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Biomedical subjects

Y Namba

Publications and source records attributed to Y Namba.

At least 109 records · Page 6Linked to original sources
PubMed1991

Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease.

During the course of our immunohistochemical studies on the change of lipids in Alzheimer's disease brains by using antibody to apolipoprotein E, a protein having a special relevance to nervous tissue, we unexpectedly found that apo E immunoreactivity was associated with amyloid in both senile plaques and cerebral vessels and neurofibrillary tangles. The immunoreactivity was also found in amyloid of kuru plaques in Creutzfeldt-Jakob disease. Pretreatment of the sections with formic acid greatly enhanced immunoreactivity of senile and kuru plaques to antibody to apo E.

Alzheimer Disease↗
PubMed1991

Presenile appearance of abundant Alzheimer's neurofibrillary tangles without senile plaques in the brain in myotonic dystrophy.

In 7 myotonic dystrophy (MyD) cases of 35- to 56-year old and 18 non-neurological age-matched controls paraffin-embedded temporal lobe sections were stained by the modified Bielschowsky method to count neurofibrillary tangles (NFTs) and senile plaques (SPs). In the parahippocampal gyrus, NFTs were observed in all the MyD cases; a few in the youngest, with an increase in number with age to the abundant appearance in the 4 cases in their 50s. The eldest also had many NFTs in the hippocampus. By contrast, the control subjects had, if any, only a few NFTs in the hippocampus and the parahippocampal gyrus. No SPs were observed in any MyD or control case. Thus, it was found that in MyD NFTs appear, unaccompanied by SPs, at an abnormally early age in the parahippocampal gyrus, with a rapid age-related increase in their number. This neuronal change may belong to the progeric features observed in this condition.

Adult↗
PubMed1991

Long-term intermittent administration of interferon-alpha in patients with chronic non-A, non-B hepatitis.

IFN-alpha was administered intermittently over a 6 month period in 39 patients with chronic non-A, non-B hepatitis confirmed by peritoneoscopy and liver biopsy. Three million units of IFN-alpha were administered 3 times a week for the first 6 months then twice, then once a week. In 26 patients (67%), GPT decreased and remained within the normal range during the course of administration, and in 9 patients (23%) GPT remained normal for over 6 months after the discontinuation of IFN-alpha. There was no significant difference of efficacy among 3 groups liver histology groups (CPH, CAH-2A, and CAH-2B), but GPT decreased significantly in patients with sporadic hepatitis compared to patients with a history of blood transfusion. Furthermore, GPT decreased significantly in patients with a history of a blood transfusion within the preceding 2 years compared to patients with a history of a blood transfusion over 7 years ago. GPT increased markedly after an early tapering to 2 doses weekly, but it did not increase after a 6 month administration. In conclusion, the long-term administration of 300 million unit IFN-alpha, 3 times weekly for 6 months, about 2.5 hundred million units in total, is thought to be an effective way to control chronic NANB hepatitis.

Adult↗
PubMed1991

Post-mortem diagnosis of human T lymphotrophic virus type-1 (HTLV-1) associated myelopathy by detection of HTLV-1 DNA in the spinal cord of a patient with post-transfusional myelopathy.

Human T lymphotrophic virus type-1(HTLV-1) is thought to be an etiological agent of HTLV-1 associated myelopathy (HAM). Therefore, a definitive diagnosis of HAM can not be made if information on the presence of antibody against HTLV-1 is not available, even though clinical and histopathological features strongly indicate the disease. In this study, HTLV-1 DNA was detected in the formalin-fixed, paraffin-embedded spinal cord of an autopsy case with post-transfusional myelopathy using the polymerase chain reaction (PCR). Ante-mortem HAM was not suspected of and the antibody has not been examined. Neuropathological examination of the sequential sections revealed a loss of axons and myelin sheaths in the white matter, resembling the histopathology of HAM. The post-mortem detection of HTLV-1 DNA by PCR may be useful for the confirmation of HAM in cases which were not provided with appropriate clinical data.

Autopsy↗
PubMed1991

The transforming potential of the c-erbB-2 protein is regulated by its autophosphorylation at the carboxyl-terminal domain.

