Biomedical subjects

Y Totsuka

Publications and source records attributed to Y Totsuka.

At least 37 records · Page 2Linked to original sources

PubMed2001

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.

Journal Article↗

PubMed2001

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Journal Article↗

PubMed2001

Induction of liver preneoplastic lesions by aminophenylnorharman, formed from norharman and aniline, in male F344 rats.

9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman, APNH), produced by the reaction of norharman with aniline in the presence of S9 mix, is a novel heterocyclic amine (HCA), with mutagenicity to Salmonella typhimurium TA 98 and YG 1024 comparable to that of other HCAs such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). This experiment was designed to investigate its potential to induce glutathione S-transferase placental form (GST-P) positive foci in the liver. Male F344 rats, 7 weeks old, were fed diet containing 0, 10, 20, or 50 ppm APNH for 4 weeks, killed by ether euthanasia and performed complete necropsy. Numbers of GST-P positive foci larger than 0.1 mm in diameter induced by APNH at the dose of 10, 20, and 50 ppm were increased in a dose dependent manner to 0.52, 1.3, and 21 foci/cm2, respectively, with areas of 0.006, 0.01, and 2.3 mm2/cm2. No such GST-P positive foci were observed in rats fed control diet. These findings suggest that APNH has hepatocarcinogenic potential in male F344 rats.

Animals↗

PubMed2001

Desmoplakin as a specific marker of lymphatic vessels.

The usefulness of immunostaining with anti-desmoplakin antibody for light microscopic identification of lymphatic vessels was examined in cryostat sections of the human tongue. The results were compared with laminin, 5'-nucleotidase (5'-Nase), and factor VIII staining. Immunoelectron microscopic observation was also performed to confirm that the vessels reacting with anti-desmoplakin were lymphatic vessels. Under the immunoelectron microscopic, the vessels reacting with anti-desmoplakin showed ultrastructural features characteristic of lymphatic vessels: thin endothelial walls, no or incomplete basal lamina, open junctions, and overlapping endothelium. In general, lymphatic vessels identified by anti-desmoplakin reacted strongly with 5'-Nase, but showed weak or no reactivity with anti-laminin and anti-factor VIII. Blood vessels showed no reactivity with anti-desmoplakin, but reacted strongly with anti-laminin and anti-factor VIII. However, some blood and lymphatic vessels showed intermediate reactivity with anti-laminin, anti-factor VIII, and 5'-Nase. It was difficult to identify these as blood or lymphatic vessels only by the reactivity differences. The results indicate that anti-desmoplakin antibody specifically distinguishes lymphatic vessels and is useful for studying the fine distribution of lymphatic vessels under light microscopy.

Biomarkers↗

PubMed2001

Development of squamous cell carcinoma from pre-existent oral leukoplakia: with respect to treatment modality.

The present study was undertaken in order to determine whether surgical treatment of oral leukoplakia reduces the risk of the subsequent development of carcinoma. This study included 142 patients with oral leukoplakia who received or did not receive surgical treatment. All subjects were followed-up for more than 6 months with a mean follow-up period of 4 years. Malignant transformation rate was lower among patients who received surgical excision (1/75) than among those who did not receive surgical treatments (4/51). However, the malignant transformation rates were high in patients who received cryosurgery (3/12) or cryosurgery plus surgical excision (1/4). There was no obvious relation between the grade of epithelial dysplasia and the rate of malignant transformation. Our results suggest that surgical excision of oral leukoplakia may reduce the risk of the subsequent development of carcinoma.

Adult↗

PubMed2001

Immunoelectron microscopic study of PECAM-1 expression on lymphatic endothelium of the human tongue.

The expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) on lymphatic and blood vessels of the human tongue was examined with fluorescence and transmission electron microscopy (TEM). The study used anti-desmoplakins antiserum for light microscopic identification of the lymphatic vessels, plus a pre-embedding immunogold electron microscopic technique for TEM observations. Before making TEM observations, cryostat serial sections were immunostained with anti-desmoplakins or anti-PECAM-1 and then embedded. Semithin sections from each cryostat section were photographed under a light microscope and compared in order to identify the lymphatic vessels expressing PECAM-1. In fluorescence microscopy, PECAM-1 expression on lymphatic vessels was weaker than that on blood vessels. TEM observations showed that PECAM-1 expression on the blood vessels was observed only on the luminal surface of the endothelium. In lymphatic vessels, PECAM-1 expression was found both on the luminal and abluminal surfaces of the endothelium. The density of the PECAM-1 reaction products was lower in lymphatic vessels than in blood vessels. The density of PECAM-1 reaction products on the luminal surface of lymphatic vessels was higher than on the abluminal surfaces. The results suggest that blood vessels are more active than lymphatic vessels in leukocyte migration. The expression of PECAM-1 on the abluminal surface of lymphatic endothelium may allow leukocytes to adhere to the endothelium and interact in their migration from tissue into lymphatic vessels.

