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Biomedical subjects

K Ikeda

Publications and source records attributed to K Ikeda.

At least 145 records · Page 8Linked to original sources

Severe bleeding tendency caused by leukemic infiltration and destruction of vascular walls in chronic neutrophilic leukemia.

Bleeding is reportedly one of the major causes of death in patients with chronic neutrophilic leukemia (CNL), but thrombocytopenia, abnormal platelet functions, or coagulopathy has been confirmed to be the cause of the bleeding tendency in only a small proportion of the patients. We report the case of a 49-year-old woman with CNL who experienced episodes of cutaneous and recurrent multiple cerebral hemorrhages without severe thrombocytopenia, detectable abnormal platelet functions, or coagulating dysfunction. Histological examination of specimens obtained at autopsy showed extensive infiltration and destruction of vascular walls by leukemic cells, which could explain her severe bleeding tendency. This study is the first to clearly show that the infiltration and destruction of vascular walls by leukemic cells can cause fatal bleeding episodes without warning from laboratory findings. Further studies are needed to elucidate the mechanism of the infiltration and destruction of blood vessels by CNL cells and to develop effective measures to control the growth and infiltration of CNL cells.

Endothelium, Vascular↗

Hydrogen peroxide and hydroxyl radical involvement in the activation of caspase-3 in chemically induced apoptosis of HL-60 cells.

Apoptosis of HL-60 cells induced by actinomycin D, H7, or daunorubicin was shown to involve the activation of caspase-3-like protease, 2 h after the addition of these drugs, based on microassay of enzyme activity by high-performance liquid chromatography. Catalase and a spin trap, N-t-butyl-alpha-phenylnitrone, which effectively inhibited the apoptosis induced by these drugs, also inhibited the activation of caspase-3-like protease. These results suggest that hydrogen peroxide and the hydroxyl radical are common mediators of caspase-3 activation caused by these chemicals, with apparently different functional mechanisms. Based on mitochondrial activity determined by oxygen consumption, complexes I, II, and IV were inhibited by actinomycin D. H7 inhibited complexes I and IV, 1 and 1.5 h respectively, after the addition of the drug to HL-60 cells. Daunorubicin inhibited complex IV, 1.5 h after the addition of the drug to HL-60 cells. Inhibition of complex IV by actinomycin D, H7, and daunorubicin were almost fully restored by the addition of cytochrome c. The release to the cytosol of cytochrome c by these drugs was also demonstrated by Western blot analysis. Addition of catalase inhibited the depression of complex IV activity induced by actinomycin D and H7. These observations indicate a direct relationship between hydrogen peroxide and the release of cytochrome c during apoptosis caused by actinomycin D, H7, and daunorubicin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Prenatal MR findings in a case of aneurysm of the vein of Galen.

We describe a case of aneurysm of the vein of Galen (AVG), which was diagnosed by intrauterine US, MRI and MRA. The baby girl was born at 35 weeks' gestation. She had severe clinical symptoms at birth and died at 29 h of age from intractable congestive heart failure. Intrauterine US detected an intracranial aneurysm and cardiomegaly due to excessive arteriovenous shunting. Intrauterine MRI (SSFSE) confirmed the diagnosis of AVG, and intrauterine MRA (2D-TOF) successfully demonstrated the anatomical structure of the AVG. MRA may be a useful additional sequence to evaluate AVG, and 2D-TOF is thought to be an appropriate technique for scanning fetal AVG.

Adult↗

Cytomegalovirus enteritis after autologous peripheral blood stem cell transplantation.

A 61-year-old male with non-Hodgkin's lymphoma (peripheral T-cell lymphoma, unspecified, clinical stage IVb) received autologous peripheral blood stem cell transplantation (PBSCT) during first remission. He was seropositive for cytomegalovirus (CMV) prior to autologous PBSCT. His posttransplant clinical course was complicated by refractory CMV enteritis, which manifested persistent abdominal pain, diarrhea, and bloody stool. Generally, gastrointestinal CMV disease is relatively rare after autologous PBSCT. However, our case indicates that CMV infection must be considered as a differential diagnosis in cases of unexplained hemorrhagic enteritis following autologous PBSCT.

