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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 127 records · Page 7Linked to original sources
PubMed1999

Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice.

In order to determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF), and related compounds on tumor growth and metastasis, bovine LF (bLF), and bLF hydrolysate and lactoferricin (bLFcin), active products generated by acid-pepsin hydrolysis were administered orally to BALB/c mice bearing subcutaneous (s.c.) implants of the highly metastatic colon carcinoma 26 (Co 26Lu). bLF and the bLF hydrolysate demonstrated significant inhibition of lung metastatic colony formation from s.c. implanted tumors without appreciable effects on tumor growth. bLFcin displayed a tendency for inhibition of lung metastasis. On the other hand, bLF did not exert marked anti-metastatic activity in athymic nude mice bearing Co 26Lu, though bLF had a tendency to inhibit the lung metastatic colony formation associated with anti-asialoGM1 antibody (Ab) treatment. AsialoGM1+ and CD8+ cells in white blood cells were increased after treatment with bLF. In vitro, the viability of Co 26Lu-F55 cells was markedly decreased when co-cultured with white blood cells from mice administrated bLF p.o., but recovered on treatment with anti-asialoGM1 Ab or anti-CD8 mAb and complement. The results suggest bLF and related compounds might find application as tools in the control of metastasis and that asialoGM1+ and CD8+ cells in the blood are important for their inhibitory effects.

Administration, Oral↗
PubMed1999

Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1:Th2 cell ratio during normal human pregnancy and preeclampsia.

We calculated the percentage of Th1, Th2, Th0 cells and the Th1:Th2 cell ratio of peripheral blood from normal pregnant subjects and preeclampsia patients using flow cytometry which can analyse both the surface marker, CD4, and intracellular cytokines, interleukin (IL)-4 and interferon (IFN)-gamma. In normal pregnancy, the percentage of Th1 cells was significantly lower in the third trimester, and the ratios of Th1:Th2 were significantly lower in the second and third trimester than in nonpregnant subjects. In contrast, the percentage of Th1 cells and the ratios of Th1:Th2 in preeclampsia were significantly higher than in normal third trimester pregnant subjects. The percentage of Th2 cells in preeclampsia was significantly lower than in third trimester of normal pregnancy. Additionally, peripheral blood mononuclear cells from these subjects and patients were cultured with phytohemagglutinin stimulation, and IL-4 and IFN-gamma concentrations were determined in the supernatant by enzymed linked immunosorbent assays. The percentage of Th1 and Th2, and the ratios of Th1:Th2 were correlated with cytokine (IFN-gamma and IL-4) secretion level. These results demonstrated that Th2 cells were predominant in the second and third trimesters of normal pregnancy, but Th1 cells predominated in preeclamptic patients.

Female↗
PubMed1999

Substrate specificity studies of Flavobacterium chondroitinase C and heparitinases towards the glycosaminoglycan--protein linkage region. Use of a sensitive analytical method developed by chromophore-labeling of linkage glycoserines using dimethylaminoazobenzenesulfonyl chloride.

Bacterial chondroitinases and heparitinases are potentially useful tools for structural studies of chondroitin sulfate and heparin/heparan sulfate. Substrate specificities of Flavobacterium chondroitinase C, as well as heparitinases I and II, towards the glycosaminoglycan-protein linkage region -HexA-HexNAc-GlcA-Gal-Gal-Xyl-Ser (where HexA represents glucuronic acid or iduronic acid and HexNAc represents N-acetylgalactosamine or N-acetylglucosamine) were investigated using various structurally defined oligosaccharides or oligosaccharide-serines derived from the linkage region. In the case of oligosaccharide-serines, they were labeled with a chromophore dimethylaminoazobenzenesulfonyl chloride (DABS-Cl), which stably reacted with the amino group of the serine residue and rendered high absorbance for microanalysis. Chondroitinase C cleaved the GalNAc bond of the pentasaccharides or hexasaccharides derived from the linkage region of chondroitin sulfate chains and tolerated sulfation of the C-4 or C-6 of the GalNAc residue and C-6 of the Gal residues, as well as 2-O-phosphorylation of the Xyl residue. In contrast, it did not act on the GalNAc-GlcA linkage when attached to a 4-O-sulfated Gal residue. Heparitinase I cleaved the innermost glucosaminidic bond of the linkage region oligosaccharide-serines of heparin/heparan sulfate irrespective of substitution by uronic acid, whereas heparitinase II acted only on the glucosaminidic linkages of the repeating disaccharide region, but not on the innermost glucosaminidic linkage. These defined specificities of chondroitinase C, as well as heparitinases I and II, will be useful for preparation and structural analysis of the linkage oligosaccharides.

