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Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 487 records · Page 27Linked to original sources

Effect of MCI-186 on brain edema in rats.

We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipid peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.

Animals↗

[Evaluation of the vasodilating effect of naftidrofuryl oxalate using isolated canine and rat artery preparations].

Using isolated ring preparations of major arteries mainly of canine origin, we attempted to explore the mechanism of the vasodilating effect of naftidrofuryl oxalate (I) at the concentration of approximately 10 microM. 1) The resting tension of canine carotid, femoral, coronary, renal and basilar arteries were not affected by I. 2) A weak or no papaverine-like activity was noted on coronary, renal and basilar arteries contracted by KCl (25 mM) or U46619 (20 nM). Porcine endothelin (30 nM)-induced contraction in the basilar artery also showed no response to I. 3) I produced a relatively strong anti-serotonergic effect in the basilar and femoral arteries, and the minimum effective concentrations of I for pretreating these arteries were 0.3 and 0.1 microM, respectively. I failed, however, to affect 8-OH-DPAT-induced contraction of the basilar artery. 4) In a low concentration such as 1 nM, I was able to release the vasodilating factor from the carotid artery. 5) The oscillatory contractions which developed in the rat thoracic aorta with phenylephrine (10 microM) were not affected by I (approximately 0.1 microM). 6) Na oxalate (approximately 1 mM) produced none of the effects of I described in 2) approximately 4). Based on the results obtained, it is concluded that I would exert its vasodilating effect not only directly via an anti-serotonergic action but also indirectly via its secretagogue-like action.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Development of a new exposure monitoring system considering pulmonary ventilation (DEM 1).

Exposure evaluation is an essential facet in the assessment of the risks of exposure to toxic materials in the workplace. Presently, samples from the breathing atmosphere are measured in order to determine the level of individual exposure to toxic substances. This method, however, does not take into account the level of physical exertion during exposure. Physical activity is known to increase pulmonary ventilation by up to 10 times that of the level at rest. Thus, measurement of pulmonary ventilation, as well as the concentration of a toxic material in the air would provide valuable data in evaluating exposure. We have developed a device that measures and records the concentration of a toxic material in the air and pulmonary ventilation as predicted by heart rate both simultaneously and continuously. In this system, real time pulmonary ventilation is predicted from heart rate by using a regression equation that was obtained from the results of our study. The percentage error of predicted pulmonary ventilation at each heart rate is within 30%. The present study assessed the feasibility of the use of heart rate as the predictor of pulmonary ventilation. Our new exposure monitoring system is the first practical device that monitors the level of exposure dependent upon pulmonary ventilation and will be useful in the reevaluation of threshold limit values (TLV's) and in working management.

Adult↗

Mesothelial papillary proliferation of the pleura associated with radiation therapy: does it have a role in the pathogenesis of mesothelioma?

Diffuse papillary proliferation of mesothelial cells in the pleura mimicking metastatic carcinoma was seen four weeks following radiation therapy for a Pancoast tumor. Such papillary proliferations are not observed incidentally and are envisioned to occur during asbestos-induced carcinogenesis. We postulate that similar papillary lesions may serve as a link in the pathogenesis of radiation-induced mesotheliomas.

Aged↗

[Radioimmunoassay of plasma calcitonin gene-related peptide (CGRP) levels in patients with endocrine tumor].

For the purpose of determining the significance of CGRP for endocrine tumors, we attempted to establish CGRP radioimmunoassay (RIA) system and to measure plasma CGRP levels in patients with endocrine tumor. One ml of plasma (EDTA-2K + aprotinin 500.KIE/ml) was applied to Sep-Pak C 18 column, and was eluted by 90% MeOH plus 0.1% TFA. The eluted samples were used for RIA. RIA was performed by two day-one day system (delayed assay). B/F separation was made by two Ab-PEG method. Cross-reactivity of antisera was 0.0025% and below 0.0001% against PTH and calcitonin in human, respectively. The standard curve of CGRP showed a dose response curve. Results of dilution and reproduction tests were excellent. Normal range of serum CGRP was 6.7 +/- 3.0 pg/ml (M +/- SD) and the cut-off level was determined to be 12.7 pg/ml. Plasma CGRP showed 128,323 and 2,010 pg/ml in three preoperative patients with medullary thyroid carcinoma, indicating extremely high levels. On the other hand, plasma CGRP levels increased in 2/7, 2/4, 2/5, and 0/3 in patients with parathyroid adenoma, benign insulinoma, carcinoid and pheochromocytoma, respectively. Correlation between CGRP level and calcitonin levels was significant (r = 0.789) in only 16 patients with medullary thyroid carcinoma. This study suggests that our CGRP RIA system was satisfactory for clinical use and measurement of CGRP may be potentially useful for clearing the pathophysiology of neuroendocrine tumors, although CGRP level was raised in patients with medullary thyroid carcinoma.

