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Biomedical subjects

Y Nagata

Publications and source records attributed to Y Nagata.

At least 181 records · Page 10Linked to original sources
PubMed1998

A novel hydrophobized polysaccharide/oncoprotein complex vaccine induces in vitro and in vivo cellular and humoral immune responses against HER2-expressing murine sarcomas.

To elicit specific cellular immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the MHC class I pathway constitutes a central issue. We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. A protein consisting of the 147 amino-terminal amino acids of oncogene erbB-2/neu/HER2 (HER2) was complexed with two kinds of hydrophobized polysaccharides, cholesteryl group-bearing mannan (CHM) and cholesteryl group-bearing pullulan (CHP), to form nanoparticles (CHM-HER2 and CHP-HER2). CHM-HER2 and CHP-HER2 were able to induce CD3+/CD8+ CTLs against HER2-transfected syngeneic fibrosarcoma cell lines. In contrast, the oncoprotein alone failed to do so. These CTLs were Kd-restricted and specifically recognized a peptide (position 63-71) that was a part of a truncated HER2 protein used as an immunogen. In addition, vaccination by CHM-HER2 complexes led to a strongly enhanced production of IgG antibodies against HER2, whereas vaccination with HER2 proteins alone resulted in a production of antibodies at a marginal level. Mice immunized with CHM-HER2 or CHP-HER2 before tumor challenge successfully rejected HER2-transfected tumors. The complete rejection of tumors also occurred when CHM-HER2 was applied not later than 3 days after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that a sort of hydrophobized polysaccharide may help soluble proteins to induce cellular immunity as well enhance humoral immunity; hence, such a novel vaccine may be of potential benefit to cancer prevention and cancer therapy.

Animals↗
PubMed1998

The effect of menopause on regional and total body lean mass.

OBJECTIVES: To investigate the effect of menopause on regional and total body lean mass. METHODS: Evaluation of 123 healthy premenopausal women (40.6 +/- 10.8 years) and 123 healthy postmenopausal women (61.8 +/- 7.5 years). All subjects were right side dominant. Regional (head, bilateral arms, trunk, and bilateral legs) and total body lean mass were measured using whole-body scanning by dual-energy X-ray absorptiometry. Baseline characteristics including age, height, weight, and menopausal state were recorded. These variables were compared between pre- and postmenopausal women. In all subjects, correlations between regional or total body lean mass and baseline characteristics were investigated using univariate and multiple regression analyses. RESULTS: Height, and lean mass of the trunk, bilateral legs and total body were significantly lower in postmenopausal women than in premenopausal women, while lean mass of the bilateral arms did not differ between the two groups. On univariate regression analysis, bilateral arms lean mass was positively correlated with height (P < 0.001). Trunk, bilateral legs, and total body lean mass were inversely correlated with age and menopausal state (P < 0.001), but were positively correlated with height (P < 0.001). After adjusting for age and height, trunk lean mass was still correlated with menopausal state (P < 0.01). CONCLUSIONS: Menopause induces lean mass loss, independent of aging and height. Trunk lean mass is more prone to decline with menopause than lean mass of other sites.

Adult↗
PubMed1998

Transglutaminase activity in serum and cerebrospinal fluid in sporadic amyotrophic lateral sclerosis: a possible use as an indicator of extent of the motor neuron loss.

The activity of transglutaminase (TGase), a marker enzyme for tissue degeneration, was examined in serum and cerebrospinal fluid (CSF) obtained from patients with sporadic amyotrophic lateral sclerosis (SALS), and compared to those from patients without SALS. When the serum TGase activity values from SALS patients were compared against the 'ALS-scale', which is used for clinical evaluation of the progression of ALS, the TGase activity values were higher at the initial stage of the disease than in non-ALS subjects, whereas they became extremely low at the late stage of ALS. The TGase activity in the CSF taken at later than middle stage from ALS patients with definite clinical motor dysfunctions was significantly lower than in that from non-ALS subjects. We have previously demonstrated marked reduction of tissue TGase activity in all regions of spinal cord tissue transections from ALS patients, not only in ventral but also lateral and dorsal regions, relative to that in non-ALS patients. These results suggest that some TGase may be leaked out of the spinal cord tissue into the CSF and then into the blood-stream during the progression of ALS, and the enzymic activity finally becomes depleted at the terminal stages of the disease when most of the spinal motor neuronal perikarya have been destroyed.

