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Biomedical subjects

Y Tabuchi

Publications and source records attributed to Y Tabuchi.

At least 37 records · Page 2Linked to original sources

Endothelin modulates L-NG-nitroarginine-induced enhancement of vasoconstriction evoked by norepinephrine.

The interaction of endothelin-1 (ET-1), a novel vasoconstrictor peptide synthesized according to the encoded amino acid sequence, with L-NG-nitroarginine (NOARG), an L-arginine-reversible inhibitor of endothelium-derived relaxing factor (EDRF) on adrenergic receptors, was investigated. Male Sprague-Dawley rats were used in this study. Mesenteric arteries were isolated and perfused with Krebs-Ringer solution at a constant flow rate. The vasoconstrictor responses to exogenous norepinephrine were determined. Low concentrations of ET-1 (10(-11) and 10(-10) M) potentiated the pressor responses to norepinephrine without affecting the baseline perfusion pressure. Simultaneous NOARG (10(-5) M) infusion with ET-1 (10(-11) M) into the mesenteric arteries caused further enhancement of the pressor responses to exogenous norepinephrine (200 ng) without affecting the baseline perfusion pressure: 126 +/- 15% to 262 +/- 45% (p less than 0.05, vehicle control: 100%). This facilitatory effect of NOARG on the pressor response to norepinephrine was attenuated with L-arginine (10(-4) M) infusion, but not D-arginine. These results suggest that ET, one of the endothelium-derived vasoconstricting factors, interacts with EDRF to modulate the tone of resistance vessels.

Animals

[Studies on the clinical evaluation of tissue polypeptide antigen (TPA) levels in the peripheral and draining venous blood of gastric cancer patients].

Correlation with TPA levels of peripheral (p) and draining (d) venous blood, and 11 histopathologic variables, postoperative recurrence and survival was examined in 40 patients with gastric cancer. Elevation of d-TPA levels was correlated with tumor location, size, macroscopic type, invasive layer of gastric wall, venous invasion, node and liver metastases and stage classification, though elevation of p-TPA levels was correlated only with liver metastasis. No significant difference of p-TPA levels was found between the patients with and without cancer recurrence. d-TPA levels (mean 1318U/l and positive rate greater than 726U/l of mean +/- 2SD in patients with benign diseases, 59%) of the former were significantly higher than those (518U/l and 15%) of the latter. Correlation between d-TPA levels and recurrent sites was not found. Most of the patients with hematogenous recurrence showed the elevated p-TPA levels, but none of the patients with local recurrence revealed the elevation. Survival in both patients with non-elevated p- and d-TPA levels was significantly better than in patients with the elevated levels. These results suggest d-TPA levels are more closely correlated with histopathologic variables and postoperative recurrent rates than p-TPA levels, preoperative determination of p- and d-TPA levels is useful for the estimation of the postoperative prognosis and patients with elevated p- and d-TPA levels should be clinically treated as patients with high recurrence and poor prognosis.

Antigens, Neoplasm

[Patients with high risk of hematogenous metastasis and recurrence in colorectal cancer: correlation with histopathologic variables and tumor markers, CEA and CA19-9, in peripheral and draining venous blood].

Correlations of hematogenous metastasis with histopathologic variables, preoperative CEA and CA19-9 levels in peripheral (p) venous blood, and those in draining (d) venous blood were examined in 78 patients with colorectal cancer. Out of 10 histopathologic variables, location of venous invasion was most significantly correlated with hematogenous recurrence: the rate (11%) of v0 and/or sm-pm v(+) in 50 patients without the recurrence was significantly lower than that (89%) in 28 patients with the recurrence. On the other hand, the rate (68%) of ss-extra(+) in the latter was significantly higher than that (32%) of the former. The mean values (6 and 14 ng/ml) and positive rates (22 and 48%) greater than 5 ng/ml of p and d-CEA in 50 patients without the recurrence were significantly lower than those (14 and 189 ng/ml, 48 and 96%) in 28 patients with the recurrence. Patients with d-p CEA gradient greater than 5 ng/ml were found, respectively, in 34% of the former and 82% in the latter. The mean value (982 U/l) and positive rate (94%) greater than 37 U/ml of CA19-9 in peripheral blood of 28 patients with the recurrence were significantly higher than those (25 U/ml and 11%) of 50 patients without the recurrence. These results suggest that colorectal cancer patients with high risk of hematogenous metastasis and recurrence are the patients with ss-extra(+), the values of d-CEA, especially d-p CEA gradient, greater than 5 ng/ml and with p-CA19-9 value greater than 37 U/ml.

