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Y Oka

Publications and source records attributed to Y Oka.

At least 343 records · Page 19Linked to original sources
PubMed1993

Marked species-difference in the vascular angiotensin II-forming pathways: humans versus rodents.

Using isolated arteries, we demonstrated a marked difference in the angiotensin II-forming systems between human and rodent vessels. In human arteries, only 30-40% of the conversion of angiotensin I to angiotensin II depended on the angiotensin-converting enzyme (ACE), and the rest of the angiotensin II formation was ascribed to chymostatin-sensitive angiotensin II-generating enzyme (CAGE). On the contrary, angiotensin II formation in rodent arteries totally depended upon ACE, without any sign of CAGE involvement. Such a marked species-difference can be relevant to the reported difference between humans and rodents in the ACE inhibitor effects on the myointimal hyperplasia after intimal balloon injury.

Adult↗
PubMed1993

In vitro pharmacology of a novel non-peptide angiotensin II-receptor antagonist, E4177.

E4177, 3-[(2'-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H- imidazo[4,5-b]pyridine, was characterized by in vitro autoradiography and by examining functional antagonism upon angiotensin II (Ang II)-induced contraction of isolated vessels. In rat adrenal cortex and liver, E4177 competitively inhibited the specific binding of 125I-[Sar1,Ile8]Ang II, with IC50 being (5.2 +/- 1.0) x 10(-8) M for the adrenal cortex and (1.2 +/- 0.3) x 10(-7) M for the liver. These IC50 values were similar to those for losartan, which showed an IC50 of (6.0 +/- 0.9) x 10(-8) M for the adrenal cortex and (1.3 +/- 0.5) x 10(-7) M for the liver. In contrast, E4177 and losartan had little effect on the binding to rat adrenal medulla where AT2-receptors predominate. These results indicate that E4177 is AT1-specific as is losartan. E4177 and losartan competitively antagonized the Ang II-induced contraction of human and rabbit arterial strips without any agonistic action. The obtained IC50 values indicated that E4177 was twice as potent as losartan in human arteries and three times more so in rabbit aortic strips. Responses to norepinephrine, serotonin, histamine or KCl were not affected by E4177. In addition, E4177 (10(-5) M) had no effect on angiotensin-converting enzyme activity. These data indicate that E4177 is a potent AT1 Ang II-receptor antagonist that may be clinically useful for the treatment of cardiovascular diseases such as hypertension.

Adrenal Cortex↗
PubMed1993

Vestibular pathology of totally deaf ears.

The temporal bone vestibular pathologies of 23 totally deaf ears (16 patients) were studied. Abnormal findings in the saccule were seen more often than in the other vestibular sensory organs. Abnormal findings in the vestibular ganglion cells were found in 7 ears. There were fewer ears with main damage in the hair cells than with main damage in the nerves.

Adolescent↗
PubMed1993

Gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve cells have intrinsic rhythmicity and project widely in the brain.

Modulation of ionic channel properties and synaptic functions by neurotransmitters and hormones is called neuro-modulation and may be the basis for many long-lasting changes in animal behavior, for example, changes in the arousal or motivational states. We have previously shown in a teleost, the dwarf gourami, that the terminal nerve (TN) cells are a major component of the gonadotropin-releasing hormone (GnRH) system and are structurally independent from the preoptic/hypophysial-GnRH system, which projects to the pituitary and facilitates gonadotropin release from the gonadotropes. While GnRH fibers originating from TN cells are distributed widely throughout the brain, they do not project to the pituitary. Thus, TN-GnRH system does not function as a hypophysiotropic hormone but probably as a neuro-modulator, capable of affecting widespread regions of the brain. In the present study, we used a whole-brain in vitro preparation to examine the spontaneous electrical activities of TN-GnRH cells and to determine the morphology of individual cells by intracellular injections of either neurobiotin or biocytin. The recorded cells were clearly identified as GnRH-immunoreactive TN cells by using combined intracellular injection and GnRH immunocytochemistry. Most of the TN cells showed endogenous slow (1-7 Hz), regular beating discharges. The intrinsic nature of this activity was demonstrated by the voltage dependency of the beating frequency, rhythm resetting, and persistence of rhythmicity after synaptic isolation. Only a small number of TN cells showed either irregular or bursting discharge patterns. Anatomical observation of intracellularly labeled cells showed that, regardless of discharge patterns, all the TN cells had multiple axonal branches that project to those areas where we had previously demonstrated dense GnRH-immunoreactive fibers. From the present results, we propose a hypothesis that may be relevant to the peptidergic and monoaminergic neuromodulatory systems in general. The modulator neurons have endogenous rhythmic activities that vary according to the animal's hormonal or environmental conditions, and they regulate the excitability of target neurons in a wide variety of brain regions simultaneously via multiple axonal branches.

