Search PubMed⌕ Search

Biomedical subjects

T Yano

Publications and source records attributed to T Yano.

At least 217 records · Page 12Linked to original sources

Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata.

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.

Absorptiometry, Photon↗

[A case of pleural and mediastinal lymph node metastases from breast cancer effectively treated with fadrozole hydrochloride in combination with cyclophosphamide].

A 63-year-old woman was diagnosed with pleural and mediastinal lymph node metastases 116 months after operation because of bilateral breast cancer. She was then treated with fadrozole hydrochloride (FH) (2 mg). Adriamycin (30 mg) administration into the pleural cavity was attempted, but did not prove effective. Thus, we tried to combine FH with cyclophosphamide (100 mg). After one month, chemoendocrine therapy relieved her complaints of cough and shortness of breath. CT revealed a remarkable decrease of pleural effusion and disappearance of mediastinal lymph nodes. She was alive 9 months after the treatment. Fadrozole hydrochloride in combination with cyclophosphamide is promising as an effective treatment in postmenopausal patients.

Antineoplastic Combined Chemotherapy Protocols↗

[Nedaplatin and etoposide combination chemotherapy in a patient with small cell carcinoma undergoing hemodialysis].

A 61-year-old man with chronic renal failure caused by polycystic kidney disease requiring hemodialysis three times weekly developed small cell carcinoma of the lung. The patient received combination chemotherapy with nedaplatin (50 mg) and etoposide (50 mg). Blood levels were monitored, showing that nedaplatin was more dialyzable than cisplatin. The patient achieved a complete response. These results suggest that nedaplatin-etoposide combination chemotherapy may be safer than cisplatin-containing regimen for patients with chronic renal failure hemodialysis and that a satisfactory response can be expected.

Antineoplastic Combined Chemotherapy Protocols↗

Defective human T-lymphotrophic virus type I provirus in T-cell prolymphocytic leukaemia.

T-cell prolymphocytic leukaemia (T-PLL) is a rare form of post-thymic T-cell neoplasm, the aetiology of which remains unknown. We examined human T-lymphotropic virus (HTLV) provirus in five HTLV-I/II seronegative patients with T-PLL. Southern blotting did not show monoclonal integration of the HTLV-I genome in any of the DNA samples. However, two of the five DNA samples contained an HTLV-I tax sequence. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and LTR regions were all negative. HTLV-I tax gene expression and p40tax antibody were not detected in samples from cases with HTLV-I tax sequence. Our findings suggest that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis, in which HTLV-I genome insertion triggers T-PLL but the deletion of various regions of the integrated provirus subsequently prevents active replication and the expression of the virus.

Adult↗

UFT plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.

A phase II study of combined-modality treatment consisting of uracil and tegafur (in a molar ratio of 4:1 [UFT]) plus cisplatin (Platinol) and concurrent radiotherapy was conducted to evaluate the activity of this regimen in patients with locally advanced non-small-cell lung cancer. Eligible patients with cytologically or histologically confirmed, unresectable stage III non-small-cell lung cancer received UFT (400 mg/m2 orally on days 1 through 52) and cisplatin (80 mg/m2 intravenously on days 8, 29, and 50). Radiotherapy, with a total dose of 60.8 Gy, was delivered in 38 fractions on days 1 through 52. Among the 17 patients entered, 16 experienced partial responses (94%; 95% confidence interval, 83% to 100%). The median time to tumor progression was 30 weeks (range, 8 to 87 weeks), and the 1-year survival rate was 80%. Hematologic toxicity was moderate. Grade 3 leukopenia occurred in 10 patients (59%), but no grade 4 hematologic toxicity was observed. No grades 3 or 4 nonhematologic toxicities were reported. These observations suggest that oral UFT plus cisplatin with concurrent radiotherapy can be safely administered to patients with locally advanced non-small-cell lung cancer. The demonstrated antitumor activity is high, making this combined-modality treatment worthy of further investigation in a multi-institution trial.

Adult↗

[A case of adriamycin and methotrexate-resistant recurrent breast cancer treated with doxifluridine and mitomycin C].

