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Kenji Ikeda

Publications and source records attributed to Kenji Ikeda.

At least 127 records · Page 7Linked to original sources
PubMed2002

Glial involvement in diffuse Lewy body disease.

Diffuse Lewy body disease (DLBD) is characterized by the presence of Lewy bodies (LB) in the neurons and neurites of cortical, subcortical, and brain stem structures. Recently, alpha-synuclein (alphaS) has been found to be a central constituent of LB. In DLBD, abnormal accumulation of alphaS has been reported in both neurons and glia, but studies on glial lesions in DLBD have been limited. We examined in detail the constituents and distribution of glial lesions in eight patients with DLBD and report the pathogenesis of the glial lesions. alphaS-positive neuronal cytoplasmic inclusions (NI), neuropil threads (NT), and coiled bodies (CB) showed similar immunostaining profiles. Without pretreatment, NI, NT, and CB were detected by all antibodies against alphaS. The immunostaining profile of star-like astrocytes (SLA) was quite different from those of NI, NT, and CB. A few SLA were stained by an antibody against the non-Abeta component portion of alphaS without pretreatment, but formic acid pretreatment dramatically enhanced SLA immunoreactivity. SLA and CB were found in all eight brains with DLBD. SLA were scarce in the brain stem, but there were hundreds of SLA per visual field at x100 magnification in the temporal cortex of most cases, while CB were found diffusely in both the cerebral cortex and brain stem, similar to NI. This suggests that the pathogenesis of SLA is different from those of NI and CB.

Aged↗
PubMed2002

Investigation of cellular metallic elements in single neurons of human brain tissues.

The purpose of this report is to introduce the potential of synchrotron radiation X-ray fluorescence (SRXRF) spectroscopy, by describing the application of this method to mapping and quantification of metallic elements in neurons from brain tissues affected by Alzheimer's disease (AD). In this study, clear images of Fe, Zn and Ca within certain single neurons were obtained. There was a high degree of correlation between Zn and Ca in the groups of cells with lower and relatively higher levels of Ca. These results demonstrate that further investigation with larger numbers of neurons using SRXRF spectroscopy may contribute to advancing the knowledge of the mechanisms of metal-induced cell degeneration in human brain tissues, including those affected by AD.

Aged↗
PubMed2002

NACP/alpha-synuclein immunoreactivity in diffuse neurofibrillary tangles with calcification (DNTC).

Diffuse neurofibrillary tangles with calcification (DNTC) is a rare tangle-predominant dementia, as well as one of the tauopathies lacking Abeta deposition. It is characterized by temporo-frontal lobar atrophy, Fahr-type calcification and, histopathologically, numerous neurofibrillary tangles in the limbic system and neocortex. Recently, accumulation of alpha-synuclein (alphaS), the precursor of the non-beta amyloid component (NAC) of Alzheimer's disease, has been shown in diverse neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, multiple system atrophy and parkinsonism-dementia complex of Guam. To clarify whether alphaS accumulates in other neurodegenerative disorders, we investigated eight DNTC brains using immunohistochemistry and demonstrated remarkable alphaS deposition in the neurons and astrocytes in many anatomical regions. Abundant Lewy bodies were observed in the amygdala (seven cases) and hippocampus (seven cases), and, to a lesser degree, in the substantia nigra (six cases) and dorsal vagal nucleus (five cases). In the hippocampus, many Lewy neurites were distributed in the stratum oriens and stratum pyramidale in the CA2-3 and the subiculum. Furthermore, numerous NAC-positive astrocytes were detected in the hippocampus and temporal cortex. This investigation reveals that neurons and astrocytes are extensively involved in remarkable alphaS pathology in the DNTC brain, and that the alphaS pathology compounds the cardinal pathological features of tau pathology. These findings suggest that (1) DNTC shares a common pathophysiological background with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy in which abnormal alphaS aggregation is observed, and (2) there is an interaction between alphaS and tau pathology that does not involve amyloid in DNTC.

Adult↗
PubMed2002

Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia.

