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Biomedical subjects

Shigenobu Kanba

Publications and source records attributed to Shigenobu Kanba.

At least 37 records · Page 2Linked to original sources
PubMed2005

Aconiti tuber increases plasma nitrite and nitrate levels in humans.

Some herbal medicines, including Aconiti tuber (Aconitum carmichaeli Debeaux, Ranunculaceae), have been recognized as being effective for the treatment of a "peripheral uncomfortable feeling of cold (hie)". We hypothesized that these compounds affect peripheral vascular function via the nitric oxide (NO) system, which leads to recovery from "hie". To answer this question, we investigated Aconiti tuber-induced changes in plasma levels of nitrite (p-NO2-) and nitrate (p-NO3-), final nitric oxide-oxidation products measurable in vivo. After written informed consent was obtained, patients suffering from "hie" were treated with several kinds of kampo (Japanese traditional herbal medicine), selected on the basis of traditional theory. Twenty-four patients took kampo formulas, some included Aconiti tuber (n=11; A-group) and others did not (n=13; C-group), for 4 weeks. p-NO2- and p-NO3- levels were measured before the start and after 4 weeks of treatment. In the A-group, the p-NO2- plus p-NO3- (p-NOx) level was significantly increased at 4 weeks (p=0.04), while that of the C-group was not. There was a statistically significant increase in the p-NOx level of the A-group as compared to the C-group (d.f.=1,22, F=9.38, p=0.006). The results suggest that Aconiti tuber may increase NO production in humans.

Aconitum↗
PubMed2005

Functional characterization of mismatch negativity to a visual stimulus.

OBJECTIVE: To record mismatch negativity (MMN) to a visual stimulus fulfilling similar criteria to those of auditory MMN (A-MMN). METHODS: Twelve normal adults were instructed to simultaneously listen to a story and to pay attention to a visual target. Three windmill patterns that differed in the number of vanes (standard, deviant, or target) were used as visual stimuli, and were randomly presented. To ensure endogeneity, standard and deviant stimuli were alternated. To vary differences between frequent (standard) and infrequent (deviant) stimuli, deviants were changed by modulating the number of vanes. To examine effects of physical features of the target stimulus on changes in detection, two target conditions were used. The deviant-related component (DRC) was obtained by subtracting event-related potentials (ERPs) to the deviant stimulus from those to the standard stimulus. RESULTS: Seven subjects completed all phases of the experiment. Behavioral performances indicated that subjects' attention was directed by auditory context and identification of the target stimulus. Visual DRC appeared 150-300 ms after stimulus onset, and consisted of an early (DRN1) and a late (DRN2) component. Magnitude of deviancy from standard stimulus significantly influenced latency of DRN2 but not its magnitude, while changes in target stimulus affected latencies of both DRN1 and DRN2. CONCLUSIONS: Our DRCs satisfied criteria for A-MMN. In contrast to A-MMN, only latency of the DRC was associated with visual sensory discrimination and attentional reorienting. SIGNIFICANCE: It is possible to record valid MMN to a visual stimulus, which allows the study of preattentive visual information processing.

Adult↗
PubMed2005

Amyloid-beta fibril formation is not necessarily required for microglial activation by the peptides.

There is increasing evidence that microglial activation has pathogenic influence on Alzheimer's disease. According to in vitro studies, microglia activated by amyloid-beta (Abeta) peptides have been reported to damage or kill neurons by the release of neurotoxic molecules such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, nitric oxide or reactive oxygen species. Although the relationship between the aggregational state of Abeta peptides and their neurotoxic activities has been well investigated, little is known about the relationship between the aggregational state of Abeta peptides and their ability to induce microglial activation. In the present study, we thus performed both structural and biochemical studies to clarify the relationship between the aggregational state of Abeta peptides and their ability to activate microglia. Our results have shown that, in the presence of interferon-gamma, the Abeta25-35(M(35)Nle) peptide had almost the same potency of activating microglia and producing TNF-alpha as the Abeta25-35 peptide on both protein and mRNA levels, in spite of the fact that former peptide represented much less amyloid fibril formation than the latter in a thioflavine-T fluorometric assay. These results suggest that Abeta fibril formation is not necessarily required for microglial activation by the peptides.

