Biomedical subjects

K Iwabuchi

Publications and source records attributed to K Iwabuchi.

At least 145 records · Page 8Linked to original sources

PubMed1995

CAG repeat expansion of Machado-Joseph disease in the Japanese: analysis of the repeat instability for parental transmission, and correlation with disease phenotype.

Machado-Joseph disease (MJD) is caused by abnormal expansion of an unstable CAG repeat in a novel gene locating on chromosome 14q32.1. We analysed this CAG repeat polymorphism with 66 Japanese MJD patients. All the patients were selectively associated with abnormal expansion of the CAG repeat. Repeat length of the mutant allele did not overlap that of normal allele and closely correlated with not only age at onset but also with clinical phenotypes. CAG repeat size is apparently related to a wide variety of phenotypic presentations in MJD.

Adult↗

PubMed1995

Production of minor lymphocyte stimulatory-1a antigens from T cell subsets.

T cell subsets that produce minor lymphocyte stimulatory (Mls) antigens were analyzed using mixed lymphocyte reaction (MLR) in vitro or clonal elimination assay in vivo. When lymph node T cells from B10.BR(Mls-1b) mice were stimulated with various T cell subsets from AKR (Mls-1a) mice in the presence of B10.BR antigen presenting cells (APC), proportions of Mls-1a reactive T cell blasts (V beta 6+, V beta 8.1+) increased. The stimulatory potency of CD8+ T cells was higher than that of CD4+ T cells. Furthermore, among either CD8+ or CD4+ T cell subset, CD44+ T cells appeared to produce larger amounts of Mls-1a antigens than CD44- T cells. More marked difference was demonstrated, when stimulator AKR T cells were being activated by immobilized anti-T cell antigen receptor (TCR) antibody during MLR. Thus, AKR T cells appeared to produce large amounts of Mls-1a antigens on appropriate stimulations. These findings were confirmed by the semiquantitative analysis of mRNA levels of MTV-7 in the AKR T cell subsets. When CD8+CD44+ T cells from (AKR x B10.BR)F1 mice were injected intravenously into [B10.BR-->B10.BR] syngeneic bone marrow (BM) chimeras 1 week after BM reconstitution and proportions of V beta 6+ T cells were quantitated 7 weeks later, significant clonal elimination of V beta 6+ T cells was induced among both thymocyte population and lymph node T cell population in a dose-dependent manner of the inoculated F1 T cells. Inoculation of CD8+CD44-F1 T cells eliminated V beta 6+ T cells less efficiently from lymph node T cells and inoculation of CD4+F1 T cells induced no significant clonal elimination of the V beta 6+ T cells. The present findings demonstrate clearly that CD8+CD44+ T cells represent the cells producing large amounts of Mls-1a antigens and inducing clonal elimination of V beta 6+ T cells in vivo.

Animals↗

PubMed1995

Spinocerebellar ataxia 1 (SCA1) in the Japanese in Hokkaido may derive from a single common ancestry.

Spinocerebellar ataxia 1 (SCA1) is caused by expansion of an unstable CAG triplet repeat located on the short arm of chromosome 6. Precise mapping has shown a positional relationship to closely linked markers in the order of D6S109-D6S274-D6S288-SCA1-AM10GA-D6S89+ ++-EDN1 from centromere to telomere. The haplotype which cosegregated with the disease was determined in 12 Japanese pedigrees with SCA1. Although the alleles of the SCA1 haplotype varied from pedigree to pedigree, depending on the distance from the SCA1 locus, the affected and presymptomatic subjects carried the same alleles at D6S288 and D6S274. All the families with SCA1 had migrated from either Miyagi or Yamagata Prefectures, neighbouring areas in the Tohoku District, the northern part of Honshu which is the main island of Japan. It seems highly likely that SCA1 in the Japanese, at least those residing in Hokkaido, derives from a single common ancestry.

Chromosome Mapping↗

PubMed1995

Effect of cigarette smoke on the mRNA and protein expression of carcinoembryonic antigen (CEA), a possible chemoattractant for neutrophils in human bronchioloalveolar tissues.

