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Biomedical subjects

H Nishino

Publications and source records attributed to H Nishino.

At least 19 recordsLinked to original sources

Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward a lesion area in the striatum.

Animals↗

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗

Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

INTRODUCTION: The predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established. METHODS: We followed 1,283 women aged 15-79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine. RESULTS: Premenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association. CONCLUSION: Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.

Adolescent↗

Bone mass and lifestyle related factors: a comparative study between Japanese and Inner Mongolian young premenopausal women.

The purpose of this study was to evaluate the ethnic difference in bone mass between Japanese and Inner Mongolian young premenopausal women and to assess the contribution of lifestyle related and anthropometric factors to bone mass. We studied 33 Japanese and 44 Inner Mongolian healthy young women, aged 20-34 years, in urban area. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) were measured at the calcaneus using quantitative ultrasound (QUS) analysis. Age at menarche, regularity of menstruation and lifestyle related factors were estimated by a self-reported questionnaire. There were no differences between the two groups in age, height, weight, BMI, regularity of menstruation, frequency of meat intake, frequency of yellow-green vegetable intake and exercise habit. Japanese women had significantly lower age at menarche and higher proportion of milk consumption habit at junior high school, senior school and present. Before adjustment, Japanese women had significantly higher SOS and SI than Inner Mongolian women. However, after adjustment for age at menarche and milk consumption habit at junior high school, both of which were significantly different between groups, no group-differences remained in either SOS or SI. These results suggest that the differences in age at menarche and milk consumption habit at junior high school, which relate to hormonal and nutritional status during puberty, may account for the differences in bone mass between Japanese and Inner Mongolian young women.

Adult↗

Argyrophilic dark neurons represent various states of neuronal damage in brain insults: some come to die and others survive.

Argyrophilic dark neurons (DNs) reflect the early histopathological state of neurons following various brain insults. We examined the fate of DNs, about to either die or recover, following two types (heavy and light damage) of brain insult. Wistar rats were injected ibotenic acid unilaterally into the hippocampal CA1 region (ibotenic acid [IA] injection) or were forced to swim (SWIM). Argyrophil III (DNs)-, activated caspase-3 immuno-, TUNEL- and hematoxylin-eosin (H-E)-staining and ultrastructural examinations were then performed. One to three hours after IA injection, typical DNs (argyrophilic both in somata and dendrites) with corkscrew-like dendrites were densely packed in the pyramidal cell layer of hippocampal CA1 around the injection site. After 12-24 h, DNs were argyrophilic only in the somata and proximal dendrites but absent in distal dendrites in the CA1 region. However, at this time typical DNs were found in remote areas. At 3 h, caspase-3 activation was detected at the injection site, which increased to a peak level after 12 h. Three to 7 days after injection, TUNEL positive cells were detected in the CA1 pyramidal cell layer. Immediately following SWIM, "brown" rather than "dark" neurons were detected in the various areas and most frequently in the CA1 pyramidal cell layer. No typical DNs were detected over the first 3 days. Some activation of caspase-3 was detected in a few CA3 pyramidal cells but no TUNEL-positive cells were detected. Ultrastructural examination revealed a diffuse distribution of aggregated silver particles in the dendrites and cytoplasm of pyramidal cells at the sites of IA injection. After SWIM, silver particles were detected mainly on mitochondria of affected cells. These data suggest that DNs provide a measure of neuronal damage: typically dark neurons with broad damage to the cytoskeleton of dendrites would die, while non-typical brown neurons, that may have a disturbance in mitochondria, predominantly survive.

Animals↗

Tracheoesophageal fistula secondary to chemotherapy for malignant B-cell lymphoma of the thyroid: successful surgical treatment with jejunal interposition and mesenteric patch.

