A study on mouse hepatitis virus receptor genotype in the wild mouse.
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Biomedical subjects
Publications and source records attributed to K Tsuchiya.
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We assessed the value of the volume-rendering method of displaying images of three-dimensional (3D) time-of-flight MR angiography (MRA) in the diagnosis of intracranial aneurysms. We obtained three-dimensional volume-rendered MRA from 21 patients with intracranial aneurysms. The images were evaluated in comparison with maximum-intensity-projection images (in 21 patients), conventional angiograms (in 21) and CT angiography (in nine). In 17 patients, 3D volume-rendered images were thought to show morphological features most clearly. They were superior to the other methods for demonstrating the precise location of the aneurysm in three patients and in showing the shape of the bleb in another three. 3D volume-rendered MRA can be effectively added to conventional imaging techniques for diagnosis of intracranial aneurysms.
Both males and females of the species of spinous country-rats (Tokudaia osimensis osimensis, T.o.o., Rodentia: Muridae), which live on Amami Oshima Island, a southern Japanese island, have 25 chromosomes. Another species of spinous country-rats (Tokudaia osimensis spp., T.o. spp., which live on Tokunoshima Island 40 km south of Amami Oshima Island, also have an odd number of chromosomes, 45. Karyotypes of males and females by the G-band method were indistinguishable in both populations. The lesser number of chromosomes (25) of T.o.o. is likely to be a result of Robertsonian fusions of 45 chromosomes of T.o. spp. that seem to be the offspring of another spinous country-rat Tokudaia osimensis muenninki (T.o.m.), which live on Okinawa Island and have 44 chromosomes including the X and Y Chrs. The lengths of the non-paired, putative X-Chr of T.o.o. and T.o. spp. occupied roughly 3.2% and 1.7% of the total lengths, respectively, hinting at translocation or exchange of a part of the X Chr and thus in violation of Ohno's Law. Southern blot analysis with murine Sry as a probe indicated that these two animals do not have Sry. When Zfx from T.o. spp. was used as a probe, both males and females of T.o.o. and T.o. spp. showed two bands, suggesting possible translocation of Zfy from the Y Chr. Comparison of physical characteristics, constituents of chromosomes, and sex-determination methods of these three Tokudaia country-rat populations suggests that each is endemic to each island and constitutes an independent species. These specialized species would provide us with clues to elucidate the mechanisms of primary sex determination and karyotype evolution in mammals.
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.
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.
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.
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.
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.
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.
We evaluated intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis, with special reference to bone mineral density (BMD) and prevention of spinal fracture. The patients were 40 women, over 50 years of age, with lumbo-dorsal pain and low BMD (less than 0.70 g/cm(2)), measured by dual-energy X-ray absorptiometry (DXA). The patients were randomly assigned to two groups. The first group (HEBP) received 200 mg of HEBP per day for 2 weeks, followed by 2 g calcium lactate and 0.5 microg alphacalcidol per day for the next 10 weeks. This 12-week cycle was repeated eight times for 2 years. The second group (Ca. D) received 2 g calcium lactate and 0.5 microg alphacalcidol per day for 2 years. Lumbar BMD was measured before the treatment and every 6 months during the treatment until 24 months, and changes were evaluated. The number of fractured vertebrae was counted on X-ray films before treatment and at the final assessment. After 6 months of treatment, a significant and continuous increase in BMD was observed in the HEBP group. Moreover, the percentage of patients with new vertebral compression fractures in the HEBP group was one-tenth of that in the Ca. D group. These results suggest that intermittent cyclical treatment with HEBP and calcium plus alphacalcidol may be effective for increasing BMD and preventing fractures in postmenopausal osteoporosis.
The A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene (mt.3243A>G) is associated with both diabetes mellitus and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recently, this mutation was found in three diabetic subjects with progressive kidney disease, suggesting that it may be a contributing factor in the development of kidney disease in patients with diabetes. The aim of this study was to evaluate the contribution of this mutation to the development of end stage renal disease (ESRD) in patients with diabetes. The study group consisted of 135 patients with diabetes and ESRD. The control group consisted of 92 non-diabetic subjects with ESRD who were receiving hemodialysis. The mt.3243A>G mutation was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found the mt.3243A>G mutation in eight patients (8/135; 5.9%), all of whom were initially diagnosed with type II diabetes. Five of the eight patients were subsequently also diagnosed with MELAS. We did not find the mutation in any of the 92 nondiabetic subjects with ESRD. The prevalence of this mutation was 6.5-fold higher in patients with diabetes and ESRD than in those with diabetes alone (8/135 vs 5/550, respectively; chi2 = 13.704; P = 0.0002). The mt.3243A>G mutation may be a contributing genetic factor in the development of ESRD in Japanese patients with diabetes.
Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that causes renal failure. One of the genes that is responsible for this disease, PKD1, has been identified and characterized. Many mutations of the PKD1 gene have been identified in the Caucasian population. We investigated the occurrence of mutations in this gene in the Japanese population. We analyzed each exon in the 3' single copy region of the gene between exons 35 and 46 in genomic DNA obtained from 69 patients, using a PCR-based direct sequencing method. Four missense mutations (T3509M, G3559R, R3718Q, R3752W), one deletion mutation (11307del61bp) and one polymorphism (L3753L) were identified, and their presence confirmed by allele-specific oligonucleotide (ASO) hybridization. These were novel mutations, except for R3752W, and three of them were identified in more than two families. Mutation analysis of the PKD1 gene in the Japanese population is being reported for the first time.
