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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

1,097 records · Page 61Linked to original sources

[Two autopsy cases of aortitis syndrome in the elderly].

Two autopsy cases of aortitis syndrome (Takayasu's aortitis) in the elderly are presented. Case 1 was an 81-year-old woman in whom hypertension was observed at age 37, and difference of right and left arm blood pressure was pointed out at age 65. She was referred to the authors' hospital at age 72. Chest X-ray and computed tomography of the thorax indicated atypical coarctation and diffuse calcification of the aorta. Case 2 was a 69-year-old woman in whom hypertension was pointed out at age 49, and blood pressure in the arms was found to differ from that in the legs at age 63. Chest X-ray and computed tomography showed diffuse calcification and marked narrowing of the descending aorta. Pathological examination revealed marked calcification in the thickened adventitia of the aorta with mild atherosclerotic change. Irregular fibrotic changes of the adventitia and degeneration of elastic fibers of the media of the aorta were noted in both cases, and were consistent with Takayasu's aortitis. This disorder is common in young women and only a small number of elderly cases are reported although its incidence is increasing. Diffuse calcification of the aorta with an absence of inflammatory signs, which is frequent in older patients, were observed in both case. Systemic hypertension is the most important risk factor with coarctation of the aorta in Takayasu's aortitis. Bypass surgery is recommended in young patients, however in elderly patients, it is generally avoided, in favor of medical control of hypertension.

Aged↗

The expression of urokinase type plasminogen activator is a novel prognostic factor in dukes B and C colorectal cancer.

Urokinase type plasminogen activator (u-PA) secreted by cancer cells is considered to play a key role in promoting invasion and metastasis of cancer cells. This study was designed to evaluate the expression and prognostic value of u-PA in Dukes B and C colorectal cancer. u-PA expression was investigated in 57 Dukes B or C colorectal cancers using a monoclonal antibody against u-PA. u-PA expression was mainly observed on the cytoplasm of cancer cells, and was associated with relapse, especially hematogenous metastasis (p=0.025, the chi2 test). Patients with high u-PA expression had a lower rate of DFS (9/22 events) compared to those with low u-PA expression (6/35 events) (p=0.061, log-rank test). This study demonstrated that u-PA expression might be a novel prognostic factor in Dukes B and C colorectal cancer.

Adult↗

Genome scanning detects amplification of the cathepsin B gene (CtsB) in transformed rat ovarian surface epithelial cells.

OBJECTIVE: To isolate a portion of the amplicon inferred to be present in a malignant rat tumor cell line, NuTu 26, by the presence of a homogeneously staining chromosomal region (hsr) and identify genes embedded within it. METHODS: Genome scanning was used to identify an EcoRI fragment (8.6 kbp) within the amplified region of the NuTu 26 genome using a recently identified rat repetitive sequence, OST17 as a probe. The 8.6 kbp amplified fragment was sequenced and used as starting material to obtain additional sequence information by screening a P1 clone-derived DNA library to identify any genes likely embedded in the amplicon. Use of the microdissected hsr as a probe for fluorescence in situ hybridization (FISH) and application of Southern, Northern, and Western blot analysis confirmed the amplification of this region in the NuTu 26 genome. RESULTS: The cathepsin B gene was within the amplicon of the hsr-containing marker chromosome of NuTu 26. FISH analysis and chromosomal banding further revealed that the marker chromosome was a derivative of chromosomes 4 and 15, i.e., der(15)t(4;15). CONCLUSION: Cathepsin B gene amplification may contribute to some aspect of the biology of ovarian cancer. This concept is strengthened by the finding that the gene is overexpressed frequently in independently transformed rat ovarian surface epithelial cells.

Animals↗

Lymphoblastoid cell lines with integrated human herpesvirus type 6.

