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Biomedical subjects

H Nagayama

Publications and source records attributed to H Nagayama.

At least 19 recordsLinked to original sources

Reliability of MIBG myocardial scintigraphy in the diagnosis of Parkinson's disease.

AIM: To evaluate the reliability of [(123)I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing Parkinson's disease (PD). PATIENTS/METHODS: A series of 391 outpatients showing one or more parkinsonian-like symptoms was longitudinally followed up for accurate clinical diagnosis. MIBG scintigraphy was performed in the patients and 10 normal controls of similar age. The heart to mediastinum uptake ratio was calculated in each person, and the values were considered abnormal if they were greater than two standard deviations below the control mean. RESULTS: MIBG uptake was decreased in most patients with PD (87.7%), and was seen in all advanced cases with Hohen-Yahr stage III or more; the sensitivity and specificity of scintigraphy for detecting PD were 87.7% and 37.4%, respectively. Surprisingly, over half of the patients without PD (66.5%) also exhibited low uptake, resulting in considerable overlap in the ratios between PD and the other disorders. CONCLUSION: MIBG scintigraphy is a sensitive, but not specific, test for PD. Low MIBG uptake does not necessarily indicate PD, but is essential for diagnosing advanced PD.

3-Iodobenzylguanidine↗

Cerebral blood flow index image as a simple indicator for the fate of acute ischemic lesion.

BACKGROUND AND PURPOSE: To evaluate the feasibility of utilizing cerebral blood flow (CBF) index images, we attempted to investigate 1) whether CBF index images can reveal the resulting infracted area, 2) whether the CBF index can correlate other modality (SPECT). METHODS: DWI and DPI were obtained in 17 patients within 12 hours of stroke onset and follow up MRI. On three DPI delivered images, namely relative regional cerebral blood volume (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, correlations between initial lesion volume of and follow up infarction volume of three images and rCBF images delivered with singular value decomposition (SVD) methods were assessed. Then 99mTc-ECD SPECT was taken immediately after MRI to correlate to MRI data. RESULTS: Among the three images, lesion volume of CBF index images against follow up infarct volume had the highest correlation (r = 0.995) to a linear fit and the slope was closest to 1.0 (0.91) and had identical accuracy to the regression coefficient of rCBF images. CBF index well correlated to SPECT delivered CBF. CONCLUSION: CBF index images can accurately predict final infarct volume. Evaluating CBF index images together with DWI can guide the initial assessment in the acute stage of cerebral ischemia.

Acute Disease↗

Granulocyte transfusion as a treatment for enterococcal meningoencephalitis after allogeneic bone marrow transplantation from an unrelated donor.

Bacterial meningoencephalitis occurring in the pre-engraftment period after bone marrow transplantation (BMT) is a rare complication, and the feasibility of granulocyte transfusion (GTX) in such cases remains to be elucidated. A 37-year-old man developed enterococcal meningoencephalitis during a severely granulocytopenic pre-engraftment period after BMT. Despite therapy with appropriate antibiotics, cultures of blood and cerebro-spinal fluid (CSF) continued to grow Enterococcus faecalis, and he developed rapid mental deterioration and seizure. Granulocytes were collected from his HLA-mismatched, ABO-matched sibling with subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) and oral dexamethazone. Transfusion of 4.4 x 10(10) granulocytes resulted in a 12-h post-transfusion granulocyte increment of 2.0 x 10(9)/l, and maintained peripheral blood granulocyte counts above 0.5 x 10(9)/l for 3 days. A rapid increase of granulocytes in CSF was also observed, and cultures of blood and CSF became negative after GTX. A transient worsening of seizure was observed as a potential side effect of GTX. The patient subsequently developed septic shock because of Pseudomonas aeruginosa and died. Further studies are warranted to evaluate the clinical efficacy of GTX for the treatment of uncontrolled infections in granulocytopenic stem cell transplant recipients.

Adult↗

A case of micrographia after subcortical infarction: possible involvement of frontal lobe function.

Most reports of micrographia associated with focal brain lesions have related this finding to damage in the left basal ganglia. Here we describe the case of a 68-year-old man presenting with reversible micrographia accompanied by hypophonia in the absence of extrapyramidal signs after cerebral infarction in the left subcortical region. At the time of the patient's admission, diffusion-weighted magnetic resonance imaging sequence showed the lesion to principally involve the corona radiata, with some involvement of the putamen. Neurologically, mild right-sided brachiofacial hemiparesis and grasp reflexes - a frontal lobe sign - were observed. As his micrographia and hypophonia improved, the patient's grasp reflexes improved in parallel. In addition, recovery of regional cerebral blood flow in the left frontal lobe was confirmed by single photon emission computed tomography (technetium-99 m HMPAO). The present case suggests the possibility that the function of frontal-subcortical circuit might also be involved in the production and improvement of micrographia and that micrographia and hypophonia may share a common pathophysiology.