Aged↗
PubMed1998

Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets.

Tec is a non-receptor type tyrosine kinase which is tyrosine phosphorylated and activated upon stimulation of hematopoietic cells with various cytokines. The role of Tec in G protein-coupled receptor- and integrin-mediated signalings has not been elucidated. We therefore investigated the regulation of Tec in human blood platelets. Tec was rapidly tyrosine phosphorylated in response to platelet agonists which activate G protein-coupled receptors such as thromboxane A2 analog (U46619), thrombin, and thrombin receptor activating peptide (TRAP). TRAP-induced phosphorylation in Tec was significantly reduced under the conditions which abrogate fibrinogen binding to GP IIb-IIIa and subsequent platelet aggregation. However, TRAP induced significant levels of the phosphorylation even under these conditions and also in thrombasthenic platelets which lack functional GP IIb-IIIa molecules, suggesting that activation of G-protein-coupled receptor causes the phosphorylation. To clarify whether integrin engagement by itself causes the phosphorylation in Tec, we examined the state of the phosphorylation in platelets activated by integrin engagement. Platelet adhesion to immobilized fibrinogen or collagen induced significant levels of the phosphorylation. Furthermore, Tec was translocated to cytoskeleton in response to TRAP in a manner dependent on platelet aggregation, suggesting that Tec can be a component of integrin-mediated signalings. These results collectively indicate that Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets.

Actins↗
PubMed1998

Increase of glial fibrillary acidic protein fragments in the spinal cord of motor neuron degeneration mutant mouse.

We analyzed protein fractions extracted from the spinal cord of the motor neuron degeneration (Mnd) mouse, a mutant that exhibits progressive degeneration of lower spinal motor neurons, by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) after solubilization of the tissue with medium containing sodium dodecyl sulfate (SDS)-urea during growth of the animal, in comparison with those of age-matched controls (C57BL/6). Several protein spots were detected around a region of pI 5.6-6.0 and molecular mass of 35-50 kDa in Mnd spinal cord tissue on the two-dimensional PAGE separation profile with Coomassie brilliant blue staining, while only a few spots around the same region were found in the control spinal cord. These spots were all immunoreactive with an antibody against glial fibrillary acidic protein (GFAP), a cytoskeleton filamentous protein specific to astroglial cells. The protein spot with molecular mass of 50 kDa showed immunoreactivity with anti-GFAP antibody, had a blocked amino-terminus, and is assumed to be intact GFAP. Several protein spots with slightly smaller molecular masses of 35 to 48 kDa lacked the head domain of the GFAP molecule as a result of cleavage at the 29th and 56th residues from the amino terminus. In Mnd spinal cord tissue, the densities of the immunoreactive GFAP bands with smaller molecular masses increased with development, and became dominant at the time of the appearance of behavioral paralytic gait around 6 to 7 months of age. These results suggest that the increased GFAPs devoid of head domains are related to the degenerative loss of motor neurons in the Mnd spinal cord. Histopathological and GFAP immunohistochemical examination of Mnd spinal cord preparation demonstrated progressive degenerative loss of motor neurons, and considerable increases in number of GFAP-stained astrocytes in the ventral horn at 7 to 9 months of age. These processes of degenerative loss of motor neurons and proliferation of reactive astrocytes with increased levels of fragmented GFAP in the Mnd spinal cord during development seem to be characteristic and preceded the deterioration of motor activities in this animal model of amyotrophic lateral sclerosis.

