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Kenji Ikeda

Publications and source records attributed to Kenji Ikeda.

At least 91 records · Page 5Linked to original sources
PubMed2004

[An autopsy case of "progressive supranuclear palsy" without psychiatric or neurological signs].

We report an autopsy case of a Japanese man with "progressive supranuclear palsy (PSP)" who showed neither neurological nor psychiatric signs. Although he died by heart failure at the age of 84 years, he had neither neurological nor psychiatric signs throughout the clinical course. Neuropathological examination revealed neuronal loss of the substantia nigra and pallidum. Neurofibrillary tangles were observed in the caudate nucleus, subthalamic nucleus, pallidum, putamen, substantia nigra, locus ceruleus, pontine nucleus, inferior olivary nucleus, and dentate nucleus, compatible with the NINDS pathological diagnosis of PSP reported in 1994. Staining by Gallyas-Braak methods disclosed tuft-shaped astrocytes in the caudate nucleus, putamen, and thalamus. To our knowledge, this is the first report of "PSP" without psychiatric or neurological signs.

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PubMed2004

[An autopsy case of senile dementia with pathological features of Parkinson's disease].

We report an autopsy case of Parkinson's disease mimicking senile dementia of the Alzheimer type. A Japanese man developed memory disturbance and visual hallucination at age 70. Although he died from pneumonia at age of 74, he had no neurological signs throughout the clinical course. The weight of his brain was 1,420 g. Macroscopic examination of the brain revealed prominent depigmentation of the substantia nigra and locus ceruleus. Histological examination disclosed neuronal loss with astrocytosis and the appearance of the Lewy bodies in the nucleus basalis of Meynert, substantia nigra, locus ceruleus, and dorsal vagal nucleus. There were widespread senile plaques in the brain, including the precentral gyrus, which was compatible with Braak stage C. A small number of neurofibrillary changes were present in the limbic areas, consistent with Braak stage III. This case is consistent with brain stem dominance with the pathological diagnosis of the Consortium on Dementia with Lewy Bodies International Workshop. That is, it is compatible with Parkinson's disease. We postulate that the clinical features of Parkinson's disease are more widespread than previously considered.

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PubMed2004

[Argyrophilic grain disease clinically mimicking Parkinson's disease with dementia: report of an autopsy case].

Argyrophilic grain disease (AGD) is a neurodegenerative dementia, which is neuropathologically characterized by the spindle-or comma-shaped argyrophilic grains scattered in the neuropil of hippocampal area. Several research reports have disclosed the pathological, biochemical and genetic characteristics of AGD, whereas the clinical aspects have not been fully investigated. Here we report an autopsy case of AGD. She developed tremor at age 63, and then developed dyskinesia, rigidity and gait disturbance. Thereafter, she had cognitive impairment and emotional disturbance at age 71, and died of pneumonia at age 76. She was clinically diagnosed as Parkinson's disease with dementia due to the presence of parkinsonism and dementia. Macroscopically, the brain demonstrated mild atrophy, and the weight was 1,240 g. Many argyrophilic grains were found in the hippocampus and amygdala. Coiled bodies and ballooned neurons were also present, while Alzheimer-type neurofibrillary changes were mild, consistent with stage 2 of Braak's classification. This case was neuropathologically diagnosed as AGD. In contrast, no remarkable pathological changes, including neuronal loss and Lewy bodies, were found in the nigra, locus ceruleus and basal nuclei. On the basis of the above-mentioned clinicopathological findings, parkinsonism with dementia is considered to be one of the clinical manifestations of AGD.

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PubMed2004

[Anterior type dementia from the viewpoint of neuropathology].

Anterior type dementia is characterized by primary degeneration in the anterior brain region and represents pick symptom. Anterior type dementia includes several pathological disease entities, almost of them usually exhibit variation of atrophic brain regions in greater or lesser degree. This variation of each disease cause confusion, namely, the same clinical manifestations occur even if it is a different disease and diversely, different clinical manifestations can occur even if it is the same disease entity. This is the reason why discrepancy between clinical diagnosis and pathology diagnosis occurs sometimes in anterior type dementia. For reasonable clinical diagnosis, anterior type dementia, separate from neuropathological diseases entity, should be deal with clinical symptom-complex, which consists of frontotemporal dementia (FTD) progressive nonfluent aphasia (PA) and semantic dementia (SD). FTD, PA and SD have, though broadly, corresponding responsible brain lesion respectively.