OBJECTIVE: Attempts were made to establish stable in vitro cell lines latently infected with human herpesvirus type 6 (HHV-6). STUDY DESIGN/METHODS: We previously studied a patient with B-cell acute lymphoblastic leukemia infected with HHV-6. The peripheral blood mononuclear cells (PBMCs) from this patient were immortalized by infection with Epstein-Barr virus (EBV) and herpesvirus saimiri (HVS). RESULTS: Infection of the PBMCs with EBV and HVS gave rise to B- and T-lymphoblastoid cell lines, respectively. Both cell lines were positive for HHV-6 DNA, as confirmed by polymerase chain reaction (PCR) and Southern blot hybridization. Fluorescence in situ hybridization (FISH) demonstrated integration of HHV-6 in these cell lines. Only one integrated site of viral DNA was detected in metaphase chromosome spreads, and it was preferentially located at the long arm of chromosome 1 (1q44). HHV-6 appeared latent in the infected cells, since neither the HHV-6 immediate-early gene transcript nor virion-associated protein was detected. CONCLUSIONS: The HHV-6-positive lymphoblastoid cell lines would be useful for study of the mechanism of HHV-6 integration.

Aged↗

Phase II dose escalation: a novel approach to balancing efficacy and toxicity of anticancer agents. Japanese Docetaxel Ovarian Cancer Study Group.

BACKGROUND: Small patient numbers in phase I trials may result in a safe but ineffective dose being recommended for phase II trials. A phase II dose escalation study may identify a dose that is both safe and effective. The Japanese phase I recommended dose of 60 mg/m2 of docetaxel (Taxotere) had been ineffective in phase II trials in ovarian carcinoma. PATIENTS AND METHODS: Patients previously treated with one platinum-based regimen for ovarian cancer received docetaxel (Taxotere) every 3 weeks. The first dose tested was 70 mg/m2. If none of the first 5 evaluable patients responded, the dose was increased. If at least one patient responded, 10 more patients were enrolled. Also, if fewer than 3 of these first 15 evaluable patients responded, the dose was increased. If at least 3 patients responded, another 15 patients were scheduled to be enrolled to confirm efficacy. Unacceptable toxicity in 4 of 5, or 10 of 15 patients would stop escalation. RESULTS: Dose escalation from 70 mg/m2 was not required because responses were noted with acceptable toxicity levels. Overall response in 25 evaluable patients treated at 70 mg/m2 was 24.0% (95% CI = 9.4-45.1%). CONCLUSION: Docetaxel 70 mg/m2 without premedication was identified as a safe and effective dose. Further testing of the phase II dose escalation design is worthwhile.

Adolescent↗

Effect of PSK on the serum level of immunosuppressive substance in splenectomized rats.

Tumor-bearing rats with and without splenectomy were used for an immunological study on the effects of PSK, an immunomodulator, with respect to the survival rate and serum level of immunosuppressive (IS) substance. There was no significant difference in survival rates between the tumor-resected and tumor-resected-plus-splenectomy groups. The IS substance level in the former group was higher than that in the latter group. Normalization of IS substance level and prolongation of survival were observed in the group administered PSK. PSK can be effective in combination with surgical treatment.

Animals↗

In vivo antineoplastic activity of mouse or human IgG conjugated with melphalan.

IgG of normal female ICR mice was obtained and covalently conjugated with an alkylating agent, melphalan. The conjugate exhibited marked antitumor activities against Sarcoma 180 and Erhlich carcinoma cells inoculated subcutaneously into ICR mice. Based upon this experiment, melphalan was conjugated with human IgG. Antitumor activities of the conjugate, named K18, were tested against a variety of murine tumor cell lines in vivo. Additionally, K18 was tested in vivo against MX-1, MK-2 and LC-10 human tumor cell lines (of the breast, stomach, and lung respectively). The results showed antineoplastic activities on both murine and human tumor cell lines, thus indicating a possible new antitumor agent.

Animals↗

Effect of PSK on prohibited immunity of splenectomized mice.

The effect of PSK (Krestine, an anti-tumor drug prepared from Coriolus versicolor) on splenectomized experimental animals was investigated. Splenectomy was performed on both a tumor-free control group and a tumor-bearing group. The administration of PSK on the splenectomized control group significantly increased the immune state of the host. In the case of the tumor-bearing group, administration of PSK resulted in restoration of the immune function as observed in the control group. Recovery of the immunological function was accelerated when tumor-bearing animals were splenectomized at the terminal stage. The results suggest that the immunomodulating effects of PSK developed at the time of the splenectomy resulted in anticancer activity.

