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Biomedical subjects

K Murahashi

Publications and source records attributed to K Murahashi.

11 recordsLinked to original sources
PubMed1998

Excitatory amino acids act on the median eminence nerve terminals to induce gonadotropin-releasing hormone release in female rats.

The present study is designed to examine the terminal regulation of gonadotropin-releasing hormone (GnRH) release by excitatory amino acids in the median eminence of ovariectomized (OVX) rats. In in vitro experiments, median eminence tissues were superfused in the medium containing glutamate or excitatory amino acid agonists, such as N-methyl-d,l-aspartate or kainate. These drugs induced a Ca2+-dependent GnRH release from median eminence fragments. The agonists also stimulated GnRH release from superfused synaptosome prepared from the median eminence tissues in a Ca2+-dependent manner. In the immunocytochemical study, immunoreactivity for glutamate or its ionotropic receptor subtypes, such as NR1, GluR1, GluR2/3, GluR6/7, and KA2, was examined in the median eminence of OVX rats under electron microscopy. Immunoreactivities for glutamate or its receptor subtypes were observed on the nerve terminals, most of which were located in close proximity to the other nerve terminals without forming synaptic contacts. In addition, quite a few synaptic contacts which were immunopositive for GluR1, GluR2/3, KA2, or glutamate were found in this area. The present results indicate that excitatory amino acids stimulate GnRH release by acting at the nerve terminals of the median eminence in a Ca2+-dependent manner in the absence of gonadal steroid. The effect of excitatory amino acids in this area might be mediated by glutamate receptors mainly in nonsynaptic fashion, such as by volume transmission.

Animals↗
PubMed1998

TGF-beta1 produced by gastric cancer cells affects mesothelial cell morphology in peritoneal dissemination.

In vitro morphologic change of mesothelial cells was observed following the addition of serum-free conditioned medium (SF-CM) from peritoneal dissemination cell line OCUM-2MD3. The same morphologic change of mesothelial cells was observed following the addition of 10 ng/ml TGF-beta1, but not following the addition of b-FGF, IGF-I, VEGF or PDGF-AA. In the in vivo study, mesothelial cells of mice treated with SF-CM from OCUM-2MD3 and TGF- beta1 were separated from one another, resulting in exposure of the submesothelial connective tissue. The molecular size of the mesothelial morphology changing activity was estimated by running the SF-CM from OCUM-2MD3 through a gel filtration column TSK-gel G2000SW. The mesothelial morphology changing activity was recognized at positions equivalent of Mr 6, 500-30,000. 25 kDa TGF-beta1 was detected in the active fraction from the TSK-gel G2000SW column and the SF-CM of OCUM-2MD3 by Western blotting using a monoclonal antibody against TGF-beta1. These findings suggest that TGF-beta1 produced by gastric cancer cells changes the morphology of mesothelial cells and may thus be closely associated with peritoneal dissemination.

Animals↗
PubMed1998

Tranilast and cisplatin as an experimental combination therapy for scirrhous gastric cancer.

We examined the effect of Tranilast on the reduction of the administered dose of cisplatin using a scirrhous gastric cancer model. Scirrhous gastric cancer cell line, OCUM-2M, and gastric fibroblasts, NF-10, were used. The IC50 values of CDDP to OCUM-2M cells were decreased by Tranilast in vitro. The combination treatment with Tranilast and CDDP decreased the xenografted tumor size. The combination therapy decreased fibrosis and mitosis, and increased apoptosis. These findings suggest that Tranilast increased the CDDP response on scirrhous gastric cancer. The combination treatment with Tranilast and CDDP may be useful as a new therapy for scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗
PubMed1996

A rapid suppressive effect of estrogen in the paraventricular nucleus on pulsatile LH release in fasting-ovariectomized rats.

