Biomedical subjects

S Arima

Publications and source records attributed to S Arima.

149 records · Page 9Linked to original sources

PubMedDate not supplied

Isolated juxtaglomerular apparatus as a tool for exploring glomerular hemodynamics: application of microperfusion techniques.

The balance of the vascular tone between afferent and efferent arterioles (AAs and EAs, respectively) is a crucial determinant of glomerular hemodynamics. Thus, it is important to study the mechanisms that control their vascular tone to understand renal physiology and pathophysiology. In order to directly study the mechanisms that regulate their vascular tone, we have developed several in vitro microperfusion preparations of these arterioles, which have the advantage of allowing us to observe the arteriolar diameter directly in the absence of systemic hemodynamic and hormonal influences. In the AA but not EA, we have directly demonstrated the presence of two intrinsic mechanisms, namely the myogenic response and macula densa-mediated tubuloglomerular feedback, that play an important role in the control of vascular tone. We also found that both mechanism-induced constrictions of AAs can be modulated by endogenous nitric oxide. In addition, several humoral factors (such as angiotensin II or prostaglandins) play an important role in the control of AA tone. On the other hand, angiotensin II is one major factor that controls the vascular tone of the EA. We have found that the vasoconstrictor effect of angiotensin II on EAs is modulated by prostaglandins produced by the upstream glomerulus. Thus, this may be a mechanism whereby the glomerulus controls its own capillary pressure by releasing prostaglandins and thereby adjusting the resistance of the downstream EA. These varying mechanisms regulating AA and EA tone play an important role in the precise control of glomerular hemodynamics.

Animals↗

PubMedDate not supplied

Vasodilation mediated by angiotensin II type 2 receptor is impaired in afferent arterioles of young spontaneously hypertensive rats.

Renal vasoconstrictor action of angiotensin II (Ang II) is exaggerated in the spontaneously hypertensive rat (SHR) before development of hypertension. We have recently demonstrated that in the rabbit afferent arteriole (Af-Art) activation of the AT2 receptor causes vasodilation, which modulates the vasoconstrictor action of Ang II mediated by the AT1 receptor. In this study, we tested the hypothesis that vasoconstrictor action of Ang II is exaggerated in SHR Af-Arts due to an impaired function of the AT2 receptor before development of hypertension. Af-Arts were microdissected from the superficial cortex of 4- to 5-week-old SHR or age-matched Wistar Kyoto rats (WKY), and perfused at 60 mm Hg in vitro. Ang II (10(-11) to 10(-8) M) decreased the luminal diameter of Af-Arts of both strains in a dose-dependent manner. However, the constriction was stronger in SHR; at 10(-10) M, the diameter decreased by 34 +/- 4% in SHR (n = 6) compared to 18 +/- 3% in WKY (n = 6; p < 0.01). Pretreatment with PD123319 (PD), an AT2 receptor antagonist, significantly augmented Ang II-induced constriction in WKY but not SHR Af-Arts; at 10(-10) M, the diameter now decreased by 41 +/- 5 and 37 +/- 1% in SHR (n = 6) and WKY (n = 6), respectively. Thus, blockade of the AT2 receptor abolished the difference in Ang II action on Af-Arts between strains. Moreover, with the AT1 receptor blockade Ang II caused dose-dependent dilation of preconstricted Af-Arts only in WKY (27 +/- 5% at 10(-8) M, n = 5), and the dilation was abolished by simultaneous treatment with PD. In contrast, no such dilation was observed in SHR Af-Arts. These results suggest that activation of the AT2 receptor modulates AT1 receptor vasoconstriction in WKY Af-Arts, while impaired modulatory function of AT2 receptor may play a role in the exaggerated vasoconstrictor action of Ang II on the Af-Art of prehypertensive SHR.

Angiotensin II↗

PubMedDate not supplied

Do the expression of CD44, apoptosis and thymidylate synthase inhibition rate correlate with the efficacy of chemotherapy in colorectal cancer?

