipopolysaccharides (LPS) was injected intraperitoneally every hour. In some mice, a monoclonal anti-IL-6 receptor antibody was administered before the first cerulein injection. The animals were killed 1 hour after the last injection. The pancreatic wet weight induced by cerulein alone was significantly higher in IL-6 transgenic mice compared with wild-type mice, but pretreatment with a specific anti-IL-6 receptor antibody did not reduce interstitial edema. When cerulein was administered with LPS, the pancreatic wet weight increased much more than when pancreatitis was induced by cerulein alone in both genotypes, and pretreatment with the anti-IL-6 receptor antibody decreased the pancreatic edema only in human-IL-6 transgenic mice. These results suggest that anticytokine antibodies may be effective in improving acute pancreatitis.

Acute Disease↗

Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin.

TZT-1027, a derivative of dolastatin 10 isolated from the Indian Ocean sea hare Dolabella auricularia in 1987 by Pettit et al., is a potent antimicrotubule agent. We have compared the activity of TZT-1027 with that of dolastatin 10 as well as the vinca alkaloids vinblastine (VLB), vincristine (VCR) and vindesine (VDS). TZT-1027 and dolastatin 10 inhibited microtubule polymerization concentration-dependently at 1 - 100 microM with IC50 values of 2.2 +/- 0.6 and 2.3 +/- 0.7 microM, respectively. VLB, VCR and VDS inhibited microtubule polymerization at 1 - 3 microM with IC50 values of 2.7 +/- 0.6, 1.6 +/- 0.4 and 1.6 +/- 0.2 microM, respectively, but showed a slight decrease in inhibitory effect at concentrations of 10 microM or more. TZT-1027 also inhibited monosodium glutamate-induced tubulin polymerization concentration-dependently at 0.3 - 10 microM, with an IC50 of 1.2 microM, whereas VLB was only effective at 0.3 - 3 microM, with an IC50 of 0.6 microM, and caused so-called "aggregation" of tubulin at 10 microM. Scatchard analysis of the binding data for [(3)H]VLB suggested one binding site (Kd 0.2 +/- 0.04 microM and Bmax 6.0 +/- 0.26 nM / mg protein), while that for [(3)H]TZT-1027 suggested two binding sites, one of high affinity (Kd 0.2 +/- 0.01 microM and Bmax 1.7 +/- 0.012 nM / mg protein) and the other of low affinity (Kd 10. 3 +/- 1.46 microM and Bmax 11.6 +/- 0.83 nM / mg protein). [(3)H]TZT-1027 was completely displaced by dolastatin 10 but only incompletely by VLB. [(3)H]VLB was completely displaced by dolastatin 10 and TZT-1027. Furthermore, TZT-1027 prevented [(3)H]VLB from binding to tubulin in a non-competitive manner according to Lineweaver-Burk analysis. TZT-1027 concentration-dependently inhibited both [(3)H]guanosine 5'-triphosphate (GTP) binding to and GTP hydrolysis on tubulin. VLB inhibited the hydrolysis of GTP on tubulin concentration-dependently to a lesser extent than TZT-1027, but no inhibitory effect of VLB on [(3)H]GTP binding to tubulin was evident even at 100 microM. Thus, TZT-1027 affected the binding of VLB to tubulin, but its binding site was not completely identical to that of VLB. TZT-1027 had a potent inhibitory effect on tubulin polymerization and differed from vinca alkaloids in its mode of action against tubulin polymerization.

Animals↗

Heart transplantation in children in foreign countries with reference to medical, transportation, and financial issues.

Heart transplantation is increasingly becoming accepted worldwide as therapy for end-stage heart failure not only in adult patients but also in pediatric practice. The new law in Japan for organ transplantation from brain-dead patients was established on 16 October 1998, but there is no definite law or protocol for brain death in children under the age of 6 years and children less than 15 years of age cannot become donors. These facts make organ transplantation from the cadavers of neonates, infants and young children almost impossible in Japan, even though there are children who need heart or heart-lung transplantation. The present authors have to date transferred 8 patients to the USA or Germany for heart transplantation: 4 successfully underwent heart transplantation, but 4 died during the waiting period overseas. There are many things to consider; not only the medical problems involved in transportation, but also the financial issues when transferring patients to other countries. This report details the experience with the 8 cases that were transferred overseas for heart transplantation, and highlights the problems that need to be considered.

Child↗

Entrainment function in the suprachiasmatic nucleus of streptozotocin-induced diabetic rats.

The term for re-entrainment to a new light-dark cycle in streptozotocin (STZ)-induced diabetic rats was significantly longer than that in control rats. In STZ-induced diabetic rats, the same level of phase delay in the suprachiasmatic nucleus neuronal firing rhythm was observed in control rats after glutamate application. Therefore, 5-HT function in the hypothalamus is thought to be decreased in STZ-induced diabetic rats. These results suggest that postsynaptic neuronal function is still maintained in the suprachiasmatic nucleus of STZ-induced diabetic rats. Therefore, 5-HT mechanisms may play an important role in the maintenance of this function.