Antigens, Tumor-Associated, Carbohydrate

[Comparison of midazolam and hydroxyzine as premedicants for combination of spinal and epidural anesthesia with midazolam sedation].

Midazolam 4 mg i.m. (Group M, n = 15) was compared with hydroxyzine 50 mg i.m. (Group H, n = 13) in a randomized double-blind study, as premedicants for patients undergoing simple total hysterectomy under combination of spinal and epidural anesthesia with midazolam sedation. Reduction of anxiety and amnesic effects about procedure under regional anesthesia with sufficient patient co-operation were greater following midazolam. The doses for intraoperative sedation of midazolam and pentazocine were the same in both groups. Mean doses of midazolam 2 mg and pentazocine 6 mg were required to induce sleep. Maintenance doses of midazolam and pentazocine were 3.7 and 11.4 mg.hr-1, respectively. No patient had recall of surgical procedure. Midazolam did not delay the postoperative resedation which lasted about 2 hours. The decrease in O2 saturation by pulse oxymetry is significant in Group M (4.5%) than Group H (2.7%). Nevertheless two patients in each group required oxygen 2 liter.min-1 via a nasal catheter. These results indicate that premedication by midazolam is more effective for procedures under regional anesthesia.

Adult

Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood.

The correlation between CA19-9 levels of portal and peripheral venous blood, and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases. Immunohistochemically, CA19-9 was found in 33 (62.5%) of 53 primary lesions. The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer, although the cancer cells in veins showed little or no CA19-9. There was little or no antigen in the cancer cells in veins, lymphatics, or metastases of 20 CA19-9 nonlocalized primary lesions. Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood. CA19-9 levels of portal blood (mean, 76.4 U/ml; positive rate, 33.3%) were not different from those of peripheral blood (mean, 91.5 U/ml; positive rate, 33.3%). Additionally, the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases, and every patient without the invasion showed no elevation of the antigen. These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics, but not by the hematogenous portal system.

Adenocarcinoma

Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia.

To elucidate further the contribution of endothelin into endothelium-dependent vasoconstriction evoked by hypoxia, we observed endothelin release during hypoxia. Endothelin was detectable in perfusate from mesenteric artery. Immunoreactive endothelin was confirmed as endothelin-1 by a reverse phase-HPLC. Endothelin release increased 4.1 +/- 1.3 to 12.4 +/- 2.0 pg/30 min without changing perfusion pressure. Thirty minutes of hypoxia stimulated endothelin release by 71 +/- 11% (P less than 0.05) and was associated with an elevation of perfusion pressure. These results suggest that endothelin contributes to endothelium-dependent vasoconstriction by hypoxia in mesenteric artery and may play an important role in the local peripheral vascular tone.

Animals

The presence of H+,K(+)-ATPase in the crypt of rabbit distal colon demonstrated with monoclonal antibodies against gastric H+,K(+)-ATPase.

Indirect evidence indicates the presence of an active H+/K+ antiporter for the secretion of acid in the distal colon. It was examined whether the H+/K+ antiporter in the rabbit distal colon was hydrogen-potassium-stimulated adenosine triphosphatase (H+,K(+)-ATPase), which acts as a proton pump in the gastric mucosa. For this purpose, four monoclonal antibodies against hog gastric H+,K(+)-ATPase were raised. Three monoclonal antibodies dose-dependently inhibited the ouabain-insensitive gastric ATP-ase activity. Antibody HK4001 completely inhibited the ATPase activity. In indirect immunofluorescence studies, all four monoclonal antibodies stained H+,K(+)-ATPase in gastric mucosae of various animal species. Two monoclonal antibodies including antibody HK4001 cross-reacted with H+,K(+)-ATPase located in crypts of the transverse and descending colon and rectum of rabbits. Because the other two antibodies did not cross-react with the H+,K(+)-ATPase in the colon, this colonic enzyme is similar but not identical to gastric H+,K(+)-ATPase. On the other hand, HK4001 and SCH 28080 did not inhibit ouabain-sensitive K(+)-dependent ATPase activity in the guinea pig distal colon, and the antibodies did not stain the enzyme in the tissue. Therefore, ouabain-sensitive H+/K+ antiporter in the guinea pig is not similar to ouabain-insensitive rabbit colonic H+,K(+)-ATPase.