The mutant c-erbB-2 protein with Glu instead of Val-659 exhibited transforming activity in NIH 3T3 cells. This protein showed enhanced tyrosine kinase activity in vitro and enhanced autophosphorylation at Tyr-1248 located proximal to the carboxyl terminus. Enhanced tyrosine phosphorylation of several cellular proteins was detected in cells expressing the Glu-659 c-erbB-2 protein. Introduction of an additional mutation at the ATP-binding site (Lys-753 to Met) of this protein resulted in abolition of its transforming ability. These data indicate that the transforming potential of c-erbB-2 is closely correlated with elevated tyrosine kinase activity of the gene product. To investigate the role of autophosphorylation in cell transformation, we introduced an additional mutation at the autophosphorylation site of the Glu-659 c-erbB-2 protein (Tyr-1248 to Phe). This mutant protein exhibited lower tyrosine kinase activity and lower transforming activity. On the other hand, when the carboxyl-terminal 230 amino acid residues were deleted from the c-erbB-2 protein, the tyrosine kinase activity and cell-transforming activity of the protein were enhanced. Thus, the carboxyl-terminal domain, which contains the major autophosphorylation site, Tyr-1248, may regulate cellular transformation negatively and autophosphorylation may eliminate this negative regulation.

Animals↗
PubMed1991

[Apolipoprotein B immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in senile dementia of Alzheimer type].

Since apolipoprotein E immunoreactivity has been shown in senile plaque and neurofibrillary tangle in Alzheimer's disease brains, we performed immunohistochemistry to examine whether or not apolipoprotein B (apoB) was associated with these abnormal structures. Sections of hippocampus from formalin-fixed, paraffin-embedded tissues were immunostained with a standard ABC method. We found that apoB immunoreactivity was associated with amyloid both in senile plaques and cerebral vessels and with neurofibrillary tangles. Positive staining was abolished with pretreatment of the antibody with the human apoB. It is suggested that the potential blood-brain barrier impairment may allow an increasing amount of serum proteins, such as apoB, to penetrate the brain and bind to these AD-associated abnormal structures.

Aged↗
PubMed1991

[Marchiafava-Bignami disease with symptoms of the motor impersistence and unilateral hemispatial neglect].

Machiafava-Bignami disease (MBD) occurs in the alcoholic patients. It is characterized clinically by interhemispheric disconnection syndrome, resulting from demyelination and necrosis of the corpus callosum. We performed a neuropsychological study of an alcoholic patient, diagnosed as MBD by X-ray computed tomography (CT) and magnetic resonance imaging (MRI). 123I IMP-SPECT of the patient revealed the reduction of the blood flow in both cerebral hemispheres without laterality though both the X-ray CT and MRI showed no abnormality in the cerebral hemispheres. In neuropsychological studies, we observed not only interhemispheric disconnection syndrome such as an unilateral left agraphia and left apraxia but also left hemispatial neglect demonstrated in right-hand performance and motor impersistence. Because there were no abnormal lesions in the right hemisphere, these symptoms might be attributable to the lesions of corpus callosum.

Alcoholism↗
PubMed1991

[HSP 70 is associated with abnormal cytoplasmic inclusions characteristic of neurodegenerative diseases].

Several degenerative diseases of the central nervous system are characterized by the presence of neuronal inclusions. One of these inclusions, neurofibrillary tangles in Alzheimer's disease, has been shown to contain ubiquitin that belongs to a group of proteins known as heat shock proteins. Subsequent studies revealed that ubiquitin is also associated with various neuronal inclusions including Lewy bodies, Pick bodies and hyaline inclusions. Very recently, ubiquitin has been found also to be associated with glial inclusions that are unique to multiple system atrophy. The close association of ubiquitin with varying cellular inclusions, together with its function in the proteolytic process, raised the hypothesis that ubiquitin may be involved in the degradation of abnormal proteins appearing in the damaged neurons and glial cells. In central nervous system, a group of heat shock proteins collectively known as HSP 70 is also present which is constitutive and/or inducible. Since HSP 70 has been suspected to play a crucial role degradation and repair of abnormal intracellular proteins, we hypothesized that HSP 70 may be associated with those inclusions, as the case with ubiquitin. To test this we performed immunohistochemical studies on brain tissues from patients with various neurodegenerative conditions by using specific polyclonal antibody to HSP 70. Brain tissues were obtained at autopsy from each three patients with Alzheimer's disease, Pick's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and multiple system atrophy. Tissues were fixed in buffered formalin and embedded in paraffin. Immunostaining was performed by the standard ABC method using diaminobenzidine as a chromogen. Sections were lightly stained with hematoxylin. Polyclonal antibodies were raised in rabbits against mouse HSP 70.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1990

65-kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites.

