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Biomedical subjects

K Miyasaka

Publications and source records attributed to K Miyasaka.

At least 163 records · Page 9Linked to original sources
PubMed1997

Apoptosis in the pancreas of genetically diabetic rats with a disrupted cholecystokinin (CCK-A) receptor gene.

In a previous study, we reported that the pancreatic wet weight in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, cholecystokinin-A (CCK-A) receptor-defective because of a congenital gene abnormality, was significantly lower than in control rats (Long-Evans Tokushima Otsuka; LETO) from 3 weeks of age. In this study we examined apoptosis of pancreatic acinar cells in OLETF rats at 5 to 6 weeks of age in comparison with that in LETO rats. We present here direct morphologic evidence of apoptosis in OLETF rats, using a 3'-OH nick end-labeling method for detecting cells with DNA strand breaks and electron microscopy. Nick end-labeling revealed a small number of positively labeled acinar cells in OLETF rats. On electron microscopic examination, small numbers of apoptotic cells were seen in the lobules in OLETF rats but not in LETO rats. These results suggest that apoptosis plays an important role in the destruction of acinar cells of OLETF rats and induces atrophy of the pancreas.

Animals↗
PubMed1997

Retardation of pancreatic regeneration after partial pancreatectomy in a strain of rats without CCK-A receptor gene expression.

This study extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas because of a genetic abnormality. We compared the changes in pancreatic regeneration in terms of wet weight and protein and DNA contents after partial pancreatectomy (30% resection) in OLETF and control (Long-Evans Tokushima Otsuka: LETO) rats and examined whether the CCK-B receptor has a role in pancreatic regeneration after pancreatectomy. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats regardless of surgical procedure, but the increase with respect to time was significantly less in OLETF than in LETO rats. The protein and DNA concentrations in the pancreas (mg/g wet tissue) were comparable for both strains after sham operation. However, they were significantly lower than pancreatectomy in OLETF rats compared to those after sham operation, whereas they were comparable in LETO rats regardless of surgical procedure. The ratio of protein content/DNA content (cell size) was significantly lower in OLETF than LETO rats under all conditions. CCK-B receptor gene expression was not enhanced after pancreatectomy. In conclusion, the CCK-A receptor is not an absolute requirement for pancreatic normal growth but is important for pancreatic regeneration.

Animals↗
PubMed1997

Stimulatory effect of synthetic luminal cholecystokinin releasing factor (LCRF) fragment (1-35) on pancreatic exocrine secretion in conscious rats.

The effects of a synthetic putative luminal cholecystokinin (CCK) releasing factor (LCRF) fragment (1-35) on pancreatic exocrine secretion were examined in conscious Wistar rats and a mutant strain of rats lacking the CCK-A receptor. Intraduodenal injection of graded doses of the LCRF fragment induced biphasic responses in Wistar rats. The injection of 0.1 microgram of the LCRF fragment produced a maximal response, while 1 microgram produced a lower response. No significant effect was observed in rats lacking the CCK-A receptor. The synthetic LCRF fragment stimulated pancreatic secretion via CCK-A receptors in conscious rats.

Amino Acid Sequence↗
PubMed1997

Antitumor activity of TZT-1027, a novel dolastatin 10 derivative.