BACKGROUND: The concentration of carcinoembryonic antigen (CEA), known as a marker of malignant transformation and chronic inflammation, is increased in bronchoalveolar lavage fluid obtained from smokers compared with fluid from non-smokers. This study investigated the mechanism and biological significance of CEA production in the lungs of smokers by evaluating protein and mRNA expression in non-carcinomatous lung parenchymal tissues and in cell lines derived from human fetal lung. METHODS: Lung parenchymal tissue free from cancer or an inflammatory lesion was obtained from five non-smokers (four with lung cancer, one with pulmonary mycetoma), five ex-smokers (all with lung cancer except for one with mesothelioma), and 14 smokers (nine with lung cancer, five with emphysema) at surgery or necropsy. Cancer tissue was also collected simultaneously from the subjects with lung cancer. CEA protein in the tissue homogenates was measured by enzyme linked immunoassay. CEA mRNA expression in the non-carcinomatous parenchymal tissue and cancer tissue was evaluated by in situ hybridisation using CEA specific riboprobe and was semiquantitated by counting the number of silver grains per cell. CEA mRNA expression was also compared in three cell lines derived from human fetal lung (IMR-90, MRC-9, and CCD-14Br) after in vitro stimulation with medium exposed to cigarette smoke or air. Chemoattractant activity of purified CEA for neutrophils and monocytes was also studied in vitro. RESULTS: CEA content in non-carcinomatous lung tissue was increased in smokers with emphysema (mean (SD) 38.0 (9.2) ng/mg protein) or with lung cancer (38.2 (21.6)) compared with non-smokers (11.0 (5.4)) or ex-smokers (5.9 (2.2)). CEA mRNA expression in non-carcinomatous tissue, expressed by average number of grains per cell, was also increased in smokers with emphysema (mean (SD) 11.2 (4.1)) or with lung cancer (14.0 (8.4)) compared with non-smokers (3.1 (0.6)) or ex-smokers (4.0 (1.7)). CEA content in carcinomatous tissues was 42.8 (37.3) for non-smokers, 38.2 (42.4)) for ex-smokers, and 59.0 (22.5) for smokers. The CEA content in carcinomatous tissue was higher than in non-carcinomatous tissue, but there was no difference between non-smokers, ex-smokers, and smokers. The numbers of grains per cell in carcinomatous tissue were higher than in non-carcinomatous tissues, but not different among non-smokers (30.3 (3.9)), ex-smokers (38.3 (13.8)), and smokers (44.3 (5.2)). CEA mRNA expression in the cell lines was upregulated after the incubation with smoke-treated medium. Purified CEA was chemoattractant for neutrophils but not for monocytes in vitro. CONCLUSIONS: mRNA and protein expression of CEA were increased in the normal lung tissue from smokers compared with non-smokers or ex-smokers. Since CEA content and mRNA expression were no different between smokers with non-small cell lung cancer and those with non-carcinomatous disease, it is unlikely that CEA expression in non-carcinomatous lung parenchymal tissue was influenced by the presence of the tumour and is consistent with the effect of smoking. This is supported by in vitro studies which show that cigarette smoke could induce CEA mRNA expression in fetal lung derived cells. In addition, CEA might play a part in recruitment of neutrophils into the lower respiratory tract.

Aged↗

PubMed1995

Simultaneous measurement of pulmonary diffusing capacity for CO and cardiac output by a rebreathing method in patients with pulmonary diseases.