The conventional concept of Pick's disease does not distinguish Pick's disease with Pick bodies (Pick body disease, PBD) from Pick's disease without Pick bodies [lobar atrophy without Pick bodies, LA-PB(-)]. Recently, intraneuronal ubiquitin-positive inclusions (ub-inclusions), which are thought to be a hallmark of amyotrophic lateral sclerosis with dementia (ALS-D), have been found also in LA-PB(-). We reconfirmed that ub-inclusions are consistently detected in LA-PB(-) as well as ALS-D. Subsequently, morphometric evaluation for involvement of the upper and lower motor neuron systems were performed in seven cases each of PBD, LA-PB(-), ALS-D and controls. As an indicator of upper motor neuron involvement, the total number of axons through the pyramis of the medulla oblongata was employed and for lower motor neuron involvement, the number of hypoglossal neurons per unit area was calculated. In LA-PB(-), axons of the pyramidal tract were significantly reduced in comparison to PBD and controls, while the lower motor neurons were preserved. Contrary to LA-PB(-), ALS-D revealed significant reduction of hypoglossal neurons but its pyramidal tract tends to be relatively preserved. These results seem to indicate that LA-PB(-) and ALS-D belong to the same spectrum and consist of subgroups with ub-inclusions and involvement of motor neuron system in common. The involvement of the upper motor neuron system is emphasized in LA-PB(-), while ALS-D accentuates the lower motor neuron system. However, the border between the two group is not always clear and there are patients who can not be definitively classified.

Aged↗
PubMed2002

Preservation of nigral neurons in Pick's disease with Pick bodies: a clinicopathological and morphometric study of five autopsy cases.

Many reports have described loss of neurons in the substantia nigra in Pick's disease (PiD). In those reports, however, "Pick's disease" includes PiD without Pick bodies (PB), and there is only limited data available on regional nigral pathology in PiD with PB. To elucidate the pathological changes of the substantia nigra in PiD with PB, we examined five cases and 12 age-matched controls by morphometry. The number and size of pigmented and nonpigmented neurons, as well as the area of the substantia nigra were examined. The area of the substantia nigra was significantly reduced in PiD with PB. The pigmented and nonpigmented neuron counts in PiD with PB were not statistically different from those in controls. There was a significant reduction in the size of pigmented neurons in PiD with PB to 82% with that in the controls. In addition, after reviewing 48 cases of PiD with PB reported in the literature, we found that none of the cases with typical frontotemporal lobe symptoms exhibited parkinsonism until the terminal stage. These data are useful for discriminating PiD with PB from other diseases showing frontotemporal characteristics, including the frontal lobe degeneration type and the motor neuron disease type of frontotemporal dementia.

Adult↗
PubMed2002

Viral genotypes and response to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan.

Acute hepatitis B virus (HBV) infection was diagnosed in 57 adults admitted to Toranomon Hospital in Tokyo, Japan. Genotypes of HBV were determined by a serological method and compared to those in 1,077 patients with chronic hepatitis B. The distribution of genotypes were: genotype A (acute, 22.8% vs. chronic, 1.9%; P < 0.00001); B (14.0% vs. 9.4%); C (43.9% vs. 87.7%, P = 0.004); D (1.8% vs. 0.2%); F (1.8% vs. 0.2%); and unable to be typed (15.8% vs. 0.6%, P = 0.001). The infection persisted in seven (12%) of them. They included six (86%) of the seven patients who received prednisolone or glycyrrhizin during an acute phase of illness and one of the 41 (2%) who did not (P = 0.01). Interferon was given to the seven patients with acute prolonged HBV infection, and four of them responded by clearing hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) from serum. Of the four responders, one was infected with HBV genotype B and three with genotype C. HBsAg persisted in the remaining three patients all of whom were infected with HBV genotype A, and HBeAg stayed positive in one of them. These results indicate that HBV genotype A prevails in Japanese patients with acute hepatitis B, and suggest a high efficacy of interferon in the adult patients with acute prolonged HBV infection, except in those infected with HBV genotype A.

Acute Disease↗
PubMed2002

Interferon for treatment of breakthrough infection with hepatitis B virus mutants developing during long-term lamivudine therapy.

