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Biomedical subjects

K Miyasaka

Publications and source records attributed to K Miyasaka.

At least 19 recordsLinked to original sources

Stimulatory effects of islet amyloid polypeptide (amylin) on exocrine pancreas and gastrin release in conscious rats.

A rat islet amyloid polypeptide (amylin), 37-residue peptide amide was synthesized by the Fmoc-based solid phase method and the biological activity of synthetic rat amylin on exocrine pancreas was evaluated for the first time in conscious rat. Amylin (1, 10 nmol/kg/h) stimulated pancreatic exocrine secretion and plasma gastrin concentration. CR-1409, a CCK receptor antagonist, did not change amylin-stimulated pancreatic secretion. However, omeprazole (proton pump inhibitor) and atropine inhibited amylin-stimulated pancreatic secretion. This study suggests that amylin may play a role in biological action in the exocrine pancreas possibly mediated by gastric acid hypersecretion.

Amyloid

Compact apparatus for measurement of ventilatory response to carbon dioxide in newborns and infants.

We developed a rebreathing system for measuring response to carbon dioxide (CO2) of newborns and infants for use at the bedside. The system based on Read's method is small, easy to operate, and includes a computer-controlled gas switching sequence, computerized calculation, and display functions. We measured the CO2 response in 11 infants with or without apnea, who were born at 26-33 weeks gestation and were 12 to 215 days old at the time of the study. Our results suggest that the presence of apnea in premature infants may correspond to a low CO2 response. The method was convenient for clinical use because it allowed an investigator to carry out bedside tests in only a few minutes. With our system we were able to assess respiratory center function in newborns and infants.

Apnea

Changes in plasma and duodenal cholecystokinin concentrations after pancreatic duct occlusion in rats.

The changes in plasma and duodenal cholecystokinin (CCK) concentrations after pancreatic duct occlusion were examined in rats. The rats were sacrificed 1, 3, 7, 10, 14, and 30 days after occlusion of the duct. Histological examination showed acute inflammation on days 1 and 3 after duct occlusion, interstitial fibrosis and regenerative changes on days 7, 10, and 14, and pancreatic atrophy on day 30. The plasma CCK concentration increased from 0.45 pM to 2.0 pM after the occlusion and then remained high throughout the observation period. In contrast to the stable increase in plasma CCK concentration, the CCK content in the duodenum increased on days 1 and 3, decreased on day 7, increased on day 10, reaching over the control level on day 14, and then returned to the control level on day 30. Administration of boiled and 10-fold concentrated rat pancreatic juice or human pancreatic secretory trypsin inhibitor for seven days after pancreatic duct occlusion reversed the decrease in duodenal CCK content. The major molecular forms of duodenal CCK were CCK-8, -33, and -58. These results indicate that (1) basal plasma CCK concentration did not reflect the duodenal CCK content, (2) duodenal CCK content was well correlated with a decrease in inflammation in the pancreas, and (3) a nonenzymatic component in the pancreatic juice reversed the decrease in duodenal CCK content and body weight caused by pancreatic duct occlusion.

Acute Disease

Isolation and bioactivity of putative cholecystokinin-releasing peptide from rat small intestinal mucosa.

Pancreatic exocrine secretion in the conscious rat is regulated by proteases in the intestine secreted by the pancreas, and cholecystokinin (CCK) is known to be involved in the mechanism. The authors proposed that the release of CCK was regulated by a CCK-releasing factor secreted into the intestinal lumen from the proximal intestine. We isolated and partially purified a CCK-releasing factor from rat small intestine by gel filtration and high performance liquid chromatography. The partially purified CCK-releasing factor increased pancreatic exocrine secretions and plasma CCK concentrations in conscious rats and this activity was abolished after the incubation with trypsin. The bioactivity of the partially purified CCK-releasing factor was confirmed.

Animals

Stimulatory and inhibitory effects of bile salts on rat pancreatic secretion.