Amino Acid Sequence↗
PubMed1998

Occurrence of peptidyl D-amino acids in soluble fractions of several eubacteria, archaea and eukaryotes.

The occurrence of peptidyl D-amino acids in the aqueous soluble fractions was investigated in various eubacteria, some archaea and some eukaryotes. The contents of the D-enantiomers of serine, alanine, proline, glutamate (glutamine), aspartate (asparagine) and phenylalanine were determined with cell- and tissue-extracts, by means of acid hydrolysis and high-performance liquid chromatography. The rate of D-enantiomer (%, the ratio in molar concentration of a D-amino acid to the total of the D-amino acid and the corresponding L-amino acid) of alanine and glutamate were high in some Gram-positive eubacteria: 11.7% in Staphylococcus epidermidis and 10.3% in Streptococcus pyogenes for alanine, and 22.3% for glutamate in Bacillus YN-1. The D-glutamate content was also high (8.0%) in the Gram-negative eubacterium, Thiobacillus ferrooxidans. D-Aspartate was common, as was D-glutamate: the highest D-aspartate content was detected in an archaeum, Pyrobaculum islandicum (4.0%). However, the content of D-aspartate was low, 0.2-1.8% in most other bacteria. The presence of D-serine was shown in some organisms, but that of D-proline was scarce. The D-enantiomer of phenylalanine was not detected in any of the organisms examined. These results indicate that of the bacteria examined herein most Gram-negative and some Gram-positive eubacteria, as well as archaea contain only low levels of D-amino acids in the soluble peptidyl fraction, and the levels were comparable to those in eukaryotes examined. To our knowledge, the general presence of peptidyl D-amino acids in these organisms, especially archaea and eukaryotic cells including those from rat liver tissues, has been shown here for the first time.

Amino Acids↗
PubMed1998

Tumor response to neoadjuvant chemotherapy correlates with the expression of P-glycoprotein and PCNA but not GST-pi in the tumor cells of cervical carcinoma.

OBJECTIVE: To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas. METHODS: We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathione S-transferase pi (GST-pi), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied. RESULTS: Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P < 0.005) and low PCNA labeling (P < 0. 05), but not GST-pi expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-pi nor PCNA was correlated with the patient survival. CONCLUSION: Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Neurochemical changes in the spinal cord in degenerative motor neuron diseases.

Human amyotrophic lateral sclerosis (ALS), a typical motor neuron disease, is characterized pathologically by selective degenerative loss of motoneurons in the CNS. We have demonstrated significant reductions of neurotransmitter-related factors, such as acetylcholine-(ACh)-synthesizing enzyme activity and glutamate and aspartate contents in the ALS, compared to the non-ALS spinal cord obtained at autopsy. We have also shown considerable reductions in activities of cytochrome-c oxidase (CO), an enzyme contributing to aerobic energy production, and transglutaminase (TG), a Ca(2+)-dependent marker enzyme for tissue degeneration, in the ALS spinal cord. We found marked increases in fragmented glial fibrillary acidic protein (GFAP), a filamentous protein specifically associated with reactive astrocytes, in the ALS spinal cord relative to non-ALS tissue. These biochemical results corresponded well to pathomor-phological neuronal degenerative loss and reactive proliferation of astroglial components in the ALS spinal cord tissue. However, these results only indicate the final pathological and biochemical outcomes of ALS, and it is difficult to follow up cause and process in the ALS spinal cord during progression of the disease. Therefore, we used an animal model closely resembling human ALS, motor neuron degeneration (Mnd) mutant mice, a subline of C57BL/6 that shows late-onset progressive degeneration of lower motor neurons with paralytic gait beginning around 6.5 mo of age, to follow the biochemical and pathological alterations during postnatal development. We detected significant decreases in CO activity during early development and in activity of superoxide dismutase (SOD), an antioxidant enzyme, in later stages in Mnd mutant spinal cord tissue. TG activity in the Mnd spinal cord showed gradual increases during early development reaching a maximum at 5 mo, and then tending to decrease thereafter. Amounts of fragmented GFAPs increased continuously during postnatal development in Mnd spinal cord. These biochemical changes were observed prior to the appearance of clinical motor dysfunctions in the Mnd mutant mice. Such biochemical analyses using appropriate animal models will be useful for inferring the origin and progression of human ALS.