Pulmonary diffusing capacity for CO (DLCO) and cardiac output (Q) were simultaneously measured by a noninvasive rebreathing method (RB) in 15 normal subjects and in 60 patients, including cardiac diseases (CD), bronchial asthma (BA), chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (PF). DLCO and Q were tested by the single breath method (SB) and the dye-dilution method (Dye), respectively. DLCO (RB) correlated well with DLCO (SB) (r = 0.890, p < 0.001). Q(RB) also correlated well with Q(Dye) (r = 0.909, p < 0.001). Factors affecting DLCO (RB) were age, height, body surface area, O2 consumption, Q, hematocrit (Het) and Q.Hct, among which Q.Hct was the prominent influential determinant. DLCO per lung volume was smaller in COPD and PF than in BA or healthy subjects, while, the ratio of DLCO/(Q.Hct) was significantly higher in COPD than in PF. Simultaneous measurements of DLCO and Q offer comprehensive characterization for functional changes in lung parenchyma.

Adult↗

PubMed1995

[Familial early onset cerebellar ataxia with hypoalbuminemia].

We describe two brothers with early onset cerebellar ataxia associated with hypoalbuminemia (EOCAH). Choreo-athetoid movements preceded the cerebellar ataxia, and serum pseudocholinesterase elevation preceded the hypoalbuminemia. The parents are first cousins. Patient 1, the 22-year-old elder brother, developed choreoathetoid movements of the neck and extremities at the age of eighteen months. He later developed slowly progressive cerebellar ataxia with decreased tendon reflexes. The choreoathetoid movements ceased at about 16 years of age. A recent examination revealed cerebellar ataxia, action myoclonus of the neck and upper limbs, diminished tendon reflexes, mild sensory disturbance in the lower extremities, and very slight amyotrophy of the feet. Patient 2, the 18-year-old younger brother, developed choreo-athetoid movements at the age of 6 years, followed by slowly progressive cerebellar ataxia with disminished tendon reflexes. No scoliosis, ECG abnormalities, or edema was detected. Serum biochemistry studies revealed elevated pseudocholinesterase (6,226 to 2,390 IU) in the patient's early teens. Serum albumin levels tended to be low (3.7 to 4.1 g/dl). Serum triglyceride and beta-lipoprotein levels were elevated in the patients' late teens. Genetic studies showed slight linkage of D9S15. The maximum lod score was 0.289 (recombination fraction rate was 0.14).

Adolescent↗

PubMed1995

[Siblings of early onset cerebellar ataxia with hypoalbuminemia].

Recently, a new syndrome of early onset cerebellar ataxia with hypoalbuminemia (EOCA-HA) was reported in Japan. The clinical features of EOCA-HA overlap with those of Friedreich's ataxia (FA), and primary hypoalbuminemia is a characteristic laboratory finding of this syndrome. Genetic linkage analysis of EOCA-HA including this newly reported family revealed that the gene for EOCA-HA is located on the long arm of chromosome 9 as FA. However, several recombination events were observed between D9S15 in EOCA-HA, whereas no recombination events were seen in FA. We report on two siblings with EOCA-HA and discuss the clinical and laboratory features. The patients were a 25-year-old man (patient 1) and a 23-year-old man (patient 2). Their parents marriage was non-consanguineous. The mode of inheritance is compatible with autosomal recessive mode. Clinically, they showed cerebellar ataxia as the initial symptom in the late infantile period and subsequently showed choreoathetosis and ocular motor apraxia at the age of approximately fifteen years. Deep tendon reflexes were reduced in late infancy and finally disappeared. Amyotrophy and sensory impairment of the legs developed at approximately twenty. Abnormal electrocardiogram and diabetes mellitus were not observed. On X-ray CT scan or MRI, the cerebella of both patients were mildly atrophic. Clinical features in these siblings were indistinguishable from those of ataxia telangiectasia, but immunodeficiency syndrome was absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Mapping of the gene for Machado-Joseph disease within a 3.6-cM interval flanked by D14S291/D14S280 and D14S81, on the basis of studies of linkage and linkage disequilibrium in 24 Japanese families.

