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Biomedical subjects

M Nishihara

Publications and source records attributed to M Nishihara.

At least 127 records · Page 7Linked to original sources

Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine single-photon emission tomography in patients with Joseph disease.

Regional cerebral blood flow (rCBF) was measured in five Japanese patients who were clinically diagnosed as having Joseph disease, also called Machado-Joseph disease or Azorean disease, using N-isopropyl-p-[123I]iodoamphetamine (IMP) and single-photon emission tomography (SPECT). Cerebellar atrophy was evaluated by a five-step rating scale as defined on X-ray computed tomography (X-CT). Compared with ten age-matched normal controls (mean cerebellar CBF +/- SD: 66.9 +/- 6.6 ml/100 g/min), rCBF in patients with Joseph disease was significantly decreased in the cerebellum (mean +/- SD: 50.2 +/- 7.3 ml/100 g/min). No significant relationship, however, was found between the decrease in rCBF in the cerebellum and the degree of cerebellar atrophy on X-CT. rCBF in the cerebellum was minimally decreased in one patient who had severe cerebellar atrophy and in two patients with moderate atrophy. These data may support the findings that Purkinje cells in the cerebellum are almost normal in Joseph disease, and that the granular and molecular layers remain intact in spite of cortical atrophy of the cerebellum. It is concluded that [123I]-IMP SPET is able to identify pathological and metabolic changes in the cerebellum that do not appear on X-CT or magnetic resonance imaging, and thus is useful for the diagnosis of Joseph disease.

Adult↗

Attenuation of the expression of circadian rhythms by chronic outputs from the VMH in rats.

To alter neural networks in a restricted area of the brain, we previously developed the hydro-polymer gel (PG) implantation technique. In this study, we found that bilateral or unilateral injection of PG (1.6 microliters) into the ventromedial nucleus of the hypothalamus (VMH), contrary to injections into the preoptic area (POA) or posterior hypothalamic area (PHA), severely attenuated circadian changes of locomotor activity in blinded female rats. In addition, PG injection into the VMH also suppressed circadian changes in serum melatonin levels and induced persistent estrus. The effect of PG injection into the VMH on free-running rhythm was blocked by a complete cut around the VMH or a dorsal cut of the VMH but not by anterior or posterior cuts of the VMH. These results suggest that PG injection into the VMH induces some form of neural output via a dorsal route of the VMH that affects the generation of circadian activity rhythm.

Animals↗

Cessation of the electrical activity of gonadotropin-releasing hormone pulse generator during the steroid-induced surge of luteinizing hormone in the rat.

Neuronal activity in the mediobasal hypothalamus was recorded during the steroid-induced surge of luteinizing hormone (LH) in ovariectomized female rats by means of multiunit activity (MUA) recording techniques. The day of subcutaneous implantation of estradiol-containing silastic tubing, which was done at 12.00 h, was designated as day 1, and progesterone (1 mg) dissolved in sesame oil was injected at 12.00 h on day 5. The hypothalamic MUA and serum LH level were monitored between 10.00 and 20.00 h on days 1, 4 and 5. All 5 animals examined showed characteristic increases (volleys) in MUA associated with pulsatile LH secretion. After implantation of estradiol on day 1, gradual and significant decreases in the serum LH level and in MUA volley frequency were observed. In the afternoon of both days 4 and 5, an LH surge occurred, though it was much greater on day 5 than day 4 due to progesterone injection on day 5. However, neither MUA volleys nor considerable changes in baseline MUA were discernible throughout the recording period on days 4 and 5. More than 5 days after the removal of estradiol-containing tubing, MUA volleys were found to reappear in all the animals. These results suggest that estradiol has an inhibitory effect on gonadotropin-releasing hormone (GnRH) pulse generator activity, and that the GnRH pulse generator is not involved in inducing the LH surge in the rat.

Animals↗

Expression of phenotypic markers during regeneration of rat tracheal epithelium following mechanical injury.