We have previously characterized a 65-kilodalton protein (p65) as an interleukin 2 stimulated phosphoprotein in human T cells and showed that three endopeptide sequences of p65 are present in the sequence of l-plastin [Zu et al. (1990) Biochemistry 29, 1055-1062]. In this paper, we present the complete primary structure of p65 based on the cDNA isolated from a human T lymphocyte (KUT-2) cDNA library. Analysis of p65 sequences and the amino acid composition of cleaved p65 N-terminal peptide indicated that the deduced p65 amino acid sequence exactly coincides with that of l-plastin over the C-terminal 580 residues [Lin et al. (1988) Mol. Cell. Biol. 8, 4659-4668] and has a 57-residue extension at the N-terminus to l-plastin. Computer-assisted structural analysis revealed that p65 is a multidomain molecule involving at least three intriguing functional domains: two putative calcium-binding sites along the N-terminal 80 amino acid residues; a putative calmodulin-binding site following the calcium-binding region; and two tandem repeats of putative actin-binding domains in its middle and C-terminal parts, each containing approximately 240 amino acid residues. These results suggest that p65 belongs to actin-binding proteins.

Actins↗
PubMed1990

Efficient tumor suppression by glioma-specific murine cytotoxic T lymphocytes transfected with interferon-gamma gene.

We have recently shown that exogenous expression of the mouse interferon-gamma (IFN-gamma) gene augmented the cell-killing potential of a line of cytotoxic T lymphocytes (CTLs) specific against a murine glioma line (203-glioma). In the present work, we further investigated the in vivo antitumor effects of the E gamma-6 and E gamma-9 sublines of this CTL line transfected with the IFN-gamma gene. Using the Winn assay to test the neutralization of subcutaneous gliomas, we determined that these CTL sublines were more effective than the E-4 parent CTL line and that suppression of the tumor growth was dependent on the number of effector cells (CTLs). Moreover, intravenous injection of E gamma-9 cells was more effective in suppressing the tumor growth than intravenous injection of E-4 cells. These results suggest that transfection of antitumor effector cells with the IFN-gamma gene could improve the efficacy of adoptive immunotherapy against cancer.

Animals↗
PubMed1990

Characterization of interleukin 2 stimulated 65-kilodalton phosphoprotein in human T cells.

We have characterized the cellular proteins which are rapidly phosphorylated by interleukin 2 (IL 2) in a human IL 2 dependent cell line. When treated with IL 2, the phosphorylation of five proteins, 65, 50, 37, 24, and 21 kDa, was found in IL 2 dependent cell lines by two-dimensional gel electrophoretic analysis. After cell conversion from an IL 2 dependent state to an IL 2 independent state, one of the five phosphoproteins, the 65-kDa protein, became constitutively phosphorylated even without addition of IL 2. Also, in other IL 2 independent cell lines, such as KUT-2 and HUT-102, constitutive phosphorylation of the 65-kDa protein occurred without IL 2-stimulation. So our researchers were focused on biochemical characterization of the 65-kDa protein. It was found that the 65-kDa protein was one of the major cellular proteins by comparing the results of two-dimensional gel electrophoretic analysis of [32P]Pi-labeled and [3H]leucine-labeled cellular proteins and peptide mapping analysis. Subcellular fractionation studies indicated that the 65-kDa protein is a cytosol protein. The 65-kDa protein was purified from cytosol of a human T cell line, and its amino acid composition and amino acid sequences of its three oligopeptides were determined. It was found that the 65-kDa protein is identical with 1-plastin.

Amino Acid Sequence↗
PubMed1990

Glucuronate-modified liposomes with prolonged circulation time.