The effects of various species of bile salts (chenodeoxycholate, deoxycholate, ursodeoxycholate and cholate, and their taurine and glycine conjugates) on pancreatic exocrine secretion were studied in conscious rats with external bile and pancreatic fistulae. For examination of the stimulatory effects of bile salts, bile and pancreatic juice were collected for a basal period of 90 minutes and returned to the intestine, and then solutions of bile salts (60 mmol/L) were infused intraduodenally at a rate of 1 mL/h for 2 hours. For examination of their inhibitory effects, pancreatic secretion was stimulated by exclusion of the bile and pancreatic juice; and then solutions of the bile salts were again infused intraduodenally. Chenodeoxycholate, glycochenodeoxycholate, ursodeoxycholate, deoxycholate, and its conjugates (glycodeoxycholate and taurodeoxycholate) significantly increased the fluid, bicarbonate and protein outputs, and bicarbonate concentration, with decrease in protein concentration. These increases were partially inhibited by infusion of either a cholecystokinin antagonist or secretin antibody. In contrast, cholate, taurocholate, tauroursodeoxycholate, glycoursodeoxycholate, and taurochenodeoxycholate inhibited pancreatic secretion and increase in the plasma cholecystokinin concentration produced by exclusion of bile and pancreatic juice. Thus, some bile salts, including taurocholate and taurochenodeoxycholate (major bile salts in rat bile) inhibited pancreatic secretion and cholecystokinin release, whereas some other bile salts increased pancreatic secretion via cholecystokinin release and secretin release.

Animals

Feasibility of PACS based on 2 years experiences of Hokkaido University PACS.

Some features of HU-PACS which is now just 2 years old are described with the results of clinical assessment on it. It is clear that many advancements in technology have made the HU-PACS to be a useful tool of clinical routines. The paper describes also problems of the system in future with general comments on technology assessment and cost benefit issues.

Cost-Benefit Analysis

MRI findings of multiple sclerosis with acute transverse myelopathy.

We classified clinically definite multiple sclerosis (MS) patients who underwent brain MRI with superconductive magnet into 2 subgroups: group A, consisting of 14 patients who had shown acute transverse myelopathy (ATM) during the course of illness; and group B, 35 patients without ATM, and the same neuroradiologist, blinded to clinical profiles of the patients, investigated the MR scans. We analyzed some parameters such as distribution, size, shape and number of the lesions. Although the total number of lesions were similar in each group, and the number of small size or patchy shape solitary lesions were not different, the moderate, large, ovoid or confluent lesions were lower in number in group A, compared with group B. The degree of cerebral white matter lesions and periventricular lesions were higher in group B. Brainstem lesions were significantly less common in group A. These results show characteristic differences in MR-detected, possibly pathological, changes between these 2 groups, and support our previous report that group A may constitute a distinct subgroup in patients with MS.

Adult

Relative humidity, not absolute humidity, is of great importance when using a humidifier with a heating wire.

OBJECTIVES: Since the introduction of a humidifier with a heating wire, we have frequently experienced severe upper airway obstruction from consolidation of secretions, previously unencountered when a humidifier without a heating wire was used. Such problems led to the suspicion that the heating wire incorporated into the breathing circuit of the heated humidifier might be the cause. Therefore, we scheduled an experiment to assess the hypothesis that relative humidity, rather than absolute humidity, is a dominant factor in the case of drying secretions in the upper airway when using such a humidifier. DESIGN: Three clinical case reports and an experiment with a tracheal model. SETTING: Intensive care units at Saitama Medical Center, Saitama Medical School, Saitama, Japan. PATIENTS: Three intubated patients. MEASUREMENTS AND MAIN RESULTS: An experiment with a tracheal model showed that gas with a higher temperature and lower relative humidity (35 degrees C, 48%) deprived the tracheal model of significantly more water (5.9 +/- 0.2 [SD] g) than gas with a lower temperature and higher relative humidity (24 degrees C, 87%) (2.9 +/- 0.4 g; p less than .01), even though the gases contained the same amount of water vapor (19 mg H2O/L) minus the same absolute humidity. CONCLUSIONS: A heated humidifier with a heating wire incorporated into the breathing circuit may be dangerous when only temperature is monitored and controlled. Relative humidity, rather than absolute humidity, is a dominant factor in the case of drying secretions in the upper airway when using such a humidifier.

Aged

Effect of taurocholate on CCK release and pancreatic secretion produced by two CCK-releasing peptides in conscious rats.