Adenosine Triphosphatases

Blood pressure response to dietary calcium intervention in humans.

Epidemiological and experimental studies have suggested that dietary calcium deficiency may lead to the development of hypertension. This article reviews findings in human trials on calcium intervention with special reference to the responses of blood pressure and biochemical variables. Calcium supplementation consistently resulted in decreased blood pressure in a subset of hypertensive and normotensive subjects, but led to increased blood pressure in some hypertensive patients. The variable blood pressure responses to calcium supplementation could not be predicted on the basis of routine biochemical parameters and appeared to be due to differences in the backgrounds of the subjects and/or the design and size of the trials. It is concluded that further studies are required on the hypotensive effect of calcium supplementation.

Blood Pressure

Hereditary motor and sensory neuropathy type 1 (HMSN1) associated with cranial neuropathy: an autopsy case report.

A family with hereditary motor and sensory neuropathy type 1 (HMSN1) is reported. Three patients suffered only pupillary abnormality, two patients showed Adie's syndrome and peripheral neuropathy, and one had cranial neuropathy. Adie's syndrome and severe peripheral neuropathy. Autopsy of the latter revealed reduction of myelinated nerve fibers in the trigeminal, facial and hypoglossal nerves. There was extensive degeneration of the posterior column of the spinal cord. At the anterior horns, loss of motor neurons was observed, particularly at the lumbar level. The anterior and posterior roots showed loss of myelinated fibers. HMSN1 is only rarely associated with cranial neuropathy, and this is probably the first autopsy-proved case.

Adie Syndrome

Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats.

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The vasoconstrictor responses to periarterial sympathetic nerve stimulation and exogenous norepinephrine were determined. Infusion of endothelin-1 increased the baseline perfusion pressure dose dependently to similar extents in the two strains. A subpressor dose of endothelin-1 (10(-10) M) enhanced the pressor response to norepinephrine; its effect was greater in WKY rats than in SHR. Endothelin-1 (10(-12) to 10(-10) M) attenuated the pressor response to sympathetic nerve stimulation, and the degree of inhibition tended to be less in SHR than in WKY rats. Higher doses (3 x 10(-10) and 10(-9) M) of endothelin-1 enhanced the pressor response to nerve stimulation in both WKY rats and SHR. Endothelin-1 inhibited norepinephrine release from rat mesenteric arteries; the inhibition was significantly less in SHR than in WKY rats. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines, whereas it inhibits presynaptic adrenergic neurotransmission. Thus, endothelin can interact with the neuroeffector junction in addition to having a vasoconstricting effect in peripheral vessels. The difference in the mode of modulation by endothelin at the vascular neuroeffector junction in SHR from that in WKY rats might explain the maintenance of hypertension.

Animals

[Immunohistochemical study of the localization and distributional patterns of CA 19-9 and CEA in primary and metastatic nodal lesions of gastrointestinal cancer].

The localized and distributional patterns of CA 19-9 and CEA have been immunohistochemically examined in 22 nodal metastasis from antigen-producing gastrointestinal cancers. CA 19-9 and CEA were found in 95% and 45% of these metastasis respectively. The same distributional and localized patterns in the metastasis as were found in the primary lesions amounted to 77% and 41% for CA 19-9, and 45% and 27% for CEA, respectively. These results suggest that the capability of producing CEA is absent or suppressed in the metastatic lesions, whereas the capability lesion but also in the metastatic lesions as well.

Antigens, Tumor-Associated, Carbohydrate

[Intermittent arterial chemoembolization in liver tumor using degradable starch microspheres].

Intermittent intra-arterial chemoembolization together with degradable starch microspheres (DSM) and anti-cancer agents (Adriamycin or Mitomycin C) was performed in 4 primary and 6 metastatic liver cancers through a totally implantable arterial infusion port system. For the HCC patients, the response was classified as 2 CR, 2 PR. In the metastatic tumor patients, the response was 1 CR, 2 PR, 1 NC and 2 PD. The overall response was 70%. This treatment is considered very effective, but a delayed mortal side-effect was confirmed in 2 patients with metastases. The histopathological finding of 1 case suggested that the reason for death was severe liver damage by prolonged retention of anti-cancer agent by the liver. It seems likely that sequential DSA evaluation of tumor vascular bed and blood flow recovery allows avoidance of such adverse reactions, as we have attempted it in the present study.

