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Biomedical subjects

M Nagasaka

Publications and source records attributed to M Nagasaka.

At least 19 recordsLinked to original sources

Effects of imidazoline-related compounds on the mechanical response to nicorandil in the rat portal vein.

The purpose of this study was to investigate the interactions of compounds structurally related to imidazoline at K+ channels located in the rat portal vein. Nicorandil, a K+ channel activator, dose dependently inhibited spontaneous contractions of the isolated rat portal vein. Glibenclamide (0.1-1 microM), an ATP-sensitive K+ channel blocker, competitively antagonized the response to nicorandil, whereas methylene blue (10 microM), a guanylate cyclase inhibitor, did not. Phentolamine, antazoline, tolazoline, and midaglizole also shifted the dose-response curve for nicorandil to the right in the dose range of 1-100 microM. The rank order of potency was glibenclamide much greater than phentolamine = antazoline = midaglizole greater than tolazoline. In contrast, clonidine, idazoxan, imidazole, 1-benzylimidazole, and yohimbine were ineffective. In addition, cromakalim (1-100 nM), a selective K+ channel activator, also inhibited spontaneous contractions of the rat portal vein, and this effect was antagonized by phentolamine in a similar way to that found with nicorandil. These results suggest that some 2-substituted imidazolines, including phentolamine, possibly act as K+ channel blockers, like glibenclamide, in vascular smooth muscle.

Animals

Small differences among body surface and epicardial QRST integral maps recorded during normal activation and experimentally simulated left bundle branch block or preexcitation in canine hearts.

QRST integral maps were constructed from 87-lead body surface electrocardiograms (ECGs) and from 45-lead epicardial electrograms during artificial pacing, which simulated left bundle branch block (LBBB) and Wolff-Parkinson-White syndrome in 12 dogs. Although the ECGs and electrograms differed in configuration for each conduction model, the body surface and the epicardial QRST integral maps showed only small differences. Correlation coefficients (r) and root mean square differences (rms) were calculated to assess quantitatively the similarities in the QRST integral maps among the different conduction models. Mean r values between the normal conduction and the left bundle branch block models were 0.95 in the body surface maps and 0.89 in the epicardial maps. Mean r values between the normal conduction and the Wolff-Parkinson-White ECG models were 0.97 in the body surface maps and 0.91 in the epicardial maps, and rms values were small enough. The small differences were also verified by the difference maps and by paired t tests. QRST integral maps on the epicardium and on the body surface were largely independent of altered activation sequences in both the left bundle branch block and the Wolff-Parkinson-White ECG models.

Animals

Hypoglycemic activities of MTP-3631, a novel thiopyranopyrimidine derivative.

MTP-3631 is a novel thiopyranopyrimidine derivative structurally different from any existent hypoglycemic agents. MTP-3631 markedly decreased basal blood glucose and improved glucose intolerance in genetically diabetic C57BL/6J ob/ob mice, which was not affected by tolbutamide. MTP-3631 also caused hypoglycemic effects in normal rats, but no change was observed in plasma insulin level. Unlike buformin, MTP-3631 did not change plasma lactate level in ob/ob mice. These results suggest that the hypoglycemic mechanism of MTP-3631 may be essentially different from those of sulfonylureas and biguanides.

Animals

Antihypertensive effects of MPC-1304, a novel calcium antagonist, in experimental hypertensive rats and dogs.

Antihypertensive effects of a novel calcium antagonist, MPC-1304, (+-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5- pyridine-dicarboxylate and its active metabolites were investigated in experimental hypertensive rats and dogs and compared with those of other dihydropyridine derivatives (nifedipine, nisoldipine, nicardipine, and nitrendipine). MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats. The antihypertensive effects of MPC-1304 were more potent than those of other dihydropyridines, and its active metabolites had antihypertensive effects comparable to those of other dihydropyridines. The hypotensive effects of MPC-1304 were stronger in hypertensive rats than in normotensive rats. During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group. When given orally to conscious renal hypertensive dogs, MPC-1304 0.1-0.3 mg/kg had a potency and duration of antihypertensive action comparable to that of nitrendipine (1-3 mg/kg). MPC-1304 increased coronary blood flow (CBF) and aortic blood flow (ABF) in conscious normotensive dogs. In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension.

Administration, Oral

[The determination of basic fibroblast growth factor (bFGF) in human placental tissue and the changes in bFGF during pregnancy].