The gene locus of Machado-Joseph disease (MJD) has recently been mapped within a 29-cM subregion of 14q chromosome. We did a linkage study of 24 multigenerational MJD Japanese pedigrees, in an attempt to narrow the candidate region of this gene. Pairwise and multipoint linkage analysis, together with haplotype segregation analysis, led to the conclusion that the MJD gene is located at the 6.8-cM interval between D14S256 and D14S81 (Zmax = 24.78, multipoint linkage analysis). D14S291 and D14S280, located at the center of this interval, showed no obligate recombination with the MJD gene (Zmax = 5.93 for D14S291 and 9.99 for D14S280). A weak, but significant, linkage disequilibrium of MJD gene was noted with D14S81 (P < .05) but not with D14S291 or D14S280. These results suggest that a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely location of the MJD gene and that it is closest to D14S81.

Adult↗

PubMed1995

[An autopsy case of corticobasal degeneration clinically misdiagnosed as Pick's disease].

We report a 69-year-old woman who was clinically diagnosed as having a frontal lobe-type of Pick's disease. The initial symptoms were personality changes and problematic behaviors. The patient showed intellectual decline, "stehende Redensarten" and abnormal attitude in interpersonal situations such as inattentiveness and indifference in the course of the disease. Brain CT revealed a marked atrophy of the frontal lobes. In the terminal stage the patient had severe dementia, mutism, parkinsonism and cervical dystonia. Neuropathologically, there was a marked atrophy of the frontal lobes. The superior frontal gyrus was most severely atrophic. Histological study revealed mild to moderate loss of neurons, hyperplasia of protoplasmic astrocytes and many balooned neurons in the deep layers of the atrophied cerebral cortex. Severe neuronal loss was even seen only in a part of the superior frontal gyrus. The cerebral white manner showed marked diffuse fibrillary gliosis. There was neuronal loss with gliosis in the thalamus, lentiform nucleus, subthalamic nucleus, substantia nigra and inferior olivary nucleus. Marked gliosis was seen in the midbrain and pontine tegmentum. Sections from several levels of the spinal cord also showed marked gliosis of the gray matter. Antibodies against human tau stained massive argyrophilic thread-like structures and oligodendroglial microtubular masses in the affected lesions. Neurofibrillary tangles were localized in the hippocampus and parahippocampal region. Neither Pick's body nor senile plaque were observed. Corticobasal degeneration (CBD) is a neurodegenerative disease initially presenting with unilateral motor disturbances. Typical initial symptoms are rigidity, akinesia and apraxia of an affected arm. The clinical phenotype might depend upon the affected areas of the cerebral cortex. Our patient initially exhibited personality changes and was clinically diagnosed as having Pick's disease. Although our case had unusual distribution pattern of the cerebral atrophy, it was pathologically diagnosed as CBD. The review of the literature suggests the presence of clinical varieties in CBD.

Aged↗

PubMed1995

[Some problems on neuropathology of Huntington disease].

The most striking neuronal loss in the brains of Huntington disease (HD) occurs in the striatum, predominant in the caudate nucleus. However, pathogenesis of this disease is supposed to be mainly based on the process of "simple atrophy" in the whole brain neurons and their axons. Therefore, although the autopsied brains of HD are atrophic and their weight are light, histopathology based on the classical method shows few abnormal findings in the cerebrum. Against this fact, "numeric atrophy" of the neurons occurs in the striatum of chorea acanthocytosis.

Atrophy↗

PubMed1994

Two cellular proteins that bind to wild-type but not mutant p53.

p53 is a tumor-suppressor protein that can activate and repress transcription. Using the yeast two-hybrid system, we identified two previously uncharacterized human proteins, designated 53BP1 and 53BP2, that bind to p53. 53BP1 shows no significant homology to proteins in available databases, whereas 53BP2 contains two adjacent ankyrin repeats and a Src homology 3 domain. In vitro binding analyses indicate that both of these proteins bind to the central domain of p53 (residues 80-320) required for site-specific DNA binding. Consistent with this finding, p53 cannot bind simultaneously to 53BP1 or 53BP2 and to a DNA fragment containing a consensus p53 binding site. Unlike other cellular proteins whose binding to p53 has been characterized, both 53BP1 and 53BP2 bind to the wild-type but not to two mutant p53 proteins identified in human tumors, suggesting that binding is dependent on p53 conformation. The characteristics of these interactions argue that 53BP1 and 53BP2 are involved in some aspect of p53-mediated tumor suppression.