BACKGROUND: We aimed to treat patients with chronic hepatitis B on long-term treatment with lamivudine who developed lamivudine-resistant hepatitis B virus (HBV) mutants along with clinical relapses. METHODS: Of 217 patients with chronic hepatitis B who had been treated with lamivudine for 1-6 years, 23 (11%) developed lamivudine-resistant hepatitis B virus (HBV) mutants. Seven of them, including 1 whose case was previously reported, received interferon (IFN) daily for 4 weeks and then two or three times a week thereafter to cope with exacerbation of hepatitis. We investigated the efficacy of this IFN therapy in 6 patients, excluding the 1 previously reported. RESULTS: In 4 patients, HBV DNA decreased to below the detectable limit of the branched DNA assay (<0.7 MEq/ml) accompanied by normalization of transaminase levels. During IFN therapy, 2 patients seroconverted to antibody to hepatitis B e antigen (HBeAg) and showed normalized transaminase levels. Interferon was required in 7 of the 111 (6%) patients with chronic hepatitis B who were positive for HBeAg, but in none of the 106 who were positive for antibody to HBeAg ( P = 0.014). CONCLUSIONS: The efficacy of IFN in controlling virological breakthroughs and exacerbation of hepatitis by infection with lamivudine-resistant HBV mutants in patients with HBeAg-positive chronic hepatitis B could enhance the versatility of lamivudine, which may have to be given to them indefinitely.

Adolescent↗
PubMed2002

Clinical characteristics of patients infected with hepatitis B virus genotypes A, B, and C.

BACKGROUND: The aim of the present study was to evaluate the clinical characteristics at first hospital consultation, according to the genotype of hepatitis B virus (HBV), in patients with chronic liver diseases and positivity for hepatitis B surface antigen (HBsAg) in metropolitan Tokyo. METHODS: The subjects consisted of 1077 patients with chronic liver diseases who were HBsAg-positive. HBV genotype was determined by an enzyme-linked immunosorbent assay (ELISA), using PreS2 monoclonal antibody, which is specific for HBV genotypes in the PreS2 region. RESULTS: The proportion of patients with genotype A was 2% (20 patients), genotype, B 9% (101 patients), and genotype C, 88% (945 patients), while 11 patients (1.0%) had other genotypes, including 2 (0.2%) each with genotypes D and F, and 7 (0.6%) that were untypeable. Patients with genotype A were significantly (P = 0.049) more likely to be positive for Hepatitis B envelope antigen (HBeAg) at the first consultation compared with those with genotype B. Patients with genotype B were significantly more likely to be HBeAg-negative at the first consultation compared with those with genotype A (P = 0.049) and genotype C (P = 0.001), significantly more likely to show minimal hepatic fibrosis (P = 0.003), and least likely to develop liver cirrhosis (P = 0.005). Patients with genotype C were likely to be HBeAg-positive (P = 0.001) and to have a positive family history of HBV infection (P = 0.0002). CONCLUSIONS: The clinical features of patients with HBV infection in metropolitan Tokyo varied depending on the HBV genotype.

Adolescent↗
PubMed2002

Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases.

We investigated the occurrence of T cells in the brain parenchyma of Alzheimer's disease (AD), non-AD degenerative dementias and controls by semi-quantitative analysis of immunohistochemically stained tissue sections. In all cases, we found at least some T cells. The number of T cells was increased in the majority of AD cases compared with other cases. The phenotype of T cells in the AD brain indicates that they are activated but are not fully differentiated. Antigen-triggered clonal expansion is not likely to take place. Local inflammatory conditions might cause accumulation and activation of T cells in the AD brain.

Aged↗
PubMed2002

Mutations of polymerase, precore and core promoter gene in hepatitis B virus during 5-year lamivudine therapy.

