Biomedical subjects

S Yuasa

Publications and source records attributed to S Yuasa.

242 records · Page 14Linked to original sources

PubMedDate not supplied

Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats.

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long-term administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to male Sprague-Dawley rats would produce a sodium-sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. NG-Nitro-L-arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail-cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long-term administration of L-NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2- and NO3- and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME-treated rats increased significantly within the first week of the study compared with control rats. L-Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment by 3 weeks of concomitant administration. 4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

Animals↗

PubMedDate not supplied

A rat model of dilated cardiomyopathy to investigate partial left ventriculectomy.

BACKGROUND: This study is the first to assess a small animal model of dilated cardiomyopathy (DCM) for evaluation of partial left ventriculectomy. METHOD: Eighteen Dahl salt-sensitive (DS) rats were divided into three groups. Six rats were fed an 8% high-salt diet from the age of 7 weeks (Group 1), and similarly six rats from 8 weeks (Group 2) and six from 9 weeks (Group 3). Blood pressure (BP) was measured by the tail-cuff method and left ventricular (LV) dimensions by echocardiography. RESULTS: In Groups 1 and 2, systolic BP rose and reached 200 mmHg by the 10th to 11th week, when all rats died within a week without signs of heart failure. However, in Group 3, systolic BP gradually rose to 196+/-15 mmHg (mean +/- SD) at the age of 14 weeks, when LV end-diastolic diameter (EDD) was 6.2+/-0.4 mm (control 5.1+/-0.7 mm) and LV fractional shortening (FS) was 77+/-3% (control 68+/-3%). At the age of 25 to 30 weeks, all rats in Group 3 showed signs of congestive heart failure, systolic BP remained high, EDD markedly increased (8.7+/-0.6 mm), and LVFS decreased (38.9+/-8.1%). From this stage, rats survived for 13.7+/-5.9 days. We employed the Group 3 model for our pilot PLV study. Eight rats had PLV with a beating heart by plicating the LV area between the papillary muscle bases. Two rats died perioperatively but the rest survived (60% survival 3 weeks after PLV). Postoperatively, the rats' LVEDD decreased and FS improved significantly. CONCLUSIONS: Using DS rats, we developed a DCM model for investigating PLV. The model may contribute to scientific investigation of PLV.

Animals↗

PubMedDate not supplied

Chemosensitivity of breast cancer lymph node metastasis compared to the primary tumor from individual patients tested in the histoculture drug response assay.

Lymph node metastasis is often the first indication of the aggressiveness of breast cancer. Effective chemotherapy in breast cancer depends on targeting the metastatic component of the disease. In order to optimize chemotherapy in the metastatic target of breast cancer, the histoculture drug response assay (HDRA) was performed on surgical specimens of primary tumor and axillary lymph node metastasis from 30 breast cancer patients. The surgical specimens were cut into approximately 10 mg pieces, and placed onto the collagen gel sponges in the medium containing previously-determined cutoff concentrations of doxorubicin (DXR), 5-fluorouracil (5-FU), cisplatin (DDP), and mitomycin C (MMC). After incubation for 7 days, the chemosensitivity of the tumor fragments was evaluated with the 3-(4,5-dimethythiazol2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) endpoint. The lymph node metastases were more resistant than the primary tumor for DXR, 5-FU, and MMC (p < 0.05) but not for CDDP. The data suggest that both primary tumor and metastases from individual patients should be tested in the HDRA to enhance clinical efficacy of chemotherapy.

Antineoplastic Agents↗

PubMedDate not supplied

Neonatally administered diethylstilbestrol retards the development of the blood-testis barrier in the rat.

Newborn rats were treated with 10 microg of diethylstilbestrol (DES) on alternate days from the 2nd to the 12th postnatal day, and the testes were sequentially examined up to 105 days of age by light, electron, and confocal laser microscopy. In control rats, spermatozoa and step 19 spermatids were observed in stage VIII seminiferous tubules at 56 days of age. Spermatogenic cells in DES-treated rats differentiated normally from birth until 21 days of age, after which differentiation continued only to the pachytene-spermatocyte stage. From this age onward, spermatogenic cells older than pachytene spermatocytes were not found until 56 days of age. After this point, the cells resumed differentiation and finally became spermatozoa by 91 days of age; that is, 35 days later than control rats. Electron and confocal laser microscopy showed that in the normal rat, the formation of the ectoplasmic specialization between adjoining Sertoli cells was observed as early as 20 days of age. In contrast, the specialization was not formed until 56 days of age in DES-treated rats. Furthermore, the delay in functional maturation of this structure as the blood-testis barrier was confirmed by intercellular tracer experiments. It is clear that neonatal administration of DES delayed the establishment of the blood-testis barrier for 4 weeks. Consequently, during this period, pachytene spermatocytes were exfoliated from the seminiferous epithelium without completion of meiosis.