Amino Acid Sequence↗

PubMed1994

The murine c-fgr gene product associated with Ly6C and p70 integral membrane protein is expressed in cells of a monocyte/macrophage lineage.

The c-fgr gene is a member of the Src family of protooncogene tyrosine kinases. A monoclonal antibody (2H2) that recognizes the specific region of the N-terminal domain of the murine c-fgr gene product (Fgr) has been established. With an immune complex kinase assay in a monocytic leukemia cell line, 2H2 monoclonal antibody was shown to precipitate a 59-kDa protein that corresponds in molecular mass to murine Fgr. Fgr was expressed highly in lymph nodes, slightly in spleen and peripheral blood leukocytes, and barely in the thymus and was not detected in bone marrow. In the presence of a mild detergent, Fgr was coimmunoprecipitated with a 70-kDa protein (p70) or with p70 plus several other molecules that were expressed on the cell-surface membrane of macrophage tumor cell lines PU5-1.8 and J774.1, respectively. By contrast, Fgr was not coimmunoprecipitated with a low-affinity receptor for the Fc portion of IgG that is associated with human Fgr. The molecule was also coimmunoprecipitated with the Ly6C molecule from a macrophage cell line (J774.1) that showed protein-tyrosine kinase activity. Peptide mapping revealed that this kinase activity was derived from Fgr. The similarity of relationship between this intramembrane p70 and/or Ly6C and cytoplasmic Fgr to relationships previously reported between T-cell antigen receptor complex, including CD4 and CD8 coreceptors, and Lck or Fyn in T cells and between surface IgM and Lyn or Blk in B cells, suggests that the Fgr and p70 or Ly6C are, indeed, associated with each other and in the murine system may be responsible for recognition of extracellular substances (either cellular or noncellular) and for signal transduction in cells of monocyte/macrophage lineage.

Animals↗

PubMed1994

Malignant fibrous histiocytoma of the bladder with focal rhabdoid tumor differentiation.

A case of primary malignant fibrous histiocytoma of the bladder is presented. This tumor involving the bladder is rare and the unusual histological features in the present case caused significant delay in accurate diagnosis. Since early diagnosis and aggressive surgical resection are essential to the effective treatment of this neoplasm, physicians should continually bear in mind the possibility of this malignant tumor whenever the pathological diagnosis is inconclusive.

Aged↗

PubMed1994

Functional studies on MEL-14+ and MEL-14- T cells in peripheral lymphoid tissues.

Functions of MEL-14+ T cells and MEL-14- T cells in peripheral lymphoid tissues were analyzed and compared. The MEL-14- T cells, representing a minor subpopulation of spleen and lymph node T cells, generated considerably higher mixed lymphocyte reaction and mitogen responses than the MEL-14+ T cells in any lymphoid tissues studied. Furthermore, upon stimulation with ConA the MEL-14- CD8+ T cells produced significantly larger amounts of IL-2 and IFN-gamma than MEL-14+ CD8+ T cells did. A similar but less marked observation was obtained with the CD4+ T cell population. Furthermore, when B10.BR mice were immunized with AKR (Mls-1a) spleen cells, the proportion of the Mls-1a reactive V beta 6+ T cells from draining lymph nodes increased and a substantial proportion of the increasing V beta 6+ T cells was shown to be MEL-14-. The present findings on the whole indicate that MEL-14- T cells in the peripheral lymphoid tissues are at functionally high levels and may represent memory cells which have been previously stimulated in vivo.

Animals↗

PubMed1994

Corn cystatin I expressed in Escherichia coli: investigation of its inhibitory profile and occurrence in corn kernels.