We examined epithelial regeneration in mechanically injured rat trachea using phenotypic markers that identify unique differentiated stages of epithelial cells. Following a focal denuding wound, the cells from the adjacent nonwounded epithelium flattened and migrated into the wounded site during the first 12 h. At 24 h, these cells dedifferentiated into poorly differentiated (PD) cells that did not precisely resemble any of the mature tracheal cells. Proliferation of PD cells produced a multilayered epithelium by 48 h. Mitotic activity, measured as mitotic rate (MR) following a 6-h colchicine metaphase blockade, was high at 24 h (MR 23.4%) and 48 h (MR 24.0%). These PD cells expressed keratin 14 and Griffonia simplicifolia I-isolectin B4 (GSI-B4) lectin binding sites, which are specific for basal cells in normal epithelium but did not react with secretory or ciliated cell markers. At 72 h, MR fell to 1.8% (control MR 0.38%). The wound was covered with a pseudostratified epithelium; secretory cell markers were present at the apex of differentiating columnar cells, and a few preciliated cells expressing ciliated cell markers appeared. Basal cells also became distinctly recognizable and expressed keratin 14 and GSI-B4 binding sites. Newly appearing secretory or ciliated cells also expressed these markers but lost them gradually as they acquired new sets of specific markers. During epithelial regeneration after mechanical injury, "dedifferentiation," "proliferation," and "redifferentiation" of epithelial cells occurred, and the PD cell was pivotal in this process.

Animals↗

Changes in endogenous growth hormone secretion and onset of puberty in transgenic rats expressing human growth hormone gene.

A chimeric gene comprising murine whey acidic protein (mWAP) and human growth hormone (hGH) was used to produce transgenic rats that express hGH and secrete it into the blood. Two lines of transgenic rats carrying the mWAP/hGH construct were established: Line 1 was characterized by relatively high levels of serum hGH, and Line 2 had relatively low levels. The secretory profiles of rat GH (rGH) as well as hGH, the transgene product, were obtained in transgenic males and females of Line 2; both hGH and rGH serum levels were flattened with no episodic fluctuations, and the overall mean concentration of rGH was significantly lower than in normal littermates. Although the animals of Line 1 showed an accelerated increase in growth rate, those of Line 2 did not. Nevertheless, the onset of puberty in females, as assessed by vaginal opening and occurrence of first ovulation, advanced by 7-8 days in both Lines of animals. Accordingly, the body weight at puberty of Line 2 transgenic females was much lower than that of normal littermates, indicating that continuous hGH expression could induce precocious puberty without enhancing the growth rate.

Age Factors↗

[A clinical study of total cystectomy for patients with bladder cancer].

We assessed the treatment outcome of total cystectomy for 67 patients with bladder cancer treated at Asahikawa Medical College Hospital between 1977 and 1991. The analyses of cause-specific 5-year survival rates by pathological stage (pT) and grade revealed a lower survival rate for higher stage, higher grade and non-transitional cell carcinomas. The condition of lymph node metastases (pN) was also correlated to the survival rate. Significant differences were observed between the survival rates of the patients with pT < or = 2 and pT > or = 3, and the patients with pNO and pN > or = 2. The cancer deaths were mainly caused by distant metastases. Preoperative irradiation showed prognostic advantage in the patients who had acquired down-staging by this treatment, and postoperative systemic chemotherapy also improved the prognosis in the patients with pT > or = 3.

Adult↗

[Reducing cross-talk in electrooculograms made with several electrodes].

In order to discuss how to handle the contralateral effect (cross-talk) when taking an electrooculogram (EOG) with two or more electrodes, a forced duction test was used to detect cross-talk potentials. The cross-talk potentials originating from the left eye were measured at the right eye for 5 subjects when the left eye was adducted and abducted alternately with a suction contact lens while the right eye was kept fixed. The cross-talk potentials detected at the right eye did not depend on the electrode position, but the contralateral EOG potentials depended on the electrode position around the left eye. The cross-talk value is calculated as the gain, 20.log [(cross-talk potential)/(contralateral EOG potential)]. The denominator of this expression considerably affects the gain since the contralateral potential depends on the position of the electrode. We propose that the effect of the cross-talk on the potential between a pair of electrodes can be cancelled with the gain value (-15.0dB: the mean value for the 5 subjects) when the contralateral electrode is set 20 mm from the outer canthus.

Electrodes↗

[A study on evaluation of CBF measurement based on microsphere model with N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT--its correction with the value of PaCO2].