Abdominal Pain↗

Enhanced tolerance against salt-stress and freezing-stress of Escherichia coli cells expressing algal bbc1 gene.

The expression of the eukaryotic bbc1 (breast basic conserved) gene (the bbc1 gene of the marine green alga Chlamydomonas sp. W-80 strain) enhanced the tolerance against salt-stress and freezing-stress in E. coli cells. The expression of the BBC1 protein in the E. coli cells carrying the algal bbc1 gene and that in the Chlamydomonas W-80 cells were examined by Western blotting analysis. The result suggests that the eukaryotic BBC1 protein expressed in the E. coli cells has a protective function against the cellular dehydration.

Adaptation, Biological↗

Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick's disease, corticobasal degeneration and progressive supranuclear palsy.

We investigated isoform composition of aggregated tau protein in brains with Pick's disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) by immunoblot analysis of sarkosyl-insoluble fractions of brain homogenates. We also examined the adjacent brain tissues immunohistochemically with a rabbit antibody, Ex10, which specifically recognizes exon 10 of tau. The Ex10 recognizes tau isoforms with four microtubule-binding repeats (4Rtau) but not those with three microtubule-binding repeats (3Rtau). Sarkosyl-insoluble tau from the brains of patients with CBD and PSP consisted of 4Rtau. Insoluble tau from the PiD brains contained both 3Rtau and 4Rtau, where 3Rtau predominated over 4Rtau. In brain tissues of CBD and PSP, Ex10 immunostained all neuronal and glial tau-positive structures. They included pre-tangles, astrocytic plaques, tuft-shaped astrocytes, and oligodendroglial coiled bodies. In PiD brains, astrocytic inclusions were also positive for 4Rtau. However, the majority of, if not all, Pick bodies and oligodendroglial tau inclusions were negative for 4Rtau. Such results suggest that, in neurons and oligodendroglia, tau isoforms involved in the pathological processes differ between CBD/PSP and PiD, and are thus disease specific. This contrasts with the astrocytic tau isoforms that accumulate similarly in all three disorders.

Astrocytes↗

Bunina body in frontal lobe dementia without clinical manifestations of motor neuron disease.

We report here an early autopsy case of a 60-year-old woman clinically diagnosed as having frontal lobe dementia without other neurological deficits. Postmortem examination revealed mild spongiosis in layers II and III of the frontal cortex, together with depletion of melanin-containing neurons in the substantia nigra. In addition to ubiquitin-positive neurites, ubiquitin-positive, tau-negative inclusions, which were previously considered to be a hallmark for motor neuron disease with or without dementia, were identified in neurons of the hippocampal dentate gyrus and of the temporal cortex. Although the patient lacked lower motor symptoms, the presence of Bunina bodies identified in the hypoglossal nuclei further supported the relationship of this case to motor neuron disease. Bunina bodies might be present in some cases of frontal lobe dementia. The presence or absence of Bunina bodies should be scrutinized even in cases without motor symptoms. In this case, creatine kinase of skeletal muscle origin was elevated, which might also be a potential indicator that suggests subclinical involvement of lower motor neurons.

Brain↗

Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease: a report of an autopsy case with a clinical course of 15 years.

This report concerns an autopsy case of atypical amyotrophic lateral sclerosis (ALS) with dementia mimicking frontal Pick's disease. The patient was a Japanese woman without hereditary burden who was 45 years old at the time of death. She developed abnormal behavior and amnesia at age 30, followed by disinhibition, aspontaneity, urinary incontinence, abulia, and rectal incontinence. Neurological signs compatible with ALS developed about 14 years after the disease onset. No respirator was used throughout the clinical course. Macroscopically, neuropathological examination showed atrophy of the frontotemporal lobes with accentuation in the convexities of the frontal lobes. Histologically, there was neuronal loss in the cerebral cortex, parahippocampal gyrus, amygdala, caudate nucleus, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to marked degeneration of the pyramidal tracts. Ubiquitin-immunoreactive neuronal inclusions were present in the frontotemporal cortical layer II neurons and motor neurons in the brain stem and spinal cord. In the hippocampal dentate granular cells, many ubiquitin-immunoreactive neurites were present without ubiquitin-immunoreactive intraneuronal inclusions. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS with dementia of long disease duration. We also note the possibility that motor neuron disease-inclusion dementia with a long clinical course may develop into ALS in the final stage of the illness.