Alzheimer Disease↗
PubMed2005

Ginseng enhances contextual fear conditioning and neurogenesis in rats.

Panax Ginseng is a commonly used galenical known to have an enhancing effect on learning. Neurogenesis in the hippocampus has been shown to be necessary for hippocampus/amygdala-dependent learning tasks. To investigate the role of Ginseng in neurogenesis and learning of rats, we administered both Ginseng and BrdU for five consecutive days. As a result, Ginseng increased the number of BrdU-positive cells in the dentate gyrus in a dose-dependent manner. Further, we administered one dose of BrdU after Ginseng treatment for five consecutive days, and the number of BrdU-positive cells did not increase significantly. However, when one dose of BrdU was given 1 day before the following five consecutive days of Ginseng treatment, the number of BrdU-positive cells markedly increased in the hippocampus. Therefore, it is likely that Ginseng enhances not proliferation but survival of newly generated neurons in the hippocampus. Second, we administered both Ginseng and BrdU to rats for five consecutive days. One day after the last Ginseng and BrdU co-administration, contextual fear conditioning (CFC) was conducted. Ginseng in a dose-dependent manner increased the % freezing time and the number of BrdU-positive cells in the dentate gyrus of rats that received CFC. Thus, an increase in CFC-related neurogenesis may be one mechanism of Ginseng's properties to enhance learning ability.

Analysis of Variance↗
PubMed2005

Effectiveness of herbal medicine (Rokumigan and Hachimijiogan) for fatigue or loss of energy in patients with partial remitted major depressive disorder.

Some patients with major depressive disorder (MDD) do not show remission of their depressive symptomatology. We investigated the efficacy of Rokumigan (TJ-87) and Hachimijiogan (TJ-7) in 20 patients with prolonged partial remitted MDD associated with fatigue or loss of energy. In these 20 patients, TJ-7 or TJ-87 was added to the previous regimen for 4 weeks. Six patients were 'much improved', six were 'minimally improved' (responders), and eight showed 'no change' (non-responders), on the Clinical Global Impression Global Improvement scale. All responders had Shofuku-fujin (tenderness or weakness of the lower abdomen). In conclusion, we experienced 12 outpatients with prolonged partial remitted MDD with fatigue or loss of energy, which was successfully treated with TJ-87 or TJ-7.

Adult↗
PubMed2004

Deficiency of theory of mind in patients with remitted mood disorder.

BACKGROUND: Recent researches on theory of mind (ToM) in patients with mood disorders have revealed deficits of ToM ability during episodes. In this study, we aimed to test ToM ability among patients with unipolar or bipolar depression currently in remission. METHODS: ToM ability and IQ obtained by Wechsler Adult Intelligence Scale-Revised (WAIS-R) were evaluated in 50 patients with remitted depression, who met the criteria of mood disorders of DSM-IV, and 50 matched healthy controls. RESULTS: The patients with mood disorders showed statistically significant impairment in a second-order false question (Fisher's Exact Test p < 0.0001). No significant difference was shown in the other three areas of ToM between the patients and the controls. In addition, no correlation of the four areas of ToM with IQ obtained by WAIS-R was found. LIMITATIONS: The relation of ToM deficit to other specific cognitive impairment was not examined. CONCLUSIONS: Our results suggest that depressive patients in symptomatic remission have a lower ability of second-order false belief. The ToM impairment suggests a decline of skillful social relationships. Evaluation of ToM ability in depressive patients in remission may be useful to provide treatment for better social adjustment.

Adolescent↗
PubMed2004

A selective increase in phosphorylation of cyclic AMP response element-binding protein in hippocampal CA1 region of male, but not female, rats following contextual fear and passive avoidance conditioning.