Atrophy↗
PubMed2003

Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain.

Familial British dementia (FBD) is characterized neuropathologically by deposition of a unique amyloid-forming protein, ABri. It is a fragment of an abnormal form of a precursor protein, BRI. In FBD, BRI is elongated by 11 amino acids due to a point mutation that prevents recognition of the normal stop codon. We have investigated the expression of normal BRI in non-FBD cases. Three antibodies were raised against sequences of BRI and were used for immunoblotting and immunohistochemistry. Each of these antibodies detected a band at approximately 35 kDa by Western blotting. In postmortem human brain tissues, BRI was detected as fine granules in the neuronal cytoplasm. Pyramidal neurons in CA3 and CA4 of the hippocampus as well as Purkinje cells in the cerebellar cortex were most intensely stained for BRI. Such a distribution of neurons strongly expressing BRI parallels the reported occurrence of ABri deposits in patients with FBD. In pathological cases, BRI was detected in dystrophic neurites in senile plaques, around lesions in ischemic cases, in torpedo and glumose changes in the cerebellum, Lewy neurites, ballooned neurons, and neurons generally in hypoxic cases. These results suggest that BRI is transported in neuronal processes and is possibly involved in some role in nerve terminals. While a physiological role of BRI in brain remains to be determined, the behavior of BRI in diverse brain lesions appears to be somewhat analogous to that of amyloid precursor protein, which is the source of the beta-amyloid protein of Alzheimer's disease.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62.

We examined the immunoreactivity of p62 in five cases of frontotemporal dementia (FTD) with ubiquitin-positive, tau-negative inclusions. Only one case had clinical features suggestive of motor neuron disease (MND). In all cases, ubiquitin-positive neuronal inclusions and neurites in the hippocampal region and cerebral neocortex were immunohistochemically positive for p62. Moreover, in the temporal region of a case of FTD with MND, many oligodendrocytes and some astrocytes were positive for p62. These results suggest that the degenerative process involves p62 in FTD and that the process takes place not only in neurons but also in glial cells.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Enhanced expression of aquaporin 4 in human brain with infarction.

A series of human brains with cerebral infarction obtained at autopsy were investigated to clarify the possible contribution of aquaporin 4 (AQP4) to the development of brain edema. Cellular localization of AQP4 and its relation to ischemic foci were examined with double-labeling immunohistochemistry. AQP4 immunoreactivity (IR) was more intense at the periphery of ischemic foci than at their center. Double-labeling study demonstrated that AQP4 IR was restricted to astrocytes and was localized to their entire processes, including their end feet facing the outer surface of capillaries. Moreover, AQP4 IR, detectable in the subpial and subependymal zone in the normal condition, was more intense in the vicinity of ischemic foci. Accumulation of AQP4 IR may reflect its participation in the development of brain edema in human brains by playing a role in the transport of water not only through blood vessel walls but also through pial and ependymal surface of the brain.

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PubMed2003

Increased expression of neuronal apolipoprotein E in human brain with cerebral infarction.

BACKGROUND AND PURPOSE: Cellular origin of apolipoprotein E (ApoE) in the human brain and its roles in physiological and pathological conditions remain to be clarified. METHODS: Immunolocalization of ApoE was investigated in a series of autopsied human brains with or without infarction. ApoE expression was also estimated on immunoblot on protein extracts from autopsied brains and a cultured neuroblastoma cell line of human origin (GOTO) subjected to an oxidative stress induced by exposure to hydrogen peroxide (0.2 mmol/L). RESULTS: In addition to astrocytes and microglia, neurons and degenerated axons in and around the ischemic foci contained ApoE-like immunoreactivity, which was more intense in recent ischemic foci. Immunoblot demonstrated an increase in expression of ApoE in brain extracts from ischemic lesion, and this increase was also pronounced in the cultured neuroblastoma cell line after the stress. CONCLUSIONS: Accumulation of ApoE in neurons in and around ischemic foci of the human brain is related to an increase in ApoE synthesis in neurons, as seen in cultured neuronal cells after oxidative stress. Intrinsic regenerative activity of neuron in reaction to external insults may be related to this increase in ApoE of neuronal origin.

