Search PubMed⌕ Search

Biomedical subjects

T Yamano

Publications and source records attributed to T Yamano.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of age and carbon tetrachloride on cytokine concentrations in rat liver.

Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in livers of young-adult and old rats administered carbon tetrachloride or vehicle. IL-1beta levels were higher and IL-6 levels were lower in old rats than in young-adult rats. Carbon tetrachloride treatment increased IL-1beta and decreased TNF-alpha and IL-6. The elevation in IL-1beta was diminished by aging. These results indicate that the increase in carbon tetrachloride hepatotoxicity that occurs in old age could be related to a dysregulation of inflammatory cytokines.

Aging↗
PubMed1999

Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96.

We have previously demonstrated that vaccination with heat shock proteins hsp70, hsp90, and gp96 elicits specific immunity against the tumor from which the hsps were purified. Although the association of tumor Ag peptides with these hsps have been suggested, the identification of the peptides or their precursors stripped from the hsps remained to be resolved. We show in this report that an Ld-restricted cytotoxic T lymphocyte epitope of a mouse leukemia RLmale symbol1 and its precursors are associated with the chaperones hsp90 and hsp70 in the cytosol and gp96 in the lumen of the endoplasmic reticulum. Hsp70 was associated with only final sized octamer, while hsp90 was found to associate with the octamer and two distinct precursor peptides. The gp96 was associated with the octamer and one of the two precursors. Thus, each of the hsps bound a distinct set of peptides. Our results have demonstrated for the first time that the hsps associate not only with final sized tumor Ag peptide but also with its precursors. The implication of this evidence is also discussed in terms of the roles of hsps in MHC class I Ag processing/presentation.

Animals↗
PubMed1999

Dermoid cyst of the spleen: report of a case.

A rare splenic dermoid cyst in an 11-year-old girl is reported herein. The patient was referred to us with the chief complaint of acute-onset abdominal pain. The lesion was demonstrated by ultrasonography, computed tomography, and magnetic resonance imaging to be a cystic lesion containing serous fluid. A splenectomy was performed. Both histopathological and immunohistochemical findings demonstrated the cyst to be a dermoid cyst of the spleen. To avoid the risk of infection following splenectomy, polyvalent pneumococcus vaccine was administered. The patient recovered uneventfully. We performed immunohistochemical studies with cytokeratin and electron microscopy to determine the origin of the cyst.

Abdominal Pain↗
PubMed1999

A case of anorexia nervosa with hyperbilirubinaemia in a patient homozygous for a mutation in the bilirubin UDP-glucuronosyltransferase gene.

UNLABELLED: Gilbert syndrome was diagnosed in a girl with anorexia nervosa and unconjugated hyperbilirubinaemia. Since the patient was starved and hyperbilirubinaemic, the loading test was not used for the diagnosis but analysis of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) instead. The patient was homozygous for a missense mutation that replaced guanine with adenine at nucleotide number 211 (211G-->A: G71R). The unconjugated hyperbilirubinaemia was apparently induced by the fasting state. Homozygous missense mutations of the gene have been generally recognized as responsible for Crigler-Najjar syndrome type II; the results obtained here, however, confirm that Gilbert syndrome may also be caused by a homozygous missense mutation of UGT1A1. CONCLUSION: Since anorexia nervosa patients are in a fasting state, they may show moderate unconjugated hyperbilirubinaemia if they have Gilbert syndrome. Gene analysis of such cases will rule out hepatic damage. Homozygous missense mutations of the bilirubin-UDP-glucuronosyltransferase gene cause not only Crigler-Najjar syndrome type II but also Gilbert syndrome.

Anorexia Nervosa↗
PubMed1999

Expression of platelet-derived growth factor B-chain and beta-receptor in hypoxic/ischemic encephalopathy of neonatal rats.