We report a case of tracheoesophageal fistula (TEF) secondary to chemotherapy for primary thyroid lymphoma. A 65-year-old man with a short history of a rapidly enlarging neck mass was diagnosed as having thyroid lymphoma of diffuse, large B-cell type. The TEF occurred during the first course of chemotherapy including cyclophosphamide, doxorubicin, vincristine and prednisolone. After placing a feeding gastrostomy without oral intake, eight cycles of chemotherapy were completed and complete remission was achieved. Although the cervical mass disappeared, TEF and esophageal stenosis persisted. Total thyroidectomy and resection of the stenotic cervical esophagus were carried out followed by interposition of the revascularized jejunum and its mesenteric patch to cover the TEF. This seems to be the first report of a TEF caused by chemotherapy for primary thyroid B-cell lymphoma. A variety of treatments for TEF including simple closure, tracheal resection, colonic bypass and muscle flap have been reported with low success rates. Our procedure using a jejunal mesenteric patch seems to be unique and may be a new treatment strategy for TEF.

Aged↗

Diglucosyl-glycerolipids from the marine sponge-associated Bacillus pumilus strain AAS3: their production, enzymatic modification and properties.

The marine strain Bacillus pumilus strain AAS3, isolated from the Mediterranean sponge Acanthella acuta, produced a diglucosyl-glycerolipid, 1,2-O-diacyl-3-[beta-glucopyranosyl-(1-6)-beta-glucopyranosyl)]glycerol, with 14-methylhexadecanoic acid and 12-methyltetradecanoic acid as the main fatty acid moieties (GGL11). On a 30 l scale, using artificial seawater supplemented with glucose (20 g/l), yeast extract (10 g/l), and suitable nitrogen/phosphate sources, growth-associated glycoglycerolipid production reached its maximum yield of 90 mg/l after 11 h. Lipase-catalyzed modification of the native substance led to the deacylated parent compound (GG11), which could be reacylated using the same enzyme system to afford a new dipentenoyl-diglucosylglycerol (GGL12) as the major product upon addition of 4-pentenoic acid to the medium. GGL11 decreased the surface tension of water from 72 mN/m to 29 mN/m and the interfacial tension of the water/ n-hexadecane system from 44 to 5 mN/m. Anti-tumor-promoting studies on this class of diglucosyl glycerol products showed that the carbohydrate/glycerol backbone (GG11) has a more potent inhibitory activity than the acylated compounds. The diglucosyl-glycerol GG11 strongly inhibited growth of the tumor cell lines HM02 and Hep G2 (50% inhibition at approximately 1 microg/ml), while the glycerolipids GGL11 and GGL12 were less active or had no effect.

Animals↗

Crown gall -- a plant tumour with biological activities.

Petroleum ether, acetone, 80% MeOH and water extracts of crown gall, a plant tumour, obtained from Eucalyptus globulus tree were screened for cytotoxic, antioxidant, antiinflammatory, embryotoxic, antitumour-promoting and antimicrobial activities. In terms of bioactivity the 80% MeOH extract was most effective followed by the acetone extract. The petroleum ether extract showed weak to moderate cytotoxic activity in dose-dependent manner against PC12 cells, mouse L fibroblasts and 1321N1 glia cells, whereas the hydroalcohol extract had no or a weak cytotoxic effect. The 80% MeOH extract exhibited strong antioxidant activity. Based on the in vitro HET-CAM assay all the extracts were effective against inflammation. The extracts did not show any embryotoxic effect at the concentrations tested. Antitumour-promoting activity (100% inhibition; 100 microg/mL) was observed in the 80% MeOH and acetone extracts. In the antimicrobial screening all extracts displayed predominantly antifungal activity against Candida sp. The extracts also showed various levels of antibacterial activity against E. faecalis, Ps. aeruginosa, Bac. subtilis and Staph. epidermidis. From the results of the investigations it can be concluded that crown gall is a valuable plant tumour tissue having interesting biological activities.

Animals↗

Suicide gene therapy using AAV-HSVtk/ganciclovir in combination with irradiation results in regression of human head and neck cancer xenografts in nude mice.