5-Hydroxytryptophan↗

Induction of growth factors in rat cardiac tissue by X irradiation.

To investigate the relationship between angiogenic growth factors and endothelial enzyme activity in capillaries after injury of rat cardiomyocytes caused by X irradiation, 7-week-old male Wistar rats were anesthetized with pentobarbitone and their hearts irradiated (X rays, 20 Gy) through a hole in the lead casing in which they were enclosed. The hearts were excised at 1 h, 1 week and 3 weeks after irradiation. Left ventricular cross sections were stained for capillary enzymes by double staining for two endothelial enzymes, alkaline phosphatase (AP) and dipeptidylpeptidase IV (DPP), immunohistochemically stained for basic fibroblast growth factor (Fgf, also known as bFgf) and vascular endothelial growth factor (Vegf), and stained for nick end-labeling of DNA by the TUNEL method. Staining for distribution of AP in the arteriolar portion was reduced at both 1 and 3 weeks after irradiation with 20 Gy, but staining for DPP in the venular portion was unchanged, suggesting a close relationship between growth factors and injury of the arteriolar capillary portion. Fgf and Vegf proteins were present within the cytoplasm of the cardiomyocytes, or around capillaries, 1 h, 1 week and 3 weeks after irradiation. Many TUNEL-stained cardiomyocyte nuclei were observed at 1 h, but they had decreased markedly at 1 week and had almost disappeared by 3 weeks after irradiation. Thus Fgf and Vegf were induced concomitantly with the decrease in the staining for endothelial AP by 20 Gy X irradiation, which also caused microeffects as indicated by TUNEL staining of many nuclei at 1 h postirradiation.

Animals↗

Inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic secretion in conscious rats.

The inhibitory effect of central administration of calcitonin-gene related peptide (CGRP) on pancreatic secretion stimulated by bile-pancreatic juice diversion was determined in conscious rats. Rats were prepared with separate cannulae for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 d after the operation without anesthesia. An injection of CGRP (1 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion as well as cholecystokinin (CCK) release induced by bile-pancreatic juice diversion. Intravenous infusion of alpha- and beta-adrenergic receptor antagonist, phentolamine and propranolol did not reverse the inhibition of pancreatic secretion. Intravenous infusion of CGRP did not affect pancreatic secretion or plasma CCK concentrations. The inhibitory action of central CGRP (i. c.v.) on pancreatic secretion and CCK release stimulated by bile-pancreatic juice diversion is partially mediated by an alpha-adrenergic mechanism, although its precise mechanism has not been elucidated.

Adrenergic alpha-Antagonists↗

Mechanism of delayed gastric emptying in naturally occurring CCK-A receptor gene knockout (OLETF) rats.

We recently found a specific strain of rats (OLETF rats) in which CCK-A receptor gene expression is lacking because of a genetic abnormality. As delayed gastric emptying has been reported in this strain, we examined its mechanism. A liquid gastric load containing phenol red was administered using an orogastric tube into the stomach in OLETF and control (LETO) rats. The stomach was removed 0, 15, 30 and 45 min after meal ingestion and the content of phenol red was measured to estimate the rate of gastric emptying. Pretreatment of reserpine enhanced gastric emptying in both strains. A tenfold dose of reserpine was required in OLETF rats to induce a similar effect to LETO rats. The plasma noradrenalin level was significantly higher in OLETF than LETO rats. When the smooth muscle of the stomach was isolated and contraction in vitro was examined, the smooth muscle functions were not deteriorated in OLETF rats. The thickness of muscle determined by hematoxylin-eosin staining was not different between strains. It is suggested that the delayed gastric emptying in OLETF rats may be due to increased sympathetic nerve function.

Animals↗

Distribution of geriatric disease-related genotypes in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA).