Aged↗

Anxiety induced by repetitive transcranial magnetic stimulation is suppressed by chronic treatment of paroxetine in rats.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on affective disorder and anxiety disorders. However, some reports have linked rTMS to a significant increase in anxiety in normal volunteers. This study investigates the effect of rTMS on anxiety and the use of acute and chronic paroxetine treatment on this animal model of anxiety. In normal rats, rTMS for 10 days induced anxiety, as shown by elevated plus maze, black and white box, and conditioned fear tests. This anxiety was suppressed by chronic, but not acute, paroxetine. These results suggest that rats receiving chronic rTMS treatment can be used as a model of anxiety and that the anxiety induced by rTMS might involve the serotonergic system.

Acute Disease↗

Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim.

We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08 x 10(7)/kg recipient body weight) were transplanted to an 8-10 Gy equivalent neutron-irradiated patient because of a lack of a suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte gamma-globulin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5 x 10(9)/l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 x 10(9)/l on day 27, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopoietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident.

Adult↗

Dose-adjusted preemptive therapy for cytomegalovirus disease based on real-time polymerase chain reaction after allogeneic hematopoietic stem cell transplantation.

We have prospectively evaluated the efficacy of real-time PCR-guided preemptive therapy for CMV diseases in allogeneic hematopoietic stem cell transplant recipients with grades II-IV acute GVHD. The dose of ganciclovir was adjusted according to the viral load determined by real-time polymerase chain reaction (PCR). On detecting CMV reactivation in the plasma, ganciclovir was initiated at a dose of 5 mg/kg body weight once daily, and the dose was increased to twice daily if viral load continued to increase after initiating ganciclovir. In 39 evaluable patients, CMV reactivation assessed by real-time PCR became positive in 30 (77%). One developed CMV gastroenteritis before PCR became positive. Thus the remaining 29 patients were treated preemptively with ganciclovir. The dose of ganciclovir was increased in 12 patients (41%) of preemptively treated patients for increasing viral load. CMV diseases were diagnosed in two patients (one gastroenteritis and one retinitis), and late CMV disease was diagnosed in one patient (gastritis). The treatment was generally well-tolerated, but three patients (10%) developed neutropenia (neutrophil count less than 1.0 x 10(9)/l). In conclusion, real-time PCR-guided preemptive therapy with decreased dose of ganciclovir is feasible and does not increase the frequency of CMV diseases if the dose is adjusted according to the viral load.

Adult↗

Lack of association between a polymorphism in the promoter region of the dopamine D2 receptor and personality traits.

Disturbances of the dopaminergic neurotransmitter system have been associated with a personality trait that involves novelty seeking. A functional polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) has been reported to be associated with schizophrenia. We examined the association between this polymorphism in the DRD2 promoter region and personality traits, as assessed with the Tridimensional Personality Questionnaire. No significant association emerged between the polymorphism in the DRD2 promoter region and personality traits. Entering sex and age as covariates in an analysis of covariance did not change the results. These data fail to confirm an association between a polymorphism in the promoter region of the DRD2 and personality traits.

Adult↗

Chemokine receptor expressions and responsiveness of cord blood T cells.

Chemokines and their receptors play a critical role in the selective attraction of various subsets of leukocytes. We examined the chemokine receptor expressions and responsiveness of cord blood (CB) T cells. Flow-cytometric analysis revealed that peripheral blood (PB) T cells expressed CCR-1, CCR-2, CCR-5, CCR-6, CXC chemokine receptor-3 (CXCR-3), and CXCR-4, while CB T cells expressed only CXCR-4 on their surface. Chemotactic migratory response of CB T cells to macrophage-inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein-1, RANTES, MIP-3alpha, monokine induced by IFN-gamma, and IFN-gamma-inducible protein-10 was significantly impaired compared with those of PB T cells. In contrast, the ability of CB T cells to migrate to MIP-3beta, 6Ckine, and stromal cell-derived factor-1alpha was greater than that of PB T cells, and these events were correlated with the expression levels of CCR-7 and CXCR-4, respectively. Engagement of CD3 and CD28 specifically up-regulated CXCR-3 expression and chemotaxis to monokine induced by IFN-gamma and IFN-gamma-inducible protein-10, whereas this stimulation down-regulated CCR-7 expression and chemotaxis to MIP-3beta and 6Ckine in PB T cells, but not in CB T cells. These results suggest that PB T cells and CB T cells exhibit distinct chemokine responsiveness via different chemokine receptor repertoire.