Animals↗
PubMed1993

Evaluation of the effects of different cardioplegic techniques on left ventricular function during coronary artery bypass surgery using transesophageal echocardiography.

Fifty consecutive patients undergoing coronary artery bypass grafting surgery were studied to evaluate the effect of intermittent anterograde cold cardioplegia (IACCH) and intermittent combined anterograde-retrograde cold cardioplegia (IRCCN) on left ventricular function using transesophageal echocardiography. Global function did not significantly change in both groups, but significantly more inotropes were required in IACCH. Newly developed abnormalities of regional wall motion after cardiopulmonary bypass, which were indicative of ischemic myocardium, were detected in the segments supplied by the right coronary artery in both groups (IACCH, 20%; IRCCN, 16%), by the left circumflex coronary artery only in IACCH (12%) and by the left anterior descending coronary artery only in IRCCN (12%). It is concluded that although global evaluation of left ventricular function did not show any significant change after IACCH and IRCCN under routine management, analysis of abnormalities of regional wall motion provided specific information. In both groups, complete protection of the myocardium was not achieved, and the characteristics of poorly protected areas were dependent on the difference in the two methods. Myocardium supplied by the right coronary artery seemed to be particularly vulnerable, and a special effort to protect these segments is mandatory for a successful outcome.

Aged↗
PubMed1993

Paratesticular leiomyosarcoma with elevated serum basic fetoprotein: a case report.

A case of paratesticular leiomyosarcoma associated with elevated serum basic fetoprotein level is reported. A 45-year-old male visited our hospital with a 6-month history of a painless left scrotal mass. High orchiectomy was performed under the diagnosis of left testicular tumor. Macroscopic and microscopic examination of the resected tumor demonstrated it to be paratesticular leiomyosarcoma. The value of serum basic fetoprotein, which is a newly identified oncofetal protein and useful as a tumor marker in some kinds of malignant neoplasm, was elevated before therapy, and its fluctuation was correlated with his clinical course. In spite of chemotherapy and resection of metastatic lesions in the lung, his condition gradually deteriorate with increasing serum basic fetoprotein level, and he died with carcinomatosis 2 years and 6 months after his admission. We suggest that basic fetoprotein is a useful tumor marker in this disease.

Antigens, Neoplasm↗
PubMed1993

Preparation of a human monoclonal antibody derived from cervical lymph nodes of a patient with anaplastic carcinoma of the thyroid.

An anaplastic carcinoma cell line, KOA-2, was established from a 59-year-old patient with anaplastic carcinoma of the thyroid who died only one month after diagnosis in association with rapid progress of her disease. A human monoclonal antibody, 3C5 (IgM), was generated by a fusion of human B lymphoblastoid cell line, HO-323, with lymphocytes from cervical lymph nodes of the patient, who had been treated with local immunotherapy. Immunocytostaining demonstrated that 3C5 reacted with KOA-2, and membrane immunofluorescence demonstrated that 3C5 reacted with cell membranes. Immunohistochemical staining studies demonstrated selective reaction of 3C5 with three malignant tumors, anaplastic carcinoma of the thyroid (2/4 sampled tested), papillary carcinoma of the thyroid (8/12), and breast cancer (2/6), but no reaction with specimens of benign thyroid disease or normal thyroid gland was demonstrated. The monoclonal antibody and the cell line established from one patient have potential use in the analysis of carcinogenesis and applications to therapy of anaplastic carcinoma of the thyroid.

Antibodies, Monoclonal↗
PubMed1992

Nonsense mutation of glucokinase gene in late-onset non-insulin-dependent diabetes mellitus.

A nonsense mutation at codon 186 in exon 5 of the gene for glucokinase, an enzyme important for glucose-induced insulin secretion, was identified in a Japanese patient with late-onset non-insulin-dependent diabetes mellitus (NIDDM). All affected members of her family were heterozygous for the mutation and had late-onset NIDDM or impaired glucose tolerance, whereas unaffected members showed normal glucose tolerance. The early insulin response to oral glucose was impaired in affected relatives, but was normal in those unaffected. These findings suggest that the glucokinase mutation raises the set-point of pancreatic beta cells for glucose-induced insulin secretion, leading to abnormal glucose tolerance in some patients with late-onset NIDDM.