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PubMed2003

Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration.

The microtubule-associated protein tau accumulates as cytoplasmic inclusions in Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We investigated the immunoreactivity of tau-positive structures using a panel of antibodies to epitopes spanning the entire length of the tau molecule. In ethanol-fixed brain tissues, most antibodies to the microtubule-binding domain (MBD) required formic acid (FA) treatment to stain tau inclusions in PSP and CBD. This is in contrast with the intense labeling of neurofibrillary tangles in AD without FA treatment. Pick bodies (PiB) in PiD showed an intermediate pattern with respect to the immunoreactivity of the MBD because accumulated tau in PiB mostly lacks the insertion of exon 10, and the proportion of tau phosphorylated at Ser262 is smaller than in other abnormal tau structures. Such immunohistochemical profiles appeared to correlate with the occurrence of the smeared tau on immunoblot analysis of brain homogenate. The smeared tau was more abundant in AD and PiD than in PSP and CBD. Since the smeared tau was N-terminally truncated and was characteristic of advanced forms of modified tau, these findings suggest that tau accumulated in AD and PiD was processed more markedly than that in PSP and CBD. The MBD of tau may be masked in the presence of the intact N terminus and require FA treatment for antibody recognition in tissue sections. Advanced modification may expose the MBD in brain tissues of AD and PiD. It is suggested that the processing of abnormally accumulated tau characterizes the pathophysiology of each tauopathy.

Aged↗
PubMed2003

Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy.

Patients with low titer (<0.5 mEq/ml) of hepatitis C virus (HCV) genotype 2a achieve high and sustained response (SR) rates to interferon (IFN) monotherapy, but we also encounter patients who are resistant to therapy. We explored the relationship between response to IFN and virological differences in such patients. We evaluated 159 consecutive naive patients with low titer of HCV genotype 2a who received IFN monotherapy. A case-control study matched for age, sex, and viral load was conducted to examine the substitution patterns in amino acid positions (amino acids) 2163-2254 of nonstructural (NS) 5A between nonresponders to ideal IFN dose (>/=500 million units) (nonresponders; NR) and responder to less than ideal dose. Overall, 82.4% achieved SR. The substitution numbers in amino acids 2193-2254 were higher in SR than NR patients (P < 0.05). High proportions of patients with substitution at amino acid 2205 (mainly threonine [T] instead of alanine [A]), dual amino acids 2169 and 2205 (mainly A-T instead of T-A), and those without substitution at amino acids 2227 were NR (P < 0.05). Four of 7 NR patients achieved SR after receiving a second course of IFN. Their amino acids patterns at positions probably associated with sensitivity to IFN did not change at the start of initial and second therapies except for one patient, and they had lower viral load and were treated with higher IFN dose in the second course compared with the initial course. Our results suggest that substitution patterns in NS5A in patients with low titer of HCV genotype 2a may affect their response to IFN, but the response to therapy may be affected by mechanisms other than substitutions in this region.

Adult↗
PubMed2003

HBe antigen loss during lamivudine therapy is not caused by mutations in precore and core promoter genes in patients with chronic hepatitis B.

HBe antigen (HBeAg) loss or seroconversion can occur during lamivudine therapy. The purpose of this study was to analyze nucleotide sequences in precore and core promoter regions, and examine the influence of mutations in these regions on the disappearance of HBeAg during lamivudine therapy. Serial serum samples were obtained from 51 patients (HBeAg loss in 26 patients) at commencement of therapy (baseline) and after 1 year of lamivudine therapy. Serum samples were amplified with PCR and nucleotide sequences of HBV were analyzed. At baseline, a precore stop codon mutation (A1896) was identified in 8 of 26 HBeAg loss patients and in 8 of 25 HBeAg non-loss patients. At 1 year, precore mutation was observed in 4 of 14 patients analyzed who showed HBeAg loss. At 1 year, however, a precore mutation was observed also in 3 of 9 analyzed patients who showed no HBeAg loss. Core promoter mutations were noted in 21 of 26 HBeAg loss patients and in 20 of 25 HBeAg non-loss patients. At 1 year, core promoter mutations were noted in 11 of 14 HBeAg loss patients and in 8 of 9 HBeAg non-loss patients. Our data suggested that during lamivudine therapy, core promoter and precore mutations do not influence HBeAg loss or seroconversion but may reduce the viral level upon HBeAg loss or seroconversion.

