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Biomedical subjects

M Nishihara

Publications and source records attributed to M Nishihara.

At least 145 records · Page 8Linked to original sources

Archaea contain a novel diether phosphoglycolipid with a polar head group identical to the conserved core of eucaryal glycosyl phosphatidylinositol.

The structure of a major ether polar lipid of the methanogenic archaeon Methanosarcina barkeri was identified as glucosaminyl archaetidylinositol. This lipid had archaeol (2,3-di-O-phytanyl-sn-glycerol) as a core lipid portion, and the polar head group consisted of 1 mol each of phosphate, myo-inositol and D-GlcN. The polar head group was identified by means of chemical degradations, phosphatidylinositol-specific phospholipase C treatment, permethylation analysis, and fast atom bombardment-mass spectrometry as glucosaminylinositol phosphate, which was linked to the glycerol backbone via a phosphodiester bond. The stereochemical configuration of the phospho-myo-inositol residue of glucosaminyl archaetidylinositol was determined to be 1-D-myo-inositol 1-phosphate by measuring optical rotation of phospho-myo-inositol prepared by nitrous acid deamination and alkaline hydrolysis from the lipid. 1H NMR of the intact lipid showed that GlcN was linked to C-6 position of myo-inositol as an alpha-anomer. It is, finally, concluded that the complete structure of this lipid is 2,3-di-O-phytanyl-sn-glycero-1-phospho- 1'[6'-O-(2"-amino-2"-deoxy-alpha-D-glucopyranosyl)]-1'-D-myo-inositol. This lipid has a hybrid nature of an archaeal feature in alkyl glycerol diether core portion and an eucaryal feature in the polar head group identical to the conserved core structure (GlcNp(alpha 1-6)-myo-inositol 1-phosphate) of glycosylated phosphatidylinositol which serves as a membrane protein anchor in eucaryal cells.

Carbohydrate Sequence↗

Hypothalamic electrical activity that relates to the pulsatile release of luteinizing hormone exhibits diurnal variation in ovariectomized rats.

The multiunit activity (MUA) was recorded in the arcuate nucleus-median eminence region in freely moving ovariectomized rats maintained under controlled lighting conditions (lights on 05.00-19.00 h) over a period of 24 h. The MUA of each rat had been confirmed to exhibit characteristic increases (volleys) in association with pulses of luteinizing hormone. In 6 MUAs examined, the frequency of MUA volleys was significantly greater in the dark period than in the light period, suggesting a diurnal variation in the release of luteinizing hormone-releasing hormone in the ovariectomized rat.

Animals↗

[Electrophysiological studies on the hypothalamic GnRH pulse generator].

Gonadal function in mammals depends on gonadotropins secreted from the pituitary gland in a pulsatile manner. This pulsatility is governed by the periodic activation of the hypothalamic GnRH pulse generator. By means of multiple unit activity (MUA) recording techniques, characteristics increases in the neuronal activity, each of which is associated with the initiation of pulsatile LH secretion, have been recorded in the medial basal hypothalamus of the monkey, rat and goat. An unambiguous unitary relationship between the increased electrical activity (volley) and the LH pulse under a variety of physiological and experimental conditions indicates that the MUA volleys represent the electrical activity of the GnRH pulse generator. Hypothalamic MUA recordings provide direct access to the central component of the neuroendocrine control system which governs reproductive function.

Animals↗

Dimethylsulfoxide enhances the absorption of chemotherapeutic drug instilled into the bladder.

We examined the effect of dimethylsulfoxide (DMSO) on the absorption of a chemotherapeutic drug instilled into the bladder. Female Wistar rats with bladder tumors underwent intravesical instillation of normal saline (S group) or 50% DMSO (D group) prior to the administration of pirarubicin (tetrahydropyranyl-Adriamycin). The absorption of pirarubicin was estimated histologically by observing its fluorescence. In the S group, fluorescence of pirarubicin was observed only in the epithelial layer of normal or hyperplastic regions and in the cells of superficial layers of the tumor. In the D group fluorescence was observed in the entire bladder wall of normal or hyperplastic regions and extended to deeper regions of the tumors than in the S group. These findings indicate enhancement of the absorption of pirarubicin by pretreatment with DMSO.

Absorption↗

Splenic macrophages enhance prolactin-induced progestin secretion from mature rat granulosa cells in vitro.