BACKGROUND/AIMS: The effects of long-term lamivudine therapy on changes in polymerase and precore/core promoter mutations are unknown. The aim of this study was to determine the changes in these regions in patients with chronic hepatitis B virus (HBV) infection treated with lamivudine for 5 years. METHODS: Serum samples obtained from 16 patients at the beginning of and during therapy were polymerase chain reaction-amplified, and nucleotide sequences of HBV analyzed. RESULTS: By the end of 5-year therapy, mutations in YMDD motif emerged in ten patients. Mutations in L526M, M550V and M550I in polymerase were found in seven, six and six patients, respectively. The L526M mutant was found at the time or after detection of M550V/I mutant in six of seven patients. At baseline, precore and core promoter mutations were found in eight and 12 of 16 patients, respectively. Mutants of precore and core promoter were replaced by wild-type virus in each of three patients infected with mutants at 1 year. However, at 5 years of treatment, precore and core promoter mutations reappeared in some patients. CONCLUSIONS: Our data showed that lamivudine initially selected from precore/core promoter mutants to wild-type virus, but precore mutation reappeared during prolonged therapy.

Adult↗
PubMed2002

Efficacy of interferon monotherapy to 394 consecutive naive cases infected with hepatitis C virus genotype 2a in Japan: therapy efficacy as consequence of tripartite interaction of viral, host and interferon treatment-related factors.

BACKGROUND/AIMS: The mechanism of variable response to interferon (IFN) monotherapy in patients infected with HCV genotype 2a is still unclear. Here we investigated the response in a large group of patients infected with genotype 2a. METHODS: We evaluated 394 consecutive non-cirrhotic naive patients infected with genotype 2a who received IFN monotherapy for 24 weeks, including initial aggressive induction therapy. Of these, 97 were also evaluated for early viral kinetics in serum and treatment efficacy. RESULTS: The overall sustained response (SR) rate was 68.3% (viral load <1.0 Meq/ml (82.4%); >/=1.0 (52.4%)). Multivariate analysis identified five independent factors associated with SR; viral load <1.0 Meq/ml, total IFN dose > or =700 million units, hepatocyte steatosis none or mild, albumin > or =3.9 g/dl, and alanine aminotransferase > or =75 IU/l. The kinetic study showed that serum viral clearance at < or =1 week was the best predictor of SR, and persistence at > or = 4 weeks was a predictor of non-SR. CONCLUSIONS: Our study suggests that viral, host and IFN treatment-related factors determine the response to IFN monotherapy in patients infected with HCV genotype 2a. Further, we report that IFN monotherapy is very effective for patients with genotype 2a, especially for those with low viral load; and that early viral kinetics is useful as a predictor of the response.

Adolescent↗
PubMed2002

Randomized, controlled trial of natural interferon-alpha therapy for e-antigen-positive chronic hepatitis B patients.

We evaluated the efficacy of long-term interferon (IFN) therapy in patients with e-antigen-positive chronic hepatitis B. The study design was a prospective, randomized controlled clinical trial. Fifty-three patients were randomly assigned into one of two groups, treated with 3 million units (MU) of IFN (low dose group; n=27) or 6 MU IFN (high dose group; n=26), administered twice weekly for 52 weeks. Responders were defined as patients whose hepatitis B virus (HBV)-DNA level, determined by branched DNA signal amplification and hepatitis B e-antigen (enzyme immunoassay) were negative and whose serum alanine transaminase (ALT) levels fell to within the normal range (ALT<50 IU/l) at 6 month after termination of IFN therapy. One patient in high dose group was dropped out because of transfer. Remainder 52 patients were examined by intention-to-treat (ITT) analysis. The response rates by ITT analysis were 40.7% (11/27) in low dose group and 20% (5/25) in high dose group. The difference between low and high dose group was not statistically significant. Univariate analysis of clinical factors that contribute to the response demonstrated that IFN therapy had a significant effect when, (1) the serum HBV-DNA level was <200 Meq/ml prior to the commencement of IFN therapy (P=0.0327). (2) Transient acute exacerbation of ALT was present during or after IFN therapy (P=0.0311). Multivariate analysis showed that the risk ratio for the development of response in patients with serum HBV-DNA level of less than 200 Meq/ml was 3.60 compared with patients with that of 200 Meq/ml or more than 200 Meq/ml (95% CI, 1.012-12.81). In conclusion, the results of this trial show that: (1) long-term twice weekly IFN therapy could be a worthwhile strategy for e-antigen-positive chronic hepatitis B patients with serum HBV-DNA level of less than 200 Meq/ml and (2) patients with transient acute exacerbation of ALT during or after IFN therapy could often respond well after exacerbation of ALT.