Cyclic AMP response element-binding protein (CREB), a transcription factor on which multiple signal transduction pathways converge, has been implicated in long-term memory. We examined whether the sex difference in the performance of contextual fear or passive avoidance conditioning is associated with a change in the activation of CREB in the hippocampus, a neural structure important for long-term memory. The activation of CREB in different subregions within the hippocampus in male and female rats was determined immunohistochemically with an antibody that specifically recognizes the phosphorylated form of CREB (pCREB). With respect to the freezing time in contextual fear conditioning and the step-through latency in passive avoidance conditioning, male rats exhibited better performance than female rats. Phosphorylation of CREB (% pCREB) as revealed by the ratio of the pCREB-immunoreactive (pCREB-ir) cell number to the CREB-immunoreactive cell number was increased in the CA1 region, but not in CA3, CA4, or in the dentate gyrus following training for both types of conditioning in males. In females, such an increase in % pCREB was not found in any hippocampal subregion at any time after conditioning or by increasing the intensity of foot shock. Orchidectomy in males did not alter either the performance of contextual conditioning or conditioning-induced CREB phosphorylation in CA1. The close relationship between behavioral performance and CREB phosphorylation in the CA1 region suggests that hippocampal CREB is involved in the sex difference in some forms of learning and memory.

Animals↗
PubMed2004

Eating disorders with binge-eating behaviour are associated with the s allele of the 3'-UTR VNTR polymorphism of the dopamine transporter gene.

OBJECTIVE: The dopaminergic system is associated with feelings of pleasure and reward and with positive hedonic processes related to food, sexual activity and certain substances. Because it is recognized that patients who have eating disorders with binge-eating behaviour have a high comorbidity of substance dependence, we examined the association between the variable number of tandem repeats (VNTR) polymorphism in the 3; untranslated region of the dopamine transporter gene (DAT1) and eating disorders with binge-eating behaviour. METHODS: The subjects were 90 female Japanese patients with eating disorders diagnosed using DSM-IV; they were compared with 115 healthy female controls. Genomic DNA was extracted from whole blood, and standard polymerase chain reaction testing was performed. We compared the frequencies of a short allele (7 or 9 repeats) and a long allele (10 or 11 repeats) in both groups. RESULTS: In the group who had an eating disorder with binge-eating behaviour, the frequency of a short allele was significantly higher compared with the control group. CONCLUSION: It seems plausible that the association between the DAT1 VNTR and binge-eating behaviour indicates that dysregulation of dopamine reuptake may act as a common pathophysiologic mechanism in eating disorders with binge-eating behaviour and in disorders related to substance use.

Adolescent↗
PubMed2003

Temporal changes in the expression of brain-derived neurotrophic factor mRNA in the ventromedial nucleus of the hypothalamus of the developing rat brain.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is important for the growth, differentiation, and survival of neurons during development. We have performed a detailed mapping of BDNF mRNA in the neonatal rat brain using a quantitative in situ hybridization technique. At postnatal day (PND) 4, hypothalamic structures showed only modest expression of BDNF mRNA, with the exception of the ventromedial nucleus (VMN), where expression was higher than that detected in the hippocampus. Abundant BDNF mRNA was also found in the bed nucleus of the anterior commissure, retrosplenial granular cortex, and the posteroventral part of the medial amygdaloid nucleus. Messenger RNAs encoding other neurotrophins, including nerve growth factor (NGF) and neurotrophin-3 (NT-3) and the BDNF receptor trkB, were not selectively localized in neonatal VMN. During subsequent developmental stages, BDNF mRNA expression in the VMN changed dynamically, peaking at PND 4 and falling to minimal levels in the adult brain. In contrast, the low levels of BDNF mRNA observed in the CA3 region of the hippocampus increased to adult levels following PND 10. As the VMN undergoes sexual differentiation, we compared BDNF, NGF, NT-3, and trkB mRNA expression in the VMN in males and females at embryonic day 20 and PND 4, but found no differences between them. These results suggest that localized and high level expression of BDNF mRNA in the neonatal VMN plays an important role in its neural organization and functional development.

Aging↗
PubMed2003

No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET.