Dolastatin 10, a pentapeptide isolated from the marine mollusk Dolabella auricularia, has antitumor activity. TZT-1027, a dolastatin 10 derivative, is a newly synthesized antitumor compound. We evaluated its antitumor activity against a variety of transplantable tumors in mice. Intermittent injections of TZT-1027 were more effective than single or repeated injections in mice with P388 leukemia and B16 melanoma. Consequently, TZT-1027 shows schedule dependency. TZT-1027 was effective against P388 leukemia not only when administered i.p., but also when given i.v. However, although TZT-1027 given i.v. was active against murine solid tumors, TZT-1027 administered i.p. was ineffective against all the tumors tested with the exception of colon 26 adenocarcinoma. The i.v. injection of TZT-1027 at a dose of 2.0 mg/kg remarkably inhibited the growth of three murine solid tumors; colon 26 adenocarcinoma, B16 melanoma and M5076 sarcoma, with T/C values of less than 6%. The antitumor activities of TZT-1027 against these tumors were superior or comparable to those of the reference agents; dolastatin 10, cisplatin, vincristine, 5-fluorouracil (5-FU) and E7010. In experiments with drug-resistant P388 leukemia, TZT-1027 showed good activity against cisplatin-resistant P388 and moderate activity against vincristine- and 5-fluorouracil-resistant P388, but no activity against adriamycin-resistant P388. TZT-1027 was also effective against human xenografts, that is, tumor regression was observed in mice bearing MX-1 breast and LX-1 lung carcinomas. TZT-1027 at 10 microM almost completely inhibited the assembly of porcine brain microtubules. Therefore, its mechanism of antitumor action seems to be, at least in part, ascribable to the inhibition of microtubule assembly. Because of its good preclinical activity, TZT-1027 has been entered into phase I clinical trials.

Animals↗
PubMed1997

Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-glucose.

Thyrotropin-releasing hormone (TRH) administered intracerebroventricularly and intravenous injection of 2-deoxy-D-glucose (2-DG) stimulate pancreatic exocrine secretion via vagal efferent nerve excitation. We examined whether centrally administered somatostatin would inhibit pancreatic exocrine secretion that was stimulated by vagal efferent nerve excitation in conscious rats. The animals were prepared with cannulas draining bile and pancreatic juice separately and with a duodenal cannula, a cerebroventricular cannula, and a right jugular vein cannula. Intracerebroventricular injection of somatostatin (0.4 or 4 nmol) significantly inhibited pancreatic secretion induced by TRH (50 or 500 pmol) in a dose-dependent manner. Intravenous injection of somatostatin had no effect on pancreatic secretion stimulated by TRH. On the other hand, somatostatin injected centrally did not affect pancreatic secretion induced by 2-DG (75 mg/kg) or basal secretion. These results suggest that TRH and 2-DG stimulate vagal efferent nerves via distinct mechanisms and that central somatostatin selectively inhibits excitation of the vagus induced by peptidergic (TRH) stimulation.

Animals↗
PubMed1997

Continuous low-dose NO inhalation does not prevent monocrotaline-induced pulmonary hypertension in rats.

We determined whether vasodilator doses of inhaled nitric oxide (NO) prevented the progression of pulmonary hypertension (PH) and vascular changes in monocrotaline-induced PH. Short-term NO inhalation in rats 3 wk after the injection of monocrotaline reduced mean pulmonary artery pressure (PAP) from 30.7 +/- 2.2 (SE) to 26.4 +/- 1.4 mmHg at 10 parts per million (ppm) and from 30.2 +/- 1.3 to 25.8 +/- 1.4 mmHg at 40 ppm. There were no differences among rats exposed to air only and rats exposed to 10 ppm of NO for 19 days after a single subcutaneous injection of monocrotaline, in mean PAP (34.3 +/- 1.9 mmHg air vs. 32.8 +/- 1.4 mmHg NO), right ventricular hypertrophy (RVH), medial wall thickness (MWT) of muscular arteries, and the percentage of muscularized arteries at alveolar wall (%AW) and duct (%AD) level. Additional groups exposed to air only and 40 ppm of NO for 19 days again showed no difference in mean PAP, RVH, MWT, and %AD, except that this dose slightly reduced %AW (60.6 +/- 3.4% air vs. 46.9 +/- 5.2% NO, P = 0.04). Urine nitrate (NO3) level was higher in rats that had inhaled NO. In contrast to chronic hypoxic PH, vasodilator doses of NO inhalation did not prevent the development of PH in this malignant form of experimental PH.

Administration, Inhalation↗
PubMed1997

Regulation of cholecystokinin release and transcription in a rat without gene expression of cholecystokinin-A receptor.