Endothelium, Lymphatic↗

PubMed2001

Urinary prostaglandin D synthase (beta-trace) excretion increases in the early stage of diabetes mellitus.

OBJECTIVE: Circulating levels of lipocalin-type prostaglandin D synthase (L-PGDS)/beta-trace reportedly increase in renal failure as well as in cardiovascular injuries. We investigated the alterations of L-PGDS in urine and plasma in the early stage of type-2 diabetic patients. METHOD: Thirty-six type-2 diabetic patients and 29 normal subjects were studied. Overnight spot urine and plasma samples were obtained in the morning. L-PGDS was measured by ELISA method using anti-L-PGDS antibody. Variables indicating renal function were determined. RESULTS: Plasma L-PGDS concentration was slightly higher in the patients with diabetes mellitus than in the control subjects, whereas the urinary L-PGDS excretion almost doubled in the diabetic patients as compared with that in the control subjects. Plasma L-PGDS was determined by plasma creatinine (Cr) concentration while urinary L-PGDS excretion was correlated solely with urinary protein excretion. There was no relationship between plasma L-PGDS concentration and urinary L-PGDS excretion. The averaged plasma concentration of L-PGDS in the diabetics with a normal Cr level in plasma, corresponding to that in the controls, was determined by the plasma Cr concentration. On the other hand, the urinary L-PGDS excretion was determined by the amount of proteinuria and greater in the diabetics with a normal Cr level in plasma than in the controls even when the patients exhibited urinary protein excretion equal to that in the control subjects. CONCLUSIONS: Urinary L-PGDS excretion increased in the early stage of kidney injury in patients with type-2 diabetes mellitus. The urinary excretion was correlated independently with urinary protein excretion even when there was no difference in urinary protein or albumin excretions, thereby suggesting that urinary L-PGDS excretion is possibly a more sensitive indicator of renal injuries than proteinuria. Urinary L-PGDS may thus predict the progression of renal injuries in diabetic patients.

Analysis of Variance↗

PubMed2001

Metabolism of sulphobromophthalein I: positional isomers of sulphobromophthalein monoglutathione conjugate.

Three positional isomers of sulphobromophthalein glutathione monoconjugate (BSP-mGSH) were detected using a paired-ion HPLC method that employs triethylamine phosphate (TEA-H3PO4) as a pairing agent. To confirm that these compounds were glutathione (GSH) conjugates, sulphobromophthalein (BSP) was incubated with a four-fold volume of GSH under alkaline ammonium hydroxide. At least 6 metabolites (3 di-GSH conjugates and 3 isomers of mono-GSH conjugates) were produced under these conditions. The three mono-GSH conjugates were each purified and identified as compounds with a molecular weight of 1,020 according to FAB mass spectrometry results. Positional isomers of BSP-GSH were provisionally distinguished via the addition of the symbols alpha, beta and delta to the end of each abbreviation, to reflect the amount of isomers present. Thus, the isomer present in the largest quantity was termed BSP-mGSH(alpha), the second most abundant isomer was termed BSP-mGSH(beta) and the third was termed BSP-mGSH(delta). Interestingly, a species difference was recognized in that rat cytosol GSH S-transferase (GST) primarily produced BSP-mGSH(alpha), whereas guinea-pig cytosol generated BSP-mGSH(delta), BSP-mGSH(alpha) and BSP-mGSH(beta) equally and rabbit cytosol mainly produced BSP-mGSH(beta).

Animals↗

PubMed2001

Ectopic adrenocorticotropin syndrome exhibiting paradoxical adrenocorticotropin responsiveness to gonadotropin-releasing hormone.

In a 37-year-old man who had Cushing's syndrome, investigations, including overnight dexamethasone suppression test, corticotropin-releasing hormone (CRH) test, pituitary MRI and inferior petrosal sinus sampling suggested the presence of ectopic adrenocorticotropin (ACTH) production. Interestingly, gonadotropin-releasing hormone (GnRH) increased plasma ACTH from 73 pg/ml to 708 pg/ml at 15 min. Furthermore, desmopressin also increased plasma ACTH whereas CRH and thyrotropin-releasing hormone (TRH) had no effect. Such paradoxical responses of plasma ACTH were observed repeatedly. A thoracic CT scan revealed a right anterior mediastinal mass, which was surgically resected. Histological and immunohistochemical examination confirmed that the tumor was an ACTH-producing carcinoid. ACTH and cortisol decreased immediately following surgery. Neither desmopressin nor GnRH administration resulted in elevation of plasma ACTH while ACTH-responsiveness to dexamethasone and CRH was restored. To our knowledge, this is the first report documenting GnRH responsiveness in ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗

PubMed2000

Tau neutrinos favored over sterile neutrinos in atmospheric muon neutrino oscillations.