Antibodies, Monoclonal↗

Severe autoimmune thrombocytopenia after allogeneic bone marrow transplantation for aplastic anemia.

Autoimmune thrombocytopenia (AITP) after bone marrow transplantation (BMT) was suggested to occur by immune dysregulation mainly in association with graft-versus-host disease (GVHD). Here we present a patient who developed severe AITP after BMT. A 40-year-old woman with severe aplastic anemia received a BMT from a partially HLA-matched brother. Despite myeloid and erythroid engraftments, platelet recovery was delayed. All bone marrow cells were 46,XY and were derived from the donor. Grade I acute GVHD involving skin developed from day 34 posttransplantation, but promptly responded to prednisolone in addition to a prophylactic dose of tacrolimus. With the tapering of prednisolone, thrombocytopenia progressed without substantial changes in the white blood cell count, hemoglobin concentration, or reticulocyte count. On day 188, the patient developed chronic GVHD involving skin and liver, which promptly responded to the readministration of prednisolone and increased tacrolimus. However, the patient's platelet count decreased to 9 x 10(9) cells/L on day 222. The platelet-associated immunoglobulin G (PAIgG) values were elevated. Bone marrow examination showed hypercellularity with plentiful megakaryocytes. The number of colony-forming units-megakaryocyte was within the normal range. The elevated PAIgG values and a correlation between thrombocytopenia and the intensity of the immunosuppressive agents strongly suggested a causative role of the autoimmune mechanisms for thrombocytopenia in this patient.

Adult↗

Extended surgery with en bloc resection of the right common iliac vessels for lymph node metastasis of mucinous colon carcinoma: report of a case.

We report herein the case of a 63-year-old woman who underwent surgery for recurrent mucinous carcinoma of the cecum. Recurrent metastatic lymph nodes had invaded the right common iliac vessels and right ureter, but she had no distant metastases and no peritoneal dissemination. Extended surgery with en bloc resection of the right iliac vessels and right ureter, and femorofemoral bypass were performed. Postoperatively, several complications developed which were successfully treated by further operations. By 1 year after surgery, she had no recurrent tumors on radiological examination, suggesting that our aggressive surgery with resection of the invaded regional vessels had effectively removed the recurrent tumors. This procedure may therefore significantly prolong the survival time and improve the quality of life of such patients.

Adenocarcinoma, Mucinous↗

Unrelated cord blood transplantation for adult patients with myelodysplastic syndrome-related secondary acute myeloid leukaemia.

Seven adult patients with myelodysplastic syndrome (MDS)-related secondary acute myeloid leukaemia (AML) were treated with total body irradiation (TBI), cytosine arabinoside (Ara-C) and cyclophosphamide (CY), followed by unrelated human leucocyte antigen (HLA)-mismatched cord blood transplantation (CBT). Granulocyte colony-stimulating factor (G-CSF) was infused continuously from 12 h before until the end of Ara-C therapy to enhance the antileukaemia effect of Ara-C. Five patients are alive and free of disease at 7-31 months after transplantation. These preliminary results suggest that adult MDS-related secondary AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

Acute Disease↗

Suppression of conditioned fear by administration of CCKB receptor antisense oligodeoxynucleotide into the lateral ventricle.

We investigated the role of CCK in the development of anxiety by determining whether CCKB receptor antisense suppressed intracellular Ca(2+) concentration in vitro or suppressed conditioned fear stress in vivo. First, for the in vitro studies, we used rat pituitary tumor GH3 cells since these cells have CCKB receptors. GH3 cells were stimulated by 10 microM CCK-4; intracellular Ca(2+) concentration was measured. The CCKB receptor antisense at 1 or 10 microM reduced the subsequent response to 10 microM CCK-4 in a time-dependent manner. Second, for the in vivo studies, the CCKB receptor antisense, sense, random sense, or saline was infused at a constant rate for 6 days into rat lateral ventricles via mini-osmotic pumps. Individual rats were then subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. Twenty-four hours later, the rat was again placed in the chamber and observed for 5 min without shocks. This study showed that CCKB receptor antisense significantly suppressed intracellular Ca(2+) concentration in GH3 cells and significantly reduced freezing behavior in rats, indicating that the CCKB receptor plays an important role in anxiety.