The effect of splenic macrophages on in vitro progestin secretion (the sum of the progesterone and 4-pregnen-20 alpha-ol-3-one concentrations in the medium) from mature rat granulosa cells was examined by means of co-culture techniques. When splenic macrophages (3.0 x 10(5) cells/ml) obtained from adult female rats on the evening of proestrus (1800 h) were added to granulosa cells (1.5 x 10(5) cells/ml) and co-cultured for 96 h in the absence of prolactin (PRL), progestin secretion from granulosa cells did not change. However, co-culture of granulosa cells with the macrophages in the presence of PRL (2 micrograms/ml) significantly enhanced progestin secretion after 48 h of culture. This stimulatory effect on progestin secretion was observed only when the number of macrophages added was more than twice the number of granulosa cells. On the other hand, splenic macrophages obtained on the evening of diestrus had no effect on progestin secretion from granulosa cells even in the presence of PRL. These results suggest that splenic macrophages can enhance PRL action so as to stimulate progestin secretion from granulosa cells and that this function of splenic macrophages varies during the estrous cycle.

Animals↗

Regional cerebral blood flow measured with I-123 IMP SPECT in a case of subcortical arteriosclerotic encephalopathy (Binswanger's disease).

N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT studies were performed on a 75-year-old patient who could be clinically classified as subcortical arteriosclerotic encephalopathy (Binswanger's disease). Regional cerebral blood flow (rCBF) was quantitatively measured by a microsphere model, and was diffusely decreased in the whole brain (mean rCBF: 36 ml/100 g/minute). After a ventriculoperitoneal shunt operation, his clinical symptoms were markedly improved, and the improvement was validated by a 32% increase of mean rCBF. However, MRI and CT images showed no significant interval changes before and after the shunt operation. Regional rCBF measurement by I-123 IMP SPECT should be performed and plays an important role in the evaluation of Binswanger's disease.

Aged↗

Splenic macrophages enhance prolactin and luteinizing hormone action in rat luteal cell cultures.

We have reported that splenic macrophages play a role in the regulation of progestin secretion in rats. In this study, splenic macrophages were obtained from cycling rats at different estrous cycle stages and co-cultured with luteal cells from mid-pseudopregnant rats in the absence/presence of prolactin (PRL) or luteinizing hormone (LH). The effect of macrophages on the luteotropic action of PRL and LH was evaluated with 2 parameters, i.e. an increase in total progestin output (progesterone plus 20 alpha-hydroxyprgn-4-en-one [20 alpha-OHP]), and an increase in the progesterone to 20 alpha-OHP (P/20 alpha-OHP) secretion ratio. Splenic macrophages obtained from proestrous or metestrous rats enhanced the PRL action to increase the P/20 alpha-OHP secretion ratio, but those from estrous or diestrous donors did not. Only macrophages from proestrous donors enhanced the PRL action to increase the total progestin output. In contrast, the LH action increasing the P/20 alpha-OHP secretion ratio was enhanced by splenic macrophages regardless of the donors' estrous cycle stages. The LH action increasing the total progestin output was enhanced only by proestrous or metestrous macrophages. Therefore, if luteal cells are co-cultured with proestrous macrophages, the luteotropic actions of PRL and LH can be fully expressed. These results indicate that splenic macrophages directly act on luteal cells and enhance the luteotropic action of PRL and LH, and that this function of splenic macrophages is modified somehow according to the donors' estrous cycle stages.

Animals↗

Hydroxyarchaetidylserine and hydroxyarchaetidyl-myo-inositol in Methanosarcina barkeri: polar lipids with a new ether core portion.

Lipids of the methanogenic archaebacterium, Methanosarcina barkeri were analyzed. The lipid content was 5.4% of dry cell and polar lipids comprised 87% of the total lipid. Polar lipids were separated into 14 spots by two-dimensional thin-layer chromatography. These were six phospholipids, seven aminophospholipids and one glycolipid, of which two phospholipids and two aminophospholipids were major constituents. After removal of polar head groups from total lipids, two kinds of glycerol diether core lipids were found. One was 2,3-di-O-phytanyl-sn-glycerol (archaeol) and the other 2-O-(3'-hydroxy-3', 7', 11', 15'-tetramethyl)hexadecyl-3-O-phytanyl-sn- glycerol (hydroxyarchaeol). Those structures were identified on the basis of chemical analysis, fast atom bombardment spectrometry, gas-liquid chromatography-mass spectrometry and 1H- and 13C-NMR spectrometry. The latter was a new core lipid which was different from hydroxyarchaeol of Methanothrix concilii. The hydroxyarchaeol core lipid comprised 60% of polar lipid in M. barkeri. The structures of core lipids are quite different from those previously reported by De Rosa et al. (Biochim, Biophys. Acta (1986) 875, 487-492) concerning M. barkeri lipids. The structures of two major polar lipids, both of which had hydroxyarchaeol as core proteins, were elucidated. These lipids were 2-O-(3'-hydroxy)phytanyl-3-O-phytanyl-sn-glycero-1-phosphoserine (hydroxyarchaetidylserine) and 2-O-(3'-hydroxy)phytanyl-3-O-phytanyl-sn- glycerol-phospho-myo-inositol (hydroxyarchaetidyl-myo-inositol). Archaetidylserine and archaetidylinositol, which had the usual archaeol core portion, were also present as minor polar lipids.