Adjuvants, Immunologic↗

Prolongation of the survival period with the biological response modifier PSK in rats bearing N-methyl-N-nitrosourea-induced mammary gland tumors.

The antitumor effects of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of Coriolus versicolor in basidiomycetes on mammary gland tumors produced in Sprague-Dawley rats by the intravenous injection of N-methyl-N-nitrosourea were investigated. PSK prolonged the survival period of tumor-bearing rats significantly, when given at the dose of 250 mg/kg twice a week for 3 weeks after the tumor reached 100 mm2 in size (p = 0.011 by log rank test and p = 0.023 by generalized Wilcoxon test). These findings suggest that PSK is effective in the prolongation of the survival period in the rat autochthonous tumor model, acting at the growth stage of the tumor during carcinogenesis.

Animals↗

Potassium channel-opening and vasorelaxant profiles of a novel compound YM099 in rat isolated portal vein and rabbit isolated aorta.

The potassium channel-opening and vasorelaxant profiles of YM099, a newly synthesized benzoxadiazol derivative K channel opener, were evaluated in vitro. In the rat isolated portal vein, YM099 and a benzopyran derivative K channel opener levcromakalim concentration-dependently inhibited the frequency of spontaneous rhythmic contractions, with IC50 values of 104 and 38 nM, respectively. In the rabbit isolated aorta, YM099 (10(-7)-3 x 10(-5) M) and levcromakalim (10(-7)-3 x 10(-5) M) also concentration-dependently relaxed the contractions induced by 20 mM KCl, but they were ineffective against the contractions induced by 50 mM KCl. These effects of YM099 and levcromakalim were competitively antagonized by a K channel blocker glibenclamide (10(-7)-3 x 10(-6) M). In the rabbit isolated aorta, YM099 (3 x 10(-8)-3 x 10(-6) M), but not the calcium antagonist nifedipine (10(-8)-3 x 10(-6) M), relaxed the contractions induced by norepinephrine (10(-6) M) or prostaglandin F2 alpha (3 x 10(-6) M). These vasorelaxant effects of YM099 were also antagonized by glibenclamide. In conclusion, YM099 is a potent vascular smooth muscle-relaxant agent and possesses a vasorelaxant effect different from that of nifedipine. These effects of YM099 may be mediated, like those of levcromakalim, by the opening of glibenclamide-sensitive K channels.

Animals↗

Effects of imipramine and amitriptyline on intraventricular conduction, effective refractory period, incidence of ventricular arrhythmias induced by programmed stimulation, and on electrocardiogram after myocardial infarction in dog.

The effects of imipramine and amitriptyline on intraventricular conduction, effective refractory period, incidence of ventricular arrhythmias induced by programmed stimulation and on electrocardiogram changes were studied after myocardial infarction in the dog. Amitriptyline, at doses of 1-3 mg/kg, significantly slowed the ventricular conduction of the infarcted zones in a dose- and frequency-dependent manner. Amitriptyline, at doses of 2 and 3 mg/kg, slowed the ventricular conduction slightly in the normal zone. The effective refractory period was prolonged by amitriptyline at a dose of 1 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Amitriptyline, at doses of 1-3 mg/kg, increased heart rate and prolonged the PQ, QRS and QT interval. Imipramine, at a dose of 3 mg/kg, slowed the conduction in infarcted zones to a lesser extent than amitriptyline. Imipramine, at doses of 1 and 2 mg/kg, did not significantly increase the incidence of ventricular arrhythmias. Imipramine, at a dose of 3 mg/kg, prolonged the QRS interval. From the present results it appears that imipramine has a lower cardiac toxicity than amitriptyline.

Amitriptyline↗

Possible involvement of calpain in the growth of estrogen receptor positive breast cancer cells.

Calpain (Ca2(+)-activated neutral protease, EC 3.4.22.17) has been reported to hydrolyze the estrogen receptor (ER). However, there has been no report available regarding the role of calpain in the growth of breast cancer cells. To investigate the role of calpain in the growth of various breast cancer cell lines, we employed a synthetic peptide, calpeptin, which is a cell permeable specific inhibitor of calpain. Calpeptin inhibited the cell growth of ER positive breast cancer cells, such as MCF-7, T-47D, and ZR-75-1 in a dose dependent manner in the presence of E2. However, the growth of ER negative breast cancer cells, MDA-MB-231, was not inhibited by calpeptin. It is suggested that calpain plays an important role in the growth of ER positive breast cancer cells.