Animals↗

Signaling events following chemokine receptor ligation in human dendritic cells at different developmental stages.

Responsiveness of dendritic cells (DC) to inflammatory CC chemokines is down-regulated during their maturation. We analyzed the mechanism underlying these events. Cell-surface expression of CC chemokine receptor (CCR)-1, -3 and -5 was increased during differentiation of immature DC (iDC) from monocytes. In contrast, these expressions were decreased during development of iDC into mature DC (mDC) to levels similar to those of monocytes. Transcriptional expression of CCR-1, -3 and -5 was increased during differentiation of iDC from monocytes, while the expression was decreased during development of iDC into mDC. Expression of CCR-7 transcript was detected in mDC, but not in monocytes or iDC. Both monocytes and iDC, but not mDC, migrated in response to inflammatory CC chemokines such as regulated on activation normal T cell expressed and secreted (RANTES)/CCL5, whereas mDC, but not monocytes or iDC, migrated to macrophage inflammatory protein (MIP)-3ss/CCL19. Receptor engagement of monocytes or iDC by RANTES (for CCR-1, -3 and -5) resulted in protein tyrosine phosphorylation events including activation of focal adhesion kinase as well as mitogen-activated protein kinase, whereas this stimulation induced little activation of these molecular events in mDC when compared with monocytes or iDC. On the other hand, stimulation with MIP-3ss (for CCR-7) induced tyrosine phosphorylation events in mDC, but not in monocytes or iDC. These results suggest that the down-regulation of cell-surface expression of CCR and of their downstream signaling events may be involved in the reduced chemotaxis of DC to inflammatory CC chemokines during their maturation.

Cell Differentiation↗

Enhancement of migratory and aggregate activities of human peripheral blood monocyte-derived dendritic cells by stimulation with RANTES.

We examined the effects of various chemokines on the functional activation of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4)-generated human peripheral blood monocyte-derived immature dendritic cells (iDC). Stimulation of iDC with regulated on activation normal T cell expressed and secreted (RANTES) resulted in the promotion of their chemotactic migratory capacity in response to RANTES when compared with that of unstimulated cells. TNF-alpha induced a homotypic aggregated cluster formation of iDC in a dose-dependent manner, whereas the combination of TNF-alpha and RANTES exhibited more potent induction. IDC stimulated with RANTES were more efficient than unstimulated iDC in the production of endogenous RANTES. Treatment of iDC with the combination of TNF-alpha and RANTES was just little effective for the enhancement of allogeneic T-cell stimulatory capacity as compared with that of TNF-alpha treated iDC. These results suggest that endogenous secretions of RANTES from iDC stimulated with RANTES be potentially involved in RANTES-induced changes of properties with respect to morphology and function.

Cell Movement↗

Biochemical alterations during medication withdrawal in Parkinson's disease with and without neuroleptic malignant-like syndrome.

The object was to assess alterations in CSF concentrations of monoamine metabolites during withdrawal of medication in patients with Parkinson's disease in relation to the presence or absence of episodes resembling neuroleptic malignant syndrome (NMS). This syndrome is a fatal condition developing after neuroleptic therapy, and a neuroleptic malignant-like syndrome (NMLS) may also occur after withdrawal of antiparkinsonian drugs in patients with Parkinson's disease. Previous biochemical assays showed that the CSF concentration of the dopamine metabolite homovanillic acid (HVA) is an independent prognostic factor for development of NMLS in patients with Parkinson's disease. In the present study, CSF concentrations of HVA, the noradrenaline (norepinephrine) metabolite 3-methoxy-4-hydroxyphenylethylene glycol, and the serotonin metabolite 5-hydroxyindole acetic acid were assayed using high performance liquid chromatography with electrochemical detection. The study population consisted of nine patients with Parkinson's disease with NMLS and 12 without NMLS, in whom metabolites were assayed during both withdrawal and remedicated periods. Concentrations of HVA in the CSF were significantly lower during the withdrawal period than the medicated period regardless of whether patients developed NMLS, and HVA concentrations were comparably increased after remedication in both groups. However, HVA concentrations were significantly lower in patients with NMLS than in those without NMLS during both withdrawal and medicated periods. Other metabolites showed no significant differences. The present data provide further biochemical evidence for extremely suppressed central dopaminergic activity during NMLS, which may indicate a narrow safety margin for medication withdrawal in patients with Parkinson's disease.

Aged↗