BACKGROUND: Tegafur-uracil(UFT;TAIHO Pharmaceutical Co.Ltd, Tokyo, Japan) is commonly used to treat digestive cancers. However, the inhibitors of metastasis in this agent have not been fully examined. To investigate a cell adhesion molecule, CD44, which may very well contribute to the pathogenesis of metastasis, we examined the association of CD44 and the thymidylate synthase inhibition rate(TSIR) with prognosis, and examined the expression of apoptosis in patients who were administrated tegafur-uracil before surgery for colorectal cancer. MATERIALS AND METHODS: This study included 66 patients who underwent curative resection of colorectal cancer. In these patients, tegafur-uracil(600 mg) was orally administered every day for 3 to 7 days before surgery, and Tegafur-uracil (400 mg) was orally administered every day for 2 years after surgery. CD44 and apoptosis were detected immunohistochemically and by the TUNNEL method, respectively. The TSIR was calculated from the total TS level, and free TS levels by modified Spears' method using fresh tumor tissue specimens. RESULTS: The TSIR of non-recurrent patients was significantly higher than that of recurrent patients(p < 0.05). The 5-year survival rate in CD44-low grade positive/negative patients (81.6%) was significantly higher than that in CD44-high grade positive patients (46.4%) (p < 0.005). The 5-year survival rate in apoptosis-high grade positive patients (89.7%) was significantly higher than that in apoptosis-low grade positive/negative patients(46.4%) (p < 0.001). With respect to the relationship between CD44 and apoptosis, the proportion of apoptosis-high grade positive patients among CD44-low grade positive/negative patients (55.3%) was significantly higher than that among CD44-high grade positive patients(28.6%) (p < 0.05). In the multivariate analysis, the CD44 expression was suggestive of an independent prognostic factor. CONCLUSION: Based on our results for TSIR, Tegafur-uracil may induce apoptosis of tumor cells in patients by the inhibition of thymidylate synthase. It was suggested that CD44 expression could be used as a possible independent predictor of survival. In addition, it was suggested that UFT, via the inhibition of CD44 expression caused the inhibition of distant metastasis.

Aged↗

PubMedDate not supplied

Immunohistochemical expression of thymidylate synthase as a prognostic factor and as a chemotherapeutic efficacy index in patients with colorectal carcinoma.

BACKGROUND: We assessed the importance of Thymidylate Synthase (TS) expression as a prognostic factor and as an index of therapeutic efficacy in patients with colorectal carcinoma. PATIENTS AND METHODS: TS expression in 66 patients with colorectal carcinoma was immunohistochemically assessed using the anti-TS antibody. TS expression, TS activity, clinicopathological characteristics and survival were evaluated and the correlation among them was studied. RESULTS: The cases studied included 53 patients with low grade positive/negative and 13 patients with high grade positive TS expression. TS levels were 8.69 +/- 10.01 pmol/g and 14.82 +/- 11.38 pmol/g, respectively. There was not correlation between clinicopathological characteristics and TS expression. Considering TS expression, the 5-year survival rate was significantly better for the 75.5% of the patients with low grade positive/negative TS than for the 38.5% of the patients with high grade positive TS (p < 0.01). CONCLUSION: The immunohistochemical expression of TS should be further investigated as a prognostic factor of survival and as an index of chemotherapeutic efficacy in colorectal carcinoma.

Antibodies↗

PubMedDate not supplied

Endogenous TNF induction therapy using rTNF-SAM2 in patients with pulmonary metastases from colorectal cancer.

BACKGROUND: Distant metastases from colorectal cancer are generally refractory to conventional therapies, with the exception of surgical resection. The aim of this study was to evaluate the clinical application of endogenous TNF induction therapy by using a mutant TNF (rTNF-SAM2) as a primer in endogenous/exogenous TNF therapy (EET therapy) in patients with pulmonary metastases from colorectal cancer. METHODS: The subjects were 17 patients, 5 of whom underwent EET therapy alone and 12 of whom underwent EET therapy and the administration of anticancer agents. RESULTS: Partial response was observed in 6 patients (50%) who underwent EET therapy with anticancer agents. In seven (53.8%) of 13 patients who showed a high serum CEA value, their CEA levels were considered to be improved. Severe toxic effects occurred in 3 of the patients studied (17.6%). The mean survival was 26.0 months among those with a partial response and 16.6 months among those with no change. No significant difference was observed between these two groups. Histological assessments indicated that tumor necrosis, fibrosis and cellular infiltration tended to intensify in cases treated with EET therapy compared with the cases who received surgery alone. CONCLUSION: EET therapy with anticancer agents is well-tolerated and effective for pulmonary metastases from colorectal cancer.

Adult↗