Bacterial Proteins↗
PubMed1999

Modifying effects of a flavonoid morin on azoxymethane-induced large bowel tumorigenesis in rats.

The modifying effect of dietary exposure to a flavonoid morin during the initiation and post-initiation phases of azoxymethane (AOM)-initiated colorectal carcinogenesis was investigated in male F344 rats. A total of 55 animals were initiated with AOM by weekly s. c. injections of 15 mg/kg body wt for 3 weeks to induce colorectal neoplasms. Rats were fed a diet containing 500 p.p.m. morin for 5 ('initiation feeding') or 28 ('post-initiation feeding') weeks. Other groups contained rats treated with morin alone (500 p.p.m. in diet) and untreated rats. At the end of the study (32 weeks), the incidence of adenocarcinoma in the large intestine of rats initiated with AOM together with (43%) or followed by (29%) a diet containing morin was smaller than that of rats given AOM alone (75%). A significant difference was found between 'post-initiation feeding' and untreated groups (P = 0.023). Although both 'initiation feeding' and 'post-initiation feeding' of morin reduced polyamine levels in colorectal mucosa and blood, 'post-initiation feeding' of morin significantly decreased the proliferating cell nuclear antigen-positive index in aberrant crypt foci. 'Post-initiation feeding' of morin significantly elevated glutathione S-transferase and quinone reductase activities in the liver and large bowel, but 'initiation feeding' caused a significant elevation of these enzymes activities only in the large bowel. These results indicate that morin could exert a weak chemopreventive effect on large bowel tumorigenesis induced by AOM when fed during the post-initiation phase.

Adenocarcinoma↗
PubMed1999

The efficacy and limitations of repeated slide conferences for improving interobserver agreement when judging nuclear atypia of breast cancer. The Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section.

BACKGROUND: The pathology section of the Japan National Surgical Adjuvant Study of Breast Cancer protocol study was set up to establish histological criteria for assessing high-risk node-negative breast cancers and standardize the subjective criteria used by collaborating pathologists for nuclear grading of cancers. METHODS: In order to standardize the nuclear atypia criteria, five slide conferences were held. A total of 57 observers assigned nuclear atypia scores to 119 breast carcinomas that were presented using a slide projector or a TV monitor and discussed their histological findings. The percentage interobserver agreements per tumor and per conference and kappa value per conference were estimated and compared among the conferences. The percentage intraobserver reproducibility per tumor between the last two conferences was compared with the percentage interobserver agreement for 20 tumors. The kappa value was also calculated for each of 27 observers to evaluate scoring reproducibility. RESULTS: The percentage interobserver agreement per conference was constant (75-78%) throughout the five meetings and the rate of tumors with > 80% agreement per tumor became higher in later conferences. The kappa value was 0.42, 0.25, 0.42, 0.51 and 0.50 for the first, second, third, fourth and fifth conferences, respectively. The tumors with a lower percentage interobserver agreement also had a lower percentage intraobserver reproducibility and such scoring variations were attributed to the intermediate nature of the degree of tumor atypia. In 26 of 27 observers, intraobserver agreement for 20 tumors was estimated from the kappa value to range from moderate to almost perfect. CONCLUSION: We concluded that the repeated slide conferences conducted by the pathology section were an effective means of standardizing the subjective histopathological criteria used to assess tumors. However, the achievement of a good scoring agreement would be difficult for tumors with an intermediate degree of atypia.

Breast Neoplasms↗
PubMed1999

Monitoring of interobserver agreement in nuclear atypia scoring of node-negative breast carcinomas judged at individual collaborating hospitals in the National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol.

BACKGROUND: In the NSAS-BC protocol, the nuclear atypia and mitotic counts are to be judged by pathologists at each participating hospital for assessing high-risk node-negative breast cancers. Therefore, maintenance of interobserver agreement in diagnosis at a higher level is mandatory during the period of patient entry. METHODS: Individual collaborating pathologists originally evaluated the histological eligibility of 107 cases. Three panel pathologists determined consensus diagnoses and 29-37 collaborating pathologists determined modal diagnoses of these cases at three slide conference sessions. The original diagnoses were compared with the consensus and modal diagnoses to estimate the percentage of erroneous judgments. RESULTS: The agreement rate in histological type and nuclear atypia score was 69% (74/107) between the original and consensus diagnoses, 76% (81/107) between the original and modal diagnoses and 86% (92/107) between the consensus and modal diagnoses. The strength of interobserver agreement at the slide conference sessions was moderate (0.447-0.535) by kappa statistics. The original, consensus and modal diagnoses were concordant in 71 cases (66%), but were discordant in 36. Of 35 invasive ductal carcinomas with discordant diagnoses, the discordance arose from the intermediate tumor nature in 15, multiple factors in 13 and erroneous diagnosis in seven (6.5%), if the characteristics of the tumor were judged from the percentage interobserver agreement per tumor at the slide conferences. CONCLUSION: Nuclear atypia scoring given at individual hospitals on case entry was almost reproducible among the pathologists. Continuous efforts are needed to improve interobserver agreement and to decrease erroneous diagnosis for protocol eligibility.