Amyotrophic Lateral Sclerosis↗

Argyrophilic grain disease mimicking temporal Pick's disease: a clinical, radiological, and pathological study of an autopsy case with a clinical course of 15 years.

This report concerns an autopsy case of argyrophilic grain disease (AGD) mimicking temporal Pick's disease. The patient was a Japanese woman without hereditary burden who was 89 years old at the time of death. She developed memory impairment and began wandering at the age of 74, followed by prominent character changes about 6 years after disease onset. A neurological examination 5 months before her death revealed poor rapport, unconcern, severe dementia, and double incontinence, without aphasia or muscle rigidity. Serial neuroradiological examination revealed progressive enlargement of the bilateral inferior horns of the lateral ventricle, reflecting progressive atrophy of the medial temporal lobes. Macroscopically, neuropathological examination showed circumscribed atrophy of the bilateral amygdalae, hippocampi, parahippocampal gyri, and lateral occipitotemporal gyri. Histologically, there was neuronal loss in the areas mentioned above, the caudate nucleus, putamen, thalamus, substantia nigra, and locus ceruleus, with ballooned neurons in the cerebral cortex and amygdala. Numerous argyrophilic grains with coiled bodies were present not only in the limbic system, but also in the affected cerebrum. Rare neurofibrillary changes were present in the limbic areas, consistent with Braak stage II, with no senile plaques. Based on these findings and a review of the literature, we note that AGD is clinicopathologically similar not only to mesolimbocortical dementia, but also to atypical senile dementia of Alzheimer type. This report may contribute to the elucidation of the clinicopathological hallmarks of AGD.

Aged↗

Distribution of basal ganglia lesions in generalized variant of Pick's disease: a clinicopathological study of four autopsy cases.

We investigated four Japanese autopsy cases of the generalized variant of Pick's disease ("basophilic inclusion body disease") both clinically and pathologically, and examined the degree and distribution of the basal ganglia lesions, including the amygdala, striatum, pallidum, and substantia nigra. The lesions in the amygdala, striatum, and pallidum were classified into three categories (slight, moderate, and severe). The lesions in the substantia nigra were qualitatively judged, compared with normal controls. Extrapyramidal signs, not noticed in the generalized variant of Pick's disease, were evident in all four cases, in addition to dementia. The degree and distribution of basal ganglia lesions in all four cases were uniform: the caudate nucleus showed severe lesions, the amygdala and putamen severe to moderate lesions, and the pallidum moderate to slight lesions. The substantia nigra in all our cases showed prominent neuronal loss, probably being one of the lesions responsible for extrapyramidal signs. In the generalized variant of Pick's disease, the degree and distribution of the alterations within the basal ganglia differs from those reported in Pick's disease with Pick bodies (PDPB) and corticobasal degeneration (CBD). In PDPB, severe lesions are present in the amygdala with relative sparing of the substantia nigra, compatible with rare extrapyramidal signs in PDPB, while in CBD, severe lesions are found in the pallidum and substantia nigra. These clinicopathological findings may contribute not only to the elucidation of clinicopathological hallmarks, but also to the progress of neuroimaging, in the generalized variant of Pick's disease.

Adult↗

Different conformation of neuronal tau deposits distinguished by double immunofluorescence with AT8 and thiazin red combined with Gallyas method.