Aging↗

PubMedDate not supplied

In vitro chemosensitivity of human soft tissue sarcoma.

Chemotherapy is essential in the treatment of small round cell sarcomas. However, as yet there is no progress concerning the efficacy of chemotherapy in the treatment of other types of soft tissue tumors (STS). The Histoculture Drug Response Assay (HDRA) is an in vitro chemosensitivity test that has a high correlation with clinical response, the usefulness of which has been reported in various kinds of solid tumors. However, there has never been a report on its use in STS until now. In this study, in order to investigate the variation in chemosensitivity in STS, fresh biopsy or surgical samples of STS were tested using the HDRA method. Drug sensitivity testing by HDRA showed that two drugs, ADM and THP, had a significantly higher inhibitory rate than CDDP, IFOS, or VP-16 in the thirty-three soft tissue sarcomas tested. Depending on the morphological type, spindle cell sarcomas were sensitive to THP, which showed significantly higher inhibition rates than CDDP, IFOS, or VP-16. Small round cell sarcomas were relatively sensitive to all of the drugs tested. However the drug sensitivity of pleomorphic cell sarcoma was low except for ADM and THP, while its sensitivity to THP was higher than about 70%. However, there are numerous other soft tissue sarcomas that do not belong to these categories; drug sensitivity testing in each of them and the devising of individualized treatment strategies seems necessary to improve the therapeutic outcome.

Doxorubicin↗

PubMedDate not supplied

A case of systemic lupus erythematosus presenting with rectal ulcers as the initial clinical manifestation of disease.

Gastrointestinal involvement is often seen in patients with systemic lupus erythematosus (SLE). All parts of the gastrointestinal tract may be affected. However, rectal involvement at onset is rare. We describe here a case of SLE in which rectal ulcers due to vasculitis occurred as the initial manifestation of the disease without involvement of any other organ. The ulcers worsened, along with the appearance of lupus nephritis 5 years later When steroid therapy was initiated, there was rapid clinical and radiographic improvement. Our case suggests that rectal ulcer is a rare but important complication of SLE and can represent the initial and sole clinical manifestation of the disease.

Adult↗

PubMedDate not supplied

Necrosis of the small intestine after resection of an abdominal aortic aneurysm.

Small bowel infarction following abdominal aortic reconstruction is extremely rare, and the prognosis remains poor. This report describes a 65-year-old man with small bowel infarction after resection of an abdominal aortic aneurysm. He was successfully treated with resection of the ischemic segment from the distal duodenum to the mid-small bowel and construction of a duodenoileostomy. The postoperative course was uneventful.

Aged↗

PubMedDate not supplied

Pirarubicin might partly circumvent the P-glycoprotein-mediated drug resistance of human breast cancer tissues.

BACKGROUND: Anthracyclines are the first line antitumor agents against breast cancer, and P-glycoprotein (Pgp) is thought to be the main resistance mechanism against these agents. We have evaluated the chemosensitivity of fresh surgical specimens of breast cancer and compared them with their Pgp-expression. MATERIALS AND METHODS: The in vitro chemosensitivity of 65 surgical specimens obtained from 63 patients with advanced breast cancer was assessed by the histoculture drug response assay (HDRA) using doxorubicin (DXR), pirarubicin [(2"R)-4'-tetrahydropyranyladriamycin: THP], and epirubicin (EPIR). Breast cancer tissues were plated onto collagen gel matrix and incubated with 15 micrograms of DXR or EPIR, or 17 micrograms of THP per ml for 7 days with MTT assessed at the endpoint. The efficacy of the agents was evaluated by the inhibition index (I.I.) of the optical density detected by ELISA reader. RESULTS: When 60% or more I.I. was regarded as in vitro sensitive at each cut-off concentration of the drugs, the overall efficacy rates were 60.7%, 48.6%, and 78.6% for DXR, EPIR, and THP, respectively. Fifty-one surgical specimens were evaluated for the immunohistochemical analysis of Pgp and the correlation between the sensitivity to anthracyclines and the expression of Pgp was compared. Pgp was expressed in 23.5% (12/51) specimens and the efficacy of anthracyclines was reduced in Pgp-positive breast cancer tissues, although this reduction was low in THP with a statistically significant difference when comparing with DXR and EPIR. CONCLUSION: The present results suggest that THP might partly circumvent the mdr1/PgP-mediated drug resistance mechanism in human breast cancer tissue and would have some different antitumor spectra on breast cancer comparing with DXR and EPIR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