PubMed Health⌕ Search

Biomedical subjects

Katsuyoshi Mizukami

Publications and source records attributed to Katsuyoshi Mizukami.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between diffusion tensor imaging and brain morphology in patients with myotonic dystrophy.

Myotonic dystrophy type 1 (MyD) is a common inherited neuromuscular disorder. In addition to neuromuscular symptoms, many MyD patients show central nervous system neuropathology. This study evaluated whether MyD patients display diffusion tensor (DT) abnormalities associated with regional cortical atrophy and clinical features. Three-dimensional T1-weighted and DT magnetic resonance images of the brain were obtained in 11 MyD patients and 13 age- and sex-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in corpus callosum subregions with DT imaging (DTI) along with volumetric changes, and correlations with clinical features were examined. Differences between MyD patients and healthy subjects were analyzed statistically. Significantly lower FA and higher MD values were found in the genu, rostral body, anterior midbody, posterior midbody and splenium in MyD patients than in control subjects (p<0.05, corrected; lower FA in the splenium was at a trend level). These corpus callosum subregions were the areas connected to cortical areas where significantly lower volumes were found in MyD patients. No significant decrease in volumes was noted in the parietal cortex, where connecting fibers pass through the isthmus in which DTI abnormalities were not detected in MyD patients. Significant negative correlations to volumes of frontal areas were noted, particularly bilateral motor areas, with cytosine thymine guanidine (CTG) triplet expansion. DTI results in corpus callosum may reflect morphological changes in the connecting cortical areas of MyD patients.

Brain↗
PubMed2006

A preliminary open-label study of 5-HT1A partial agonist tandospirone for behavioural and psychological symptoms associated with dementia.

The aim of this study was to assess the efficacy and safety of tandospirone, a 5-HT1A partial agonist, for treatment of behavioural and psychological symptoms of dementia (BPSD). Thirteen outpatients with DSM-IV diagnosis of Alzheimer's type or vascular dementia were enrolled in this study. Their BPSD and cognitive functions were evaluated with the Neuropsychiatric Inventory (NPI) and Mini-Mental State Examination, respectively, for an 8-wk period of treatment. The maximum benefit of tandospirone was achieved at a mean dose of 19.6 mg/d. There were significant improvements in the NPI subscores for delusion, agitation, depression, anxiety, and irritability at 2 or 4 wk after the start of administration of tandospirone. No patients experienced severe adverse effects. The results suggest that tandospirone was effective at improving BPSD symptoms and well-tolerated in elderly demented patients.

Aged↗
PubMed2006

Efficacy of milnacipran on the depressive state in patients with Alzheimer's disease.

An open-labeled study was conducted to examine the efficacy of selective serotonin and noradrenaline reuptake inhibitor (SNRI), milnacipran in treating depression in Alzheimer's disease (AD) patients. Eleven patients with AD showing major depressive symptoms were examined. Ten of 11 patients demonstrated an over 50% decrease in their HAM-D scores from the baseline, and 8 of 11 patients reached remission (HAM-D score<==7) within 12 weeks of the start of milnacipran treatment, and their GAF score was also remarkably improved. Although in 11 patients, two patients showed a mild hypomanic state and one patient showed daytime somnolence, these problems were quickly solved after a decrease in the daily dose or discontinuation of milnacipran. In addition, the treatment had no negative effects on cognitive function of the patients. Our study results suggest that milnacipran is a promising medicine for depressive state in AD patients.

Aged↗
PubMed2006

Efficacy of perospirone in the management of aggressive behavior associated with dementia.

We assessed the efficacy of the serotonin dopamine antagonist, perospirone (PER) on aggressive and agitated behavior in demented patients. Eighteen outpatients with dementia diagnosed according to the DSM-IV were enrolled in this study, and their behavioral symptoms and cognitive impairments were assessed with the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) and Mini-Mental State Examination (MMSE) instruments for a period of 6 weeks. The maximum benefit of PER was achieved at a mean dose of 7.4 mg/day. Post-hoc analysis showed significant improvement in verbal outbursts after 4 weeks and in agitation scores after 4 and 6 weeks. Only 2 patients dropped out of the study, because of adverse effects, and no serious adverse effect was observed. The data suggest that PER is effective in improving aggressive and agitated behavioral symptoms in demented patients and that it is safe to use in elderly patients.

Aged↗
PubMed2006

Beneficial effects of perospirone on aggressive behavior associated with dementia.