Different kinds of tau deposits were quantitatively investigated with thiazin red (TR), a fluorochrome that binds to fibrillary structures like neurofibrillary tangles (NFTs), in brains obtained at autopsy from patients with Alzheimer's disease (AD), Pick body (PB) disease, corticobasal degeneration (CBD) or diffuse NFTs with calcification (DNTC). After recording double-labeling fluorescence images with anti-paired helical filament tau (AT8) and TR, the sections were subjected to Gallyas method (GAL). This enabled three different staining properties to be compared on the identical neuron. AT8-positive neocortical neurons of AD and DNTC were fibrillary and uniformly positive for TR and GAL, consistently forming NFTs. NFTs lacking AT8 immunoreactivity (IR) were more frequent in DNTC than in AD, suggesting that evolution of NFTs is more accelerated in DNTC. Scarce TR staining in tau-positive neocortical neurons of CBD suggests their paucity of fibrillary structure. Since the affinity of TR for PB was not consistent, this may be dependent not only on the amount but also the characteristics of fibrillary structures. PBs were further characterized by the scarcity of GAL staining. This approach, which quantitatively clarifies differences between AT8-IR, TR and GAL, provides a morphological basis for further investigations of the different conformational states of tau from its deposition to fibril formation of various types.

Aged↗

Distribution of cerebral cortical lesions in Pick's disease with Pick bodies: a clinicopathological study of six autopsy cases showing unusual clinical presentations.

We investigated six Japanese autopsy cases of Pick's disease with Pick bodies (PDPB) both clinically and pathologically, and examined the distribution of their cerebral cortical lesions using hemisphere and/or bisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Two patients with a clinical diagnosis of primary progressive apraxia and of slowly progressive aphasia had speech apraxia as their initial signs, and the other two patients were suspected as having Alzheimer's disease, with the clinical diagnosis of the remainder two patients being presenile dementia and depression, respectively. Extrapyramidal signs, believed to be rare in PDPB, were present in four patients. Severe lesions were multicentrically present in the cerebral cortices of all six cases. In two patients with speech apraxia, severe lesions were seen in the primary motor area, which generally has not been regarded as an "atrophic center" in Pick's disease. Furthermore, in a patient with depression, severe lesions were more widespread in the convexity than in the orbital region of the frontal lobe. The parietal lobes, including the postcentral gyrus usually believed to be spared in Pick's disease, were severely involved in three patients. We postulate that the clinical features of PDPB have a much wider spectrum than previously believed. In addition, we believe that the distribution of the cerebral cortical lesions in PDPB is more widespread than previously assumed, and that clinical manifestations of PDPB depend to some extent on the topographic distribution of the cerebral cortical lesions.

Aged↗

Comparative analyses of the distribution of various transposable elements in Pyricularia and their activity during and after the sexual cycle.

We examined the distribution and activity of six transposable elements found in the blast fungus, Pyricularia spp. Sixty-eight isolates from various gramineous plants were used for the survey, and the elements were plotted on a dendrogram constructed on the basis of their rDNA-ITS2 sequences. MGR586 and Pot2 (Class II elements), Mg-SINE (SINE-like element) and MGR583 (LINE-like retrotransposon) were widely distributed among the Pyricularia isolates, suggesting that they are old elements which arose in, or invaded, the Pyricularia population at very early stages in its evolution. By contrast, the distribution of the LTR-retrotransposons MAGGY and Grasshopper was limited or sporadic, suggesting that they are relatively new elements which recently invaded the Pyricularia population by means of horizontal transfer events. The activity of these elements was evaluated by Southern analysis in progenies derived from a cross between a Setaria isolate and a Triticum isolate. Many new MAGGY signals were observed, which were absent in the parental isolates, at various stages of the sexual cycle and following vegetative growth. In contrast, the other elements yielded few, if any, such signals. Analysis of the sequences flanking the new MAGGY insertions revealed that they were each associated with a 5-bp target-site duplication at both ends of the insertion. These data suggested that MAGGY was the most active of the elements tested for transposition in Pyricularia.

Blotting, Southern↗

Heat shock, copper sulfate and oxidative stress activate the retrotransposon MAGGY resident in the plant pathogenic fungus Magnaporthe grisea.