The application of adeno-associated virus (AAV) vectors to cancers is limited by their low transduction efficiency. Previously, we reported that gamma-ray enhanced the second-strand synthesis, leading to the improvement of the transgene expression, and cytocidal effect of the herpes simplex virus type-1 thymidine kinase (HSVtk) and ganciclovir (GCV) system. In this study, we extended this in vitro findings to in vivo. First, the laryngeal cancer cell line (HEp-2) and HeLa were treated with AAVtk/GCV, the number of surviving cells was reduced as the concentration of GCV increased. Furthermore, the 4 Gy irradiation enhanced the killing effects of AAVtk/GCV by four-fold on HeLa cells and 15-fold on HEp-2 cells. Following the in vitro experiments, we evaluated the transgene expression and the antitumor activity of the AAV vectors in combination with gamma-ray in nude mice inoculated with HEp-2 subcutaneously. The LacZ expression was observed in the xenografted tumors and significantly increased by gamma-ray. The AAVtk/GCV system suppressed the tumors growth, and gamma-ray augmented the antitumor activity by five-fold. These findings suggest that the combination of AAVtk/GCV system with radiotherapy is significantly effective in the treatment of cancers and may lead to reduction of the potential toxicity of both AAVtk/GCV and gamma-ray.

Animals↗

Melatonin-secreting pineal gland: a novel tissue source for neural transplantation therapy in stroke.

Chronic systemic melatonin treatment attenuates abnormalities produced by occlusion of middle cerebral artery (MCA) in adult rats. Because the pineal gland secretes high levels of melatonin, we examined in the present study whether transplantation of pineal gland exerted similar protective effects in MCA-occluded adult rats. Animals underwent same-day MCA occlusion and either intrastriatal transplantation of pineal gland (harvested from 2-month-old rats) or vehicle infusion. Behavioral tests (from day of surgery to 3 days posttransplantation) revealed that transplanted stroke rats displayed significantly less motor asymmetrical behaviors than vehicle-infused stroke rats. Histological analysis at 3 days posttransplantation revealed that transplanted stroke rats had significantly smaller cerebral infarction than vehicle-infused rats. Additional experiments showed that pinealectomy affected transplantation outcome, in that transplantation of pineal gland only protected against stroke-induced deficits in stroke animals with intact pineal gland, but not in pinealectomized stroke rats. Interestingly, nonpinealectomized vehicle-infused stroke rats, as well as pinealectomized transplanted stroke rats, had significantly lower melatonin levels in the cerebrospinal fluid than nonpinealectomized transplanted stroke rats. We conclude that intracerebral transplantation of pineal gland, in the presence of host intact pineal gland, protected against stroke, possibly through secretion of melatonin.

Animals↗

Greater trunk muscle torque reduces postmenopausal bone loss at the spine independently of age, body size, and vitamin D receptor genotype in Japanese women.

Bone mineral density (BMD) is affected by muscle strength. Recently, vitamin D receptor (VDR) genotype was reported to affect muscle strength as well as BMD in Caucasian women. The aim of this study was to evaluate independent effects of muscle strength of the trunk on BMD at the spine and its change over time in Japanese women. We followed 119 healthy postmenopausal women for 4 years and determined the change in BMD at the spine by dual energy X-ray absorptiometry. Isometric peak torque and isokinetic concentric and eccentric peak torque of the trunk flexors and extensors were measured. The VDR genotype was determined by the PCR-RFLP method based on Apa I and Taq I endonuclease digestions defining the absence/existence of the restriction sites as A/a and T/t, respectively. The subjects were 60.1 +/- 6.6 years old, had 0.808 +/- 0.159 g/cm2 of BMD at baseline. The mean annual change in BMD (delta BMD) was -5.6 +/- 10.4 mg/cm2 during the follow-up period. The VDR genotype, defined by Taq I enzyme, significantly related to BMD at baseline and delta BMD showing that the subjects with genotype TT had the lowest BMD at baseline and lost bone most rapidly. However, its effect on muscle strength was not significant. All the trunk muscle strength indices showed significant positive effects on delta BMD, that is, the effects in increasing the gain and reducing the loss of BMD, after controlling for the effects of age, body size and the VDR genotype. The eccentric trunk extensor torque had a significant positive effect on delta BMD in a dose-dependent manner. The effect of this torque was the greatest among all the muscle indices. The net effect of the trunk extensor torque on delta BMD was greater than that of the VDR genotype. The trunk muscle strength was suggested to affect BMD change independently of age, body size, and the VDR genotype. Exercise programs to increase the strength of the trunk muscles would be beneficial for the prevention of osteoporosis regardless of the VDR genotypes.