The role of luminal bile salts (taurocholate) in regulation of rat pancreatic secretion was examined by studies on the effects of luminal stimulants on the pancreas during infusion of various concentrations of taurocholate into the duodenum of conscious rats. Rats with external bile and pancreatic fistulae were used. For 24 h before the experiment, pancreatic juice was excluded from the intestine but bile was continuously returned to the duodenum. From the beginning of the experiment, 8-200 mM of taurocholate was infused at a rate of 1 ml/h instead of returning the bile. Pancreatic juice was collected for a 2-h period and then 2 micrograms of pancreatic secretory trypsin inhibitor-61 (PSTI-61) (= monitor peptide) or partially purified putative CCK-releasing peptide from rat intestine (intestinal CCK-RP) was injected into the duodenum (1 ml/min). Continuous infusion of taurocholate maintained a constant rate of pancreatic secretion, except at a concentration of 8 mM, which resulted in a slight increase in pancreatic secretion. Both PSTI-61 and intestinal CCK-RP significantly increased pancreatic secretions during infusion of 20 or 40 mM taurocholate, but had no significant effect during infusion of 80 or 200 mM taurocholate. Therefore, higher concentrations of taurocholate in the intestine prevented the stimulatory effects of luminal stimulants, probably by preventing the latter from reaching CCK cells.

Animals

Comparison of the incidence of intracranial hemorrhage following conventional mechanical ventilation and high frequency oscillation in beagle puppies.

Controversy exists as to whether high frequency oscillation (HFO) increases the risk of intraventricular hemorrhage (IVH) compared with conventional mechanical ventilation (CMV). We compared the risk of intracranial hemorrhage after phenylephrine-induced hypertension, combined with a hypovolemic, hypotensive insult followed by rapid volume replacement in two groups of newborn beagle puppies (one group on a piston pump HFO and the other on CMV). A total of 12 beagle puppies (6 on HFO and 6 on CMV) survived the protocol. Arterial blood gas analysis and arterial blood pressures through the study were of the same magnitude in both groups. The length of time for which the puppies remained hypertensive and hypotensive also did not vary significantly between the groups. Intraventricular hemorrhages were observed in two of six CMV puppies and two of six HFO puppies. One animal in each group had a white matter hemorrhage. Subarachnoid hemorrhages were seen in 4 animals on CMV and 3 on HFO. This study indicated that HFO does not increase the risk of any kind of intracranial hemorrhage, including IVH, in beagle puppies.

Animals

Protective effect of human pancreatic secretory trypsin inhibitor on cerulein-induced acute pancreatitis in rats.

We examined the protective effect of human pancreatic secretory trypsin inhibitor (PSTI), a specific trypsin inhibitor secreted from pancreatic acinar cells into the pancreatic duct, on cerulein-induced acute pancreatitis in conscious rats. The protective effect of human PSTI-RS, an analogue of PSTI with Arg-44 to Ser substitution which has a longer half-life in vitro, was also examined. Intraperitoneal administration of a pharmacological dose of cerulein to conscious rats induced acute pancreatitis, characterized by light microscopy as cellular disorganization of the acini and interstitial edema. Intravenous infusion of human PSTI (10, 50 or 250 micrograms/rat/h) into rats with cerulein-induced acute pancreatitis decreased their pancreatic wet weight and plasma amylase concentration. It also caused a dose-dependent decrease in vacuoles in acinar cells and interstitial edema. Human PSTI-RS, which has a longer half-life in vivo, was more effective than native PSTI at the same dose rate (10 micrograms/rat/h) in reducing pancreatitis. These results suggest that human PSTI may have a beneficial effect on acute pancreatitis.

Animals

Experimental models of acute and chronic sialoadenitis in the guinea pig.