The aim of this study was to assess the efficacy of the serotonin-dopamine antagonist perospirone in treating aggressive and agitated behavior in patients with dementia. Six patients were referred to the outpatient clinic of Ishizaki Hospital and were followed for 6 weeks. Their psychiatric diagnoses were made using the DSM-IV. Their behavioral symptoms and degrees of cognitive impairment were measured using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) and the Mini-Mental Examination State. The changes in BEHAVE-AD scores were investigated. Maximum benefit was achieved at a mean perospirone dose of 9.0 mg/day. No patient experienced severe adverse effects. Post-hoc analysis showed significant improvement in the total BEHAVE-AD and aggressiveness subscale scores within 2 weeks. This study suggests that perospirone is effective in improving aggressive and agitated behavioral symptoms in demented patients and is safe to use in elderly patients.

Aged↗
PubMed2006

MDR1 gene polymorphism in Japanese patients with schizophrenia and mood disorders including depression.

P-Glycoprotein (ABCB1-type P-gp), a membrane protein encoded by the multi drug resistant gene (MDR1), expressing on the blood brain barrier protects the brain from many drugs including dexamethasone. Psychiatric disorders, schizophrenia and depression, have known to have abnormal hypothalamus-pituitary-adrenal (HPA) activity, which is assessed by non-suppression of cortisol in dexamethasone suppression test. The poor response to dexamethasone in these patients' population suggested the impaired activity on dexamethasone penetration into the brain via P-gp, which was associated with MDR1 polymorphisms. We, therefore, examined five SNPs of the MDR1 gene, -1517 T>C (promoter), -41 A>G (intron -1), -129 T>C (exon 1b), 2677 G>A,T (exon 21) and 3435 C>T (exon 26), in Japanese patients with schizophrenia (n=121) and mood disorders (n=62), and compared with the control subjects (n=160). The frequency of MDR1 mutant alleles at -1517, -41 and -129 in patients with mood disorders was significantly lower (2.4, 5.6, 2.4%, respectively) than those of controls (7.8, 13.7, 7.8%, respectively) (p<0.05). The frequencies of MDR1 2677 G/A and A/A genotype in mood disorders was significantly higher (17.7, 6.5%, respectively) than controls (11.2, 0%, respectively) (p<0.05). The 2677A allele frequency in mood disorders (20.2%) was significant higher than controls (10.9%) (p<0.05). Haplotype of 129-2677-3435 (T-A-C) in mood disorders was significantly higher (14.4%) than controls (8.0%) (p<0.05). There was no significant difference in allele and genotype frequencies between the patients with schizophrenia and controls. These findings suggested that predispose to mood disorders, not schizophrenia, was associated with possible alteration of P-gp activities corresponding MDR1 polymorphism at least partly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

GABA(A) receptor gamma subunits in the hippocampus of the rat after perforant pathway lesion.

Immunohistochemical and Western blotting techniques were employed to examine the alterations in immunostaining of the gamma-amino butyric acid (GABA) receptor subunits gamma 1/3 and 2 within the hippocampus of the rat brain at 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion. At 1, 3, and 7 days post-lesion, we observed a remarkable decrease in gamma 1/3 neuropil staining in the deafferented zone (i.e., the outer molecular layer of the dentate gyrus ipsilateral to the lesion), although at 3 and 7 days post-lesion, staining intensity was considerably recovered. At 14 days post-lesion, the gamma 1/3 immunostaining was indistinguishable from that of controls and it appeared yet more robust at 30 days post-lesion. We also observed a slight decrease in gamma 2 neuropil staining until 7 days post-lesion, and an increase in gamma 2 staining at 30 days post-lesion. Western blot analysis demonstrated data that was relatively consistent with our immunohistochemical observations, although gamma 3 was hardly detectable. Our study suggests that gamma subunits of the GABA(A) receptor in the dentate gyrus display a plastic response to the deafferentation of the perforant pathway.

Animals↗
PubMed2005

Immunohistochemical study of the hnRNP A2 and B1 in the hippocampal formations of brains with Alzheimer's disease.

To elucidate the post-transcriptional regulation in the subjects with Alzheimer's disease (AD), we employed immunohistochemical techniques and examined the expression of the heterogeneous nuclear ribonucleoprotein (hnRNP) A2 and B1 in the hippocampus with neurofibrillary tangle (NFT) neuropathology. In the mildly affected subjects (Braak stages I and II), the most intense A2 immunoreactivity was observed in the CA3 to CA1 neurons. In the moderately (Braak stages III and IV) and severely affected subjects (Braak stages V and VI), the CA1 region demonstrated a decrease in the number of A2 immunoreactive neurons and in immunoreactivity in the remaining neurons, while within the CA4 to CA2 in the severely affected subjects, the majority of neurons showed increased A2 immunoreactivity. An intense B1 immunoreactivity was observed throughout the CA subfields. In the CA1 subfield of the moderately affected subjects and in the extensive hippocampal regions of the severely affected subjects, a decrease in B1 immunoreactivity was observed. Double-immunolabeling studies demonstrated that tangle-bearing neurons reduced A2 and B1 immunoreactivity. Our study suggests that hnRNP A2 and B1 display different responses in the AD hippocampus, and further suggests that the post-transcriptional regulation is disturbed in neurons of the AD hippocampus.

