Biomedical subjects

H Tashiro

Publications and source records attributed to H Tashiro.

335 records · Page 19Linked to original sources

PubMedDate not supplied

Altered plasma levels of cytokines in patients with ischemic heart disease.

BACKGROUND: Cytokines play an important role in mediating inflammatory-proliferative responses, including atherosclerosis. Alterations in the plasma levels of cytokines in patients with ischemic heart disease (IHD) remain to be examined. OBJECTIVE: To examine the possible alterations in the plasma levels of cytokines in patients with IHD and in controls. METHODS: Thirty-one patients with IHD and 16 controls were studied. The cytokines measured in our study included interleukin-6, macrophage-colony-stimulating factor (MCSF), transforming growth factor-beta (TGF-beta), and seven other major cytokines. The measurements were performed by using an enzyme-linked immunosorbent assay method. RESULTS: The MCSF levels were significantly higher in patients with IHD than they were in controls (P < 0.01), whereas the TGF-beta levels were significantly lower in patients with IHD than they were in controls (P < 0.01). Moreover, the levels of MCSF and those of TGF-beta were correlated negatively (P < 0.05). The interleukin-6 levels tended to be higher in patients with unstable angina. The plasma levels of other cytokines were below the detection levels in most cases. CONCLUSIONS: Results from studies in vitro suggested that the process of atherosclerosis is accelerated and inhibited by MCSF and TGF-beta, respectively. The present results thus suggest that the alterations in the plasma levels of MCSF and TGF-beta may be involved in the pathogenesis of IHD in humans.

Aged↗

PubMedDate not supplied

Faecal clearance of alpha 1-antitrypsin reflects disease activity and correlates with rapid turnover proteins in chronic inflammatory bowel disease.

Faecal clearance of alpha 1-antitrypsin was measured in patients with ulcerative colitis and Crohn's disease and compared with disease activity and markers of protein-calorie malnutrition. Patients with active ulcerative colitis and Crohn's disease showed elevated clearance of alpha 1-antitrypsin and clearance declined in most patients with induction of remission. However, even with inactive disease, elevated protein loss persisted in some patients, presumably reflecting residual inflammation in the intestinal mucosa. There was a significant correlation between clearance of alpha 1-antitrypsin and serum levels of retinol-binding protein and transferrin in patients with ulcerative colitis and with retinol-binding protein in patients with Crohn's disease. Clearance of alpha 1-antitrypsin reflects disease activity in inflammatory bowel disease and correlates with serum levels of rapid-turnover proteins such as retinol-binding protein and transferrin, which are markers for the presence of protein-calorie malnutrition.

Adult↗

PubMedDate not supplied

Significant changes in intestinal lymphatic system and immune response elicited by Peyer's patch excision in adult rats.

The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP-excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.

Animals↗

PubMedDate not supplied

Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue tegafur in rats.

BACKGROUND: S-1 is a new antitumor agent which was developed based on biochemical modulation of fluorouracil. S-1 consists of tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. S-1 has been reported to enhance therapeutic effects and to reduce the gastrointestinal toxicity as compared with 5-fluorouracil. In this study performed in rats, S-1 was used to assess the relationship between gastrointestinal mucosal toxicity and changes in intestinal barrier function. METHODS: Fifteen rats were equally divided into three groups: group A (untreated controls), group B (FT and CDHP mixture), and group C (FT and CDHP in combination with Oxo). The animals in groups B and C received equitoxic doses of the drugs in their food for 14 consecutive days. The intestinal permeability was determined on the basis of the urinary recovery of orally administered lactulose and mannitol (L/M). Injury to the small intestines was evaluated by light microscopy. The cell surface expression of CD44 was evaluated immunohistochemically. RESULTS: Recovery of L/M in urine (expressed as a fraction of the dose administered) was 0.15 +/- (SE) 0.08, 0.23 +/- 0.13, and 0.09 +/- 0.04 in groups A, B, and C, respectively. The intestinal permeability in group B was significantly higher than that in group C (p < 0.05). Treatment with FT and CDHP (groups B and C) induced injury to the small intestine and decreased expression of CD44 within the intestinal mucosa, but the extent of damage was reduced by coadministration of Oxo (group C). CONCLUSION: This experimental study suggested that the gastrointestinal toxicity resulting from administration of anticancer drugs is accompanied by an impaired gut barrier function measurable as an increase in intestinal permeability to L/M.

Animals↗

PubMedDate not supplied

A multivariate analysis of prognostic factors including tumor response after endocrine therapy in advanced breast cancer patients.

Although clinicians want to know how tumor response affects the survival of advanced cancer patients, the direct comparison of response with survival is severely discouraged because of biases essentially involved. In 159 patients with advanced breast cancer treated with adreno-oophorectomy, we analyzed the survival of the patients using the Kaplan and Meier method with the landmark method (landmark time of 3 months after treatment). A multivariate analysis with the Cox proportional hazard model for survival with explanatory variables including response of patients at the landmark time (3 months after therapy) was performed in order to find probable prognostic factors. By the Kaplan and Meier curves with the landmark method, response category showed a significant difference in the survival of the patients (log rank test; p < 0.0001). In the Cox model in the patients of landmark time of 3 months after therapy, we found that response was the most powerful factor for survival out of 10 variables (p = 0.0001), and the dominant site of metastasis significantly and independently modified the survival length (p = 0.001). ER status was indifferent in the analysis; however, when the response category was not included, ER was shown to be most influential. We propose that a combination of the Cox model with the landmark method would be a rational and useful approach to estimate probable prognostic factors including treatment outcome variables such as response for the survival analysis in advanced cancer patients.

