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T Yokoe

Publications and source records attributed to T Yokoe.

At least 19 recordsLinked to original sources
PubMed2006

Inhibitory effects of fluvastatin on cytokine and chemokine production by peripheral blood mononuclear cells in patients with allergic asthma.

BACKGROUND: Statins have anti-inflammatory effects on immune cells. OBJECTIVE: To investigate the immunomodulatory effects of fluvastatin on peripheral blood mononuclear cells (PBMCs) after allergen-specific and non-allergen-specific stimulation in patients with asthma and in healthy subjects. METHODS: PBMCs from seven patients with asthma who showed elevated immunoglobulin (Ig)E to house dust mite were isolated and stimulated with Dermatofagoides farinae, purified protein derivative, and phytohaemagglutinin (PHA) in the presence or absence of fluvastatin. PBMCs from seven healthy subjects were stimulated with PHA. The effects of fluvastatin on cell proliferation and production of cytokines (interferon [IFN]-gamma and interleukin [IL]-5) and chemokines (chemokine CXC motif, ligand [CXCL10], and CC chemokine ligand [CCL17]) were measured. Migration of T helper (Th)1 and Th2 cell lines was also investigated. The expression of CXCR3 and CCR4 was analysed with flow cytometry. Steroid-insensitive PBMCs induced by preculture with IL-2 and IL-4 were also evaluated. Some experiments were performed in the presence of mevalonic acid. RESULTS: Fluvastatin inhibited the proliferation of PBMCs and decreased the production of IL-5, IFN-gamma, CCL17, and CXCL10 after allergen-specific and non-allergen-specific stimulation; all these effects, except for decreased CXCL10 production, were partially reversed by mevalonic acid. Culture supernatants obtained in the presence of fluvastatin prevented the migration of Th1 and Th2 cell lines in a dose-dependent manner. In addition, CCR4 and CXCR3 expression on CD4(+) T cells was not affected by the presence of fluvastatin. Fluvastatin inhibited the proliferative response of steroid-insensitive PBMCs to phytohaemagglutinin. CONCLUSION: Fluvastatin has inhibitory effects on cytokine and chemokine production, and thus might be used as a potential therapeutic agent in severe asthma.

Adult↗
PubMed2006

Association between lipid peroxidation and inflammation in obstructive sleep apnoea.

In the present study, the authors examined the relationship between lipid peroxidation and inflammation in patients with obstructive sleep apnoea (OSA). A total of 40 obese patients with OSA were studied, along with 18 obese and 12 lean subjects without OSA. Overnight excretion of 8-isoprostane in urine and serum levels of high-sensitivity C-reactive protein (hsCRP) were measured. In addition, the effects of 3 months' treatment with nasal continuous positive airway pressure (nCPAP) were studied in 20 obese patients with moderate-to-severe OSA. Overnight urinary excretion of 8-isoprostane and serum levels of hsCRP were significantly higher in patients with moderate-to-severe OSA compared with patients with mild OSA and obese or lean subjects without OSA. Overnight urinary excretion of 8-isoprostane significantly correlated with apnoea-hypopnoea index, duration of hypoxia during sleep, body mass index, and serum levels of hsCRP in patients with OSA. The severity of OSA was an independent factor predicting the urinary excretion of 8-isoprostane. nCPAP significantly decreased urinary excretion of 8-isoprostane and serum levels of hsCRP. In conclusion, these results suggest that both obstructive sleep apnoea severity and obesity can independently contribute to elevations in urinary excretion of 8-isoprostane. Therefore, obstructive sleep apnoea may increase the risks of cardiovascular morbidity in obese patients.

C-Reactive Protein↗
PubMed2002

Prognostic significance of dihydropyrimidine dehydrogenase expression in breast cancer.