Expression of platelet-derived growth factor B-chain and of its specific receptor (beta-receptor) was investigated in immature brains with hypoxic/ischemic injury. After the left common carotid arteries of seven-day-old rats were ligated and pups were placed in a hypoxic chamber, the protein and messenger RNA of both B-chain and beta-receptor were assessed using immunocytochemistry and northern analysis, respectively. Transcripts for B-chain were localized by in situ hybridization. Faint but definite expression of B-chain and beta-receptor was seen in the brains of untreated neonatal controls. Three to 48 h after hypoxia B-chain protein was generally increased above control levels, but focally decreased expression was seen in infarcted areas. Enhanced induction of messenger RNA of B-chain was seen in the both sides of cerebral cortices and hippocampi at 3 h. Strongly increased positivity for B-chain protein and mRNA occurred in the neurons surrounding the infarct. In situ hybridization still showed this up-regulation seven days after hypoxia. Beta-receptor protein expression was enhanced in some neurons immediately surrounding the infarct at 3 h of hypoxia, and marked up-regulation was seen at 16 h. Beta-receptor messenger RNA remained at control levels. Immunocytochemistry showed strong immunoreactivity for the beta-receptor on the neurons surrounding the infarct at 72 h. These results indicate that a neonatal hypoxic/ischemic insult induces neuronal up-regulation of the platelet-derived growth factor B-chain as well as beta-receptor immediately after hypoxia. While this up-regulation is relatively transient in most neurons, sublethal damage to neurons immediately surrounding an infarct induces sustained up-regulation. Through autocrine and paracrine mechanisms, platelet-derived growth factor B-chain molecules may act as a neuroprotective factor in immature brain experiencing with hypoxic/ischemic injury.

Animals↗
PubMed1999

Disappearance of hypointense multiple sclerotic lesions on FLAIR MRI.

A child is presented who displayed hypointense multiple sclerotic lesions on fluid-attenuated inversion recovery sequences by magnetic resonance imaging, with the possible pathologic tissue changes of these hypointense lesions evaluated. The magnetic resonance imaging results in this patient demonstrated the disappearance of low-signal lesions on fluid-attenuated inversion recovery in multiple sclerosis, and the improvement of this patient's condition was likely compatible with sequential magnetic resonance imaging findings. Some hypointense lesions in the supratentorial white matter that appear on fluid-attenuated inversion recovery images in multiple sclerosis patients may include reversible brain lesions, suggesting extracellular fluid collection not accompanied by axonal loss or gliosis.

Adolescent↗
PubMed1999

Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma.

MAGE gene family encodes peptides recognized by autologous cytotoxic T lymphocytes in a major histocompatibility complex (MHC) class-I restricted fashion. In the present study, we have performed reverse-transcription polymerase chain reaction (RT-PCR) for the genes, as well as immunohistochemical analysis and Western blotting of MAGE-1 and -3 proteins in 33 surgically resected hepatocellular carcinomas (HCCs). MAGE-1 and -3 mRNAs were constitutively expressed exclusively in 78 and 42% of HCCs respectively. On immunohistochemistry with monoclonal antibodies, 77B for MAGE-1 and 57B for MAGE-3, MAGE-1 and -3 proteins were recognized in cytoplasm of only six among 33 (18%) and two of 29 HCCs (7%) respectively. The distribution pattern was mostly focal in HCC nodules. By contrast, the Western blot analysis revealed that the MAGE-1 (46 kDa) and -3 proteins (48 kDa) were expressed in 80 and 60% of 15 HCCs examined respectively. The proteins of MAGE-1 and -3 were also expressed exclusively in HCCs regardless of the histological grading and clinical staging. Our results indicate that the detection of the genes by RT-PCR or the proteins by Western blotting is useful for differentiating early HCCs from non-cancerous lesions, and that the peptides derived from MAGE-1 and -3 proteins might be suitable targets for immunotherapy of human HCC.

Adult↗
PubMed1999

Enhancement of the anti-tumor effect of 5'-deoxy-5-fluorouridine by transfection of thymidine phosphorylase gene into human colon cancer cells.

Thymidine phosphorylase (dThdPase) is an enzyme that converts 5'-deoxy-5-fluorouridine (5'DFUR) to the toxic substance 5-fluorouracil (5-FU); it is also known to be a platelet-derived endothelial cell growth factor. In order to investigate the feasibility of suicide gene therapy against colorectal cancer by means of the combination of 5'DFUR and the converting enzyme dThdPase, we transfected the dThdPase gene into the human colon cancer cell line SW480 and analyzed the growth pattern as well as the sensitivity to 5-FU or 5'DFUR of the dThdPase-transfected cells. The 50% inhibition (IC50) values of 5-FU against the SW480 parental cells, control vector-transfected cells SW480/V1, and dThdPase-transfected cells SW480/dThdPase were approximately 4.9, 6.3, and 2.9 microM, respectively. The IC50 of SW480/dThdPase was lower than that of SW480 or SW480/V1, although the differences were not statistically significant. The IC50 values of 5'DFUR for SW480, SW480/V1, and SW480/dThdPase were approximately 300, 330, and 3.2 microM, respectively. The sensitivity to 5'DFUR of SW480/dThdPase was increased by about 100-fold compared with that of SW480 or SW480/V1. With only 10% transfection efficacy, a high enough sensitivity to 5'DFUR was obtained to suppress the cell growth, indicating that a strong bystander effect was induced by this system. The in vivo growth of the s.c. transplanted SW480/dThdPase tumor in nude mice was significantly suppressed by i.p. injection of 5'DFUR compared with that in control mice that received phosphate-buffered saline (PBS) treatment. These results suggest that gene therapy using the combination of 5'DFUR and the dThdPase gene may be a useful approach for treatment of colon cancer.