Animals↗

Modulation of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) induced HL-60 cell death by tetrahydrobiopterin.

The effect of 5,6,7,8-tetrahydrobiopterin (BPH4) on HL-60 cell damage induced by a nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP), was investigated. The activity of lactate dehydrogenase (LDH), a marker of cell damage, was elevated dose- and time-dependently after treatment with SNAP. The cells underwent apoptosis, as judged from the characteristic morphological findings and the electrophoretic ladder pattern of DNA fragments. Apoptosis observed at an early time, 5 hours post-treatment with SNAP, was inhibited by BPH4. However, BPH4 significantly increased cell death observed at a later time, 20 hours after the treatment. These results suggest that BPH4 may be involved in modulating the cytotoxicity, including cell death, mediated by NO.

Apoptosis↗

Urokinase type plasminogen activator receptor is a novel prognostic factor in breast cancer.

BACKGROUND: There have been many reports that the u-PA system plays an important role in cancer invasion and metastasis. The binding of u-PA to its specific cell-surface receptor, u-PAR, is necessary for the activation of u-PA system. The aim of this study is to evaluate the role and the prognostic value of u-PAR in cancer invasion and metastasis. PATIENTS AND METHODS: u-PAR expression in 104 breast cancers was investigated immunohistochemically using a monoclonal antibody against u-PAR. RESULTS: u-PAR expression was mainly observed both on cancer cells and stromal cells. Patients with high u-PAR expression in cancer cells or stromal cells had a high relapse rate compared with patients with low u-PAR expression by the Kaplan-Meier method (p = 0.035 and 0.011, respectively). In uni- and multivariate analysis, u-PAR expression in stromal cells was significantly correlated with relapse (p = 0.017 and 0.043, respectively). CONCLUSIONS: This study has shown that not only cancer cells but also stromal cells have an important roles in breast cancer invasion and metastasis, and that u-PAR expression in cancer cells and stromal cells might be a novel prognostic factor in breast cancer.

Adult↗

Mechanism of growth inhibition by calpain inhibitor in MCF-7 cells.

BACKGROUND: A calpain inhibitor, calpeptin, inhibited the cell growth of ER (estrogen receptor) positive breast cancer cells, such as MCF-7, T-47D, and ZR-75-1 in the presence of E2. The mechanism of this inhibition has not been clarified yet. MATERIALS AND METHODS: MCF-7 cells were employed to investigate the mechanism of the inhibition. We studied the effect of calpeptin on the secretion of insulin-like growth factor-I (IGF-I) and transforming growth factor (TGF-alpha). RESULTS: The secretion of IGF-I or TGF-alpha was not changed by calpeptin either in the presence or absence of E2. Moreover, the binding of IGF-I or TGF-alpha to MCF-7 cells augmented by the addition of E2 was not affected by calpeptin. CONCLUSIONS: These results indicated that the inhibition of cell growth in MCF-7 by calpeptin was not due to the modulation of autocrine growth factors and their receptors.

Breast Neoplasms↗

Thrombomodulin is a new biological and prognostic marker for breast cancer: an immunohistochemical study.

BACKGROUND: Thrombomodulin (TM) is a natural anticoagulant which inhibits thrombin. Recent studies have reported that TM is correlated with vascular diseases and a few cancers. The aim of this study was to evaluate the role and the prognostic value of TM in breast cancer. PATIENTS AND METHODS: TM expression in samples from 60 invasive breast cancer patients was examined immunohistochemically with a polyclonal antibody against TM. RESULTS: TM staining was observed mainly on both the cytoplasm and cell surface in cancer cells and on endothelial cells around or in cancer tissue. TM expression in cancer cells was not correlated with the clinicopathological features. However, low TM expression was significantly correlated with a high relapse rate (p = 0.047 by the chi 2 test and 0.05 by the Kaplan-Meier method). CONCLUSIONS: TM might play an active role in cancer invasion and metastasis, and serve as a new prognostic factor in invasive breast cancer.

Adult↗