We have investigated dihydropyrimidine dehydrogenase expression as a prognostic marker in breast cancer. A total of 119 women with breast cancer undergoing surgery between 1985 and 1996 were included in this study. Eighty-seven patients were treated with postoperative chemotherapy including 5-fluorouracil or 5-fluorouracil derivatives. Fifty-nine (50%) of 119 patients were determined to be immunostaining-positive for dihydropyrimidine dehydrogenase. There was no significant difference between dihydropyrimidine dehydrogenase staining and tumour size, lymph node status, clinical stage, oestrogen receptor status, histologic grade, or 5-fluorouracil administration. When evaluated in patients treated with 5-fluorouracil or 5-fluorouracil derivatives, patients with dihydropyrimidine dehydrogenase-positive tumours had a significantly (P<0.05) poorer disease-free survival compared to those with dihydropyrimidine dehydrogenase-negative tumour. No conclusion can be drawn about the prognostic impact of dihydropyrimidine dehydrogenase status in patients who were not treated with 5-fluorouracil regimes due to the small number of such cases in this series. Lymph node and dihydropyrimidine dehydrogenase status were independent prognostic factors for disease-free survival, and lymph node status for overall survival using multivariate analysis. In conclusion, dihydropyrimidine dehydrogenase is a possible prognostic factor in patients with breast cancer treated with 5-fluorouracil or 5-fluorouracil derivatives.

Adult↗
PubMed2002

Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.

BACKGROUND: Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells. OBJECTIVE: We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma. METHODS: Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied. RESULTS: Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01). CONCLUSION: Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.

Adult↗
PubMed2001

Analysis of IL-12 receptor beta 2 chain expression of circulating T lymphocytes in patients with atopic asthma.

Th2 cell predominance relative to Th1 cells contributes to pathological immune responses in patients with atopic asthma. IL-12 is a key cytokine in the induction of Th1 cells, and downregulation of IL-12 production is reported in these patients. However, IL-12 receptor expression of their T lymphocytes has not been clarified. In this study, expression of IL-12 receptor beta 2 on T cells and secretion of cytokines which affect IL-12 receptor beta 2 expression by their PBMC were examined. We found that IL-12 receptor beta 2 expression of the T cells is reduced. This is partly due to the diminished production of IL-12 and enhanced secretion of IL-4 by their PBMC. IL-18 production is not significantly modulated in these patients. Furthermore, intrinsic defects of the CD4(+) T cells, which reduce their IL-12 receptor beta 2 expression in response to IL-12 and/or IL-18 stimulation, are evident and are importantly involved in the Th1/Th2 imbalance of patients with atopic asthma.

Adolescent↗
PubMed2001

Recurrence of breast cancer following local excision alone for ductal carcinoma in situ.

OBJECTIVE: To assess recurrence of breast cancer following local excision alone for ductal carcinoma in situ. METHODS: Eighteen patients who received complete resection for noninvasive ductal carcinoma between 1982 and 1997 were investigated in this study. The mean age of the patients was 45 (29-78) years old. The initial presentation was a clinically palpable tumor in 4 patients, nipple discharge in 6, and microcalcification on mammograms in 8. Patients with palpable tumor underwent wide excision with at least a 2-cm free margin. Patients whose mammograms showed microcalcification underwent lumpectomy, and those who showed nipple discharge underwent duct-lobular segmentectomy. Five patients who underwent lymph node dissection up to level I or II had no lymph node metastasis. The mean follow-up period was 86 months. RESULTS: Local recurrence in the conserved breast was seen in five (27.8%) of 18 patients. The actuarial five-year event-free survival was 76.2%. The histological type of the recurrent tumor was ductal carcinoma in situ in three patients and invasive carcinoma in two. There was no difference in age at initial operation or histological subtype between patients with and without recurrent disease, but patients presenting with nipple discharge initially had a significantly shorter ipsilateral disease-free interval than those presenting with tumor or microcalcification on mammograms. All patients with local recurrence in the conserved breast were treated with breast-conserving surgery or subcutaneous mastectomy. CONCLUSION: Local recurrence frequently occurs in patients presenting with nipple discharge treated by duct-lobular segmentectomy for noninvasive ductal carcinoma. Either wide excision with a larger free margin or adjuvant radiation therapy following duct-lobular segmentectomy should be considered for these patients.

Adult↗
PubMed2001

Tamoxifen-failed male breast cancer with a high level of circulating estrogen: report of a case.