The purpose of this study is to develop an assay system for quantification of bFGF in human tissue and to investigate the changes in bFGF content in the human placenta during pregnancy. Sixty-two placental tissue samples from various stages of normal pregnancies were collected. Approximately 28 micrograms bFGF was obtained per 1 kg of placental tissue. The recovery rates were 17.1 +/- 7.4%. The purified samples were confirmed as bFGF by SDS-PAGE and enzyme-linked immunoelectrotransfer blot (EITB) with anti-human bFGF monoclonal antibody. The bFGF readings in the human placenta determined by RIA were 11.81 +/- 2.11 fmol/mg protein (first trimester), 20.45 +/- 4.85 (early second trimester), 9.52 +/- 5.02 (late second trimester), 7.41 +/- 2.07 (third trimester), and 7.75 +/- 1.86 (post trimester). The placental bFGF were significantly high in the early stage of second trimester and declined gradually during the remainder of the pregnancy. The RIA values were correlated closely with the values obtained by bioassay. These results demonstrate that our assay system provides a tool for the quantification of bFGF in biological samples and suggest that bFGF, the active mitogen and angiogenic factor, participates in the formation of the human placenta.

Angiogenesis Inducing Agents

Detection of myocardial infarction in the presence of Wolff-Parkinson-White syndrome by QRST isoarea map in dogs.

The possibility of detecting myocardial infarction (MI) in the presence of Wolff-Parkinson-White (WPW) syndrome by means of body surface QRST isoarea maps was studied in eight dogs. Eighty-seven body surface ECGs were recorded simultaneously. Recordings were taken during right atrial (RA) and right atrial and right ventricular (RA + RV) sequential pacing, which simulated WPW syndrome, during control periods and at 1-hour intervals for up to 5 hours after occlusion of the left anterior descending coronary artery. In ECGs during the RA drive, diagnostic findings of MI such as abnormal Q waves were observed but became obscure during the RA + RV drive. On the contrary, the QRST values over the anterior chest during both drives were positive soon after coronary occlusion, decreased gradually as time passed, and became abnormally negative after 5 hours. The QRST isoarea maps during RA and RA + RV pacing showed quite similar patterns and were highly correlated with each other throughout this study (r greater than 0.95). These findings demonstrate that localized abnormalities resulting from MI are evident in QRST isoarea maps even in the presence of preexcitation and fusion.

Animals

[Organized chronic subdural hematoma; report of two cases].

Two cases of organized chronic subdural hematoma were presented. The first case had a one-year history of disorientation and right hemiparesis. CT scan revealed a low density area with linear high density in its medial margin, suggesting chronic subdural hematoma on the left frontal convexity. Surgery was performed expecting to remove the hematoma. There was, however, only a little fluid inside with thick membranous tissue. The second case, who has Crouzon disease, presented a one-year history of pseudobulbar palsy and tetraparesis after surgery for chronic subdural hematoma and hydrocephalus. The diagnosis of organized subdural hematoma was made at the time of reoperation which was performed expecting to remove the recurrent chronic subdural hematoma. Plain CT, done after admission to our hospital, showed homogeneous low density area remaining in the bilateral frontal convexity. Infusion scan revealed marked enhancement of the medial margin of the low density area. The lesion was demonstrated as a low intensity area by T1-weighted magnetic resonance images (MRI). Marked enhancement was noted around the low intensity area after the infusion of Gd-DTPA. Although it is very hard to make a diagnosis of organized chronic subdural hematoma using only the CT scan preoperatively, combination of the CT scan and MRI with Gd-DTPA enhancement seemed to be very useful for this purpose.

Adult

Effect of mannitol on intracranial pressure-volume status and cerebral haemodynamics in brain oedema.

Continuous measurement of CBV and CBF by means of laser-Doppler flowmetry was performed to analyze the temporal profile of cerebrovascular response to water accumulation in an infusion model of brain oedema. Using this method, the effect of mannitol on CBV was also examined to determine how mannitol improves the intracranial pressure-volume relationship. The results show that: (1) The presence of an oedema generator elicits a continuous reduction of CBV and a transient reduction of CBF. With cessation of this mechanical force of oedema production, CBV and CBF return to control levels. (2) Mannitol increases CBV and PVI. The improvement of PVI might be due to an increase in CBV as well as ICP reduction.

Animals

The effects of cerebral haemodynamics on the progression of cold-induced oedema.