The prognostic value of tumor apoptosis was studied in patients with oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Forty-eight patients with oropharyngeal squamous cell carcinoma who received radical radiotherapy between 1990 and 1995 were enrolled in the study. The radiation treatment for all patients involved the administration of 65 Gy in 26 fractions over a 6.5-week period. The apoptotic index (AI; the apoptotic cell count per 1000 tumor cells ) was distributed from 0 to 10 with a median at 2 and a mode of 1. There was a significant linear correlation between the AI and mitotic index (MI) (r=0.393, 95% confidence interval: 0.129-0.605). The cause-specific 5-year survival for patients with AI greater than the median was 46% and for the counterpart was 41%. There was no difference in cause-specific survival between AI/MI greater than the median (50%) and AI/MI smaller than the median (36%). The number of patients was too small to draw definite conclusions, but the AI and the AI/MI before treatment were not shown to have a prognostic value for oropharyngeal squamous cell carcinoma in our study. The primary sites and treatment methods may influence the prognostic value of AI even for the same histological types.
We constructed comparative cytogenetic maps of the Chinese hamster to mouse, rat and human by fluorescence in-situ hybridization using 36 cDNA clones of mouse, rat, Syrian hamster, Chinese hamster and human functional genes. In this study, 30 out of the 36 genes were newly mapped to Chinese hamster chromosomes. The chromosomal homology of the Chinese hamster was identified and arranged in 19, 19 and 18 segments of conserved synteny in mouse, rat and human, respectively. Additionally, two of the 19 segments homologous to mouse chromosomes were initially identified in this study.
We constructed the comparative cytogenetic maps of X chromosomes in three rodent species, Indian spiny mouse (Mus platythrix), Syrian hamster and Chinese hamster, using 26 mouse cDNA clones. Twenty-six, 22 and 22 out of the 26 genes, which were mapped to human, mouse and rat X chromosomes in our previous study, were newly localized to X chromosomes of Indian spiny mouse, and Syrian and Chinese hamsters, respectively. The order of the genes aligned on the long arm of human X chromosome was highly conserved in rat and the three rodent species except mouse. The present results suggest a possibility that the rat X chromosome retains the ancestral form of the rodent X chromosomes.
Two hundred and four unrelated Japanese patients with rheumatoid arthritis (RA) were typed for HLA by serological typing and DNA typing. The serological typing revealed that frequencies of HLA-A11, DR4, DR53 and DQ4 were increased and those of DR8 and DQ1 were decreased in the patients. The DNA typing has precisely defined the disease-associated HLA class II alleles; DRBl*0405, DQAl*03 and DQBl*0401 showed positive associations, while negative associations were found with DRBl*0803, DQAl*0103 and DQBl*0601. The risk for RA was found to be closely associated with particular amino acid sequences of DR-beta chain, including glycine residue at the 86th position in addition to those between 70 and 74, which are known to confer binding specificity and affinity to antigenic peptides. The observation that the frequency of HLA-A11 was increased in the DRBl*0405-positive patients suggested the interaction of these two alleles in the susceptibility to RA. On the other hand, the frequency of DPB1*0201 was increased in the DRBl*0405-negative patients and the frequency of HLA-A2 was increased in the DPBl*0201-positive patients, especially in the younger onset group. These findings suggested that the combination of HLA-A2 and DPBl*0201 may confer the susceptibility in the DRBl*0405-negative patients. Our results suggested the possibility that the susceptibility to RA is controlled by the interaction of HLA-A and DRBl genes or by that of HLA-A and DPBl genes in different patient subgroups.
When Kasba (Chuzan) virus (an orbivirus) was injected intracerebrally into 1-, 2- or 4-week-old mice, non-purulent necrotizing encephalitis developed and the mice showed nervous symptoms and became moribund. The necrotic lesions were more severe in younger animals. In 1-week-old mice, viral titres rose until 7 days post-infection, while in 2- and 4-week-old animals the titres reached a peak on day 3 and then declined gradually. Glial fibrillary acidic protein-positive astrocytes increased in the white matter, hippocampus and subpial area of the cerebral cortex of infected animals, and lectin-RCA-1-positive cells, thought to be microglial cells, increased in the necrotic lesions. The number of these glial cells increased even after viral titres had declined. In this study there were no survivors in any age group, but survival time increased with age.
On the basis of studies in laboratory rats, mast cells were originally classified into two subgroups, namely, mucosal mast cells (MMCs), which contained chymase, and connective tissue mast cells (CTMCs), which contained both tryptase and chymase. This classification has been applied to other animal species, despite the fact that the MMCs and CTMCs of such species sometimes consist of mixed populations of mast cells in terms of tryptase and chymase constitution. This report describes the protease constitution of mast cells in 17 species of nine genera (Acomys, Apodemus, Cricetulus, Meriones, Millardia, Mus, Rattus, Sigmodon and Vandeleuria) of the family Muridae. MMCs with negative tryptase activity were detected only in the intestinal mucosa of six subspecies of Mus musculus, two Rattus spp. and Vandeleuria oleacea, and only Apodemus sylvaticus possessed CTMCs with no tryptase activity. Since mast cells conforming to the conventional classification were observed only in three of the nine genera examined, we propose that mast cells of rodents of the family Muridae should be classified by their protease constitution rather than by their location.