Adrenalectomy↗

PubMedDate not supplied

Alteration of mucosal immunity after long-term ingestion of an elemental diet in rats.

The effects of an elemental diet on lymphocyte transport in intestinal lymph and immune responses of gut-associated lymphoid tissue were investigated in rats. The control animals were fed a conventional diet. After 4 week of feeding, the total calorie intake and body weight gain showed no differences between the two groups. The number and total area of Peyer's patches and the ratio of height of villi to height of crypt showed no significant differences between the two groups. The rate of lymph flow in intestinal lymphatics showed no significant change in treated animals compared with the control rats. However, an elemental diet induced a significant decrease in lymphocyte flux in intestinal lymphatics compared with that in control rats. Lymphocyte subsets in intestinal lymph revealed a significant decrease in CD3-positive cells, especially CD4-positive cells in the elemental diet-treated group. A significant decrease in the number of immunoglobulin A-containing cells and a decreased CD4/CD8 ratio in T-cell subsets were observed in the lamina propria of ileal mucosa in the elemental diet-treated group by morphometric analysis in the immunohistochemical study. Specific antibody-secreting cells in intestinal lymph were also investigated after rats were intraduodenally primed with cholera toxin and challenged with the same toxin after an interval of 2 weeks. No significant difference was seen between the two groups in any of the numbers of anti-cholera toxin immunoglobulin-secreting cells in any immunoglobulin A, immunoglobulin G, or immunoglobulin M class as determined by the enzyme-linked immunospot assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

An autopsy case of spinocerebellar ataxia type 6 with mental symptoms of schizophrenia and dementia.

We herein report the findings of an autopsy case of spinocerebellar ataxia type 6 (SCA6) which revealed a mild CAG-repeat expansion in the alpha1A voltage-dependent calcium channel (CACNL1A4) gene on chromosome 19p13. A 39-year-old man who showed slowly progressive mental disorders and gait ataxia was clinically diagnosed to have cortical cerebellar atrophy (CCA) and schizophrenia. None of his relatives revealed any symptoms such as spinocerebellar disease, however, his younger brother had shown some mental disorders. The patient eventually died at 52 years of age, and an autopsy was thus performed. The main histopathological findings included a severe neuronal cell loss of Purkinje cells and inferior olivary nuclei. The number of Purkinje cells in our case had decreased severely in comparison to that in either OPCA or age-matched control cases, and the Purkinje cells in the cerebellar hemisphere were more affected than those in the cerebellar vermis. The neurons of the dentate nucleus and pontine nuclei were well-preserved, and no pathological changes were seen in cerebral cortices or basal ganglia. The clinicopathological findings were similar to those of late cortical cerebellar atrophy (LCCA), Holmes' cortical cerebellar atrophy (Holmes type) or SCA6 cases reported previously. Using genomic DNA extracted from archival paraffin-embedded sections in the frontal lobe, cerebral basal ganglia and cerebellum, the identical mild CAG-repeat expansions in the CACNL1A4/SCA6 gene were revealed in all samples examined. These findings suggest that in cases with LCCA or Holmes type atrophy, we should thus examine the CAG-repeat expansions in the SCA6 gene, and the genomic DNA extracted from paraffin-embedded sections was thus found to be useful in diagnosing SCA6 retrospectively.

Adult↗

PubMedDate not supplied

Clinicopathological features of long-term survivors of scirrhous gastric cancer.

BACKGROUND/AIMS: Prognosis of scirrhous gastric cancer remains low. To determine the clinicopathological features that are correlated with prognosis, we studied long-term survivors of scirrhous gastric cancer (survival duration more than 5 years) in comparison with patients with short survival. METHODOLOGY: Among 2719 gastric cancer patients who underwent surgery at Matsuyama Red Cross Hospital, 211 cases were diagnosed as scirrhous type gastric cancer. Seventeen patients survived more than 5 years, and the rest had short survival (less than 5 years). Comparison of clinicopathological factors was done by chi 2 analysis. Multivariate analysis was done in order to focus on the prognostic factors. RESULTS: The 5-year survival of the total 211 patients was 12%. The 5-year survival of patients who underwent curative surgery (67 cases) was 30%, which was significantly higher than that of the non-curative surgery group (144 cases, 6%). Significant differences were noted in the following variables: peritoneal dissemination, hepatic metastasis, lymph node dissection, pattern of infiltrating growth, depth of invasion, histological lymph node metastasis, histological stage, and histological curability. Patients with either hepatic metastasis or peritoneal dissemination did not survive 5 years. Multivariate analysis revealed that the most significant independent prognostic factor was histological curability, followed by peritoneal dissemination. CONCLUSIONS: There is a possibility of long-term survival for patients with scirrhous gastric cancers without hepatic metastasis, peritoneal dissemination, or extensive lymph node metastasis. Curative surgery is important, suggesting that the extended operation is rational if possible.