Aged↗
PubMed2005

Immunohistochemical and immunoblot analysis of gamma-aminobutyric acid B receptor in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot techniques were employed to examine the distribution and expression of GABA(B) receptors in the prefrontal cortex of postmortem subjects with schizophrenia and bipolar disorder. GABA(B)R1a/b immunoreactivity was observed in the neuronal soma and dendrites as well as in the neuropil in the control subjects. GABA(B)R1a/b immunolabeling in neurons from the subjects with schizophrenia and bipolar disorder was less intense than in those from the control subjects. In control subjects, the distribution of GABA(B)R2 immunoreactivity was found to be similar to that of GABA(B)R1a/b. GABA(B)R2 immunolabeling in neurons from the bipolar disorder group appeared less intense than that of the normal controls as well as that in schizophrenic groups. Immunoblot analysis demonstrated a significant decrease in GABA(B)R1a levels in schizophrenic subjects, while there was a significant decrease in GABA(B)R1a, GABA(B)R1b, and GABA(B)R2 levels in bipolar subjects compared with the controls. The present study suggests that the GABA(B) receptor is involved in the pathophysiology of schizophrenia and bipolar disorder, and further suggests that the patterns of changes in GABA(B) receptor subtypes are different between these two disorders.

Adult↗
PubMed2005

Changes in hippocampal GABABR1 subunit expression in Alzheimer's patients: association with Braak staging.

Alterations in the gamma-aminobutyric acid (GABA) neurotransmitter and receptor systems may contribute to vulnerability of hippocampal pyramidal neurons in Alzheimer's disease (AD). The present study examined the immunohistochemical localization and distribution of GABA(B) receptor R1 protein (GBR1) in the hippocampus of 16 aged subjects with a range of neurofibrillary tangle (NFT) pathology as defined by Braak staging (I-VI). GBR1 immunoreactivity (IR) was localized to the soma and processes of hippocampal pyramidal cells and some non-pyramidal interneurons. In control subjects (Braak I/II), the intensity of neuronal GBR1 immunostaining differed among hippocampal fields, being most prominent in the CA4 and CA3/2 fields, moderate in the CA1 field, and very light in the dentate gyrus. AD cases with moderate NFT pathology (Braak III/IV) were characterized by increased GBR1-IR, particularly in the CA4 and CA3/2 fields. In the CA1 field of the majority of AD cases, the numbers of GBR1-IR neurons were significantly reduced, despite the presence of Nissl-labeled neurons in this region. These data indicate that GBR1 expression changes with the progression of NFT in AD hippocampus. At the onset of hippocampal pathology, increased or stable expression of GBR1 could contribute to neuronal resistance to the disease process. Advanced hippocampal pathology appears to be associated with decreased neuronal GBR1 staining in the CA1 region, which precedes neuronal cell death. Thus, changes in hippocampal GBR1 may reflect alterations in the balance between excitatory and inhibitory neurotransmitter systems, which likely contributes to dysfunction of hippocampal circuitry in AD.

Adenosine Triphosphatases↗
PubMed2005

Brain magnetic resonance imaging and single photon emission computerized tomography findings in a case of relapsing polychondritis showing cognitive impairment and personality changes.

A 57-year-old female with relapsing polychondritis (RP) showing CNS complications is described with reference to the MRI and SPECT findings. At the age of 56, the patient was diagnosed with RP based on her symptoms, which included bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, and ocular inflammation, as well as vestibular dysfunction. During the course of the disease, she suffered from aseptic meningitis accompanied by delirium, which was resolved by treatment with cyclophosphamide, in addition to prednisolone concurrent with the improvement of her physical condition. After the meningitis improved, she developed a number of cognitive impairments, including time disorientation, agraphia, acalculia, constitutional apraxia, and personality changes. Simultaneously, we observed, via SPECT, a decrease in cerebral blood flow (CBF) in several regions, including the bilateral frontal, lateral temporal, and parietal regions. This is the first study to report on the CNS manifestations of RP with reference to MRI and SPECT findings.