The paraventricular nucleus (PVN) and A2 are novel estrogen feedback sites where estrogen may modulate the neural response to adrenergic inputs during fasting. In the present study, the effects of local estradiol (E(2)) perfusion through a microdialysis probe placed in the PVN or A2 on pulsatile luteinizing hormone (LH) secretion and on norepinephrine (NE) release in the PVN were examined in 48-h fasting ovariectomized (OVX) rats to determine whether local estrogen administered in the PVN or A2 rapidly inhibits LH secretion during fasting and whether this inhibition is mediated by an increase of NE release in the PVN. Five days after ovariectomy, animals (n=5 per group) stereotaxically implanted with a guide cannula for microdialysis in the PVN (experiment 1) or both PVN and A2 (experiment 2) were deprived of food for 48 h. Blood samples and dialysates were then collected every 6 min for 3 h and every 12 min (experiment 1) or 20 min (experiment 2) for 3 h, respectively. The PVN or A2 was perfused with E(2) (5 ng/ml in artificial cerebrospinal fluid) through a microdialysis probe after the first hour of sampling. E(2) perfusion in the PVN caused a rapid and significant suppression of mean plasma LH levels and LH pulse frequency in fasting rats but no changes in unfasting animals. NE release in the PVN was not affected by the local E(2) perfusion of the PVN in either fasting or unfasting groups. This perfusion in A2, however, did not cause any apparent changes in plasma LH and perfusate NE levels in the PVN and A2. The present results indicate that estrogen feedback action at the PVN suppresses LH secretion rapidly during fasting and does not involve an increase of NE release in the PVN.

Animals↗
PubMed1996

Reduction of glucose availability suppresses pulsatile luteinizing hormone release in female and male rats.

Glucose availability controls reproductive activity through modulation of LH secretion. The aim of the present study was to determine whether the glucoprivic suppression is potentiated by gonadal steroids and if glucoprivic suppression of pulsatile LH release is sexually differentiated. Pulsatile LH secretion was examined in rats after peripheral (jugular) administration of the competitive inhibitor of glycolysis, 2-deoxyglucose (2DG). Fourteen days after gonadectomy, blood samples were collected every 6 min for 3 h. One hour after the onset of sampling, 2DG was administered peripherally (200, 400, or 800 mg/kg BW, iv), and food intake was determined after 2DG injection in gonadectomized males and females in the presence or absence of sex steroids (testosterone or estradiol). To test the ability of the pituitary to produce LH under glucoprivic conditions, LHRH was injected every 30 min for 2.5 h in ovariectomized (OVX) rats 30 min after treatment with 400 mg/kg 2DG. At all peripheral doses of 2DG in females and at the middle and high doses of 2DG in males, mean plasma LH and LH pulse frequency decreased (P < 0.05) in the presence of steroids. However, in the absence of sex steroids, the lowest dose in females and the middle dose in males were not effective. Pituitary function appeared normal, because increases in mean plasma LH in response to the exogenous LHRH occurred in OVX rats treated with the middle dose of 2DG. Food intake significantly (P < 0.05) increased after 2DG injection in all groups except estrogen-treated OVX females at the low and high doses of 2DG. These findings suggest that glucoprivic suppression of LH pulses is potentiated by gonadal steroids in both sexes. Moreover, the hypothalamo-hypophyseal axis of the female rat seems to be more sensitive to the decreased glucose availability induced by 2DG than that of the male.

Animals↗
PubMed1996

Suppression of luteinizing hormone pulses by restriction of glucose availability is mediated by sensors in the brain stem.

The availability of metabolic fuels such as glucose is known to influence reproductive function. Peripheral administration of 2-deoxyglucose (2DG), a competitive inhibitor of glycolysis, inhibits pulsatile LH secretion in the rat and growth-retarded lamb. We hypothesized that such glucoprivic suppression of LH secretion is mediated by the lower brain stem, because studies of both ingestive and reproductive behavior implicate lower brain stem structures, such as the area postrema, as a site that is sensitive to glucose availability. In the present study, the effect of a 2DG infusion, targeted to the fourth ventricle, on pulsatile LH secretion was examined in male rats. The males were castrated or castrated and immediately implanted with testosterone. Blood samples were collected through an indwelling atrial cannula every 6 min for 4 h for LH determination. After the first hour of blood sampling, 2DG (4 or 40 mg/kg) was infused into the fourth ventricle at a flow rate of 0.2 microliter/min through a cannula that had been stereotaxically implanted 1 week before sampling. The high dose of 2DG (40 mg/kg), but not the low dose (4 mg/kg), suppressed pulsatile LH secretion and increased food intake in both castrated and testosterone-treated castrated rats. LH secretion and food intake were not affected by the infusion of xylose (40 mg/kg) as an isoosmotic control. The site specificity of the 2DG treatment was confirmed by histological examination after an isovolumetric infusion of dye (0.2 microliter/min). These results suggest that glucose availability could influence LH secretion as well as feeding through a central sensor in the lower brain stem and are consistent with the idea that the area postrema might be an important glucosensor involved in the modulation of LH secretion.