To evaluate the regional cerebral blood flow measurement with N-isopropyl-p-[123I]iodoamphetamine (IMP), we performed 123I-IMP SPECT and 133Xe inhalation method on 9 patients with mild cerebrovascular diseases and so on. A tracer dose of 123I-IMP (111 MBq) was injected i.v. and the data were obtained 15 min later. Regional CBF was measured by the microsphere model and arterial blood sampling method. However, mean cerebral blood flow values was not in agreement with both methods. We supposed the reason of the disagreement was due to the difference of PaCO2 when the studies were performed. Hence, CBF measurement with 123I-IMP was performed on the other patient's population with loading of hyperventilation before the IMP injection. Comparing with the control state with normal breathing, we calculated the rate of change of mean CBF between the state with normal breathing and the state with hyperventilation that was 1.02 ml/100 g/min/mmHg PaCO2. After the correction with the rate, we observed a much significant relation between the mean CBF measured with 123I-IMP SPECT and 133Xe inhalation method. When compared CBF values with loading studies or certain therapies, the correction of CBF with the rate of change of PaCO2 is one of the very important factors to be considered. Moreover, 133Xe inhalation method without the correction of PaCO2 can not be a golden standard method for rCBF measurement.

Adult↗

Interaction between excitatory and inhibitory amino acids in the ventromedial nucleus of the hypothalamus in inducing hyper-running.

We have previously shown that blockade of neurotransmission mediated by gamma-aminobutyric acid (GABA) in the ventromedial nucleus of the hypothalamus (VMH) by the microinjection of a GABAA receptor antagonist, bicuculline methiodide (BM), exclusively induced running activity in the rat. The purpose of the present study was to examine the role of receptors for excitatory amino acids (EAAs) in the VMH in inducing hyper-running and to clarify the interaction between GABA and EAAs in the VMH in controlling running activity. Although the injection of neither N-methyl-D-aspartate (NMDA) nor quisqualate into the VMH induced hyper-running, kainate (KA) produced running activity in a dose-dependent manner with similar features to that induced by BM. This effect of KA was blocked by a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX). GABA injected simultaneously with KA into the VMH failed to affect hyper-running induced by KA. On the other hand, DNQX significantly suppressed the BM-induced running activity. These results suggest that endogenous EAAs acting on the KA-type receptor in the VMH facilitates running activity and that the release of such EAAs from the nerve terminal is presynaptically inhibited by GABA.

Animals↗

Developmental expression of activin/inhibin beta A, beta B, and alpha subunits, and activin receptor-IIB genes in preimplantation mouse embryos.

We demonstrated previously that activin A released the two-cell block of mouse embryos cultured in vitro and stimulated early embryonic development. We then confirmed immunohistochemically the presence of the beta A, beta B, and alpha subunits in early embryos together with the oviductal epithelium facing those embryos. The results of in situ hybridization and reverse-transcription polymerase chain reaction here show the presence of mRNA transcripts for activin/inhibin beta A, beta B subunits in the ovary, oviduct, unfertilized egg, and embryo at the early preimplantation stage. However, the mRNA of the inhibin alpha subunit was not expressed in any of these. Considering our previous demonstration of the immunoreactive beta A, and beta B subunits of activin/inhibin polypeptides in the cytoplasm of 1- and 2-cell embryos, we suggest that activins appearing in the oviduct and in embryos are not only transferred from the follicular fluids, but produced by the oviduct, oocytes, and embryos themselves. Since the mRNA of the inhibin alpha subunit was absent at those stages, the beta A and beta B subunits may not exist as the inhibin molecule. The mRNA of activin receptor-IIB was detected in the ovary, in embryos at the 1-cell and the 8-cell/morula stages, and also in the unfertilized egg, although to a lesser extent, but not in the oviduct or in the 2-cell-stage embryo either in vivo or cultured in vitro. These results suggest that activin is physiologically involved in the process of early development of mouse embryos.

Activin Receptors↗

SPECT imaging in a case of primary respiratory tract amyloidosis.

SPECT findings in a very rare case of primary amyloidosis localized in the laryngotracheobronchial area are reported. SPECT using Tc-99m PYP revealed widespread uptake in the larynx and the entire tracheobronchial tree up to the subsegmental divisions; the areas corresponded to diffuse thickening and calcification of the walls on CT. SPECT using Ga-67 citrate also showed marked uptake in the same area, consistent with the findings shown by SPECT using Tc-99m PYP.

Adult↗

Identification, cDNA cloning, and gene expression of soluble starch synthase in rice (Oryza sativa L.) immature seeds.