We report herein the case of a 40-year-old man with grade II invasive ductal carcinoma of the breast (pT1, pN0, M0: stage I) in whom a recurrence developed shortly after completion of a 2-year course of tamoxifen and 5-fluorouracil therapy following a mastectomy. Although the metastatic tumor was estrogen receptor-positive, hormone therapy combined with chemotherapy had no significant effect on tumor growth, and the patient died from disseminated tumors 2 years 6 months after completion of the adjuvant therapy. It is noteworthy that the circulating estradiol level increased from 18.0 to 892.3 pg/ml during the period of tumor progression and dissemination. We interpret these findings as an indication of high aromatase activity in the metastatic tumors. We suggest that extending tamoxifen treatment to 5 years or longer be recommended for the standard adjuvant hormone therapy of male breast cancer to prevent the early recurrence of hormone-responsive disease.

Adult↗
PubMed2000

Highest microvessel count as a long-term prognostic factor in Japanese breast cancer patients.

The aim of this study was to determine whether microvessel density (MVD) could add useful information in predicting the prognosis of breast cancer patients. In our study, MVD was calculated by counting microvessels per x200 field in the highest neovascularized area of the tumor (highest microvessel count, HMC). HMC significantly increased according to the increased number of positive nodes. Higher HMC significantly correlated with worse relapse-free survival (RFS) of patients with negative node, one to three positive nodes in the axilla or with stage I and II tumors. HMC, however, was not predictive for RFS of patients with four or more positive nodes or with stage III tumors. Multivariate analysis revealed that HMC was second only to nodal status and tumor size as being predictive for RFS. These results suggest that HMC could be used in selection of patients with early-stage breast cancer who are at high risk for having occult metastasis.

Adult↗
PubMed2000

Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report.

BACKGROUND: We reported that IL-6 and IL-8 levels at the beginning of treatment are predictive indicators of response to therapy and prognosis of patients with recurrent breast cancer. The aim of this study was to investigate the trend of IL-6 and IL-8 levels in heavily pretreated patients with recurrent breast cancer. METHODS: Cytokine level trends in 12 patients heavily pretreated with anthracyclines were studied. Patients were divided into two groups according to the objective response. There were 5 partial response (PR)/no change (NC), and 7 progressive disease (PD) patients. Blood was taken every four weeks. IL-6 was measured by chemiluminescent enzyme immunoassay. IL-8 was measured by ELISA. RESULTS: The pretreatment level of IL-6 in the PR/NC group (11.0+/-2.1 pg/ml) was significantly lower than that (15.3+/-2.7 pg/ml) in the PD group. However, there was no difference in IL-8 level between the PR/NC group (12.5+/-5.5 pg/ml) and the PD group (11.5+/-1.1 pg/ml). IL-6 levels in the PR/NC group were maintained within normal levels or decreased to within normal levels after treatment, while levels of IL-6 in the PD group gradually increased until the time of patient death. A decrease in IL-8 level after treatment was observed in only one patient in the PR/NC group. Mild increase of IL-8 levels was observed in the PD group. CONCLUSION: Continuous elevation of IL-6 levels indicates poor prognosis in heavily pretreated patients with recurrent breast cancer. Combination therapy including agents that reduce IL-6 levels will be a new strategy for aggressively treating recurrent breast cancer.

Antibiotics, Antineoplastic↗
PubMed2000

A case report of advanced male breast cancer with an objective response to tamoxifen treatment.

A 70-year-old man presented with a firm tumor in his right breast first noticed eight years ago. The tumor had enlarged gradually and had produced an ulcer with bleeding. On physical examination, a huge tumor entirely occupied the right breast and extensively had infiltrated the chest wall. Chest X-ray and CT showed massive pleural effusion and multiple small nodular lesions in the lung. Invasive ductal carcinoma of the breast was diagnosed by incisional biopsy,confirming advanced breast cancer with lung metastases and bilateral pleural effusion(T4cN2M1, Stage IV). Because ER and PgR levels were 110 fmol/mg and 190 fmol/mg, respectively, and because his general condition was poor, we selected medical treatment with tamoxifen(TAM). Thirty-two weeks later, the tumor had showed pronounced reduction with scarring. The patient underwent local excision of the scar tissue. The quality of life of the patient was favorably improved and no severe adverse events were observed. The tumor in the chest wall recurred two months after the end of TAM treatment, possibly because the patient did not accept continuous TAM therapy. The patient died from complications of brain metastasis 32 months after the start of TAM treatment. We report a rare case of advanced male breast cancer and on the effectiveness of continuous TAM treatment.