Acute and chronic sialoadenitis were induced in ovalbumin-immunized guinea pigs by a single or repeated (once a day for 5 days) instillation of antigen into the parotid gland via the parotid duct. The acute sialoadenitis was characterized by infiltration of inflammatory polymorphonuclear leukocytes and the chronic one, by extensive tissue destruction together with infiltration of mononuclear leukocytes. In acute sialoadenitis, myeloperoxidase activity in the parotid gland, which was a marker of accumulation of neutrophils, was elevated, but in the chronic stage, it returned nearly to the control level. This observation is in accord with the histological findings that infiltrating cells in acute and chronic sialoadenitis were mainly polymorphonuclear and mononuclear leukocytes, respectively. Although cyclophosphamide suppressed the inflammation, both in acute and chronic sialoadenitis, indomethacin exerted its anti-inflammatory effect only in the acute stage. Our experimental models of acute and chronic sialoadenitis were easy to prepare, and had a high incidence. As the typical features of inflammatory development from acute to chronic phases were observed in these models, these models may be useful for studying the mechanism of the chronic course in immunologically induced inflammation and the effects of drugs on each phase and the chronic course of inflammation.

Acute Disease

[Effect of ursodeoxycholate on pancreatic exocrine secretion in vitro and in vivo study].

In the present study, we examined the effect of ursodeoxycholate (UDCA) and it's taurine conjugate (TUDC) on rat pancreatic exocrine secretion using dispersed pancreatic acini (in vitro) and conscious rats (in vivo). In in vitro study 300 microM UDCA significantly increased 10(-12)-10(-9) M CCK-8 stimulated amylase release and change of intracellular Ca2+ concentration, but TUDC did not have these effects. In in vivo study intraduodenal infusion of UDCA but not TUDC stimulated pancreatic exocrine secretion. Intravenous infusion of secretin antibody decreased bicarbonate output, however, this increase was not prevented by CCK antagonist. Thus, it was suggested that UDCA has direct action on pancreatic acini and UDCA infused intraduodenally stimulates pancreatic secretion, possibly via the release of a secretin-like substance. The taurine conjugate has weak bioactivity on pancreatic exocrine secretion in both in vitro and in vivo.

Amylases

[Current status of pediatric home mechanical ventilation in Japan].

The first nationwide survey of pediatric home mechanical ventilation (HMV) was conducted. From 35 out of 149 medical centers investigated, 49 cases of HVM were reported. The patients ranged in age from 1 to 20 years, and the causes of respiratory failure were neuromuscular diseases (51%), central hypoventilation (33%), respiratory disorders (10%) and cervical cord injury (6%). Since 1983 when 2 patients were discharged home on mechanical ventilation, more and more ventilator-dependent children have been sent home every year. However, home mechanical ventilation is not yet well recognized in Japan as an option for pediatric patients with chronic respiratory failure, and there are many problems to be solved. Firstly, very few, if any, hospitals have a designated home care team composed of physicians and other specialists. Secondly, the current health insurance system scarcely covers the cost of home ventilation. Thirdly, development of home use equipment, in particular, portable ventilators and monitors is imperative. There are 107 hospitalized patients in 56 institutions who are reportedly able to go home if a support system is established. A program for pediatric home mechanical ventilation should be urgently developed on a national basis.

Adolescent

[Evaluation of cerebral blood circulation using fast magnetic resonance imaging (turbo-FLASH)].

In its initial stage of development, poor time resolution was supposed to be inevitable for magnetic resonance imaging (MRI). The development of the gradient echo technique, however, has made an opening for a breakthrough to a fast MRI technique. However, conventional gradient echo technique is not fast enough to disclose the cerebral blood circulation. A new technique (turbo-FLASH), which combines gradient echo and preparation pulse, has opened the door to a true dynamic (high time resolution) MRI. The authors performed a basic study of this new fast imaging technique (Turbo-FLASH) for the evaluation of cerebral blood circulation. Using this dynamic MRI, the conventional Gd-DTPA administration (0.1mmol/kg, intravenous manual administration) has produced sufficient contrast to reveal a difference of the extent of enhancement between normal gray matter and white matter. In patients of cerebral infarction, the infarcted brain does not show any significant increase of signal intensity after the administration of contrast medium, whereas the normal brain shows a sharp increase of signal intensity after the administration of contrast medium. Indeed, many puzzling questions remain to be solved for clinical application of this new dynamic MRI. For example, the optimal quantity of contrast medium and optimal parameters for this sequence (T1 weighted or T2 weighted?) are still unknown. But, in any case, this dynamic MRI is expected to be a clinically powerful tool for the evaluation of cerebral blood flow.

Brain

[MR imaging of the spinal cord--with special emphasis on the factors influencing spinal cord measurement].