Adult

Endothelin activates the vascular renin-angiotensin system in rat mesenteric arteries.

The effects of endothelin on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries by measuring vascular renin activity and angiotensin II released into the perfusate. Infusion of endothelin (10(-9)M and 10(-11)M) increased the vascular renin activity and angiotensin II release. Pretreatment with nicardipine (10(-6)M), a calcium channel blocker, significantly suppressed these effects of endothelin. These results suggest that endothelin activates the vascular renin-angiotensin system via intracellular calcium metabolism. Vascular angiotensin II produced by endothelin may modulate the local effect of endothelin on the resistance vessels.

Angiotensin II

[CEA levels of draining venous blood and draining-peripheral CEA gradient in colorectal cancer patients: correlation with postoperative survival].

Correlation between preoperative CEA levels in draining venous blood (d CEA) and draining-peripheral (d-p) CEA gradient, and postoperative survival of 94 patients with colorectal cancer patients was examined. The positive rates of d CEA and d-p CEA gradient greater than 5 ng/ml (55.9% and 37.2%) in 59 alive patients were significantly (p less than 0.05) lower than those (77.1% and 57.1%) in 35 patients died of cancer recurrence within 4 years. Survival curve of the patients with positive d CEA and d-p CEA gradient were significantly (p less than 0.01) lower than those of the patients with negative d CEA and d-p CEA gradient. Survival curve of the patients with d-p CEA gradient greater than 10 ng/ml was significantly (p less than 0.001) lower than that of the gradient less than 10 ng/ml, and 4-year survival rates were 37.5% in the former patients and 68.3% in the latter patients. These results suggest that d CEA and d-p CEA gradient may be used as prognostic indicators of colorectal cancer patients. Clinically, the patients with positive d-p CEA gradient greater than 10 ng/ml are necessary to be treated as patients having very poor prognosis.

Carcinoembryonic Antigen

[Mitotic activity of cancer in the colorectum: correlation with histopathologic variables and survival].

An in vivo stathmokinetic method was used to analyze the mitotic activity (MA) of cancer cells from 43 colorectal cancer patients in order to examine the correlation between MA, and histopathologic variables and survival of patients. Significant relationship was not found between MA and 7 variables of cancer lesions consisting of tumor size, macroscopic type, depth of invasion, venous and lymphatic invasion, node metastasis and stage. However, tumor differentiation was significantly related to MA: mitotic indices (MI, mean +/- S.D.) were 20.7 +/- 8.8% in 37 differentiated adenocarcinomas and 38.2 +/- 8.4% in 6 undifferentiated adenocarcinomas. The latter was significantly (p less than 0.001) higher than the former. The survival curve of 23 patients with low MA (MI less than 20.0%) was significantly (generalized Wilcoxon test, Z = 2.17, p less than 0.05) better than that of 17 patients with high MA (MI greater than 20.0%), though difference in 2 (lymphatic invasion and tumor differentiation) out of 12 variables of background was found between them. The survival curve of 17 patients with differentiated adenocarcinoma of low MA also was significantly (Z = 1.98, p less than 0.05) better than that of 17 patients with differentiated adenocarcinoma of high MA, even though no significant difference of 12 variables in background was found between them. These results suggest that MA of cancer cells may be independent of prognostic variables of cancer lesions and may be utilized as a new prognostic variable of colo-rectal cancer.

Adenocarcinoma

Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery.

The effect of endothelin(ET) on adrenergic neurotransmission was examined in isolated perfused rat mesenteric arteries. Porcine ET(10(-12) to 10(-10)M) attenuated the pressor response to sympathetic nerve stimulation (NS). It also stimulated the release of prostaglandin E2 (PGE2), but its inhibition of the pressor response to NS was not affected by indomethacin treatment. ET also caused dose-dependent inhibition of [3H]norepinephrine release during NS. Higher doses of ET rather enhanced the pressor response to NS. These results suggest that ET inhibits presynaptic adrenergic neurotransmission without mediation of PGE2, while it potentiates the responsiveness of the postsynaptic alpha-adrenergic receptor. Thus ET appears to act directly on the neuroeffector junction as well as on the peripheral vasculature.

Adrenergic Fibers