Animals↗
PubMed1996

Paraventricular norepinephrine release mediates glucoprivic suppression of pulsatile luteinizing hormone secretion.

Restriction of glucose availability by 2-deoxyglucose (2DG) suppresses pulsatile LH release. The aim of the present study was to determine whether norepinephrine (NE) release in the paraventricular nucleus (PVN) is involved in the glucoprivic suppression of LH secretion in ovariectomized rats. Twelve days after ovariectomy, animals were stereotaxically implanted with a guide cannula for microdialysis in the PVN. Two days later, the PVN was perfused continuously with Ringer's solution or Ringer's solution containing a catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine (100 microM), through a microdialysis probe inserted in the guide cannula 2 h before the beginning of sampling, which lasted 3 h. Blood samples were collected every 6 min through an atrial cannula, and dialysates were collected every 20 min. One hour after the beginning of sampling, 2DG (400 mg/kg BW) was administered iv through the atrial cannula. Paraventricular NE levels significantly increased immediately after 2DG injection (P < 0.05), and both mean LH concentrations and the frequency of LH pulses decreased. By contrast, when alpha-methyl-p-tyrosine was administered into the PVN, 2DG did not produce an increase in paraventricular NE, and no depression of LH secretion occurred. These results suggest that the PVN mediates the glucoprivic suppression of LH pulses via the release of NE.

Animals↗
PubMed1987

Bilateral simultaneous sudden deafness.

Although sudden deafness has many causes, it is often a sensorineural hearing loss with an abrupt onset and unknown origin. The majority of these latter cases are unilateral in their occurrences, while bilateral simultaneous involvement is rarely seen. During the past 13 years, we have treated 997 patients with sudden deafness. All patients were seen at our university hospital within 2 weeks after the onset of their hearing losses and were observed until the hearing level was fixed. Among them, 10 patients were found to have bilateral simultaneous onsets. The average age and the incidence of vestibular symptoms were similar to those with unilateral deafness. The hearing recovery was much better in the ear with the lesser deafness. No improvement was observed on the side with no sound perception. Those patients in whom common cold and fever seemed to trigger the onset of deafness were also noted to have high viral antibody titers, and were more commonly seen than were those cases with unilateral deafness.

Adult↗
PubMed1986

A comparative study of mumps deafness and idiopathic profound sudden deafness.

We performed a 10-year comparative study on 95 cases (98 ears) of mumps deafness and 97 cases (97 ears) of profound sudden deafness and found the following results. The age of onset of deafness was less than 9 years in the majority of patients with mumps deafness, while it was frequently 30-50 years in those patients with sudden deafness. Among these latter patients, no cases occurred under 9 years of age. The incidence of tinnitus and vestibular symptoms was more frequent in the patients with sudden deafness, but no significant difference was noted in cases over 10 years of age. When determining prognosis, no cases of hearing improvement were encountered in mumps deafness, while about 70% of sudden deafness showed improvement.

Adolescent↗
PubMed1983

Prognosis and pathogenesis of sudden deafness with scaling out.

Recovery of hearing in sudden deafness is said to be such that the severer the hearing loss and the longer the period from the disease onset to the start of treatment, the poorer the recovery of hearing. However, the prognosis of the so-called scaling out cases has not yet been fully studied. We have therefore studied 96 patients with severest sudden deafness who consulted us within 14 days after disease onset and who had scaling out in all the frequencies. We evaluated the extent to which recovery of hearing could be expected and whether any characteristics are seen in pathogenesis, etc. The results showed that there was no patient who experienced complete recovery, even when treatment was started as early as within 4 days. Recovery of hearing was better in low frequencies than in high frequencies. The site of the lesion was the inner ear in many cases, and some had retrocochlear lesions. Concerning pathogenesis, we think the difference in degree of lesion should be considered important, rather than there may be a substantial difference, compared to that of slight deafness.

Adolescent↗