Animals↗
PubMed1998

[Two cases of coronary artery aneurysm including one case of the left main coronary artery aneurysm].

We report two cases of coronary artery aneurysm including one case of the left main coronary artery aneurysm. The coronary angiogram of one patient, a 68-year-old male, having anterior chest pain on exertion, revealed left anterior descending coronary artery (segment 6) aneurysm of 7 mm in diameter with 90% stenosis distal to the aneurysm and 75% stenosis in the right coronary artery (segment 2). The coronary angiogram of another patient, a 69-year-old female, having chest pain unrelated to exertion, revealed left main coronary artery aneurysm of 25 mm in diameter and delayed filling of contrast medium into the left anterior descending coronary artery. We decided to operate by the reason of not only significant coronary artery stenosis but risks of myocardial infarction due to embolization into distal coronary arteries and rupture of the aneurysm. We performed coronary artery bypass graftings using the great saphenous veins and closure of the coronary arteries running into and out the aneurysm under cardiopulmonary bypass. It is recommended that ligation of the coronary arteries connecting to the aneurysm or resection of the aneurysm followed by coronary artery bypass grafting is performed before developing myocardial infarction or rupture of aneurysm.

Aged↗
PubMed1998

Limb salvage and survival rates among elderly patients with advanced limb ischemia.

The purpose of this study was to clarify the incidence of limb salvage and patient survival rates among elderly patients with advanced leg ischemia. We reviewed the records of 159 patients treated for advanced ischemia over a 15-year period at Aichi Medical University, 74 of whom were aged over 75 years and 85, between 65 and 74 years. There was a collective total of 186 limbs; 82 in the older group and 104 in the younger group. The older group had a greater proportion of women, and a higher incidence of coronary heart disease, pulmonary dysfunction, and acute onset of advanced ischemia than the younger group. Limb salvage was achieved in 73% of the affected limbs in the older group and in 92% of the limbs in the younger group. The poor limb salvage rate in the older group was mainly related to the high initial amputation rate. Early recognition of the sentinel ischemic signs before the ischemia is essential, especially in the elderly. Timely revascularization should be attempted whenever possible, and it should not be abandoned simply because the patient is deemed too old. The 1-, 3-, and 5-year survival rates in the older group were 59%, 28%, and 23%, respectively, which were markedly poorer than the expected survival rates of the age- and sex-matched Japanese population at 1, 3, and 5 years, which were 93%, 79%, and 65%, respectively. Thus, advanced limb ischemia carries a poor prognosis to the point of being life-threatening, and further continuous systemic management with the collaboration of physicians and surgeons must be provided even after the patient has left the hospital.

Aged↗
PubMed1998

Nonfunctional paraganglioma of the pancreas: report of a case.

We report herein the case of a 61-year-old man found to have a rare nonfunctional paraganglioma of the pancreas. Interestingly, the preoperative data and images showed similar characteristics to neuroendocrine tumors of the pancreas. Both paragangliomas and neuroendocrine tumors of the pancreas belong to the category of Amine Precursor Uptake and Decarboxylation (APUD) tumors (APUDomas). Thus, it is important to examine the serum level of pancreatic endocrine hormones and a variety of peptides to differentiate paragangliomas of the pancreas from other pancreatic tumors. Paragangliomas of the pancreas grow slowly, so radical resection is recommended to achieve curability with a good prognosis.