Biomarkers, Tumor↗

Enhancement by streptozotocin of O2- radical generation by the xanthine oxidase system of pancreatic beta-cells.

Spin-trapping techniques and electron spin resonance (ESR) spectroscopy were used to study the relationship between the effect of streptozotocin (STZ) on pancreatic beta-cells and free radical formation by these cells. Results showed that STZ enhanced generation of the DMPO-OH radical adduct, which is a degradation product of the superoxide anion (O2-) in the presence of cellular components, in a hypoxanthine-xanthine oxidase (XOD) system with a homogenate of beta-cells. This enhancing effect was also observed in a system without cellular components; STZ increased the signal height due to the O2- radical in a concentration-dependent manner and caused a maximum of 150% enhancement at a concentration of 1.5 mM. Thus, STZ seemed to enhance the generation of the O2- radical in the XOD system, probably by some mechanism of its interaction with XOD. Pancreatic beta-cells exhibited a high XOD activity and a very low superoxide dismutase activity. Therefore, the present result supports the possibility that the cytotoxic effect of STZ is closely related to free radical generation in pancreatic beta-cells.

Animals↗

[Biochemical diagnosis of pheochromocytoma by determining normetanephrine and metanephrine concentrations in single voided urine].

Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.

Adrenal Gland Neoplasms↗

Structure and expression of gene coding for sex-specific storage protein of Bombyx mori.

A major plasma protein termed "SP 1" accumulates in a sex- and stage-specific manner in the larval hemolymph of the silkworm, Bombyx mori. We have cloned the genomic sequence coding for SP 1 and analyzed its primary structure. The SP 1 mRNA sequence is encoded by five exons interspersed with four introns. Initiation site for the SP 1 gene transcription was identified at nucleotide level. Sequence homologous to the SV 40 enhancer "core" structure exists in two adjacent locations in the first intron. The 5' flanking region of the SP 1 gene contains a sequence highly homologous to the putative hormone-receptor complex binding site found in the ecdysteroid-sensitive genes of Drosophila melanogaster. Developmental change in the level of the SP 1 mRNA precursor in the fat body faithfully reflects that of SP 1 mRNA, indicating that the biosynthesis of SP 1 in B. mori is regulated in a sex- and stage-specific fashion at the level of transcription.

Amino Acid Sequence↗

Cloning of mRNA sequence coding for sex-specific storage protein of Bombyx mori.

A major plasma protein, referred to as SP 1, exhibits sex- and stage-specific expression during the larval development of the silkworm, Bombyx mori. We have isolated a plasmid clone bearing a part of mRNA sequence coding for SP 1 and quantitated the amount of SP 1 mRNA by means of RNA blot hybridization using the cDNA probe. The developmental change in the amount of SP 1 mRNA in the fat body closely reflected that of the hemolymph concentration of SP 1, indicating that the biosynthesis of SP 1 is regulated in a sex- and developmental stage-specific fashion at the level of mRNA.

Adipose Tissue↗

[Impaired vasopressin secretion in patients with myotonic dystrophy].

Hypernatremia has occasionally been observed in patients with myotonic muscular dystrophy (MyD). To elucidate the possibility of osmoregulatory dysfunction, we investigated hypothalamo-posterior pituitary function as well as serum electrolytes in eight patients with MyD. Blood samples were obtained early in the morning after overnight dehydration. Renal function was estimated by blood urea nitrogen, serum creatinine and creatinine clearance. Posterior pituitary function was evaluated by direct measurement of plasma vasopressin (AVP) during a 5% hypertonic saline infusion. Plasma AVP concentrations were determined by sensitive radioimmunoassay. In five patients, circulating blood volume (CBV), plasma renin activity (PRA) and serum aldosterone (S-Aldo.) were also measured. The mean serum sodium level (143.9 +/- 1.7mEq/1: Mean +/- SD) was significantly higher than in the controls (139.4 +/- 2.2mEq/1). A 5% hypertonic saline infusion showed a subnormal increase in AVP and diminished thirst, despite sufficient elevation of plasma osmolality, in all patients as compared with healthy adults. Renal function was intact. Biochemical evidence of dehydration, estimated by PRA, S-Aldo and CBV, was unremarkable in four of the five patients. These findings suggest that patients with MyD have neurogenic disorders of osmoregulation in addition to previously reported endocrine abnormalities. Impaired AVP secretion in response to osmotic stimuli and reduced thirst might be responsible for such failure.

Adolescent↗