Animals↗
PubMed1999

Decreased urinary concentrations of type IV collagen in amyotrophic lateral sclerosis.

OBJECTIVES: Type IV collagen (IV-C) abnormalities of skin and serum have been reported in patients with amyotrophic lateral sclerosis (ALS). However, there has been no study of urinary IV-C in ALS. The present study investigates urinary IV-C and the relation to its skin content in patients with ALS. MATERIAL AND METHODS: We studied IV-C immunoreactivity of skin and measured urinary levels of IV-C in ALS patients and controls. RESULTS: The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for IV-C as compared with those of controls. Immunostaining became even weaker as ALS progressed. The urinary level of IV-C in ALS patients was significantly decreased as compared to diseased controls (P<0.001) and healthy controls (P<0.001), and was negatively and significantly associated with duration of symptoms (r=-0.85, P<0.001). There was an appreciable positive correlation between urinary IV-C levels and the density for IV-C immunoreactivity in ALS patients (r=0.84, P<0.01). CONCLUSION: These data suggest that a metabolic alteration of IV-C may occur in ALS patients and decreased levels of urinary IV-C may be related to the decreased IV-C immunoreactivity of skin in ALS.

Aged↗
PubMed1998

Sck interacts with KDR and Flt-1 via its SH2 domain.

Vascular endothelial growth factor (VEGF) is one of the major angiogenesis regulators. It binds to its tyrosine kinase receptors, KDR and Flt-1. However, little is known about their downstream signal transduction properties. We screened human brain cDNA library using the yeast two-hybrid system with the KDR cytoplasmic region as bait to find KDR binding proteins. After 6.2 x 10(6) clones were screened, we identified Sck, one of the Shc homologues, as a KDR binding protein. Sck also binds to Flt-1 and their binding is dependent on the kinase activities of KDR and Flt-1. Extensive site-directed mutagenesis of KDR revealed that Y1175 of KDR is a major binding site for Sck. As Sck contains the SH2 domain and PTB domain, we tested whether they bind to KDR and Flt-1. The SH2 domain of Sck binds to both of them. Deletion of the SH2 domain from Sck resulted in the complete loss of binding. On the other hand, the PTB domain of Sck does not bind to KDR and Flt-1. These results indicate that Sck binds to KDR and Flt-1 via its SH2 domain and might play an important role in VEGF signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis.

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.

Adult↗
PubMed1998

Enhanced expression of full-length TrkB receptors in young rat brain with hypoxic/ischemic injury.

Expression of TrkB receptors were studied in the cerebral cortex of normal rats and young rats with hypoxic/ischemic injury. TrkB expressing cells were present in the piriform cortex at birth and increased in number with age, and were finally present in the entire cerebral cortex. Density of TrkB cells reached adult levels at P30. They were morphologically regarded as pyramidal neurons and interneurons. Hypoxic/ischemic injury induced a tentative increase of full-length TrkB receptors. A novel appearance of TrkB expressing neurons and enhanced immunostaining on both cell soma and dendrites were observed in the peri-infarct areas and increased number of TrkB expressing neurons were detected in the contralateral cortex after carotid artery ligation. This increase was no longer evident after 48 h of hypoxia. Double immunostaining using antiserum against GFA or OX-42 revealed no co-localization of TrkB receptors and these molecules, while there were only slight co-localization of TrkB and calbindin-D28k molecules. The altered levels in responses to injury indicate that TrkB may play a crucial role in the early protective mechanism of the neurons with hypoxic/ischemic injury through ligands BDNF and/or NT-4/5.

Age Factors↗
PubMed1998

Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2.