Aged↗
PubMed2000

Primary squamous cell carcinoma of the breast during lactation: a case report.

A case of primary squamous cell carcinoma of the breast during lactation is reported. The patient was a 32-year-old woman, in post-partum lactating 18 months after delivery, who was referred to our hospital following detection of a lump in her left breast during physical examination in mass screening for breast cancer. The tumor, palpated in the upper outer quadrant of the left breast, was firm, well-defined and 2.8 x 2.6 cm in size. Ultrasonograms identified an irregular-shaped hypoechoic lesion and mammograms revealed a well-defined, circumscribed tumor. Based on these findings, breast cancer was suspected and an excisional biopsy was performed. The resected specimen was a firm, solid and circumscribed tumor with central hemorrhage. Microscopic findings demonstrated that the tumor consisted of an invasive ductal carcinoma with marked squamous metaplasia, such as keratinization and squamo-columnar junction. Breast-conserving surgery was performed and no lymph node involvement was noted. Both estrogen and progesterone receptors of the tumor were negative. Generally, the size of both squamous cell carcinoma and carcinoma during the lactation period tends to be larger than ordinary carcinomas. In this case, the cancerous lesion was detected at a relatively early stage. Although the cancerous lesion was detected at a relatively early stage and no lymph node involvement was noted, lung metastases occurred within 12 months of the surgery. Malignant potential is generally considered to be high in cases of squamous cell carcinoma of the breast with lactation and thus intensive treatment potentially resulting in severe side effects was considered to be necessary for this patient.

Adult↗
PubMed1999

Granular Cell Tumor of the Breast Diagnosed by Core Needle Biopsy: A Case Report.

Granular cell tumor rarely occurs in the breast. We report a 69-year-old woman with a right breast mass that simulated carcinoma on palpation, mammography, and ultrasonography. Aspiration biopsy cytology showed no malignant atypical cells. Core needle biopsy was performed to obtain an accurate diagnosis. The lesion was histologically confirmed to be a granular cell tumor. Immunostaining was positive for S-100 protein and vimentin, and negative for keratin, carcinoembryonicantigen, estrogen receptor and gross cystic disease fluid protein-15. The tumorwas treated by wide local excision. Surgeons should be aware that granular cell tumor can resemble breast cancer in order to avoid performing a needless radical mastectomy.

Journal Article↗
PubMed1999

The efficacy of technetium-99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands.

The efficacy of the technetium-99m-2-methoxyisobutylisonitrile (Tc-MIBI) scan and intraoperative methylene blue staining was analyzed in a consecutive series of 15 patients with primary hyperparathyroidism who underwent neck surgical exploration. A total of 17 abnormal parathyroid glands were removed, 7 of which were confirmed histologically as adenomas and 10 as hyperplasias. The Tc-MIBI scan and the thallium-201-technetium-99m subtraction (Tl/Tc) scan preoperatively localized 11 (69%) of 16, and 6 (40%) of 15 abnormal parathyroid glands, respectively. The Tc-MIBI scan correctly localized two ectopic abnormal parathyroid glands which were not localized by the Tl/Tc scan or ultrasonography (US). However, it also demonstrated false-positive accumulations caused by thyroid diseases in two patients. There were 4 abnormal parathyroid glands not detected by the preoperative imaging techniques, whereas all 17 abnormal parathyroid glands were stained with methylene blue, the infusion of which caused no adverse effects or toxicity. In conclusion, Tc-MIBI scanning and intraoperative methylene blue staining are effective techniques for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

Adenoma↗
PubMed1999

Effect of suplatast tosilate (IPD-1151T) on cytokine production by allergen-specific human Th1 and Th2 cell lines.