Breast Neoplasms↗
PubMed1999

Cross-country comparisons of colon and rectal cancer mortality suggest the existence of differences in risk factors in eastern and western Europe.

A comparison of relative mortality rates from colon and rectal cancers in World Health Organization data for various countries in Europe was undertaken to determine whether the two sites demonstrate a direct link. A significant correlation between figures for colon and rectal cancers was found throughout Europe but limited to males and only at the p < 0.05 level. Cluster analysis revealed marked differences between countries of the former west and east European blocks, the latter having much higher values for rectal cancers. Separation of countries on this basis gave rise to significant correlation between the two sites for both sexes (p < 0.05 and p < 0.001, respectively, for western and eastern males; and p < 0.05 and p < 0.001 for females). In order to assess the possible contribution of factors associated with squamous cell cancers (SCCs), data for buccal and cervical cancers, both more prevalent in eastern than in western Europe, were also compared. Whereas a significant correlation was evident between female rectal and cervical cancers overall and in the western countries (p < 0.05) this was not the case for the eastern countries. The results suggest that the observed excess of rectal cancer mortality in eastern European countries may not be simply due to factors contributing to SCCs, but that country level comparisons of individual harmful and beneficial influences, alone and in combination, might allow the underlying reasons to be explained.

Analysis of Variance↗
PubMed1999

European registry comparisons provide evidence of shared risk factors for renal, colon and gallbladder cancer development.

In order to assess links between renal cell cancer (RCCs) and transitional cell cancers (TCCs) of the kidney and cancer development in other organs of the abdominal cavity, incidence data from the Cancer Incidence in Five Continents (Vol VII) were compared between various cancer registries in Europe. Significant correlations which persisted on partial analysis were observed between RCCs and carcinomas of the colon and gallbladder, as well as between the latter themselves. Kidney TCCs, in contrast, were associated with tumours of the urinary bladder. In addition, significant correlations between hepatocellular, but not cholangiocellular carcinomas, and gallbladder and colon cancers were observed. Data for pancreas and gallbladder neoplasms also correlated. Prostate cancer incidences, while positively linked to RCCs, negatively correlated with gallbladder rates. The results point to shared risk factors for RCCs and adenocarcinomas in a number of organs, suggesting a role for humoral agents. The present findings also underline the necessity of distinguishing between tumour types within organs in epidemiological investigations of causal influences.

Adenocarcinoma↗
PubMed1999

Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat.

A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm3 volume) at the 0.2% dose (P<0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98+/-0.41 per cm2 lung tissue section, P<0.05) compared to the control group (3.48+/-0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.

Adenoma↗
PubMed1999

Histological factors associated with initial bone metastasis of invasive ductal carcinoma of the breast.

Bone is one of the most common sites of recurrence of breast cancer. Therefore, it would be clinically very useful if breast cancers with a high probability of bone metastasis (BM) could be identified by histopathological examination of the primary lesions. To elucidate histological characteristics associated with predisposition to initial BM, we examined nine histopathological parameters in the primary lesions of 110 invasive ductal carcinomas (IDCs) of the breast with 0 to 3 regional node metastases. These cases had recurrence between 4 months and 10.1 years after the initial radical surgery. The first metastatic site was bone in 24 cases, whereas other sites were involved in 86 cases. IDCs growing in a strand growth pattern or with fibrotic focus (FF) had a significantly higher frequency of initial BM than those growing in a non-strand growth pattern or without FF, respectively. Strand growth pattern was a significant predictor of the initial BM in multivariate analysis. In all 54 IDCs that developed BM during the follow-up period, osteolytic metastasis was significantly more frequent in the group with FF than in that without FF. This study demonstrated that strand growth pattern and the presence of FF are significant histopathological factors associated with initial BM. The combination of those predictive factors along with prognostic factors may provide a useful approach to identify patients at high risk for initial BM, enabling early treatment for the recurrent cancer.