MAGGY is a gypsy-like retrotransposon isolated from the plant pathogenic fungus Magnaporthe grisea. The ability of various stresses to activate MAGGY was tested in the original and in a heterologous host (Colletotrichum lagenarium), using beta-glucuronidase (GUS) as a reporter. The MAGGY promoter was activated in M. grisea by either heat shock, copper sulfate, or oxidative stress, but not by the antifungal substance p-coumaric acid. Transcriptional up-regulation of MAGGY RNA was also observed following heat shock and oxidative stress. The MAGGY promoter remained responsive to the above-mentioned stresses when transformed into a M. grisea isolate that had no endogenous MAGGY elements. In C. lagenarium, however, the MAGGY promoter showed only basal expression of GUS and no further up-regulation was induced by any of the stress treatments, suggesting that the stress-responding cis-element(s) in the MAGGY promoter is not functional in a wider range of fungi. The relationship between the activation of MAGGY by stress and phenotypic diversification in M. grisea, including variations in pathogenicity, is discussed.

Amino Acid Sequence↗

Incidence of the appearance of the red color sign on esophageal varices and its predictive factors: long-term observations of 359 patients with cirrhosis.

PURPOSE: The red color sign observed by endoscopic examination is a reliable predictive factor for variceal bleeding. The aim of this study was to calculate the incidence of the appearance of the red color sign and to evaluate its predictive factors. METHODS: Endoscopic examination was repeatedly performed in 359 consecutive patients diagnosed as having liver cirrhosis with or without esophageal varices, during a median follow-up period of 2651 days. RESULTS: The incidence of the appearance of the red color sign on esophageal varices at the end of the tenth year was compared among patients without varices (11.4%), those with small varices (45.4%), and those with mid-size varices (65.0%). The difference was significant (P < 0.0001). The number of varices (P = 0.0010), size of varices (P = 0.0064), platelet count (P = 0.0168), and alpha-fetoprotein level (P = 0.0207) were significantly correlated with the appearance of the red color sign, as estimated by the multivariate Cox hazard model. To exclude the influence of carcinogenesis, observation was stopped when hepatocellular carcinoma was discovered. Additive predictive factors with significance were: number of varices (P = 0.001), size of varices (P = 0.027), and platelet count (P = 0.0315). CONCLUSIONS: Endoscopic signs of esophageal varices and platelet count were significant predictors for the appearance of the red color sign.

Color↗

Twice-daily administration of interferon-beta for chronic hepatitis C is not superior to a once-daily regimen.

PURPOSE: Although interferon (IFN) is commonly used for the treatment of chronic hepatitis C virus (HCV) infection, eradication of the virus occurs in only a small proportion of patients with genotype 1b and a high virus titer. Modified IFN therapies have been tried, with only limited benefit. Recently, the administration of IFN-beta twice per day has been reported to be more effective than the usual once-daily administration regimen. The aim of this study was to evaluate whether twice-daily IFN results in a sustained response in patients with chronic HCV infection with genotype 1b, and a high virus titer. METHODS: Twenty patients with genotype 1b and high HCV RNA level (more than 1 MEq/ml by branched DNA probe assay) were randomly assigned to receive either twice-daily 3 MU of IFN beta (group A) or once-daily 6 MU of IFN-beta (group B) for 4 weeks. All patients received a further daily dose of 6 MU IFN-beta for 12 weeks, followed by IFN-alfa three times a week for 16 weeks. RESULTS: Although a rapid fall in HCV RNA levels was noted in group A, a sustained response was observed in only one of nine patients in this group, and none of group B. Adverse effects of IFN were more frequent and pronounced in group A than in group B. CONCLUSIONS: We conclude that further modification, which combines the early strong anti-viral effects of the twice-daily regimen with long-term sustained response, is necessary for effective therapy of HCV patients with genotype 1b and high HCV RNA levels.

Adult↗

Interferon therapy for flare-up of hepatitis B virus infection after emergence of lamivudine-induced YMDD motif mutant.

A 61-year-old man with chronic hepatitis B was treated with interferon (IFN)-alpha for flare-up after the emergence of a lamivudine-induced YMDD motif mutant. The YMDD mutant emerged 13 months after the initiation of lamivudine therapy. Despite this, lamivudine therapy was continued. Acute exacerbation occurred 25 months after the emergence of the YMDD mutant. Treatment with IFN-alpha resulted in rapid loss of hepatitis, B virus DNA, resolution of hepatitis, and clinical recovery.

Amino Acid Motifs↗