A 49-year-old woman was diagnosed with local recurrence and cervical lymph node and bone metastases 55 months after surgery for breast cancer. She was treated with goserelin acetate and tamoxifen but the disease was assessed as progressive after 8 months. Five courses of CMF therapy were performed but lung, pleural and mediastinal lymph node metastases were detected. Then, five courses of CAF therapy were carried out, but a contralateral breast metastasis was detected and the patient complained of shortness of breath. The CAF therapy was assessed as PD. We attempted administration of doxifluridine (5'-DFUR) and mitomycin C (MMC) on an outpatient basis. After 6 months, no progressive disease was detected and she was relieved of her shortness of breath. The combination therapy was assessed as long NC. Combination therapy with 5'-DFUR and MMC is thus a useful treatment for adriamycin- and methotrexate-resistant breast cancer, especially in terms of quality of life.

Antimetabolites, Antineoplastic↗

[Correlation between clinical aggressiveness of thymic epithelial tumors and expression of tumor suppressor gene products (p53, p27)].

It is impossible to predict malignant potential of thymomas by conventional histopathological examination. In order to find a malignant marker of thymoma, we immunohistochemically examined the expression of the products of p53 and p27kip1, potential tumor suppressor genes in thymic epithelial tumors. The thymic epithelial tumors examined in the present study included 13 non-invasive thymomas, 7 invasive thymomas, and 4 thymic carcinomas. The thymic epithelial cells showed abnormal accumulation of p53 protein in 2 of 13 non-invasive thymomas (15.4%), 4 of 7 invasive thymomas (50%), and 3 of 4 thymic carcinomas (75%). The frequency of p53-expression paralleled with clinical aggressiveness. On the other hand, p27 showed no correlation with clinical aggressiveness. In conclusion, the present results suggest that the presence of p53-positive epithelial cells might be a useful indicator to predict malignant potential of thymoma.

Cell Cycle Proteins↗

Attenuated liver fibrosis and depressed serum albumin levels in carbon tetrachloride-treated IL-6-deficient mice.

Chronic intermittent injection of carbon tetrachloride (CCl4) for more than 10 weeks induced liver fibrosis in mice, as evidenced by positive Azan staining and increased intrahepatic collagen content. Preceding the onset of liver fibrosis, interleukin-6 (IL-6) gene expression was enhanced in liver and immunoreactive IL-6 was detected in infiltrating inflammatory cells. To delineate the role of IL-6 in this process, we treated IL-6-deficient mice with CCl4 in a similar manner for 12 weeks, after which fibrotic changes were less evident and serum albumin levels were lower in IL-6-deficient than wild-type mice. Moreover, CCl4-induced expression of transforming growth factor beta1 and hepatocyte growth factor genes in liver was significantly reduced in IL-6-deficient mice. Thus, IL-6 may be vitally involved in fibrotic changes and maintenance of serum albumin levels, partly by modulating intrahepatic expression of these cytokines.

Animals↗

[5-FU sensitivity and thymidylate synthase in gastric cancer].

The relationship of 5-FU-sensitivity to thymidylate synthase (TS) was investigated in a total of 82 gastric cancers of stage III or IV. The sensitivity test was done by Histoculture Drug Response Assay and TS expression was stained immunohistochemically using anti-TS antibody. Sensitivity to 5-FU of more than 50% of the inhibitory index (high sensitivity) was observed in 28.1% of the materials, less than 50% (low sensitivity) in 71.9% and less than 20% in 50.0%. The expression of TS was found in 25.6% of the patients. The incidence of positive TS expression was 34.5% in the high sensitivity group, against 22.0% in the low sensitivity group, with no statistical difference between them. No particular relationship was found between 5-FU-sensitivity group and TS expression rate when the tumor-histology was divided into high and low differentiation. In the present study, the ratio of patients negative for TS among the high 5-FU-sensitivity group both was 65.2%, both of which have been reported as producing high survival rates. In contrast, the ratio of patients positive for TS in the low 5-FU-sensitivity group was 22.0%. From these results, TS is considered to be responsible for approximately 40-50% of either high or low 5-FU-sensitivity, respectively, when the lower TS expression in the present study was taken into consideration and corrected.