Vascular endothelial growth factor (VEGF) binds to its receptor tyrosine kinase Flt-1 and KDR/Flk-1 and stimulates their autophosphorylation. However, little is known about their downstream signal transduction properties. We examined the interactions of certain proteins with a SH2-domain with Flt-1 and KDR using the yeast two-hybrid system and found that Nck, SHP-2, PLC gamma, and PI3K p85 bind to Flt-1. Extensive site-directed mutagenesis of Flt-1 revealed their major binding sites. Nck, SHP-2, and PI3K bind to Y1213 of Flt-1. Nck also binds to Y1333 of Flt-1. These results suggest that Nck, SHP-2, PLC gamma, and PI3K play important roles in Flt-1 signal transduction and that Y1213 of Flt-1 is a major binding site of PI3K, Nck, and SHP-2.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Age-related change in cadmium-induced hepatotoxicity in Wistar rats: role of Kupffer cells and neutrophils.

The hepatotoxicity of cadmium was studied in 1-, 2-, and 6-month-old male Wistar rats. Liver damage, indicated by the increase in serum alanine aminotransferase activity 24 h after sc administration of 3 and 6 mg/kg cadmium, was observed only in 6-month-old rats. Dose-dependent increases in the cadmium content of the liver were similar for all three age groups. Basal and induced metallothionein contents were higher in livers of 1-month-old rats than in those of 2- and 6-month-old rats. In contrast, the basal glutathione content of the liver was higher in 6-month-old rats than in 1- and 2-month-old rats, and glutathione content increased slightly in all three age groups after cadmium administration. Thus, the higher susceptibility to cadmium-induced hepatotoxicity in 6-month-old rats seemed not to be explained by differences in cadmium uptake or by the metallothionein and glutathione contents of the liver. Inactivation of Kupffer cells with gadolinium chloride or depletion of neutrophils with cyclophosphamide relieved cadmium hepatotoxicity only in 6-month-old rats. In addition, 6-month-old rats were more susceptible than 2-month-old rats to lipopolysaccharide-induced hepatotoxicity. The results suggest that age-associated changes in Kupffer cell function and infiltration of neutrophils are important determinants of cadmium-induced hepatotoxicity in rats.

Age Factors↗
PubMed1998

Comparative effects of repeated administration of cadmium on kidney, spleen, thymus, and bone marrow in 2-, 4-, and 8-month-old male Wistar rats.

Male Wistar rats at 2, 4, and 8 months were given s.c. injections of CdCl2 at doses of 0.5, 1, and 2 mg Cd/kg, 3 days/week, for 4 weeks. Dose-related adverse effects observed at the end of the injections were as follows: decrease in body weight gain, increases in liver, kidney, and spleen weights, decrease in red blood cell counts, and increase in white blood cell counts accountable by an increased percentage of neutrophils in peripheral white blood cells. Essentially, all of these changes were age-related, i.e., the extents of the effects in each age group were in the order of 8- > 4- > 2-month-old rats when compared at the same dose level of Cd. The sensitive indicators of histological changes were increase in hematopoietic cells in bone marrow and fibrous tissue proliferation in the thymus > fibrous tissue proliferation and hyperplasia of lymph follicle in the spleen > renal tubular degeneration. These histological changes became to be marked at lower doses with aging. Dose-dependent increases in total Cd concentrations in the liver, kidney, and spleen were slightly higher with aging, while metallothionein (MT) contents in these organs were induced exactly in the same pattern as Cd concentrations in each organ in various age groups. This study revealed that the adverse effects after repeated administration of Cd on the kidney, spleen, thymus, and bone marrow worsened with increasing animal age and that this phenomenon could not be explained simply by differences in Cd disposition or MT induction in the organs of the different age groups.

Age Factors↗
PubMed1998

Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of bilirubin UDP-glucuronosyltransferase gene.

We report a case of Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of the bilirubin UDP-glucuronosyltransferase gene. Homozygous missense mutations of the gene have previously been recognized as responsible for Crigler-Najjar syndrome type II. We conclude that Gilbert syndrome in some patients results from homozygous missense mutations of the UDP-glucuronosyltransferase gene.

Child↗
PubMed1998

Hypertension in Leigh syndrome--a case report.

A female patient, who was diagnosed with Leigh syndrome at 15 months of age, developed fulminating severe hypertension and died at 8 years of age. Hypertension has not been reported as an important clinical symptom in Leigh syndrome. Laboratory findings indicated that it was not associated with endocrinopathic diseases such as pheochromocytoma and aldosteronism, or renal diseases. Brain MRI scan showed symmetrical lesions in the basal ganglia and medulla oblongata including the nucleus tractus solitarius. This nucleus is known to play an important role in maintaining blood pressure. Since the medulla oblongata is a vulnerable site, potential development of hypertension should be taken into consideration when managing Leigh syndrome.

3-Iodobenzylguanidine↗