An Otsuka Long-Evans Tokushima Fatty (OLETF) rat does not possess cholecystokinin (CKK)-A receptor gene expression because of a genetic abnormality. We examined the CCK release and its transcription in OLETF rats in comparison with control (Long-Evans-Tokushima-LETO) rats. Animals at 5-6 and 24-25 weeks of age were used. The level of CCK mRNA and CCK concentration in the small intestinal mucosa, and the level of CCK-A receptor mRNA in the pancreas were examined. To examine CCK release, rats were prepared with external bile and pancreatic fistulae. The basal plasma levels of CCK and those at 2 h after bile-pancreatic juice diversion were measured by radioimmunoassay. The levels of CCK mRNA, and tissue CCK concentration increased significantly with age in both strains, but the values in OLETF rats were significantly lower than those in LETO rats. The CCK-A receptor mRNA level also increased with age in LETO rats. The plasma CCK concentration was significantly increased by bile-pancreatic juice diversion regardless of age and strain; however, the level of plasma CCK in OLETF rats at 24-25 weeks of age was significantly lower than that of LETO rats. It is suggested that the long-term defect of CCK-A receptor may decrease CCK release and transcription.

Animals↗
PubMed1997

Intraalveolar expression of tumor necrosis factor-alpha gene during conventional and high-frequency ventilation.

The effects of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFO) on intraalveolar expression of the tumor necrosis factor-alpha (TNF-alpha) gene were studied in surfactant-depleted rabbits. After lung lavage with saline, 13 rabbits were administered either CMV (n = 6) or HFO (n = 7) for 1 h at an FiO2 of 1.0 and a mean airway pressure of 13 cm H2O. Lung lavage was then repeated. The rabbits' RNA was extracted from the lavage cells, and mRNA for TNF-alpha was quantitated by reverse-transcription polymerase chain reaction using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an internal standard. At 1 h of ventilation, PaO2 was slightly lower with CMV than HFO, while lavage cell counts and cytology were similar between the two groups. The ratio of TNF-alpha mRNA to GAPDH mRNA increased with CMV (control, 0.48 +/- 0.04 [SE] versus 1 h, 1.02 +/- 0.14, p < 0.01) but did not change with HFO (0.55 +/- 0.07 versus 0.73 +/- 0.09). In a separate series of experiments, ten surfactant-depleted rabbits continued to be ventilated for 4 h either by CMV (n = 5) or HFO (n = 5). Conventional mechanical ventilation resulted in a progressive hypoxemia, decreased lung compliance, increased number of neutrophils in lung lavage fluid, and substantial morphological changes including hyaline membrane formation and neutrophil accumulation, whereas HFO was associated with minimal changes in such physiological and pathological abnormalities. These results suggest that activation of alveolar macrophages and production of proinflammatory cytokines may play a pivotal role in the early stage of ventilator-induced lung injury, and that ventilator mode (CMV or HFO) substantially modulates macrophage activation and hence the degree of lung injury.

Animals↗
PubMed1997

Concealed air leak associated with large tidal volumes in partial liquid ventilation.

Current ventilator strategies aim at maintaining an open lung and limiting both peak inspiratory pressures and tidal volumes to avoid alveolar distension. Perfluorocarbons, as well as being excellent solvents for oxygen and carbon dioxide, have the unique properties of being able to recruit dependent lung regions and improve pulmonary mechanics. Optimal ventilator strategies for partial liquid ventilation (PLV) have not yet been clearly defined. In the surfactant-depleted rabbit model, an approach involving a large tidal volume (VT) (15 ml/kg) and lung filled to FRC with perfluorocarbon (PFC) was compared with strategies involving a moderate VT (9 ml/kg) and partially filled lung (6 ml/kg), a moderate VT (9 ml/kg) and lung filled to FRC with PFC, and a large VT (15 ml/kg) and partially filled lung (6 ml/kg). PEEP was maintained at 5 cm H2O except in the moderate VT, partial-filling group, in which a PEEP of 9 cm H2O was used to maintain the rabbits for the duration of the experiment. Oxygenation was satisfactory in all groups, and peak inspiratory pressures were not significantly different. However, five of the 13 animals in the large-VT, PFC-filled lung group died of a pneumothorax prior to completion of the experiment. Of the eight animals in this group surviving the experiment, two had radiographic evidence of pneumothoraces, with an additional three animals having autopsy evidence of air leak. Of the 22 animals in the other groups, all survived with the exception of a single rabbit in the large VT, partial-filling group, which had both radiographic and autopsy evidence of air leak. We conclude that there is a significant risk of barotrauma in a PLV strategy in which a large VT is used in association with a lung filled to FRC with perfluorocarbon. Adequate gas exchange can be achieved with alternative ventilation strategies in combination with PLV.