Antimetabolites, Antineoplastic↗

[The dissecting aortic aneurysm associated with polymyalgia rheumatica: a case report].

We report a patient with a dissecting aortic aneurysm associated with polymyalgia rheumatica (PMR). The patient is a 55-year-old Japanese man without a history of hypertension, diabetes mellitus and syphilis. He was admitted to an emergency hospital because of severe back pain, and was diagnosed as having a dissecting aneurysm of the descending aorta. After the admission, he began to notice severe muscle pain in his bilateral shoulder. Although his back pain gradually improved, his muscle pain progressively worsened, and his lower extremities were also involved. Then, he was introduced to our hospital. On neurological examination, he was alert and oriented. His cranial nerves were all intact. There was no muscle weakness nor sensory disturbance. Laboratory studies revealed that his erhythrocyte sedimentation rate was extremely high without elevation of the serum level of creatine phoshpokinase, rheumatoid factors and c-reactive protein. He was diagnosed as having PMR, and oral administration of prednisolone++ was started. Within several days, his muscle pain dramatically disappeared. As is known, there is a close relationship between PMR and temporal arteritis of giant cell arteritis. In general, PMR is a benign disease and responds well to steroid therapy, and prevalence of the giant cell arteritis is low in Japanese people. However, it should be kept in mind that the dissecting aneurysm is a relevant, severe complication of PMR because arteritis can be latently present in PMR.

Aortic Dissection↗

[Outpatient chemotherapy with oral UFT (tegafur and uracil) and cisplatin against metastatic non-small cell lung carcinoma--an effective case].

A 64-year-old man underwent a left pneumonectomy for squamous cell carcinoma of the left lung in July 1995. In May 1996, right pelvic bone metastasis occurred and was well controlled by the concurrent chemoradiotherapy; UFT (600 mg/body, day 1-14) and cisplatin (80 mg/m2, day 8) with a total 50.4 Gy of irradiation. In August 1996, left renal metastasis occurred, but regressed after two cycles of combination chemotherapy with UFT and cisplatin. In January 1997, multiple lung metastasis occurred. In accordance with the patient's request, combination chemotherapy was performed at the outpatient clinic. UFT (250 mg/m2) was given orally every day while cisplatin (60-80 mg/m2), fractionated in 3 or 5 days, was intravenously administered at an interval of 4 weeks or longer. The patient has continued the treatment for one year without serious (G3, 4) adverse events. During the treatment, the tumor growth was slow with a repeated cycle of progression and regression. The outpatient chemotherapy using UFT and cisplatin is considered to be useful, especially for the better quality of life of patients.

Administration, Oral↗

Volatile anesthetics and a volatile convulsant differentially affect GABA(A) receptor-chloride channel complex.

1. General anesthetics at clinical concentrations are known to affect neurotransmitter-gated ion channels in postsynaptic membranes. 2. Volatile anesthetics suppress excitatory transmissions, whereas they potentiate inhibitory chloride currents evoked by GABA or glycine. Hexafluorodiethyl ether (a volatile convulsant) markedly depresses the GABA(A) response but not the glycine-evoked chloride current or the glutamate-induced excitatory response. 3. Molecular biology has revealed that GABA(A) receptor is a heteromeric pentamer composed of alpha, beta, gamma, delta, and/or rho subunits. In baculovirus-Sf9 expression system, the gamma subunit was crucial for potentiation of the GABA-induced chloride current by volatile anesthetics. 4. Following sustained presence of GABA and high concentrations of isoflurane, simultaneous washout of both agents evoked a slowly decaying surge current, whose nature is controversial.

Anesthetics, Inhalation↗

Two diverged complement factor B/C2-like cDNA sequences from a teleost, the common carp (Cyprinus carpio).