Journal Article↗
PubMed2002

Long-term clinical remission induced by corticosteroid withdrawal therapy (CSWT) in patients with chronic hepatitis B infection: a prospective randomized controlled trial--CSWT with and without follow-up interferon-alpha therapy.

The effectiveness of corticosteroid withdrawal therapy (CSWT), with or without follow-up interferon-alpha (IFN-alpha), has not been reported for HBe antigen (HBeAg) -positive patients with chronic hepatitis B. We conducted a prospective randomized controlled trial in 42 patients with HBeAg- and HBV-DNA-positive chronic hepatitis B (HBV genotype C: 38 patients) to assess the possible additive effect of follow-up IFN-alpha after CSWT compared with CSWT alone. HBeAg seroconversion rates in the CSWT-alone and the combination group were 11.1% vs 11.8% at 24 weeks, 27.8% vs 12.5% at 52 weeks, 33.3% vs 18.8% at 76 weeks, and 38.9% vs 18.8% at 104 weeks, respectively. The final HBeAg seroconversion rates after CSWT alone were twice those following combination therapy. We conclude that CSWT alone is a very short-term treatment of just three weeks that may be more effective for long-term clinical remission than CSWT followed by IFN-alpha in Japanese genotype C-dominant hepatitis B patients.

Adrenal Cortex Hormones↗
PubMed2002

Parkinson's disease mimicking senile dementia of the Alzheimer type: a clinicopathological study of four autopsy cases.

This report concerns four Japanese autopsy cases of Parkinson's disease (PD) mimicking senile dementia of the Alzheimer type. Three patients with a clinical diagnosis of senile dementia of the Alzheimer type developed memory disturbance as the initial sign, and a patient with a clinical diagnosis of atypical senile dementia presented with hallucination and delusion as the initial sign. Dementia was evident in all four patients, and slight parkinsonism appeared in the middle to late stages of the disease in two patients. Macroscopical examination of the brain disclosed slight depigmentation of the substantia nigra and prominent depigmentation of the locus ceruleus in all four cases. Histological examination of the four patients showed neuronal loss with astrocytosis and the appearance of Lewy bodies in the substantia nigra, locus ceruleus, and dorsal vagal nucleus. The nucleus basalis of Meynert was involved in three cases, in which this structure was examined. The total Lewy body scores of the four cases were 1 in three cases and 0 in the other, compatible with PD. Massive appearance of senile plaques, consistent with Braak stage C, was found in one case, and the slight appearance of senile plaques, consistent with Braak stage A, was evident in two cases. One case had no evidence of senile plaques. In all four cases, slight neurofibrillary changes were present in the limbic areas, compatible with Braak stages II to III. Based on these clinicopathological findings and a review of the literature, we concluded that PD simulating Alzheimer's disease without overt parkinsonism rarely exists. Furthermore, we postulate that the clinical features of PD are more widespread than previously believed.

Aged↗
PubMed2002

Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy: a report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions.

This report concerns an autopsy case of amyotrophic lateral sclerosis (ALS) with circumscribed temporal atrophy. The patient was a Japanese woman without hereditary burden who was 71-year-old at the time of death. She developed dysarthria and gait disturbance at age 69, followed by dysphagia. A neurological examination about 1 year 11 months after the onset of the disease revealed absence of character change and of dementia. Neuroradiological examination disclosed circumscribed atrophy of the anterior part of the right temporal lobe. The patient died of respiratory failure 2 years after the disease onset. No respirator administration was performed throughout the clinical course. Macroscopically, neuropathological examination showed circumscribed atrophy of the right first temporal gyrus. Histologically, there was neuronal loss in the cerebral cortex, including the first temporal gyrus, the parahippocampal gyrus, subiculum, amygdala, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to loss of Betz cells, obvious degeneration of the pyramidal tracts, and the presence of Bunina bodies. Ubiquitin-immunoreactive intraneuronal inclusions were present in the hippocampal dentate granular cells, frontotemporal cortical layer II neurons, and motor neurons in the brain stem and spinal cord. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS without dementia, showing temporal lobe atrophy macroscopically, in addition to pathological hallmarks compatible with ALS with dementia. We also note the possibility that there is a forme fruste of ALS with dementia showing no overt dementia clinically.