Adolescent↗
PubMed1992

Characterization of GLUT3 protein expressed in Chinese hamster ovary cells.

We have expressed GLUT3 protein, an isoform of a facilitative glucose transporter, in Chinese hamster ovary cells by transfection of its cDNA using an expression vector. The expressed GLUT3 protein was detected by Western-blot analysis as a broad band of 45-65 kDa, indicating intensive glycosylation of the protein. The expressed GLUT3 protein was observed, by immunofluorescence staining, to be located mainly at the plasma membrane, and its expression was associated with a marked increase in glucose-transport activity. Kinetic analysis revealed that the Km value of GLUT3 protein for 3-O-methylglucose uptake was approx. 35% of that of GLUT1 protein, whereas the Km value of GLUT3 protein for 2-deoxy-D-glucose uptake was very similar to that of GLUT1 protein. The Vmax. value of GLUT3 protein for 3-O-methylglucose and 2-deoxyglucose uptake was approx. 20-50% of that of GLUT1 protein. GLUT3 protein was well photolabelled with [3H]cytochalasin B or a mannose derivative, 2-N-4-[3H](1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos -4-yloxy)-2- propylamine. Thus GLUT3 protein has very similar characteristics to GLUT1 protein including its subcellular localization, but exhibits lower Km and Vmax. values for 3-O-methylglucose uptake.

3-O-Methylglucose↗
PubMed1992

Replacement of intracellular C-terminal domain of GLUT1 glucose transporter with that of GLUT2 increases Vmax and Km of transport activity.

The intracellular C-terminal domain is diverse in size and amino acid sequence among facilitative glucose transporter isoforms. The characteristics of glucose transport are also divergent, and GLUT2 has far higher Km and Vmax values compared with GLUT1. To investigate the role of the intracellular C-terminal domain in glucose transport, we expressed in Chinese hamster ovary cells the mutated GLUT1 protein whose intracellular C-terminal domain was replaced with that of GLUT2 by means of engineering the chimeric cDNA. Cytochalasin B, for which GLUT2 protein has much lower affinity, bound to this chimeric protein in a fashion similar to GLUT1. In contrast, greater transport activity was observed in this chimeric glucose transporter compared with the wild-type GLUT1 at 10 mM 2-deoxy-D-glucose concentration. The kinetic studies on 2-deoxy-D-glucose uptake revealed a 3.8-fold increase in Km and a 4.3-fold increase in Vmax in this chimeric glucose transporter compared with the wild-type GLUT1. Thus, replacement of the intracellular C-terminal domain confers the GLUT2-like property on the glucose transporter. These results strongly suggest that the diversity of intracellular C-terminal domain contributes to the diversity of glucose transport characteristics among isoforms.

Amino Acid Sequence↗
PubMed1992

Expression and possible function of glucose transporter protein GLUT1 during preimplantation mouse development from oocytes to blastocysts.

A micro-Western analysis method both sensitive and quantitative enough to analyze oocytes and embryos is developed. GLUT1 protein is present in mouse oocytes and preimplantation embryos and levels are increased by fertilization and with time in ensuing embryonic development; the levels were 20-fold greater in blastocysts than in unfertilized oocytes. Similar increases were observed in glucose uptake by oocytes and embryos, suggesting that they may depend on GLUT1 expression. These results suggest that GLUT1 expression may explain a switch in substrate preference of the embryo from pyruvate to glucose during preimplantation development.

Animals↗
PubMed1992

Domains responsible for the differential targeting of glucose transporter isoforms.