Animals↗
PubMed1997

Demonstration of the distal end of the oesophagus by transabdominal ultrasound.

This study aimed to demonstrate the distal end of the oesophagus using a transabdominal ultrasound technique (TUS) and to measure the normal oesophageal wall thickness in adults. 65 patients without oesophageal disease and 38 normal volunteers were examined by TUS. A left subcostal approach was used to demonstrate the oesophagus. The wall thickness and length were measured in both the supine and 45 degrees right side up oblique (RUO) positions. The abdominal oesophagus was visualized in 80% of patients in the supine position and 92% in the RUO position. Satisfactory demonstration was obtained in 67% of patients in the supine and 85% in the RUO position. The oesophageal wall thickness averaged 2.8 mm (range 2.0-4.0 mm, SD 0.7 mm). The visualized length in these subjects averaged 2.3 cm in the supine position and 3.0 cm in the RUO position, which included approximately 1.5 cm of the lowest portion of the thoracic oesophagus in addition to the abdominal oesophagus. TUS can demonstrate the abdominal oesophagus in the majority of patients and has the potential to provide information on disorders of structure and motility.

Abdomen↗
PubMed1997

Interactive communication in high-technology home care: videophones for pediatric ventilatory care.

OBJECTIVE: To develop and to assess the clinical impact of a near-television quality home digital videophone system (Integrated Services Digital Network [ISDN] 64, 320 x 200 resolutions, 10 to 12 frames per second), which would provide respiratory care specialists' resources to primary care physicians and their pediatric patients receiving home respiratory care. METHOD: A prospective study comparing the preceding 6 months and following 6 months of implementation of a videophone system on seven pediatric home respiratory care patients (group I) and a prospective analytical study of three patients (group II) being introduced to home ventilatory care were carried out. Clinical effectiveness and time-saving benefits were studied. RESULTS: There were large reductions in the number of house calls by the physicians (from 5 to 0), unscheduled hospital visits by patients (from 24 to 5), and hospital admission days (from 22 to 10), with a fivefold increase in phone calls (from 11 to 58) in group I. This reduced the net number of hours spent by both patients and physicians in unscheduled medical care by 95 hours for the patients and 51.2 hours for the physicians. A total of 45 videophone calls, of which 27 were related to mechanical concerns and 18 to medical concerns, were made in group II. There were 7 mechanical and 10 medical problems of clinical significance, but all were directly handled by physicians by videophone. The majority (35 of 45) of videophone calls were made in the first 3-month period, indicating a decrease in nonspecific concerns after this period. The specifications of the system we used were found acceptable by both patients and health care professionals. The system seemed to be useful in effectively using the time of specialists and in relieving the anxieties of families. No deleterious effects were noted. The current initial cost is substantial but rapidly falling. The running cost is similar to a regular telephone bill when one ISDN 64 line is used. CONCLUSIONS: The videophone system using ISDN 64 can now be considered a practical and effective tool to recruit specialist resources into home care and to improve the quality of pediatric home ventilatory care. This study encourages the use of videophones to help establish designated home care support systems that may extend beyond national borders and time zones.

Adolescent↗
PubMed1997

Reducing nurses'. Workload using a computerized nursing support system linked to the hospital information system.