For the purpose of obtaining liposomes with long circulation time in blood, we synthesized 1-O-palmityl-D-glucuronic acid (PGlcUA) and incorporated it into the liposomal membranes. The clearance of the PGlcUA-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and PGlcUA (40:40:20 as a molar ratio) from blood and their tissue distribution were compared with those of dipalmitoylphosphatidylglycerol (DPPG)-liposomes (DPPC/cholesterol/DPPG = 40:40:20). When [3H]inulin-loaded PGlcUA-liposomes and DPPG-liposomes were intravenously injected into rats, the half-life of the PGlcUA-liposomes in the blood appeared to be 1.7-fold longer than that of DPPG-liposomes. Radioactivities present in plasma and various tissues were measured 22 h after administration of these liposomes, and radioactivity remaining in the plasma was 2.5-fold greater when PGlcUA-liposomes were injected. The distribution pattern of [3H]inulin in PGlcUA-liposomes was similar to that in DPPG-liposomes. The radioactivity recovered in urine was 25% lower in rats treated with PGlcUA-liposomes than in those treated with DPPG-liposomes. Since both PGlcUA- and DPPG-liposomes exhibited similar size distribution and zeta-potential, glucuronic acid, rather than negative charge, on the liposomal surface appears to endow liposomes with a longer circulation time in the bloodstream.

Animals↗
PubMed1989

Expression of proto-oncogene products during drug-induced differentiation of a neuroblastoma cell line SK-N-DZ.

Four human neuroblastoma cell lines exhibited differences in their ability to differentiate into neuron-like cells in response to three different treatments, serum deprivation, or additions of dibutyryl cyclic-AMP or retinoic acid. Expression of N-myc gene product was reduced in neuroblastoma cell line SK-N-DZ differentiated by retinoic acid as compared with untreated cells. On the contrary, expression of c-src gene product, pp60c-src, was considerably enhanced in differentiated SK-N-DZ cells. Tyrosine phosphorylation of several cellular proteins was found to be enhanced in differentiated cells. Alteration in expression of these proto-oncogene products might be important in the differentiation of neuroblastoma cells into neuron-like cells.

Bucladesine↗
PubMed1989

Detection of fos oncogene products by monoclonal antibody FO-120 in lymphoproliferative disorders.

We investigated the expression of fos oncogene proteins in lymphoproliferative disorders, using a monoclonal antibody (FO-120) that was prepared against a synthetic oligopeptide of fos protein (amino acid sequence from 127 to 152). Although peripheral blood leukocytes were rarely positive for FO-120, they were transiently stained after lectin (PHA) stimulation. After culture with IL-2 for 1 or 2 weeks, less than 40% of the lymphocytes weakly reacted with FO-120, whereas strongly positive cells were detected in more than 70% of cells in half the T-cell lines established from preleukemic state of adult T-cell leukemia (pre-ATL) and all of ATL derived T-cell lines. All in vivo specimens of non-Hodgkin's malignant lymphomas, except for one case of T-cell lymphoma were also strongly positive. In addition, the extent of the antibody reactivity correlated with the histopathological grade of malignancy in B-cell lymphoma. The reactivity to most AILD-IBL lesions overlapped with that to T-lymphomas, and could be distinguished from that to reactive lesions. FO-120 appears to be a useful tool for detecting early neoplastic changes in lymphoproliferative disorders.

Antibodies, Monoclonal↗
PubMed1989

Comparison of fecal microflora of elderly persons in rural and urban areas of Japan.

The Fecal microflora of 15 healthy elderly persons with a median age of 84 years in a rural area whose inhabitants tend to be long-lived (Yuzurihara-area, Uenohara, Yamanashi Prefecture) was compared with the microflora of individuals with a median age of 68 years in an urban area (Tokyo). The diet of the elderly persons in the Yuzurihara area is characterized by a high intake of dietary fiber. Total numbers of anaerobic bacteria were significantly smaller in the elderly persons in the Yuzurihara area than those in the Tokyo area. A significantly large number of bifidobacteria, but not of lecithinase-negative clostridia, was observed in the elderly persons in the Yuzurihara area. Large numbers and high incidences of bacilli and lecithinase-positive clostridia (mainly Clostridium perfringens) were found in the elderly persons in the Tokyo area. Twenty-five genera and over 81 species were isolated from the elderly persons in the Yuzurihara area, and 25 genera and over 92 species were isolated from the elderly persons in the Tokyo area. Furthermore, significantly larger numbers of Bifidobacterium adolescentis and Fusobacterium mortiferum strains were found in the Yuzurihara group, but significant reductions in the Bacteroides buccae-oris group, B. thetaiotaomicron, Bacteroides spp., C. coccoides, C. paraputrificum, and Clostridium spp. were observed in the same group. A significantly higher isolation rate of Bacillus subtilis was observed in the elderly persons in the Tokyo area. The difference in the fecal microflora between elderly persons in Yuzurihara and those in the Tokyo area might be due to a difference in the intake of dietary fiber.

Aged↗