Archaea↗

Naloxone increases the frequency of the electrical activity of luteinizing hormone-releasing hormone pulse generator in long-term ovariectomized rats.

Characteristic increases in neuronal activity accompanied by the initiation of each luteinizing hormone (LH) pulse have been successfully recorded in freely moving ovariectomized rats by means of multiunit activity (MUA) recording techniques. In the present study, the effect of the opioid receptor antagonist naloxone on this neuronal activity was examined in rats ovariectomized for 6-10 weeks. Electrodes were chronically implanted into the medial basal hypothalamus (n = 78) or the medial preoptic area (n = 29). During the MUA recording, blood samples were taken through an indwelling atrial cannula at 3- or 6-min intervals to determine the serum LH concentration. Naloxone was administered intravenously for 1 h by either intermittent injection every 6 min (0.05 mg/kg, 10 times) or continuous infusion (0.1, 0.2 and 0.5 mg/kg/h). Explosive rises in the MUA (volleys) associated with the initiation of LH pulse were recorded in 7 animals in which the tips of electrodes were located in the arcuate nucleus-median eminence region. In 5 animals studied, the mean (+/- SE) duration and interval of the MUA volleys were 2.1 +/- 0.1 and 22.1 +/- 0.9 min, respectively. Naloxone given every 6 min significantly increased the duration to 2.6 +/- 0.1 min, and decreased the interval to 9.5 +/- 0.9 min. This naloxone treatment disturbed the clear pulsatility of LH secretion observed in the pretreatment control period. Analysis of the effects of naloxone infused at 3 different doses revealed that the facilitatory effects of naloxone on the duration and frequency of the MUA volleys were dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chronic recording of electrophysiological manifestation of the hypothalamic gonadotropin-releasing hormone pulse generator activity in the goat.

A characteristic increase in multiple-unit activity (MUA volley) synchronized with the pulsatile secretion of luteinizing hormone (LH) by the pituitary gland was recorded from electrodes chronically implanted in the medial basal hypothalamus of ovariectomized goats. The MUA volley always preceded the LH pulse, and the temporal correlation was consistent even when the pulse frequency was altered with an anesthetic or exogenous steroids. The electrophysiological manifestation of the hypothalamic 'pulse generator' governing the secretion of gonadotropin-releasing hormone was thus demonstrated in the ruminant.

Animals↗

Interactions between the noradrenergic and opioid peptidergic systems in controlling the electrical activity of luteinizing hormone-releasing hormone pulse generator in ovariectomized rats.

The effects of noradrenergic and opioid peptidergic receptor blockade, either alone or in combination, on the electrical activity of luteinizing hormone-releasing hormone (LHRH) pulse generator were studied in ovariectomized rats fitted with chronically implanted electrode arrays in the medial basal hypothalamus. Both alpha- and beta-adrenergic receptor antagonists, i.e. phenoxybenzamine (5 mg/kg i.v.) and propranolol (5 mg/kg i.v.), respectively, significantly increased the intervals between characteristic increases (volleys) in hypothalamic multiunit activity (MUA), which were associated with the initiation of LH pulses. In contrast to this, an opioid receptor antagonist naloxone (2 mg/kg i.v.) significantly decreased the intervals between the MUA volleys. Naloxone given after the injection of propranolol induced MUA volleys with a latency of a few minutes. However, when given after the injection of phenoxybenzamine, naloxone failed to induce such immediate MUA volleys. These changes in the intervals between the MUA volleys were faithfully reflected by the pulsatile LH secretion. These results suggest that norepinephrine facilitates LHRH pulse generator activity through both alpha- and beta-adrenergic-receptors, and that the action of opioid peptides on it requires an alpha-adrenergic receptor-mediated mechanism.

Animals↗

Sex differences in the basal firing rate and the responsiveness to opioid peptides of rat hippocampal neurons.