A computerised nursing support system (CNSS) linked to the hospital information system (HIS) was developed and has been in use for one year, in order to reduce the workload of nurses. CNSS consists of (1) a hand held computer for each nurse (2) desk-top computers in the nurses' station and doctors' rooms (3) a data server (4) an interface with the main hospital information system. Nurses enter vital signs, food intake and other information about the patients into the hand held computer at the bed-side. The information is then sent automatically to the CNSS data server, which also receives patients' details (prescribed medicines etc.) from the HIS. Nurses and doctors can see all the information on the desk-top and hand held computers. This system was introduced in May 1995 into a university hospital ward with 40 beds. A questionnaire was completed by 23 nurses before and after the introduction of CNSS. The mean time required to post vital data was significantly reduced from 121 seconds to 54 seconds (p < 0.01). After three months 30% of nurses felt CNSS had reduced their workload, while 30% felt it had complicated their work; after five months 70% noted a reduction and 0% reported that CNSS had made their work more complex. The study therefore concludes that the interface between a computerised nursing support system and the hospital information system reduced the workload of nurses.

Humans↗
PubMed1997

[Repeated low-flow sevoflurane anesthesia: effects on hepatic and renal function in beagles].

We studied the effects of repeated low-flow sevoflurane anesthesia for 6 hours. Five beagle dogs received 1.3 MAC (3%) sevoflurane anesthesia. Anesthesia of 6 hours was repeated on at the 7th day after the first anesthesia. Compound A gas samples were collected from the inspiratory limb during anesthesia. Concentrations of serum and renal fluoride, hepatic and renal function parameters were measured during and up to 7 days after the first and second anesthesia. The peak concentration of compound A was 23.7 +/- 3.6 ppm at 2 hours and the same level remained during the anesthesia. Plasma fluoride level exceeded 50 mmol.l-1 during anesthesia and rapidly decreased to the preanesthesia level thereafter. Serum GOT increased slightly only on the first postanesthesia day. No significant changes in other blood chemistry studies were observed. The excretion of renal tubular enzymes did not increase during and after anesthesia. Repeated low flow sevoflurane anesthesia in beagles did not affect hepatic and renal function significantly.

Acetylglucosaminidase↗
PubMed1996

Decrease in exploratory behavior in naturally occurring cholecystokinin (CCK)-A receptor gene knockout rats.

We recently found a specific strain of rats (Otsuka Long Evans Tokushima Fatty; OLETF rats) lacking cholecystokinin (CCK)-A receptor because of a genetic abnormality. Since CCK is an abundant neurotransmitter peptide in the brain, we examined whether these animals exhibit any behavioral abnormalities by conducting open-field tests. OLETF rats showed hypolocomotor activity and a decrease in the incidence of rearing in open-field tests. CCK release from the synaptosomes, and levels of CCK and CCK-B receptor mRNAs were the same as those observed in normal rats. It is suggested that the decreased exploration in OLETF rats may be due to the lack of CCK-A receptor.

Animals↗
PubMed1996

Upregulation of antioxidant enzyme activities by deprenyl. Implications for life span extension.

In order to elucidate the exact role of antioxidant enzyme activities such as superoxide dismutase (SOD) in the aging process of animals, we compared various enzyme activities in different brain regions and in the liver of young (6-8 mo) and old (28-30 mo) Fischer-344 (F-344) rats. While Mn-SOD activities were elevated 3-5-fold in specific brain regions such as hippocampus, striatum and substantia nigra in brains of old male rats compared with the young, in females both forms of SOD (Cu, Zn- and Mn-) enzyme activities remained essentially unchanged with aging. Continued subcutaneous infusion of deprenyl for 3 weeks caused a 2-3-fold increase in activities of both Cu Zn- and Mn-SOD and a 50-60% increase in CAT activities in striatum and substantia nigra but not in hippocampus, cerebellum or the liver. Further, long-term treatment of old male rats with deprenyl caused a significant increase in the remaining life expectancy from 24 months of age by 34%. In conclusion, activities of antioxidant enzymes in these regions examined do not show any uniform age-associated change, suggesting that changes in these enzyme activities do not have any specific role in the life span of rodents in general terms. In contrast, the results of our deprenyl study suggests the possibility that the protection of catecholaminergic neurons by an upregulation of SOD and CAT activities plays a significant role in the life span of animals.

Animals↗