Adult↗
PubMed2003

Natural histories of hepatitis C virus infection in men and women simulated by the Markov model.

The Markov model was introduced to simulate natural histories of hepatitis C virus (HCV) infection in men and women. The data set was constructed on 942 HCV carriers who were examined at least once a year without receiving antiviral therapies. Based on 2,251 patient-year data, the probabilities of transition between any two of the four clinical states, i.e., asymptomatic carrier state, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in 1 year were calculated. Hepatocellular carcinoma was defined as the absorbing state from where no transitions occur. Probability matrices thus obtained on six each subsets of HCV infection (asymptomatic carrier state, chronic hepatitis and liver cirrhosis in men and women) in their forties, fifties, and sixties, were used to simulate long-term outcomes of HCV infection. Male asymptomatic carriers aged 40 years were expected to retain the asymptomatic carrier state in 2.6%, evolve into chronic hepatitis in 48.4%, liver cirrhosis in 14.6% and hepatocellular carcinoma in 34.4% after 30 years when they reached 70 years of age, in contrast to 1.9%, 45.3%, 32.8% and 20.0%, respectively, of female asymptomatic carriers. Likewise, male patients with chronic hepatitis aged 40 years were expected to remain with chronic hepatitis in 43.8%, evolve into liver cirrhosis in 15.0% and hepatocellular carcinoma in 41.1%, contrasting with 38.9%, 32.7% and 22.0%, respectively, of female patients during 30 years. The Markov model could simulate the outcomes of 153 HCV carriers identified among blood donors after 5 years. The Markov simulation would help in assessing the long-term outcome of HCV infection and making decisions in the management of HCV carriers toward prevention of hepatocellular carcinoma.

Adult↗
PubMed2003

Virological and biochemical relapse according to YMDD motif mutant type during long-term lamivudine monotherapy.

Whether the type of lamivudine-resistant virus in hepatitis B virus (HBV) influences the clinical outcome, it is not completely understood. We evaluated the serial changes in YMDD motif mutant in 60 Japanese genotype C-HBV patients who received long-term lamivudine monotherapy. YIDD or YVDD alone tended to stop shifting to the mixed type (YVDD and YIDD) within 12 months after the detection of mutant virus. Hence, the characteristics, virological relapse (DNA breakthrough) and biochemical relapse (breakthrough hepatitis) of 49 patients, who could be classified into three types (continuous YVDD, continuous YIDD, and the mixed type), were investigated. YVDD and YIDD type tended to have the opposite background with regard to age, histology, and viral load. The mixed and YIDD types tended to have similar backgrounds, except for viral load. In the mixed type, both the HBeAg-positive rate and viral load as risk factors for emergence of the mutant tended to be high. Mutant virus, DNA breakthrough and breakthrough hepatitis emerged significantly earlier in the mixed type than the two other types. The incidence of severe breakthrough hepatitis accompanied by icteric flare-up tended to be higher in the mixed type than the other types. Our results suggest that the YMDD motif mutant type might emerge from different backgrounds and modulate the virological and biochemical relapse after the emergence. Large-scale studies of each mutant type should be conducted in the future to confirm these findings.

Adult↗
PubMed2003

Type C-chronic hepatitis patients who had autoimmune phenomenon and developed jaundice during interferon therapy.