The human serotonin transporter (5-HTT) gene has a polymorphism in the 5'-flanking promoter region that is called the serotonin transporter gene-linked polymorphic region (5-HTTLPR). In lymphoblast cell lines, the promoter activity of the 5-HTT gene is dependent on 5-HTTLPR allelic variants. The transcriptional activity of the l allele was more than twice as high as that of the s allele. The s allele is considered to be associated with mood disorders and anxiety-related personality traits. To evaluate the functional differences of 5-HTTLPR in the brain in vivo, we examined the allelic variations of 5-HTTLPR and measured 5-HTT binding in the living human brain using positron emission tomography (PET) with C(11)-labeled trans-1, 2, 4, 5, 6, 10-beta-hexahydro-6-[4-(methylthio) phenyl]pyrrolo[2,1-a]isoquinoline (McN5652) as a ligand. Twenty-seven healthy male subjects participated in this study. Although the human lymphoblast cells with the l/l genotype was reported to produce higher concentrations of both mRNA and protein of 5-HTT than those with the l/s or s/s genotype in a human lymphoblast in vitro study, 5-HTT binding in vivo was not significantly different among subjects with the three genotypes (l/l: 0.842 +/- 0.184, l/s: 0.708 +/- 0.118, s/s: 0.825 +/- 0.209). In conclusion, this study does not support the assumption that the genotype-dependent differences of 5-HTTLPR directly contributes to the regulation of the 5-HTT binding site in the living human brain.

Adult↗
PubMed2003

Nitric oxide induced heat shock protein 70 mRNA in rat hypothalamus during acute restraint stress under sucrose diet.

1. Sucrose feeding increases the level of stress-induced heat shock protein 70 mRNA in the rat hypothalamus. However, the mechanism by which a sucrose diet induces mRNA remains unclear. The issues investigated in this study were (1) whether a sucrose diet affects nitric oxide production in the hypothalamus, and (2) whether nitric oxide mediates the sucrose and stress-induced elevation of heat shock protein 70 mRNA. 2. To address the first question, we measured the level of nitrate, a final nitric-oxide-oxidation product measurable in vivo, using a microdialysis method. To address the second question, we administered a nitric oxide synthase inhibitor. NG-nitro-L-arginine methyl ester, prior to stress, then measured the mRNA level of heat shock protein 70 by the reverse transcription-competitive polymerase chain reaction method. 3. After the initiation of restraint stress, rats fed a sucrose-containing diet, unlike those fed standard chow, displayed a transient nitrate elevation. This nitrate elevation was attenuated by pretreatment with NG-nitro-L-arginine methyl ester. The mRNA level increases in rats fed a sucrose diet were dose-dependently attenuated by NG-nitro-L-arginine methyl ester. 4. These data suggest that a sucrose diet induces heat shock protein 70 under stress by enhancing nitric oxide production in the hypothalamus.

Animals↗
PubMed2003

Long-term imipramine treatment increases nitrate levels in the rat hypothalamus.

1. Animal experiments have shown nitric oxide synthase inhibitors to have antidepressant-like properties. However, the effects of clinically available antidepressants on nitric oxide production in the brain remain unclear. In the present study, we examined whether imipramine, a conventional antidepressant, changes the levels of type-II nitric oxide synthase mRNA and nitrate, a final nitric-oxide-oxidation product measurable in vivo, in the rat brain. 2. Type-II nitric oxide synthase mRNA was detected using a reverse transcription-polymerase chain reaction method and nitrate was measured with a combination of high-performance liquid chromatography and the Griess reaction. 3. In untreated rats, type-II nitric oxide synthase mRNA was not detected in the hypothalamus, hippocampus, cerebral cortex, brain stem, or cerebellum. However, after 28-day oral administration of imipramine, it was detected in every brain region tested. Nitrate levels in the hypothalamus and cerebral cortex increased after 28-day treatment. In the hypothalamus, nitrate levels increased dose-dependently. These dose-dependent nitrate level changes were prevented by pretreatment with a nitric oxide synthase inhibitor. Moreover, the preventive effect of NG-nitro-L-arginine methyl ester was reversed by coadministration of L-arginine, a nitric oxide substrate. 4. These results suggest that chronic imipramine treatment induces nitric oxide synthase gene expression in the brain, followed by augmented NO production.

Animals↗