Phenotypes of various genes related to geriatric diseases and the aging process were assessed in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). The subjects were 1,297 participants in the NILS-LSA. They were community-living males and females aged 40 to 79 years who were randomly selected from the area of the NILS. Genotypic and allelic frequencies of genes in the subjects were analyzed. Age and gender differences in the distribution of genotypes were also tested. The genotypic frequencies were as follows: (1) Angiotensin I-converting enzyme (ACE) genotype was I/I 46.2%, I/D 38.3% and D/D 15.5%. (2) alpha 1-adrenoreceptor genotype was C/C 84.4%, C/T 12.7%, and T/T 3.0%. (3) Apolipoprotein E genotype was epsilon 2/epsilon 2 0%, epsilon 2/epsilon 3 7.9%, epsilon 3/epsilon 3 70.0%, epsilon 3/epsilon 4 20.8%, epsilon 2/epsilon 4 0%, and epsilon 4/epsilon 4 1.4%. (4) Cholecystokinin type-A receptor (CCKAR) nucleotide-81 (nt-81) genotype was A/A 59.1%, A/G 35.1%, and G/G 5.9%. The CCKAR nucleotide-128 genotype (nt-128) was G/G 74.3%, G/T 23.6%, and T/T 2.2%. The combination of nucleotide (nt-81, nt-128) was (A/A, G/G) 59.1%, (A/G, G/G) 14.1%, (G/G, G/G) 1.1%, (A/G, G/T) 21.0%, (G/G, G/T) 2.6%, and (G/G, T/T) 2.1%. There were no subjects with (A/A, G/T), (A/A, T/T) or (A/G, T/T) genotypic combinations. (5) beta 3-adrenoreceptor genotype was T/T 66.8%, T/A 28.5%, and A/A 4.7%. (6) Dihydrolipoamide succinyltransferase (DLST) nucleotide 19117 genotype was A/A 25.1%, A/G 49.7%, and G/G 25.1%. The DLST nucleotide 19183 genotype was C/C 55.8%, C/T 38.2%, and T/T 5.9%. The combination of nucleotide (nt19117, nt19183) was (A/A, C/C) 6.7%, (A/G, C/C) 24.1%, (G/G, C/C) 25.1%, (A/G, C/T) 25.6%, (A/A, T/T) 5.9%, and (A/A, C/T) 12.6%. There were no subjects with (A/G, T/T), (G/G, T/T) or (G/G, T/C) genotypic combinations. (7) Transforming growth factor-beta 1 genotype T/T 35.2%, T/C 44.6%, and C/C 20.2%. (8) The platelet-activating factor acetylhydrolase genotype was M/M 71.7%, M/m 27.2%, and m/m 1.2%. The mitochondria DNA 5178 genotype A was 42.1% and C was 57.9%. There were no significant gender or age differences in tested genotypic and allelic distribution except for the DLST and apolipoprotein E. Differences in the genotypic frequencies of distribution using the Hardy-Weinberg equilibrium were significant in the ACE and alpha 1-adrenoreceptor genotypes.

Adult↗

Cerebral blood flow on xenon CT: correlation with the blood flow detected at the common carotid artery on ultrasonography.

To correlate cerebral blood flow (CBF) on xenon CT with the flow at common carotid artery (CCA) detected by color doppler ultrasonography, 82 patients (29 men, 53 women; 20-90 yrs) were examined. They included normal volunteers (n = 33), patients with cerebral infarction (n = 8), multiple lacunar infarcts (n = 12), dementia (n = 14), and parkinson disease (n = 15). Flow at the CCA was graded as extremely low (< 0.3 l/min), low (0.3-0.4), and normal (> 0.4). CBF was measured in the following distribution: anterior, middle, posterior cerebral arteries (ACA, MCA, PCA); white matter border zones (BZ); basal ganglia (BA), thalamus in two slices. CBF may be reduced in the BZ, cortical and deep gray matter with extremely low flow at CCA. We suggest that color doppler ultrasonography may aid in triage of patients for further CBF evaluation. As some overlap in CBF exists between normal and diseased groups with respect to low flow at CCA, color doppler ultrasonography must be evaluated in combination with xenon CT to reflect cerebral blood flow.

Adult↗

Breath-hold gadolinium-enhanced three-dimensional MR thoracic aortography: higher spatial resolution imaging with phased-array coil and three-dimensional surface display.

The aim of this study was to examine signal intensities of data sets from MR thoracic aortography and to evaluate three-dimensional surface display (3DSD) for postprocessing. Twenty-five patients were imaged with gadolinium-enhanced 3D fast gradient echo sequence. The intensity at the aortic arch was significantly higher than that at the mediastinal fat (p<0.0001). The signal-to-noise ratio was lower at the aortic arch than at the ascending and descending aorta, whereas the contrast-to-noise ratio was fairly high at the aortic arch. Although in one case (4%) the intensity at the arch was smaller than that at the mediastinal fat, 3DSD was successfully performed in all cases. Superiority of 3DSD over maximum intensity projection was obtained in 67% of the cases. 3DSD was evaluated to be superior to maximum intensity projection in all cases of thoracic aortic aneurysm and coarctation of aorta. Higher resolution MR thoracic aortography could be successfully performed with phased-array coil and 3DSD.

Aortic Dissection↗

[Preliminary report: use of clinical criteria for the determination of pediatric brain death and confirmation by radionuclide cerebral blood flow].

The medical records of all brain dead patients (n = 228) at the Hospital for Sick Children, Toronto from January 1990 to December 1999 were reviewed. A radionuclide cerebral blood flow study (RCBFS) as a supportive and confirmatory test was performed on 27 patients and the clinical diagnosis of brain death was confirmed on all of them. A RCBFS was performed on 10 out of 27 patients because full clinical evaluation could not be performed due to severe facial injuries or cervical injuries. A RCBFS was performed on 17 patients who underwent a full clinical evaluation, of which 15 cases were due to uncertainty in the clinical etiology of the deep coma and 2 cases were due purely to the need to persuade the family. In recent years, RCBFS was not used as extensively on patients who underwent a full clinical evaluation, reflecting social acceptance and a higher level of clinical certainty in diagnosing brain death in children. This study supports the opinion that brain death can be accurately diagnosed in pediatric patients with clinical criteria alone and confirmatory tests are not necessary in most cases.

Adolescent↗