Brain Mapping↗
PubMed2004

GABAA receptor gamma subunits in the prefrontal cortex of patients with schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABAA receptor gamma subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. Immunohistochemically, gamma 1/3 immunolabeling in the neuronal soma in the prefrontal cortex from subjects with bipolar disorder was more intense than that of the controls and the subjects with schizophrenia. The intensity of gamma 1/3 immunolabeling of the schizophrenic subjects was comparable with that of the controls. Immunoblot analysis demonstrated a significant increase in the gamma 1 subunit in the bipolar subjects, whereas no remarkable difference was detected in the schizophrenic subjects. The present study suggests that the GABAA receptor gamma subunit is differentially involved in schizophrenia and bipolar disorder, and that the gamma subunit is up-regulated in the prefrontal cortex of subjects with bipolar disorder.

Adult↗
PubMed2004

Immunohistochemical and immunoblot study of GABA(A) alpha1 and beta2/3 subunits in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.

A number of investigations have provided a growing body of evidence of the involvement of the gamma-aminobutyric acid (GABA) transmitter system in the pathophysiology of schizophrenia and bipolar disorder. In this study, immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABA(A) receptor alpha1 and beta2/3 subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. alpha1 immunoreactivity was observed in the neuropil of the prefrontal cortex and in the neuronal soma in specimens from both groups, as well as from normal controls. alpha1 immunolabeling in the neuronal soma from the schizophrenic group was more intense than that of the other two groups. The distribution of beta2/3 immunoreactivity was similar to that of alpha1. beta2/3 immunolabeling in the neuronal soma from the schizophrenia and bipolar disorder groups was more intense than that of the normal controls. The densitometry measurements, as well as the immunoblot analysis for alpha1 and beta2/3 were highly consistent with the alpha1 and beta2/3 immunohistochemistry results. The present study suggests that the expression of these two GABA(A) receptor subunits was altered in subjects with schizophrenia and bipolar disorder, but that the patterns of change differed between those with these two disorders.

Adult↗
PubMed2004

Immunohistochemical study of hnRNP B1 in the postmortem temporal cortices of patients with Alzheimer's disease.

In order to examine the post-transcriptional regulations in Alzheimer's disease, we employed immunohistochemical techniques and examined the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 in the inferior temporal cortex of subjects with Alzheimer's disease. In the mild cases, intense B1 immunoreactivity was observed in neurons of layer V, and less intense immunoreactivity was observed in layers II and III. The overall distributions and intensities of B1 immunoreactivity were undistinguishable among mild, moderate, and severe cases. Double-immunolabeling with MC1 and B1 demonstrated that B1 immunoreactivity was preserved in the majority of neurofibrillary tangle (NFT)-bearing neurons. Our study suggests that hnRNP B1-associated post-transcriptional regulations are preserved in the inferior temporal cortex of Alzheimer's disease.

Aged↗
PubMed2004

A case of neurosyphilis showing a marked improvement of clinical symptoms and cerebral blood flow on single photon emission computed tomography with quantitative penicillin treatment.

A 31-year-old woman manifested significant emotional symptoms and personality change due to neurosyphilis; her clinical symptoms were improved with quantitative penicillin treatment. On admission, magnetic resonance imaging (MRI) showed no abnormal findings, while N-isopropyl-p-[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT) initially showed a remarkable increase in cerebral blood flow (CBF) in the cerebral cortex. This increase disappeared after improvement of the patient's clinical symptoms with treatment. It appears that the increase in CBF might have reflected an active inflammatory state of neurosyphilis and that its disappearance might therefore represent successful treatment with penicillin for neurosyphilis. Our case study suggests that single photon emission computed tomography (SPECT) is a useful method for evaluating an inflammatory state and for assessing the effect of therapy on neurosyphilis.

Adult↗
PubMed2004

[Incidence of adverse drug reactions in geriatric wards of university hospitals].

Adverse drug reactions (ADR) in elderly people, which have been shown to increase with age, are often attributed to functional decline and polypharmacy. A multi-institutional retrospective survey was undertaken to investigate the current status of ADR in geriatric wards of university hospitals. The inpatient database from 2000 to 2002 in 5 university hospitals was studied, and a total of 1,289 patients were analyzed. The incidence of ADR, as determined by attending physicians, was 9.2% on the whole but varied from 6.3% to 15.8% among the institutions. The factors significantly related to ADR were number of diagnoses, number of geriatric syndromes, number of prescribed drugs, increase of more than two drugs during admission, longer hospital stay, emergency admission, depression and apathy. These results are mostly consistent with previous reports and will provide important information on pharmacotherapy in elderly people.

Aged↗