Facilitative glucose transporter isoforms, GLUT1 and GLUT4, have different intracellular distributions despite their very similar structure. In insulin-responsive tissues such as adipose tissues and muscle, GLUT4 protein resides mainly in the intracellular region in a basal condition and is translocated to the plasma membrane upon stimulation of insulin. In contrast, GLUT1 protein was distributed about equally between plasma membranes and low density microsomal membranes in 3T3-L1 adipocytes. Furthermore, GLUT1 and GLUT4 were reported to be differentially targeted to the plasma membrane and intracellular region, respectively, when expressed in Chinese hamster ovary cells and HepG2 cells. To elucidate the differential intracellular targeting mechanisms, several chimeric glucose transporters in which portions of GLUT4 are replaced with corresponding portions of GLUT1 have been stably expressed in Chinese hamster ovary cells. Immunofluorescence and immunoelectron microscopy as well as measurement of glucose transport activity revealed that two domains of GLUT4, which are not the NH2- or COOH-terminal domain, determine its targeting to the intracellular vesicles. The first domain contains the consensus sequence of the leucine zipper structure, suggesting that a dimer-forming structure of the glucose transporter might be required for its proper targeting. The other domain contains 28 amino acids, nine of which are different between GLUT1 and GLUT4. Immunoelectron microscopy revealed that the chimeric transporters containing both of these two domains of GLUT1, only the first domain of GLUT1, and none of the domains, exhibited a different cellular distribution with approximately 65, 30, and 15% of the transporters apparently on the plasma membrane, respectively. The addition of insulin did not alter the apparent cellular distributions of these chimeric transporters. These domains would be specifically recognized by intracellular targeting mechanisms in Chinese hamster ovary cells.

Animals↗
PubMed1992

Gonadotropin-releasing hormone (GnRH) cells of the terminal nerve as a model neuromodulator system.

Modulation of ionic channel properties by neurotransmitters and hormones is called neuromodulation and may be the basis for many long-lasting changes in animal behavior, e.g. changes in the arousal or motivational states. Gonadotropin-releasing hormone (GnRH), originally identified as a hypophysiotropic hormone, is now believed to act also as a neuromodulator. From studies of electrical activities and morphology of terminal nerve cells (major source of GnRH) of a fish brain, a general hypothesis regarding modulator neurons is proposed; modulator neurons have endogenous oscillatory activities which vary according to the animal's hormonal or environmental conditions. These modulator neurons, in turn, regulate neuronal excitabilities in a wide variety of brain regions simultaneously via multiple axonal branches.

Animals↗
PubMed1992

Ultrastructural characterization of gonadotropin-releasing hormone (GnRH)-immunoreactive terminal nerve cells in the dwarf gourami.

Recently we have been studying gonadotropin-releasing hormone (GnRH) cells of the terminal nerve (TN) in the dwarf gourami, which may serve as a good model system for the study of neuromodulator functions. Here we report on the ultrastructural characterization of TN-GnRH cells using postembedding immunoelectron microscopy. The GnRH immunoreactivities could be demonstrated on dense-cored vesicles (DCVs) in cell bodies, fibers and varicosities. However, we could find no evidence of GnRH-immunoreactive synapses which are characterized by active zones. This may suggest that GnRH is released non-synaptically from DCV-containing fiber varicosities and that it exerts its modulatory action on GnRH receptors located on nearby as well as distant target neurons.

Animals↗
PubMed1992

Deletion of C-terminal 12 amino acids of GLUT1 protein does not abolish the transport activity.

We engineered the GLUT1 cDNA to delete C-terminal 12 amino acids of encoded GLUT1 protein. This mutated GLUT1 protein expressed in CHO cells by transfection of its cDNA was demonstrated to reside on the plasma membrane by cell surface labeling technique, and retain the transport activity, similar to that of the wild-type GLUT1. In addition, metabolic labeling of the intact cells with 35S indicated that the half-life of the mutated GLUT1 was not significantly different from that of the wild-type GLUT1. These results suggest that C-terminal 12 amino acids of GLUT1 are not important for the transport activity and the stability of the protein. Taken together with our previous results on the mutant without C-terminal 37 amino acids, the amino acids between the 37th and the 13th from the C-terminus appear to be essential for the transport activity.

Animals↗
PubMed1992

Glucose binding enhances the papain susceptibility of the intracellular loop of the GLUT1 glucose transporter.

Digestion of human GLUT1 protein in erythrocytes with 5 micrograms/ml papain for 5 min yielded several fragments. By using several site-specific antibodies, two of these fragments containing the intracellular loop domain between M6 and M7 were demonstrated to be further digested by a prolonged incubation with papain. The addition of 0.2 M D-glucose enhanced this digestion between M6 and M7 by approximately 3.5-fold, while the addition of 0.2 M D-sorbitol exhibited no effects. These results strongly suggest that D-glucose binding induces the conformational change of the intracellular loop domain between M6 and M7 of GLUT1 protein. Since the homology of the amino acid sequence was low in this intracellular domain among the five facilitative glucose transporter isoforms, this intracellular loop might contribute to the difference in their Km and Vmax values for glucose uptake.

Erythrocyte Membrane↗