Adenocarcinoma, Scirrhous↗

PubMedDate not supplied

Steroid hormone receptors and response to high-dose medroxyprogesterone acetate in advanced breast cancer.

Forty-six patients with advanced breast cancer were treated with oral high-dose medroxyprogesterone acetate (MPA) as a second line endocrine treatment, with a 28% 13/46) response rate. There was a significant difference in response to MPA between patients with estrogen (ER)- or progesterone (PgR)-receptors and those with negative receptors assayed just before the treatment (ER+, 7/10, ER-, 0/9 of response rates, p = 0.007, PgR+, 4/4: PgR-, 3/15, p = 0.02). The combination of ER and PgR was observed to be best in predicting the response (p = 0.02). The ER status as well as the combination of ER and PgR, but not PgR alone detected in the primary tumors, correlated well with the response (ER+, 10/23: ER-, 0/15, p = 0.0094, PgR+: PgR-, p = 0.13, ER+PgR+, ER+PgR-, ER-PgR-:p = 0.024). The correlation between steroid hormone receptors and response to MPA in advanced breast cancer was established from the literature. Response rate to MPA was shown to be 42% (69/169) in ER+ cancer patients, and 10% (9/90) in ER- cancer patients (p = 0.00004). There was no correlation between PgR status and the response. Changes of receptors were studied in relation to the response. When ER+ or PgR+ tumors retained their positivity until MPA treatment, a good response was obtained, while there were almost no responders if one or both receptors changed from positive to negative, or remained negative. In conclusion, the response to MPA can be predicted by the steroid hormone receptors.

Antineoplastic Agents↗

PubMedDate not supplied

A possible direct action of a gonadotropin-releasing hormone agonist, goserelin, on the clonogenic growth of human breast cancer.

Direct inhibitory effects of a gonadotropin-releasing hormone agonist (GhRh agonist, goserelin, GOS) were studied on the in vitro clonogenic growth of human breast cancer, in comparison with estradiol-17 beta (E2) and tamoxifen (TAM). Estrogen (ER) and progesterone receptors (PgR) were asseyed in the adjacent cancer tissues using the DDC method. In 19% or 12 out of 64 cancers, E2, 10(-8) M, was shown to be effective in increasing the number of colonies per dish to 150% or more of the control. On the other hand, 16% (10/64) responded to TAM or GOS, respectively, i.e. the plating efficiency decreased to 50% or less of the control. While E2 and TAM had a tendency to have better effects in ER-positive tumors than ER-negative ones, the inhibitory effect of GOS was not dependent on the presence or absence of ER or PgR in the tumor. The GOS sensitivity did not correlate with the E2 dependence or the TAM sensitivity. These results suggest that a possible direct action of GOS may not be mediated by the ER system.

Adult↗

PubMedDate not supplied

Mitomycin C, methotrexate, and vincristine with medroxyprogesterone acetate or prednisolone for doxorubicin resistant advanced breast cancer--a randomized control study.

This randomized study was designed to compare the efficacy and toxicity of MMV chemotherapy (mitomycin C(MMC), methotrexate (MTX) and vincristine(VCR)), MMVM (MMV+medroxyprogesterone acetate(MPA)) and MMVP (MMV+prednisolone(P)), and to evaluate potential additional effects of MPA or P to the chemotherapy in doxorubicin (ADR)-refractory cancer patients. A total of 108 advanced breast cancer patients who had been resistant to ADR or who had relapsed after response were randomized to the three treatment arms: MMC 4mg/m2, MTX 35mg/m2 and VCR 0.7mg/m2, i.v., on days 1 and 8; repeated every 3 weeks. MPA 1,200 mg/day or P 10mg/day was given orally in the MMVM and MMVP arms, respectively. An interim analysis showed that the response to MMV was marginally significantly lower than the other groups; entry to the arm was thus interrupted. 102 patients were evaluable. Totally, response rates of 9.5%(2/21) in MMV, 37.5%(15/40) in MMVM and 29.2%(12/41) in MMVP were obtained. There was a significant difference in the response between the MMVM and MMV arms (p = 0.0206), and a marginal difference between MMVP and MMV (p = 0.0784). Although overall survivals in the 3 groups were equivalent, the time to progression of patients treated with MMVM and MMVP was shown to be significantly longer than MMV patients. Hematological adverse effects, especially thrombocytopenia, were significantly diminished by the addition of hormones, particularly MPA, to the chemotherapy, thus increasing total doses of chemotherapeutic agents. It was shown that in ADR-resistant cancers MMVM had an effect equivalent to that in ADR-sensitive breast cancers. The authors conclude that MMVM may be a candidate for a noncross resistant regimen for ADR-resistant cancers, as well as an effective 2nd line chemoendocrine treatment of advanced breast cancer.

Adult↗