The previously published atmospheric neutrino data did not distinguish whether muon neutrinos were oscillating into tau neutrinos or sterile neutrinos, as both hypotheses fit the data. Using data recorded in 1100 live days of the Super-Kamiokande detector, we use three complementary data samples to study the difference in zenith angle distribution due to neutral currents and matter effects. We find no evidence favoring sterile neutrinos, and reject the hypothesis at the 99% confidence level. On the other hand, we find that oscillation between muon and tau neutrinos suffices to explain all the results in hand.

Journal Article↗

PubMed2000

Delay of DNA-adduct repair and severe toxicity in xeroderma pigmentosum group A gene (XPA) deficient mice treated with 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (PhIP).

Group-A xeroderma pigmentosum (XPA) gene-deficient mice are defective in nucleotide-excision repair and highly susceptible to ultraviolet-B-, and 9,10-dimethyl-1,2-benz[a]anthracene (DMBA)-induced skin carcinogenesis. In this study, changes of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP)-DNA adduct formations in the liver, colon and lung, as assessed by the 32P-postlabeling method and immunohistochemical analysis, and carcinogenic and/or toxic susceptibility of both sexes of XPA-deficient mice (XPA-/-) to PhIP, which is a carcinogenic heterocyclic amine, was examined. Levels of PhIP-DNA adduct formations in the liver, colon and lung, were almost twice as high in XPA-/- as in wild type mice (XPA+/+) mice, 7 days after a single i.g. administration of PhIP, and their delay in recovery was observed in XPA-/- mice. For the long-term experiment, XPA-/- and XPA+/+ type mice were treated with 80 ppm PhIP in the diet for the first 4 weeks followed by 40 ppm after a 2-week recovery period (long-term experiment I), or 40 ppm PhIP throughout the experiment (long-term experiment II). Severe toxicity, as evidenced by body weight retardation and poor survival, was observed in the PhIP treated XPA-/- mice of both sexes, but not in the XPA+/+. At week 40 the experiments were terminated and histopathological examinations were performed after complete autopsy. Only lymphomas/leukemias were observed as neoplastic lesions, but no significant differences were observed between the groups. As non-neoplastic lesions, degenerating changes, for example in the pancreatic acinar cells, were observed with XPA-/- mice tending to be more sensitive than XPA+/+ mice. The present study demonstrated that PhIP-DNA adduct formations in the liver, colon and lung of XPA-/- mice were demonstrated and their recovery rate was more delayed than XPA+/+ mice, and furthermore, more severe toxicity to PhIP in XPA-deficient mice was observed, but they were not susceptible to PhIP carcinogenicity under the conditions of the experiment.

Animals↗

PubMed2000

BAG-1 expression correlates highly with the malignant potential in early lesions (T1 and T2) of oral squamous cell carcinoma.

BAG-1 is a Bcl-2-binding protein that functions as an anti-apoptotic molecule. In this report we show a possible correlation between BAG-1 expression levels and the probability of oral squamous cell carcinoma (SCC) progression. We investigated BAG-1 expression levels in 22 patients diagnosed with early lesions (T1 and T2) of oral SCCs using immunohistochemistry and western blotting. High steady-state levels of BAG-1 were detected in 13 out of 22 cases (59%). High BAG-1 expression was observed more frequently in cases with nodal metastasis (89%) than in those without nodal metastasis (38%) (P<0. 03), suggesting that BAG-1 expression levels may correlate with the pathological stage of oral SCCs. Furthermore, BAG-1 expression levels correlated with the WHO grade, i.e. 45% in grade-I cases as opposed to 72% in grade-II cases (P<0.02). These data suggest that an analysis of BAG-1 expression may be useful in establishing a prognosis for patients with oral SCCs, and especially in predicting the metastatic potential of SSCs.

Adult↗

PubMed2000

Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin.

Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over-expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed2000

Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes.