Humans↗
PubMed1998

cDNA cloning and predicted primary structure of scallop sarcoplasmic reticulum Ca(2+)-ATPase.

Sarcoplasmic reticulum (SR) Ca(2+)-ATPase of the scallop cross-striated adductor muscle was purified with deoxycholate and digested with lysyl endopeptidase for sequencing of the digested fragments. Overlapping cDNA clones of the ATPase were isolated by screening the cDNA library with an RT-PCR product as a hybridization probe, which encodes the partial amino acid sequence of the ATPase. The predicted amino acid sequence of the ATPase contained all the partial sequences determined with the proteolytic fragments and consisted of the 993 residues with approximately 70% overall sequence similarity to those of the SR ATPases from rabbit fast-twitch and slow-twitch muscles. An outline of the structure of the scallop ATPase molecule is predicted to mainly consist of ten transmembrane and five 'stalk' domains with two large cytoplasmic regions as observed with the rabbit ATPase molecules. The sequence relationship between scallop and other sarco/endoplasmic reticulum-type Ca(2+)-ATPases is discussed.

Amino Acid Sequence↗
PubMed1998

An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays.

A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) was performed on Japanese adults. Serum samples collected between 1985-9 from a total of 536 healthy adults, female prostitutes, males with sexually transmitted diseases (STD), homosexual men, and pregnant women were studied by immunodot assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1 infections correlated mostly with age and was widely prevalent among subjects < 40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and was associated with risk behaviours for prostitution, infection with STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes (80%), lowest among pregnant women (7%), and intermediate in STD patients (23%) and homosexuals (24%). Because HSV-1 infection during childhood has been decreasing, primary genital HSV-2 infection, with its higher frequency of clinical manifestations, will become a greater burden to the public health in Japan.

Adult↗
PubMed1998

Alteration of enzymatic activities implicating neuronal degeneration in the spinal cord of the motor neuron degeneration mouse during postnatal development.

Oxidative stress is suggested as a significant causative factor for pathogenesis of neuronal degeneration on spinal cord of human ALS. We measured some enzymic activities implicating neuronal degeneration process, such as cytochrome c oxidase (CO), superoxide dismutase (SOD), and transglutaminase (TG) in spinal cord of an animal model of ALS, motor neuron degeneration (Mnd) mouse, a mutant that exhibits progressive degeneration of lower spinal neurons during developmental growth, and compared them with age-matched control C57BL/6 mice. CO activity in Mnd spinal cord decreased during early postnatal period, while SOD activity reduced in later stage. In Mnd tissue, TG activity in lumbar cord was increasing during early stage, but tended to decline in later period gradually. These biochemical alterations became evident prior to the appearance of clinical motor dysfunction which were observed in later stages of development in Mnd spinal cord.

Aging↗
PubMed1998

Developmental changes in the NGF content in the brain of young, growing, low-birth-weight rats.

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla oblongata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Animals↗
PubMed1998

Increases in fragmented glial fibrillary acidic protein levels in the spinal cords of patients with amyotrophic lateral sclerosis.

Using one-dimensional polyacrylamide gel electrophoresis, we analyzed protein fractions extracted from the spinal cords of patients with amyotrophic lateral sclerosis (ALS). Several protein bands with molecular weights of 35-55 kDa were stained with Coomassie brilliant blue much more intensely in the ALS than in the non-ALS spinal cord. Glial fibrillary acidic protein (GFAP) immunoreactivity showed a significant decrease of 50 and 45 kDa band and increase in fragmented 36 and 37 kDa bands, which represented GFAP fragments devoid of 59 and 40 residues from the N-terminal, respectively, as determined by protein sequence analysis. Immunohistochemical examination of ALS spinal cord transections demonstrated increased GFAP-stained astrocytes in the shrunken ventral horn with massive degeneration of motoneurons. These results will provide new insight into the possible role of astrocytes in the pathophysiology and/or pathogenesis of ALS.

Amino Acid Sequence↗