Three forms of soluble starch synthase were resolved by anion-exchange chromatography of soluble extracts from immature rice (Oryza sativa L.) seeds, and each of these forms was further purified by affinity chromatograph. The 55-, 57-, and 57-kD proteins in the three preparations were identified as candidates for soluble starch synthase by western blot analysis using an antiserum against rice granule-bound starch synthase. It is interesting that the amino-terminal amino acid sequence was identical among the three proteins, except that the 55-kD protein lacked eight amino acids at the amino terminus. Thus, these three proteins are products of the same gene. The cDNA clones coding for this protein have been isolated from an immature rice seed library in lambda gt11 using synthetic oligonucleotides as probes. The deduced amino acid sequence of this protein contains a lysine-X-glycine-glycine consensus sequence for the ADP-glucose-binding site of starch and glycogen synthases. Therefore, we conclude that this protein corresponds to a form of soluble starch synthase in immature rice seeds. The precursor of the enzyme contains 626 amino acids, including a 113-residue transit peptide at the amino terminus. The mature form of soluble starch synthase shares a significant but low sequence identity with rice granule-bound starch synthase and Escherichia coli glycogen synthase. However, several regions, including the substrate-binding site, are highly conserved among these three enzymes. Blot hybridization analysis demonstrates that the gene encoding soluble starch synthase is a single-copy gene in the rice genome and is expressed in both leaves and immature seeds. These results suggest that soluble and granule-bound starch synthases play distinct roles in starch biosynthesis of plant.

Amino Acid Sequence↗

Ether polar lipids of methanogenic bacteria: structures, comparative aspects, and biosyntheses.

Complete structures of nearly 40 ether polar lipids from seven species of methanogens have been elucidated during the past 10 years. Three kinds of variations of core lipids, macrocyclic archaeol and two hydroxyarchaeols, were identified, in addition to the usual archaeol and caldarchaeol (for the nomenclature of archaeal [archaebacterial] ether lipids, see the text). Polar head groups of methanogen phospholipids include ethanolamine, serine, inositol, N-acetylglucosamine, dimethyl- and trimethylaminopentanetetrol, and glucosaminylinositol. Glucose is the sole hexose moiety of glycolipids in most methanogens, and galactose and mannose have been found in a few species. Methanogen lipids are characterized by their diversity in phosphate-containing polar head groups and core lipids, which in turn can be used for chemotaxonomy of methanogens. This was shown by preliminary simplified analyses of lipid component residues. Core lipid analysis by high-pressure liquid chromatography provides a method of determining the methanogenic biomass in natural samples. There has been significant progress in the biosynthetic studies of methanogen lipids in recent years. In vivo incorporation experiments have led to delineation of the outline of the synthetic route of the diphytanylglycerol ether core. The mechanisms of biosynthesis of tetraether lipids and various polar lipids, and cell-free systems of either lipid synthesis, however, remain to be elucidated. The significance and the origin of archaeal ether lipids is discussed in terms of the lipid composition of bacteria living in a wide variety of environments, the oxygen requirement for biosynthesis of hydrocarbon chains, and the physicochemical properties and functions of lipids as membrane constituents.

Euryarchaeota↗

Ovarian control of gonadotropin hormone-releasing hormone pulse generator activity in the rhesus monkey: duration of the associated hypothalamic signal.

The activity of the GnRH pulse generator in the rhesus monkey is associated with abrupt increases in multiunit electrical activity (MUA) volleys recorded from the mediobasal hypothalamus that precede each pulse of LH in the peripheral circulation. In long-term ovariectomized animals the duration of these MUA volleys is 10-25 min and consists of a brief initial 'overshoot' followed by a plateau phase that ends in a rapid decline to baseline activity. In intact monkeys, however, the MUA volley lasts only 1-3 min, a duration equivalent to the overshoot in ovariectomized animals. In addition, the maximal frequency of neuronal activity during each MUA volley is reduced in normal animals when compared to castrates. As shown in earlier studies, estradiol given to ovariectomized monkeys causes a reduction in the duration of MUA volleys to that characteristic of intact animals within 3-5 h. In contrast to this acute effect of estradiol, the increase in MUA volley duration following ovariectomy is a gradual phenomenon, 4-6 weeks being required to achieve the MUA volley duration observed in long-term ovariectomized monkeys. A similar slow time course was observed for the increase in maximal neuronal frequency during each MUA volley. This protracted effect of ovariectomy on MUA volley duration and firing rate may be the consequence of hypothalamic remodelling but this consideration must be tempered by the observation that estradiol reverses these phenomena within hours.