Aged↗
PubMed2002

Basal ganglia lesions in 'Pick complex': a topographic neuropathological study of 19 autopsy cases.

The distribution of basal ganglia lesions, including the amygdala, striatum (caudate nucleus, putamen), pallidum, and substantia nigra, were reinvestigated in 19 Japanese autopsy cases of 'Pick complex', consisting of five patients with corticobasal degeneration (CBD), 10 patients with Pick's disease with Pick bodies (PDPB), and four patients with generalized variant of Pick's disease (gvPD). The lesions in the amygdala, striatum, and pallidum were classified into three categories (severe, moderate, and slight). The lesions in the substantia nigra were qualitatively judged, compared with normal controls. In CBD, basal ganglia lesions in all five cases were uniform: the pallidum showed severe lesions, the striatum moderate lesions, the amygdala slight lesions, and obvious neuronal loss of the substantia nigra was verified in all five cases. Basal ganglia lesions in 10 cases of PDPB were also uniform: the amygdala disclosed severe to moderate lesions, the striatum moderate to slight lesions, the pallidum slight lesions, while obvious neuronal loss of the substantia nigra was found in only two of nine cases in which this structure was examined. Furthermore, basal ganglia lesions in all four cases of gvPD were uniform: the caudate nucleus showed severe lesions, the putamen and amygdala severe to moderate lesions, the pallidum moderate to slight lesions, and obvious neuronal loss of the substantia nigra was confirmed in all four cases. This study, using conventional staining such as hematoxylin-eosin and Holzer, clarified that there were prominent lesions in the pallidum in CBD, in the amygdala in PDPB, and in the caudate nucleus in gvPD, respectively. In addition, nigral involvement was usually found in CBD and gvPD, but was rarely seen in PDPB. These neuropathological findings may help to elucidate the pathological heterogeneity of basal ganglia lesions in 'Pick complex'.

Aged↗
PubMed2002

Viral dynamics and pharmacokinetics in combined interferon alfa-2b and ribavirin therapy for patients infected with hepatitis C virus of genotype 1b and high pretreatment viral load.

OBJECTIVE: The aim of this study was to clarify the viral dynamics and single- and multiple-dose pharmacokinetics of ribavirin and interferon (IFN) alfa-2b in the virologic response to combination therapy with both compounds in patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. METHODS: Fourteen patients received high-dose daily induction therapy followed by intermittent maintenance therapy with IFN alfa-2b and daily oral ribavirin for 24 weeks, and followed up for 24 weeks after treatment. Single- and multiple-dose pharmacokinetic studies and viral dynamics were assessed by serial measurements of serum concentrations of both compounds and HCV RNA, respectively, at weeks 1 and 24. RESULTS: During treatment, all 14 patients showed biochemical response (i.e., normalization of serum alanine transaminase activity), while 11 showed virologic response (i.e., undetectable serum HCV RNA level by qualitative polymerase chain reaction assay). Sustained biochemical and virologic response after cessation of treatment was noted in 8 and 2 patients, respectively. Serum ribavirin concentrations asymptoted by 4 weeks of treatment. Serum ribavirin concentrations in steady state, and maximum concentration and accumulation rate of ribavirin after multiple dosing were significantly higher in the presence of sustained virologic response. HCV-related parameters were not significantly associated with sustained virologic response. CONCLUSIONS: Continuous exposure and tissue accumulation of ribavirin may be necessary for sustained virologic response to combination therapy in chronic hepatitis C with genotype 1b and high viral load. Pharmacokinetic analysis of ribavirin provides information on its mechanism of action and for developing more rational treatment for IFN-resistant HCV.

Adult↗