Mammalian complement components factor B and C2 act as proteolytic subunits of the C3 convertases in the alternative and the classical activation pathways, respectively, and are believed to have diverged from a common ancestor by gene duplication. However, it is unclear when the B/C2 duplication occurred. Here, we describe two diverged B/C2-like cDNA clones (B/C2-A and B/C2-B) isolated from a bony fish, the common carp (Cyprinus carpio). B/C2-A shares the same domain structure as the factor B and C2 complement components of vertebrates reported so far and shows a close similarity to zebrafish B and medaka fish B/C2. These teleost sequences show almost the same degree of similarity to C2 and B of higher vertebrates. In contrast, B/C2-B has a novel structural feature in that it contains four short consensus repeat modules and does not have a close relative upon phylogenetic analysis. Northern blotting revealed the presence of two transcripts with different sizes for both the B/C2-A and B/C2-B in the hepatopancreas of the carp. Southern blotting suggested the presence of multiple genes for B/C2-A and a single gene for B/C2-B. Although structural features of B/C2-B are slightly more C2-like than B-like, B/C2-B has a crucial amino acid substitution in the serine protease domain, which makes it unlikely that B/C2-B functions as a C3 convertase. A possible phylogenetic relationship between the two carp sequences and mammalian C2 and B is discussed.

Amino Acid Sequence↗

Regenerative response in acute renal failure due to vitamin E deficiency and glutathione depletion in rats.

In this study, we investigated some factors contributing to renal regeneration after acute renal failure (ARF) induced by vitamin E (VE) deficiency and glutathione (GSH) depletion. Acute renal failure was induced by feeding rats a vitamin E-deficient diet for 6 weeks and then injecting buthionine sulfoximine (BSO), a glutathione-depleting agent. The level of hepatocyte growth factor (HGF), a renotropic factor for regeneration in the kidney, showed a transient increase at 5 hr after the BSO treatment. Subsequently, renal ornithine decarboxylase (ODC) activity, a marker of G1 phase, and labeling index (LI) of proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis (S phase), reached peaks at 10 and 53 hr after the injection, respectively. Thus, it appears that the increase in ornithine decarboxylase activity and subsequent elevation in proliferating cell nuclear antigen labeling index following the increase in the hepatocyte growth factor level in the kidneys are closely related to the renal regenerative response after acute renal failure.

Acute Kidney Injury↗

Structure-function studies of iron-sulfur clusters and semiquinones in the NADH-Q oxidoreductase segment of the respiratory chain.

Our recent experimental data on iron-sulfur clusters and semiquinones in the complex I segment of the respiratory chain is presented, focusing on the Paracoccus (P.) denitrificans and bovine heart studies. The iron-sulfur cluster N2 has attracted the attention of investigators in the research field of complex I, since the mid-point redox potential of this cluster is the highest among all clusters in complex I, and is pH dependent (60 mV/pH). It is known that this cluster is located either in the NQO6 (NuoB in E. coli/PSST in bovine heart nomenclature) or in the NQO9 (NuoI/TYKY) subunit in the amphipathic domain of complex I. Our preliminary data indicate that the cluster N2 is located in the NuoB rather than the long-advocated NuoI subunit, and may have a unique ligand structure. We previously reported spin-spin interactions between cluster N2 and two distinct species of semiquinone (designated SQNf and SQNs) associated with complex I. A parallel intensity change was observed between the SQNf (g = 2.00) signal and the N2 split g parallel signal, further supporting our proposed interaction between SQNf and N2 spins.

Animals↗

Localization-dependent translation requires a functional interaction between the 5' and 3' ends of oskar mRNA.

The precise restriction of proteins to specific domains within a cell plays an important role in early development and differentiation. An efficient way to localize and concentrate proteins is by localization of mRNA in a translationally repressed state, followed by activation of translation when the mRNA reaches its destination. A central issue is how localized mRNAs are derepressed. In this study we demonstrate that, when oskar mRNA reaches the posterior pole of the Drosophila oocyte, its translation is derepressed by an active process that requires a specific element in the 5' region of the mRNA. We demonstrate that this novel type of element is a translational derepressor element, whose functional interaction with the previously identified repressor region in the oskar 3' UTR is required for activation of oskar mRNA translation at the posterior pole. The derepressor element only functions at the posterior pole, suggesting that a locally restricted interaction between trans-acting factors and the derepressor element may be the link between mRNA localization and translational activation. We also show specific interaction of two proteins with the oskar mRNA 5' region; one of these also recognizes the 3' repressor element. We discuss the possible involvement of these factors as well as known genes in the process of localization-dependent translation.

Animals↗