Animals↗

Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine and its redistribution in ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: The relation between the redistribution phenomenon and regional cerebral blood flow and its clinical significance were investigated in stroke patients. METHODS: Single-photon emission computed tomography studies using N-isopropyl-p-[123I]iodoamphetamine were performed on 16 patients (26 to 77 years old) with chronic infarction and 10 age-matched normal control subjects. Regional cerebral blood flow was quantitatively measured by a microsphere model, and the redistribution on delayed images was analyzed in ischemic lesions. RESULTS: Supratentorial mean cerebral blood flow and the ratio of gray matter to white matter in normal subjects were 52.7 +/- 5.0 mL/100 g per minute and 2.34, respectively. Low-activity areas of ischemic lesions on early images were classified into two abnormal zones, an infarct area and a peri-infarct area. These regions were characterized by regional blood flow averaging 9 to 20 mL/100 g per minute and 22 to 41 mL/100 g per minute, respectively. Redistribution, which was minimally present in the infarct area, was markedly enhanced in the peri-infarct area. After bypass surgery, we observed a significant increase of blood flow (+22%) in the peri-infarct area. CONCLUSIONS: The data indicate that the redistribution phenomenon depends on the maintenance of a minimal blood flow that would sustain cellular function and that this phenomenon is useful to evaluate bypass surgery in patients with chronic infarction.

Adult↗

Effect of calyculin-A, phosphatase inhibitor, on 20 alpha-hydroxysteroid dehydrogenase activity in rat luteal cell culture.

The effects of calyculin-A (CL-A), a phosphatase inhibitor, on 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity were studied in rat luteal cell cultures to examine whether protein phosphatases were involved in the regulation of the enzyme activity. Luteal cells were harvested from the rats on day 6 of pseudopregnancy. In the absence of prolactin (PRL), the stimulatory effect of CL-A (10(-9) M) on 20 alpha-HSD activity was observed during the first 3 h period of the culture, but was not discernible thereafter. Since the enzyme activity of luteal cells during pseudopregnancy is known to be suppressed by PRL, the results suggest that this effect of CL-A could be manifested only as long as the effect of endogenous PRL was remained. On the other hand, CL-A enhanced the 20 alpha-HSD activity of the cells cultured for 24 h, where a spontaneous increase in 20 alpha-HSD activity was blocked by exogenously supplementing the culture medium with PRL. These results suggest that a CL-A sensitive phosphatase(s) may be involved in the action of PRL in suppressing the increase in 20 alpha-HSD activity in rat luteal cells.

20-Hydroxysteroid Dehydrogenases↗

[A new graphic method for evaluation of distribution volume on N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT].

We developed a new graphic method using N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT of the brain, the graph on which all three parameters, cerebral blood flow, distribution volume (Vd) and delayed count to early count ratio (Delayed/Early ratio), were able to be evaluated simultaneously. The kinetics of 123I-IMP in the brain was analyzed by a 2-compartment model, and a standard input function was prepared by averaging the time activity curves of 123I-IMP in arterial blood on 6 patients with small cerebral infarction etc. including 2 normal controls. Being applied this method to the differential diagnosis between Parkinson's disease and progressive supranuclear palsy, we were able to differentiate both with a glance, because the distribution volume of the frontal lobe significantly decreased in Parkinson's disease (Mean +/- SD; 26 +/- 6 ml/g). This method was clinically useful. We think that the distribution volume of 123I-IMP may reflect its retention mechanism in the brain, and the values are related to amine, especially to dopamine receptors and its metabolism.

Aged↗

[A study of crossed cerebellar diaschisis on 123I-IMP SPECT images and its redistribution phenomenon].

Crossed cerebellar diaschisis (CCD) is interpreted as a functional deactivation, presumably caused by a loss of excitatory or inhibitory afferent inputs on the corticopontocerebellar pathway and others. A redistribution phenomenon (RD) is usually observed in the contralateral cerebellum with CCD on delayed images of 123I-IMP SPECT. This phenomenon was analyzed in a view point of rCBF measurement in 24 patients with brain tumor, infarction and so forth. Regional CBF was measured by the microsphere method with 123I-IMP and a delayed-to-early counts ratio (D/E ratio) was used. As a result, there was no relation between rCBF and the D/E ratio in the cerebellum, which means that RD is occurred by other factors except for rCBF in the cerebellum. Regional CBF and the D/E ratio in the contralateral and ipsilateral cerebellum was 46.3 ml/100 g/min, 1.01 and 57.0 ml/100 g/min, 0.86, respectively. These results mean that the high activity of IMP gradually decreased in the ipsilateral cerebellum, while, the low activity in the contralateral cerebellum was almost stable, and the difference of both activity reduced after 5 hours and RD was observed on the delayed image. The data indicate that retention mechanism of IMP and vascular permeability are not affected in the cerebellum with CCD.

Adolescent↗