On MR images the spinal cord is seen differently in size depending on imaging parameters and displaying window; consequently the findings may be interpreted erroneously as swelling or atrophy of the spinal cord. The purpose of this paper was to evaluate factors influencing spinal cord size on images and to determine the optimal condition estimating the size of the spinal cord. At first we selected 4 cases suspected of cervical spinal disorders which had been examined by both MRI and myelography with tomography. Sagittal diameter of the spinal cord was measured on a film and it was significantly different of those three. That is, the measurement value was greater on T1 weighted image (T1WI) and smaller on T2 weighted image (T2WI) than myelo-tomography. To evaluate the effect of imaging parameters, image reconstruction and image displaying window quantitatively, studied were the cadaveric cervical spinal cord and gelatin phantom tube with a diameter of 13 mm and 9 mm placed in a saline-filled plastic tube. The measurement value was significantly greater on T1WI and smaller on T2WI than true size of the objects. Numbers of phase encoding (128 and 256) significantly affected the measurement value, both on T1WI and T2WI, as well. Ringing artifact of high or low signal was observed at the boundary area of the objects and saline (so-called truncation artifact). However, when the window-level of displaying image was raised stepwisely the measurement value was proportionally decreased and it reached to real value when the level was adjusted at the mean MR signal intensity of the object and saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrophy

[Magnetic resonance imaging in Parkinson's disease--the evaluation of the width of pars compacta on T2 weighted image].

The width of substantia nigra (SN) in 59 cases with idiopathic Parkinson's disease as well as 21 normal controls was analyzed by T2 weighted image (T2WI) of 1.5 Tesla high-field magnetic resonance image (MRI). All patients and controls underwent MRI with the spin-echo sequences used TR/TE: 3000/30 (short TE), and TR/TE:3000/80 (long TE), in 5-mm-thick volumes. The width between the red nucleus and the cerebral peduncle showing low signal intensity areas was measured as that of SN and its ratio to the distance from the aqueduct to the midline of the cerebral peduncle was also measured. The calculated values of the width of SN and its ratio were analyzed by Mann-Whitney test. The significant reduction in the width of SN and its ratio in Parkinson's disease were disclosed as below; the mean calculated values of the width of SN were 2.95 +/- 0.51 mm in controls, 2.68 +/- 0.99 mm in Parkinson's diseases on long TE images (P less than 0.01), and the mean ratio of the width of SN were 13.58 +/- 4.21% in controls, 10.52 +/- 3.07% in Parkinson's diseases on long TE images (P = 0.0002). The narrowing of SN in Parkinson's disease was more prominent in men, and advanced cases with Yahr stage III and IV. Considering that the pars reticulata, which is normally containing iron, shows low signal intensity on long TE images, the width of pars compacta could be measured more precisely on this sequences. The evaluation of the ratio of SN in midbrain on long TE images seemed to be more sensitive than the calculated values in detecting the narrowing of SN and pars compacta in Parkinson's disease.

Adult

Effects of TZI-41127, a novel selective 5-lipoxygenase inhibitor, on A23187-induced pleurisy in rats.

Intrapleural injection of the ionophore A23187 in rats induced leukotriene (LT) production, prostaglandin E2 production, plasma exudation and leukocyte accumulation in the pleural cavity. We evaluated the inhibitory effects of orally administered drugs on 5-lipoxygenase activity by their ability to reduce the content of both peptido-LTs (LTC4, LTD4 and LTE4) and LTB4 in this model. TZI-41127, a novel selective 5-lipoxygenase inhibitor, significantly reduced the peptido-LTs and LTB4 content with ED50 values of 4.2 and 6.1 mg/kg, respectively, whereas it only reduced the prostaglandin E2 content (cyclooxygenase activity) by 31.1% even after 100 mg/kg. Phenidone inhibited 5-lipoxygenase activity more selectively than cyclooxygenase activity. BW755C inhibited cyclooxygenase activity more selectively than 5-lipoxygenase activity. Indomethacin selectively inhibited cyclooxygenase activity. These results suggest that: (1) A23187-induced pleurisy is an convenient in vivo model for studying drug effects on 5-lipoxygenase and cyclooxygenase activities and (2) TZI-41127 is an orally active and comparatively selective inhibitor of 5-lipoxygenase activity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz