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Biomedical subjects

M Kinoshita

Publications and source records attributed to M Kinoshita.

At least 19 recordsLinked to original sources
PubMed1992

Expression of DRG during murine embryonic development.

We had previously characterised a cDNA which encodes a novel GTP-binding protein DRG. The expression of drg gene is down-regulated during the embryonic development of murine central nervous system. Further analysis of drg mRNA and protein in adult mouse tissues and various cell lines of different origins indicated that it is expressed widely, albeit at low and variable levels. In situ hybridisation analysis of mRNA expression in sections of mouse embryos indicated that drg is expressed strongly in various embryonic tissues. The expression of drg mRNA is greatly reduced in newborn animals. At cellular level, DRG protein can be detected in the cytoplasm. These observations suggest that DRG may play multiple roles in development and normal cell metabolism.

3T3 Cells↗
PubMed1992

Differential regulation of rat AT1a and AT1b receptor mRNA.

Rat type 1 angiotensin II receptor has two subtypes, namely type 1a and type 1b. The regulation of the expressions of these two subtype receptor mRNAs was studied by using a competitive polymerase chain reaction method. The expression of the type 1a mRNA in the liver was negatively and that of the type 1b mRNA in the adrenal was positively modulated by bilateral nephrectomy. In the ventricle of 16 week old Spontaneously hypertensive rat, the expression level of the AT1b receptor mRNA was higher than that in the ventricle of the age-matched Wistar-Kyoto rat, while the expression levels of the AT1a mRNA in the ventricle were almost similar between the two strains at this age. Although type 1a and type 1b have almost similar functional properties, the expressions of their mRNAs were differentially regulated.

Adrenal Glands↗
PubMed1992

Increased plasma concentrations of aspartate, glutamate and glycine in Parkinson's disease.

We measured fasting plasma amino acids in 20 patients with Parkinson's disease (PD) and 20 controls matched for age and sex. PD patients had significant elevations in plasma levels of aspartate, glutamate and glycine. The levels of other amino acids were not significantly different from those found in controls. No correlation was noted between PD severity and the degree of abnormality of plasma amino acids. We conclude that excitatory amino acids may be altered in patients with PD, and raise the possibility that neuroexcitotoxic mechanisms may be involved in the neurodegeneration of PD.

Aged↗
PubMed1992

Archaebacterial lipid models: highly salt-tolerant membranes from 1,2-diphytanylglycero-3-phosphocholine.

1,2-Di(3RS,7R,11R-phytanyl)-sn-glycero-3-phosphocholine and its glycerol epimers were synthesized as model lipids of archaebacterial halophiles. These amphiphiles, upon sonication of aqueous suspensions, gave rise to small unilamellar vesicles (SUV) of 300-800 A in diameter and about 80 A in the membrane thickness. The liposomes were very stable for at least a month even in a highly concentrated suspension or 5 M aqueous NaCl. The vesicles could retain Na+ and Cl- ions as well as 5(6)-carboxyfluorescein in the aqueous interior at temperature as high as 70 degrees C. The liposomes of ordinary diester lipids such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and egg-yolk lecithin were less stable and more permeable than those of the diphytanyl lipids.

Archaea↗
PubMed1992

[Evaluation of aortic distensibility using cine MR imaging].

Regional aortic distensibility was measured noninvasively using cine MR imaging to determine whether it correlates with aging or risk of coronary artery disease (CAD). Twenty-two patients with CAD confirmed by angiography and 33 without CAD underwent cine MR imaging. Thirty-two sequential images were obtained in one cardiac cycle. The cross sectional area of the descending thoracic aorta was measured on both diastolic (A) and systolic (A') images. Aortic distensibility (A.D.) was calculated from the following equation: A.D. = (A'-A)/A/delta P. (delta P represents pulse pressure). Results of a simple regression analysis showed that decreased regional aortic distensibility was significantly correlated with the age of the patients (r = -0.762, p less than 0.005). In addition, the parameter was lower in patients with CAD than those without CAD (p less than 0.05). In conclusion, regional aortic distensibility derived from cine MR imaging is a useful parameter to evaluate not only aging but also pathological atherosclerosis of the aorta. In addition, this parameter might have some potential to evaluate the prediction of CAD in patients with normal serum cholesterol.

Adolescent↗
PubMed1992

TRH analogue, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) enhances neurite outgrowth in rat embryo ventral spinal cord in vitro.

We have studied effects of TRH analogue, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) (from Tanabe, Osaka, Japan) on explanted ventral and dorsal spinal cord cultures from 13- and 14-day-old rat embryos. TA-0910-treated cultures had significantly increased neurite outgrowth with cultures of ventral spinal cord, but not with cultures of dorsal spinal cord. The effect was dose-dependent. A possible role for TRH in amyotrophic lateral sclerosis remains to be defined.

Animals↗
PubMed1992

Plasma amino acid levels in patients with amyotrophic lateral sclerosis.

Evidence for a generalized defect in glutamate in patients with amyotrophic lateral sclerosis (ALS), associated with widespread alterations in the central nervous system level of this excitatory amino acid. We measured fasting plasma amino acid in 10 ALS patients and 10 controls matched for age and sex. ALS patients had statistically significant elevations in plasma level of aspartate, glutamate, and glycine. The plasma levels of other amino acids were not significantly different from those found in controls. No correlation between ALS severity or activity and degree of abnormality in amino acids was established.

Amino Acids↗
PubMed1992

Binding of brevetoxins and ciguatoxin to the voltage-sensitive sodium channel and conformational analysis of brevetoxin B.

The marine toxins known generically as brevetoxins, as well as their structural relative ciguatoxin, are known as polyether ladder toxins, and bind uniquely to site 5 of the voltage-sensitive sodium channel. Rat brain synaptosome binding data show similarities in binding affinity for brevetoxins having the same structural (ladder) backbone, but different affinities between brevetoxins having different backbones. Ciguatoxin has a different backbone from the brevetoxins, but binds even more strongly to the same site. Could the flexibility of the backbone be related to their relative toxicities? As part of an effort to identify the common pharmacophore for the toxins, Monte Carlo methods were used to generate conformational models of the polyether ladder toxin brevetoxin B (PbTx-2) which shows significant flexibility at the juncture of the two 7-membered rings.

Animals↗
PubMed1992

Myasthenia gravis developing after discovery of thymoma.

We report 4 cases of myasthenia gravis in which myasthenic symptoms developed after a thymoma was known to be present. They include 3 invasive thymomas and one thymoma. In 3 of them, myasthenic symptoms developed 2-7 months after removal of the thymoma; in 1 case, myasthenic symptoms developed 11 years after the thymoma was known to be present. We also discuss here the possible pathogenetic mechanism of post-thymomectomic myasthenia gravis, and propose that it is due to the natural course of the disease.

Adult↗
PubMed1992

Uncoupling of atrial natriuretic peptide extraction and cyclic guanosine monophosphate production in the pulmonary circulation in patients with severe heart failure.

OBJECTIVES: This study was designed to evaluate the role of endogenous atrial natriuretic peptide in the pulmonary circulation in patients with chronic heart failure. BACKGROUND: Plasma atrial natriuretic peptide concentrations in patients with heart failure have been reported to be higher than those in normal subjects and to increase as the severity of heart failure progresses. Although endogenous atrial natriuretic peptide is thought to improve the condition of patients with heart failure by reducing preload and afterload, recent findings have indicated that a high plasma atrial natriuretic peptide level is a prognostic predictor in patients with heart failure. METHODS: To evaluate the pathophysiologic role of endogenous atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels were determined in the main pulmonary artery and pulmonary capillary wedge region in 80 patients with chronic congestive heart failure (New York Heart Association functional classes II to IV). RESULTS: The plasma atrial natriuretic peptide level decreased significantly from the main pulmonary artery to the pulmonary capillary wedge region, whereas the plasma cGMP level increased significantly from the main pulmonary artery to the pulmonary capillary wedge region. In patients with mild chronic heart failure (n = 50), the plasma atrial natriuretic peptide level correlated with the cGMP level in the main pulmonary artery (gamma = 0.71, p less than 0.001). The atrial natriuretic peptide extraction level, calculated as (Atrial natriuretic peptide in the main pulmonary artery--Atrial natriuretic peptide in the pulmonary capillary wedge region) x Cardiac output x (1-hematocrit/100) (ng/min), also correlated with the cyclic guanosine monophosphate production level, calculated as (cGMP in the pulmonary capillary wedge region--cGMP in the main pulmonary artery) x Cardiac output x (1-hematocrit/100) (nmol/min) (gamma = 0.78, p less than 0.001). In contrast, such correlations were not found in patients with severe chronic heart failure (n = 30). In these patients, the atrial natriuretic peptide extraction level was significantly higher but there was no significant difference in the cGMP production level between the two groups (mild and severe chronic heart failure). Therefore, the molar ratio of cGMP production to atrial natriuretic peptide extraction in the pulmonary circulation was significantly lower in patients with severe chronic heart failure (88 +/- 16 vs. 480 +/- 41, p less than 0.001). CONCLUSIONS: These results indicate that down-regulation of atrial natriuretic peptide receptors coupled to guanylate cyclase may occur in the pulmonary vascular beds of patients with severe chronic heart failure.

Adolescent↗
PubMed1992

The role of metal allergy and local hyperhidrosis in the pathogenesis of pompholyx.

Pompholyx (Dyshidrosis) is a disease of unknown etiology presenting as symmetrical, vesicular hand and foot dermatitis. To clarify the pathogenetic role of sweat and metal allergy, twenty five patients with pompholyx were examined with respect to their perspiration volume using equipment that continuously recorded the local perspiration volume. Patients were also examined for metal allergy by patch testing and oral challenge tests. The perspiration volumes were measured using recently developed equipment for continuous recording of local perspiration volume (Kenz-Perspiro oss-100). The perspiration volume of pompholyx patients was found to be 2.5 times higher than that of age-matched normal controls. Twenty percent of the patients showed sensitivity to chromate, 16% to cobalt, and 28% to nickel on patch testing. Six patients with positive results were challenged orally in a controlled trial with 2.5 mg nickel, 1 mg cobalt, or 2.5 mg chromium. Four of them (67%) showed vesicular reactions on their hands with challenge testing. These results indicated a sensitivity to metal compounds which, in combination with local hyperhidrosis, may contribute to the development of vesicular lesions in pompholyx.

Adolescent↗
PubMed1992

ras mutations in endocrine tumors: mutation detection by polymerase chain reaction-single strand conformation polymorphism.

To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Mutations of the H-, K-, N-ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N-ras codon 61, and one contained the mutated H-ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H-ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors.

Adult↗
PubMed1992

Inhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin beta 1 subunit antibody.

We investigated the expression of beta 1 integrins in human carcinoma cell lines, and the anti-metastatic and anti-invasive effects of a newly established anti-human beta 1 subunit monoclonal antibody designated NCC-INT-7. All the examined carcinoma cell lines expressed beta 1 integrins upon immunoblot analysis. NCC-INT-7 completely inhibited the adhesion of carcinoma cells to laminin, fibronectin, collagens and acetone-fixed tissues including lung, liver and brain. In an in vitro invasion model, NCC-INT-7 inhibited the invasion of human bladder carcinoma cell line T24 and human gastric carcinoma cell lines TMK-1, MKN-45 and MKN-74 through an artificially reconstructed basement membrane. In an in vivo nude mouse peritoneal dissemination model using MKN-45 and TMK-1, NCC-INT-7 significantly reduced the number of tumor nodules in the mesentery. In an in vivo nude mouse liver metastasis model using a serially transplantable human colonic carcinoma, COL-2-JCK, NCC-INT-7 significantly reduced the number of tumor nodules in liver. These results indicate that beta 1 integrins play an important role in the tissue attachment, migration, invasion and metastasis of human carcinoma cells, and that this new monoclonal antibody is useful for studies aimed at prevention of metastasis.

Animals↗
PubMed1992

Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients.

Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil-derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells.

Adolescent↗