Analysis of Variance↗
PubMed1999

Lactoferrin inhibits hepatitis C virus viremia in patients with chronic hepatitis C: a pilot study.

Hepatitis C virus (HCV) is associated with the development of cirrhosis and hepatocellular carcinoma. We recently found that bovine lactoferrin, a milk protein belonging to the iron transporter family, effectively prevented HCV infection in cultured human hepatocytes (PH5CH8). We tested the hypothesis that lactoferrin inhibits HCV viremia in patients with chronic hepatitis C. Eleven patients with chronic hepatitis C received an 8-week course of bovine lactoferrin (1.8 or 3.6 g/day). At the end of lactoferrin treatment, a decrease in serum alanine transaminase and HCV RNA concentrations was apparent in 3 (75%) of 4 patients with low pretreatment serum concentrations of HCV RNA. However, 7 patients with high pretreatment concentrations showed no significant changes in these indices. This pilot study suggests that lactoferrin is one potential candidate as an anti-HCV reagent that may be effective for the treatment of patients with chronic hepatitis.

Adult↗
PubMed1999

Lack of carcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in cynomolgus monkeys.

The carcinogenic potential of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was evaluated in cynomolgus monkeys. The animals received MeIQx, beginning at the age of one year, at doses of 10 or 20 mg/kg body weight by gavage five times a week for 84 months and were autopsied 8 months thereafter. Although sporadic development of aberrant crypt foci in the colon and glutathione S-transferase pi-positive foci in the liver as well as hyperplastic changes of the lymphatic tissue in the lung and gastro-intestinal tract were observed in several monkeys, this was not treatment-related. No neoplastic or preneoplastic lesions were found in other organs. Serum chemistry data and organ weights were also within the normal ranges. From these data, it is concluded that MeIQx is not carcinogenic in the cynomolgus monkey under the conditions examined. This lack of carcinogenicity is probably related to the poor activation of MeIQx due to the lack of constitutive expression of CYP1A2 as well as an inability of other cytochrome P450s to catalyze N-hydroxylation of MeIQx in the cynomolgus monkey.

Animals↗
PubMed1999

Distribution of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells.

PROBLEM: To examine whether normal pregnancy involves type 2 T-helper (Th2) immune condition or not. METHOD OF STUDY: We measured the percentage of Th0, Th1, and Th2 and the Th1/Th2 cell ratios of human peripheral blood and endometrial T cells using flow cytometry, which can analyze both the surface marker CD3, and intracellular cytokines, interleukin 4 (IL-4) and interferon gamma (IFNgamma). RESULTS: No significant differences were found in the percentages of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in the peripheral blood T cells of nonpregnant women and women in early pregnancy. On the other hand, the percentage of Th1 cells was highest during the proliferative phase of the endometrium, followed by the secretory phase and early pregnancy decidua. The percentage of Th2 cells was highest in early pregnancy decidua and lowest during the proliferative phase of the endometrium. The Th1/Th2 ratio was 147.48+/-96.68 during the proliferative phase of the endometrium, 37.74+/-21.33 during the secretory phase, and 1.31+/-0.48 in the early pregnancy decidua. CONCLUSIONS: These data indicate that Th1 cells predominate in the nonpregnant endometrium, especially during the proliferative phase, while Th2 cells predominate in early pregnancy decidua.

Adult↗
PubMed1999

Immunoadsorption plasmapheresis as a treatment for pregnancy complicated by systemic lupus erythematosus with positive antiphospholipid antibodies.

PROBLEM: Our purpose was to study the effect of maternal immunoadsorption plasmapheresis (IA) on the outcome of pregnancies complicated by systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies, which were known to have a strong correlation with abortion or stillbirth. METHOD OF STUDY: Eight pregnancies in 7 patients with SLE were treated according to our protocol. They were all positive for the lupus anticoagulant. The treatments provided in these cases were as follows: an oral low-dose steroid; oral low-dose aspirin; and IA. The outcomes of the pregnancies were then studied. RESULTS: Of eight pregnancies, seven resulted in preterm deliveries, and cesarean sections were performed at 26-36 weeks of gestation. In one case, intrauterine fetal death occurred at 24 weeks of gestation. The other seven pregnancies resulted in live births (survival rate of 87.5%). CONCLUSION: IA improves the outcome of pregnancy complicated by SLE with positive antiphospholipid antibodies, without increasing steroid dosage.

Adult↗