The basal firing rate and the responsiveness to dynorphin and leu-enkephalin of the neurons in the pyramidal cell layer of the hippocampus were studied in intact male, castrated male, castrated female, and castrated female rats injected s.c. with 20 micrograms estradiol benzoate (EB) for 3 days. Most of the neurons studied had low spontaneous firing rate (less than 5 Hz) and burst-like activity in all the groups. The basal firing rates in castrated males and females were not different from those in intact males and castrated females treated with EB, respectively. However, neurons in intact and castrated males had significantly higher firing rates than those in castrated females with and without EB treatment, respectively. When effective, both iontophoretically applied dynorphin and leu-enkephalin evoked predominantly excitatory responses. Either castration of males or EB treatment to castrated females did not affect the neuronal responsiveness to these peptides. On the other hand, the responsiveness of neurons to leu-enkephalin, but not to dynorphin, was significantly different between castrated male and female rats. These results suggest that sex steroids do not affect the basal firing rate as well as the responsiveness to opioid peptides of the pyramidal cells in the hippocampus in adult animals. However, sex differences in the basal firing rate and in the responsiveness to leu-enkephalin might account for the differences in hippocampal functions between male and female rats.

Action Potentials↗

[Combination of transarterial chemoembolization and endocrine therapy for liver metastases of breast cancer].

Nine patients with multiple metastases including liver from breast cancer were treated with transarterial chemoembolization through hepatic artery using 40-50 mg of 4'-epi-adriamycin and Lipiodol, followed by 800-1,200 mg/day of medroxyprogesterone acetate. Of 9 patients thus treated, there were 4 partial response (44%), 2 no change and 3 progressive disease. Duration of disease control ranged from 4 to 46 months (mean 24.5 months). Seven out of 9 patients died within 6 to 37 months (mean 15.3 months) after diagnosis of liver metastases. The 3- and 5-year survival rates were 45% and 11%, respectively. We conclude that this therapy is a useful treatment modality for controlling liver metastases of breast cancer.

Adult↗

Duration of phasic electrical activity of the hypothalamic gonadotropin-releasing hormone pulse generator and dynamics of luteinizing hormone pulses in the rhesus monkey.

The secretion of luteinizing hormone (LH) by the pituitary gland is a pulsatile phenomenon. In the rhesus monkey, each pulse of LH in the peripheral circulation is associated with a characteristic increase in multiunit electrical activity (MUA) recorded from the medial basal hypothalamus. These "volleys" of electrical activity initiate the release of gonadotropin-releasing hormone (GnRH) into the pituitary portal circulation from the terminals of neurosecretory cells. Their duration varies from 1-3 min in normal, adult intact females to 10-25 min in long-term ovariectomized monkeys. A variety of pharmacological interventions also modify volley duration. The purpose of this investigation was to determine the physiological significance of alterations in volley duration. The dynamics of LH pulses in ovariectomized animals were observed in a number of experimental circumstances in which MUA volley duration was reduced from a maximum of 23 min to a minimum of 4 min without significantly altering their frequency. The magnitude of each LH pulse was assessed by calculating the area under the curve delineated by the time course of LH above baseline. In eight experiments, a linear regression of these values on volley duration failed to reveal a significant correlation between MUA volley duration and the magnitude of LH pulses. These results suggest that all of the GnRH secreted per pulse is released at the onset of each MUA volley, the remainder of the increase in electrical activity having no further action on GnRH secretion, although effects on other systems cannot be excluded.

Activity Cycles↗

Corticotropin-releasing factor and gonadotropin-releasing hormone pulse generator activity in the rhesus monkey. Electrophysiological studies.

The effect of corticotropin-releasing factor (CRF) on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, the central neuronal system governing pulsatile pituitary luteinizing hormone (LH) secretion, was studied electro-physiologically in 6 ovariectomized rhesus monkeys bearing bilateral arrays of recording electrodes implanted in the mediobasal hypothalamus. 'Volleys' of increased multiunit activity (MUA) were recorded for 6-10 h in animals placed in primate chairs. The circulating concentrations of LH and cortisol were determined by radioimmunoassay in blood samples taken every 10 min for 3-4 h prior to the administration of CRF (200 micrograms, i.v.) and for 3-6 h thereafter. CRF resulted in a significant decrease in the frequency of pulse generator activity in 4 of 6 animals, a significant decrease in the duration of MUA volleys and a rise in circulating cortisol levels in all 6 monkeys. Treatment with metyrapone (30 mg/kg, i.m.), an inhibitor of adrenal steroidogenesis that prevented the CRF-induced rise in serum cortisol levels, did not reverse the inhibitory effects of CRF on the frequency or duration of MUA volleys. The opiate antagonist naloxone (0.8 mg/kg, i.v., 10 min prior to CRF followed by 0.8 mg/kg/h infusion) blocked the effects of CRF on MUA volley frequency in 2 of 3 animals, but failed to block the effect of CRF on MUA volley duration, suggesting that endogenous opioids may mediate the action of CRF on pulse generator frequency but not on duration.

Animals↗