Of a total of 2342 patients with type-C chronic hepatitis treated with interferon (IFN) at this hospital, 3 patients developed jaundice during the course of IFN therapy, but all 3 of them exhibited negative conversion of hepatitis C virus (HCV)-RNA following readministration of IFN. All 3 patients were assessed as having "probable autoimmune hepatitis (AIH)" in accordance with the AIH scoring system, indicating association with an "autoimmune phenomenon". Readministration of IFN at a low-dose induced activation of the autoimmune phenomenon, leading to fulminant hepatocellular impairment. As a result, HCV-RNA content dropped dramatically, possibly contributing to the negative conversion of HCV-RNA noted following the readministration of IFN. At present, no adequate therapy has been established for type-C chronic hepatitis with autoimmune manifestations. However, in conclusion, our findings suggested that: IFN should be a frontline regiment: (1). if autoantibody titers are low or patients are rated as having "probable AIH" or lower in accordance with the AIH scoring system, indicating a strong link to chronic hepatitis or (2). if IFN is expected to be efficacious on the basis of genotype of HCV-RNA level; even if there is acute exacerbation of type-C chronic hepatitis, IFN should be re-administered in the HCV-RNA level has dropped subsequently.

Adult↗
PubMed2003

Clinical features of hepatitis B virus genotype A in Japanese patients.

BACKGROUND: Hepatitis B virus (HBV) genotype A is predominant in northern Europe and central Africa. In the present study, we examined the clinical features associated with HBV genotype A disease in the Tokyo metropolitan area. METHODS: We investigated 53 cases of HBV surface antigen (HBsAg)-positive Japanese patients with HBV genotype A. The 53 cases were further classified as to their serum alanine aminotransferase (ALT) status being within the normal range (asymptomatic carriers, n = 17), chronic hepatitis (n = 15), liver cirrhosis (n = 4), and acute hepatitis (n = 17). RESULTS: Chronic hepatitis patients had significantly higher HBV DNA levels (P = 0.003) and hepatitis B e antigen (HBeAg) positivity rates at the initial visit than did asymptomatic carriers or patients with liver cirrhosis (P = 0.003 and P = 0.054, respectively). The efficacy of treatment (HBeAg seroconversion rate) was 75% in 12 chronic hepatitis patients, which was excellent. A family history of HBsAg positivity was identified in eight (15%) families (five asymptomatic carriers, three with chronic hepatitis). However, none of the mothers in the study was positive for HBV genotype A. CONCLUSIONS: Maternal transmission of HBV has often been reported in Japan, but our present findings suggest that horizontal infection of HBV genotype A is more prevalent in the Tokyo metropolitan area. Our data indicate that HBV genotype A exhibits a mode of infection different from that of conventional HBV previously seen in Japan.

Adolescent↗
PubMed2003

Significance of multicentric cancer recurrence after potentially curative ablation of hepatocellular carcinoma: a longterm cohort study of 892 patients with viral cirrhosis.

BACKGROUND: Tumor recurrence is common after potentially curative ablation of hepatocellular carcinoma; therefore, the incidence of intrahepatic metastasis and multicentric carcinogenesis was evaluated. METHODS: A cohort of 892 patients with cirrhosis caused by either hepatitis B virus (n=246) or hepatitis C virus (n=646) was followed up without interferon administration. RESULTS: Hepatocellular carcinogenesis rates were 28.0% at the end of the fifth year, 49.2% at the tenth year, and 61.3% at the fifteenth year. Sex, hepatitis virus, alpha-fetoprotein, platelet count, age, and indocyanine green retention test value significantly affected the carcinogenesis rate. Of 372 patients with tumor development, 162 (43.5%) received surgical or radical locoregional therapy. On the assumption that a second carcinogenesis after sufficient ablation of well-differentiated cancer was attributable to multicentric carcinogenesis, recurrence rates after curative therapy in all the 162 patients, and the recurrence rates in 39 patients with solitary, small, and well-differentiated histology were analyzed: the rates were 58.2% and 30.9% at the third year, 75.9% and 53.4% at the fifth year, and 89.6% and 79.9% at the tenth year, respectively. The estimated incidence of multicentric recurrence was, therefore, 31% or higher at the third year and 53% or higher at the fifth year. The actual second carcinogenesis rates (multicentric recurrence) were approximately 1.6 times as high as those of the virtual second carcinogenesis rates calculated from statistical simulation. CONCLUSIONS: A longterm cohort study disclosed that multicentric carcinogenesis was the principal mechanism of recurrence after curative ablation of hepatocellular carcinoma and that the concept of "carcinogenic stage" should be introduced to improve the understanding of carcinogenic events in viral cirrhosis.

Adult↗