A cold-injury lesion was made on the brain of 14 of 21 adult mongrel cats. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were observed in both groups during the next 6 to 9 hours using a laser Doppler flow meter. Intracranial pressure (ICP), water contents, and blood pressure were also measured. Hyperemia frequently reached a peak early in the test period in the gray matter and somewhat later in the white matter. In a few cases, hyperemia was observed to occur late in the test period in the gray matter and even later in the white matter. The least frequent pattern was a continuous decrease of CBF and CBV in gray matter over time and of CBF in white matter. Intracranial pressure rose rapidly and correlated well with the early hyperemia. The water content was significantly increased in the white matter. However, the difference in the rate of the increment of the water content was not significant from 7-9 hours after injury. Hyperemia seems to cause the severe impairment of the microcirculation during oedema formation induced by cold injury. A time difference of hyperemia was detected in the gray matter and the white matter.

Animals

An electron microscopic and electron probe study of the microcirculation in cold-induced oedema.

An ultrastructural study of adult mongrel dogs and cats was made to evaluate the changes in the microcirculation during cerebral oedema formation. Two to five cold injuries were made in one hemisphere in dogs and one lesion was made in cats. In several dogs arterial hypertension was induced with a balloon in the aorta. Intracranial pressure (ICP) and water content were measured. The specimens from the oedematous region were studied with transmission electron microscopy (TEM) and electron probe x-ray micro-analysis (EPMA). The TEM data showed swelling of the endothelium and astrocytic foot processes, enlarged perivascular spaces and increased number of endothelial vesicles. The EPMA findings indicated increases in Fe and Ca content in the perivascular spaces. In some cases, the amount of chloride in red cells was increased. The altered distributions of these metals suggested tissue injury and impairment of red cell and vessel wall functions.

Animals

Bradykinin (BK) enhances diuresis and natriuresis in saline volume-expanded dogs.

15 micrograms bradykinin was given with large amount of physiological saline solution intravenously to dogs. Significantly greater diuresis and natriuresis were obtained compared with those of simple saline volume expansion experiments. Bradykinin in small doses which were selected as giving no influence on blood pressure enhanced additively diuresis and natriuresis, similarly with subpressor doses of A II, AVP, and MX in saline volume expanded dogs. Since all four agents are having cellular Ca-mobilizing action in common, it is suggested that phosphoinositide system may be involved in this enhancement of renal sodium and water excretion.

Aldosterone

Clinical study of radioisotope clearance from the cerebrospinal fluid space using single photon emission computed tomography.

Radioisotope cisternography with statistical analysis was evaluated in 18 patients with suspected hydrocephalus shown by conventional CT, and 4 control patients. Regions of interest were located at cisterna magna, basal cistern, lateral cistern Sylvii, interhemispheric cistern, and lateral ventricle using three dimensional SPECT images. A value for the constant K was determined for each exponential radioactivity decay curve. On the basis of SPECT-derived K values our patients were grouped into hydrocephalus, nonhydrocephalus, and control patients. Twelve of 14 hydrocephalus patients were treated by shunt operation. Our less-invasive method showed reliable criteria for assessing the cerebrospinal fluid circulation.

Adolescent

Sirenoid monopodia with defects of right abdominal wall and lower limb associated with chromosome abnormality.

We have experienced a case of sirenoid monopodia with extreme deformity, which was studied pathoanatomically and genetically. The pathoanatomical studies revealed complicated deformities such as absence of the right abdominal wall, sacrum, right side of the os coxae and lower extremity, etc., and a chromosome study revealed 46XX, t (1 p-, Xq+), -8, +M. Various authors have discussed the genetic factors of anomaly of vascular development and concluded that all cases except for a few familial types would appear to be sporadic. In the present paper we report on an extreme type of sirenoid monopodia with right lower limb defect associated with chromosome abnormality. It is supposed that impoverished blood supply to the right lower portion of the body may have been the cause of this case, but the involvement of genetic factors is still unknown.

Abdominal Muscles

Allogeneic bone marrow transplantation in children: Tokai experience 1982 to 1984.

Ten children between the ages of five and fifteen years old with leukemia (two with acute nonlymphocytic leukemia in first remission, four with acute lymphocytic leukemia in first or second remission, one with acute lymphocytic leukemia in relapse, and one with chronic myelocytic leukemia in chronic phase), malignant lymphoma (one) or severe aplastic anemia (one) were given transplants from HLA-matched or mismatched family members between March, 1982 and April, 1984. Two patients died of leukemia relapses on days 107 and 257 following transplantation. One patient died of cardiac failure on day 157. One patient who received HLA-mismatched marrow from his father died of pulmonary edema and acute graft versus host disease on day 32. Six are alive 268-843 days post transplantation. None of the ten patients developed interstitial pneumonia due to cytomegalovirus which is one of the major causes of death reported in other published studies.

Acute Disease