Suplatast tosilate (IPD-1151T) is an antiallergic agent that suppresses airway eosinophil infiltration in asthma. We investigated the effects of IPD-1151T on proliferative response and cytokine production by human antigen-specific T cell lines. Purified protein derivatives (PPD)-specific T helper 1 (Th1) cell lines and Dermatophagoides farinae (Der f)-specific T helper 2 (Th2) cell lines were established from patients with asthma sensitized with house dust mite. Stimulation of PPD-specific and Der f-specific T cell lines with relevant antigens resulted in production of mostly interferon (IFN)-gamma and of interleukin (IL)-4 and IL-5, respectively. IPD-1151T did not inhibit the proliferative responses of either the Th1 or Th2 cell line to antigens. Although IPD-1151T did not inhibit IFN-gamma production by PPD-specific Th1 cell lines, it did inhibit IL-4 and IL-5 production by antigen-stimulated Der f-specific Th2 cell lines in a dose-dependent manner. IPD-1151T directly inhibited cytokine production by Der f-specific Th2 cell lines stimulated with immobilized anti-CD3 antibodies. Although IPD-1151T did not inhibit the clonal expansion of memory T cells among PBMCs into PPD-specific Th1 and Th2 cell lines, it did inhibit IL-4 and IL-5 production by Der f-specific Th2 cell lines but not IFN-gamma production by PPD-specific Th1 cell lines. These results suggest that IPD-1151T selectively inhibits Th2-type cytokine production.

Allergens↗
PubMed1999

Natural history of fibroadenomas based on the correlation between size and patient age.

BACKGROUND: Several recent studies have reported that most fibroadenomas remain static or regress when they are managed conservatively; however, no such studies have evaluated the breast disorder in Japanese women. To understand the natural history of fibroadenomas in Japanese women, we examined the correlation between the sizes of the fibroadenomas and the women's age. METHODS: Fifty-eight consecutive patients (age range, 17-51 years; mean, 33.9 years) with histologically confirmed fibroadenoma were enrolled in this study. The sizes of the excised fibroadenomas were analyzed in relation to the women's ages. RESULTS: The fibroadenomas decreased significantly in size (Y, mm) with patient age (X, years) (P = 0.0012) according the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540). From this equation, the mean sizes of the fibroadenoma in women aged 20, 30 and 40 years were expected to be 20.2 mm (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8-22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively. The mean annual decrease in the size of the fibroadenomas was 0.340 mm. CONCLUSIONS: Our results indicate that in Japanese women fibroadenomas increase in size more frequently in younger than in older women. Moreover, it is speculated that most fibroadenomas might stop growing when they reach an approximate maximum diameter of 20 mm, after which time they might remain static or regress.

Adolescent↗
PubMed1999

A case control study on the effectiveness of breast cancer screening by clinical breast examination in Japan.

A case-control study was conducted in Miyagi and Gunma prefectures, Japan, to evaluate the effectiveness of breast cancer screening by clinical breast examination (CBE) alone in reducing breast cancer mortality. Case subjects, who were female and had died of breast cancer, were collected from residential registry files and medical records. Control subjects matched in sex, age and residence were randomly selected from residential registry files. The screening histories during 5 years prior to the cases having been diagnosed as breast cancer were surveyed using the examinee files of the screening facilities. Finally, the data of 93 cases and 375 controls were analyzed. The odds ratio (OR) of breast cancer death for participating in screening at least once during 5 years was 0.93 (95% confidence interval (95% CI) 0.48-1.79). The cases were more symptomatic than the controls when screened. If the participants who had had symptoms in their breasts were classified as not screened, the OR decreased to 0.56 (95% CI 0.27-1.18). The case control study suggests that the current screening modality (CBE) lacks effectiveness (OR = 0.93), although it might be effective for an asymptomatic population (OR = 0.56). The number of cases was small, and a larger case-control study is desirable to define whether CBE is effective or not. However, it is necessary to consider the introduction of mammographic screening to reduce breast cancer mortality in Japan.

Adult↗
PubMed1999

Mitogen-activated protein kinase cascade in breast cancer.

The mitogen-activated protein (MAP) kinase is considered to play a central role in diverse cellular events including carcinogenesis and tumor progression. Indeed, expression of MAP kinase, tyrosine-phosphorylated MAP kinase, and Raf-1 protein was greater in cancerous human tissues than in the surrounding noncancerous glands. In a 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma model, estrogen promoted and ovariectomy and antiestrogen, tamoxifen (TAM) inhibited the tumor growth. Ovariectomy suppressed expression of MAP kinase, tyrosine-phosphorylated MAP kinase and Raf-1, whereas estrogen as well as TAM induced expression of MAP kinase and Raf-1 under castrated conditions. Since it was reported that MAP kinase was activated during the progression of breast carcinoma cells, such estrogenic actions of TAM toward the MAP kinase cascade might be responsible for malignant progression.

Animals↗