Hepatocyte growth factor (HGF) is thought to play a role in cell motility and invasion. Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. We have previously reported that the Ets-oncogene family transcription factor E1AF positively regulates transcription of MMP genes in transient expression assays and that overexpression of the E1AF gene confers an invasive phenotype on breast cancer cells. Here we examined the effect of HGF on E1AF and MMP gene expression in terms of the invasive potential of the oral squamous cell carcinoma cell line HSC3. HGF stimulated expression of the E1AF gene. The levels of MMP-1, -3 and -9 mRNAs increased in cells treated with HGF and correlated with E1AF upregulation. In contrast, no obvious upregulation of MMP-1 and -9 mRNA was observed in ASE1AFHSC3 cells transfected with the antisense E1AF expression vector into parental HSC3 cells. The wild-type MMP-9 gene promoter was activated by endogenous E1AF in HSC3 cells, and chloramphenicol acetyltransferase (CAT) activities increased when HGF was added to transfected cells. On the other hand, CAT activity was reduced to almost two-thirds of the wild-type activity when HSC3 cells were transfected with a CAT reporter plasmid driven by a mutant MMP-9 promoter lacking the Ets-binding site, and induction of CAT activity was not observed upon addition of HGF. Analysis of organotypic raft cultures revealed that HSC3 cells invaded and degraded collagen gel actively upon addition of HGF. These results suggest that HGF induces expression of the Ets-related E1AF transcription factor gene whose product in turn activates MMP genes and leads to oral cancer cell invasion.

Adenovirus E1A Proteins↗

PubMed1999

Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods.

Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.

Carbolines↗

PubMed1999

Lymphatic endothelium of the human tongue expresses multiple leukocyte adhesion molecules.

The expression of leukocyte adhesion molecules on lymphatic vessels of the human tongue was examined using histochemical and immunohistochemical methods. Three different types of lymphatic vessels were distinguished: type I vessels expressed intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and endothelial cell-selectin (ELAM-1); type II vessels expressed ICAM-1 and PECAM-1; and type III vessels expressed PECAM-1 only. The lymphatic vessels located very close to the oral epithelium (lymphatic capillaries) and the other lymphatic vessels near the oral epithelium were type I. The lymphatic vessels in the submucosal connective tissue (collecting lymphatic vessels) were type II and type III. The results suggest that there may be functional differences in the lymphatic endothelium, where lymphatic capillaries are more active than collecting lymphatic vessels in lymphocyte migration from tissue into the lymphatic vessels.

Aged↗

PubMed1999

Single treatment with cisplatin or UFT, but not their combination treatment enhances the metastatic capacity of mouse fibrosarcoma cells.

To elucidate the roles of chemotherapeutic agents in tumor progression, we examined whether cis-diamminedichloroplatinum (II) (cisplatin) and UFT would promote malignant progression of a weakly tumorigenic and poorly metastatic fibrosarcoma cell line OR-32SK in vivo. C57BL/6 mice, transplanted with QR32SK, were treated with either cisplatin or UFT alone and in combination. After treatment with or without cisplatin and/or UFT, we established in vitro culture cell lines from the tumors arising in the mice on day 21 and then i.v. injected the established cell lines into syngeneic mice. As a result, the cell lines established from cisplatin-treated mice and UFT-treated mice had significantly higher metastatic capacity in lung compared to the ones from control untreated mice (64 and 65%, respectively, versus 26.7%). The cell lines established from the mice with the combination therapy showed lower lung metastasis (11%) than the ones from control untreated mice. Furthermore, we found the incidences of these experimental metastases were closely related with in vitro chemotactic activities and the production of MMP-9 of the cultured cell lines. These results indicate that cisplatin and UFT as a single agent promote the chemotactic activities and the production of MMP-9 in non-metastatic fibrosarcoma cells, resulting in the conversion to highly metastatic ones, and that cisplatin and UFT in combination failed to promote the chemotactic activities and the conversion. These results suggest that the combination therapy with cisplatin and UFT is useful in preventing the emergence of more malignant tumor cells after chemotherapy.

Animals↗

PubMed1999

High malignant transformation rate of widespread multiple oral leukoplakias.

OBJECTIVE: This study was undertaken in order to investigate clinicopathologic characteristics and malignant potential of widespread multiple oral leukoplakias. PATIENTS AND METHODS: The present study includes 12 patients with widespread multiple leukoplakias (widespread patients) and 99 with localized lesions (localized patients), and all patients were followed for more than 6 months with the mean follow-up period of 4 years. RESULTS: Gingiva and tongue were the major affected sites of leukoplakias in the localized patients, whereas gingiva and buccal mucosa were predominantly affected in the widespread patients. The rate of developing carcinoma was significantly (P < 0.02) higher in the widespread patients (3/12) than in the localized patients (5/99), although there was no significant difference in the rate of dysplastic lesions between these groups. CONCLUSION: These results indicate that the widespread leukoplakias have a higher potential for the development of carcinoma than do the localized lesions.

Adult↗