Absorptiometry, Photon↗

Homozygous Machado-Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms.

A male patient carrying the homozygous gene for Machado-Joseph disease (MJD) presented at age 43 with sleep disturbances and psychiatric symptoms followed by ataxic speech and gait. A polysomnogram (PSG) showed decreased rates of sleep time and stage rapid eye movement (REM) and an increased rate of 'stage 1-REM with tonic EMG' (Tachibana et al., 1975); all compatible with REM sleep behaviour disorder (RBD). Molecular gene analysis at age 59 showed that the CAG repeat units in the MJD gene were 60 and 60, smaller than the reported lengths for homozygous MJD patients (63-70 and 66-72). In addition to sleep disturbances, in particular RBD, psychiatric symptoms may be important clinical features in both heterozygous and homozygous MJD.

Diagnosis, Differential↗

Cancer chemopreventive activity of naphthoquinones and their analogs from Avicennia plants.

As a part of screening studies for cancer chemopreventive agents (anti-tumor promoters), six natural and four synthetic naphthoquinones and five of their analogs were tested for their inhibitory activities against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Some of the 1,4-naphthoquinones and their analogs were found to show remarkably potent activities, without showing any cytotoxicity. 1,4-Furanonaphthoquinone (5) and its analog (9) isolated from Avicennia plants (Avicenniaceae), having an alcoholic OH group on the dihydrofuran-ring, displayed the most potent activity. Furthermore, avicenol-A (9) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The result of the present investigation indicated that some of these 1,4-naphthoquinones and their analogs might be valuable as potent cancer chemopreventive agents.

9,10-Dimethyl-1,2-benzanthracene↗

Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, ten flavonoid derivatives (1-10) synthesized from morin and quercetin were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these compounds, pentaallyl ethers (9, 10) showed significant inhibitory effects on EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. Further, quercetin pentaallyl ether (10) exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Animals↗

Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, from Polygonum lapathifolium.

To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.

Animals↗

Circadian rhythm of melatonin release in pineal gland culture: arg-vasopressin inhibits melatonin release.

The mammalian pineal gland is known to receive a noradrenergic sympathetic efferent signal from the suprachiasmatic nucleus (SCN) via the superior cervical ganglion. Arg-vasopressin (AVP) containing neurons in the SCN is one of the output paths of circadian information to the other brain areas. AVP release from the SCN is suppressed by melatonin. In turn, we determined the direct effect of AVP on melatonin release using pineal gland explant culture. AVP (1 microM) suppressed melatonin release. Noradrenaline stimulated melatonin release was attenuated by AVP. In turn, the expression of the melatonin synthesis enzyme arylalkylamine N-acetyltransferase mRNA in the rat SCN was reported. We measured melatonin content in the SCN in rats kept under the light-dark cycle and constant dim light. Melatonin in the SCN was higher during the dark period than that in the light. A similar tendency was also observed in the SCN of animals kept under a constant dim light. It was suggested that the reciprocal regulation of melatonin release and AVP release occurs in the SCN and pineal gland.

Animals↗

Anti-tumor promoting effects of multiflorane-type triterpenoids and cytotoxic activity of karounidiol against human cancer cell lines.

Forty-nine multiflorane-type triterpenoids consisting of 11 compounds isolated from the seeds of Trichosanthes kirilowii (Cucurbitaceae) and 38 of their derivatives have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in Raji cells as a primary screening test for anti-tumor promoters. All of the compounds tested showed an inhibitory effect against EBV-EA activation, and among which 43 were revealed to possess remarkable activity with potencies either comparable to or stronger than that of glycyrrhetic acid, a known natural anti-tumor promoter. Their structure-activity relationship is discussed. Evaluation of the cytotoxic activity of karounidiol (27) against human cancer cell lines exhibited cytotoxicity especially against a human renal cancer.

Anticarcinogenic Agents↗