Corn cystatin I was expressed in Escherichia coli as a mature protein. It was purified by gel filtration on Sephadex G-50, ion-exchange HPLC, and reversed-phase HPLC. The purified protein showed strong inhibitory activities against papain (Ki: 3.7 x 10(-8) M), and cathepsins H (Ki: 5.7 x 10(-9) M) and L (Ki: 1.7 x 10(-8) M), whereas it inhibited cathepsin B to a lesser extent (Ki: 2.9 x 10(-7) M). Western blot analysis using antibody raised against corn cystatin I revealed that in the corn kernel, the protein occurs with a molecular mass of approximately 13 kDa. Localization in the aleurone layer and embryo of the corn kernel was shown by immunostaining microscopy.

Cloning, Molecular↗

PubMed1994

Comparative analyses of thymocyte and thymic low-density adherent cell functions.

Thymocytes which have developed in the C3H thymus showed depressed proliferative responses to stimulation with anti-CD3 antibody as compared with those which have developed in the thymus of other strains of mice (i.e. AKR). The present study was conducted to analyze immunological functions of the thymic stromal cell population (low-density adherent cells, LDAC) in the C3H mice using allogeneic bone marrow (BM) chimeras established by BM transplantation in the reciprocal combination of AKR and C3H mice as donor or recipient. The thymic LDAC from C3H mice or the [AKR(donor)-->C3H(recipient)] chimeras contained a high proportion of Mac-1+ cells as compared to AKR mice or the [C3H-->AKR] chimeras. The proportion of Mac-1+ cells paralleled the IL-1- and PGE2-secreting ability of the LDAC cultured either in the presence or absence of LPS and also paralleled the antigen-presenting cell functions of the LDAC. Furthermore, after anti-CD3 stimulation the PGE2 inhibited more profoundly proliferative responses of [AKR-->C3H] or normal C3H thymocytes than those of the [C3H-->AKR] chimera or normal AKR thymocytes. A PGE2 inhibitor, indomethacin, reversed the depressed responses of the thymocytes which had developed in the C3H thymus. These findings suggest that the lower responsiveness of thymocytes from [AKR-->C3H] chimeras to anti-CD3 stimulation may be attributable to large amounts of PGE2 secreted by LDAC and/or to increased sensitivity of thymocytes themselves to PGE2.

Animals↗

PubMed1994

Methenamine-silver staining: a simple and sensitive staining method for senile plaques and neurofibrillary tangles.

An improved methenamine-silver impregnation method is presented which exhibits sensitivity for amyloid substances comparable to that of anti-beta protein immunostaining. In optimally treated sections, this technique stained both beta-amyloid deposits and neurofibrillary tangles, which are known to have a beta-pleated structure. This simple procedure allows a large number of sections to be stained for routine examination.

Alzheimer Disease↗

PubMed1994

[Three patients of complicated form of autosomal recessive hereditary spastic paraplegia associated with hypoplasia of the corpus callosum].

We report three patients with slowly progressive spastic paraplegia and dementia; MRI on these patients revealed hypoplasia of the corpus callosum. The mode of inheritance was supposed to be autosomal recessive. Patient 1 (26-year-old man) is an elder brother of patient 2 (21-year-old man). Their parents are first cousins. Patient 3 (woman), a sporadic case, died of pneumonia at the age of 44. Their motor development after the birth was normal, but patient 3 was mildly mentally retarded. Gait disturbance due to spastic paraplegia developed at the age of nine (patient 2), fifteen (patient 1) and nineteen (patient 3), respectively. They also showed slowly progressive mental deterioration. Patient 1 has also suffered from mild amyotrophy and sensory disturbance in the distal part of the extremities since the age of 25. Patient 3 was bed-ridden at the middle of her thirty's because of generalized amyotrophy and sensory disturbance in addition to spastic quadriplegia and profound dementia. Their MRI reveal the thinning of the corpus callosum. We think the thinning must be hypoplasia of the corpus callosum, because the cerebrum showed normal appearance on MRI in patient 1 and patient 2. These clinical findings and imaging studies are essentially similar to those of the cases reported by Iwabuchi et al (1991). We propose autosomal recessive HSP associated hypoplasia of the corpus callosum as a new type of HSP.

Adult↗