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Biomedical subjects

Y Tabuchi

Publications and source records attributed to Y Tabuchi.

At least 19 recordsLinked to original sources

Analysis of proliferative activity using antiproliferating cell nuclear antigen antibody in colorectal cancer.

Using anti-PCNA antibody (PC10), an immunohistochemical study of the expression of PCNA in formalin-fixed and paraffin-embedded materials of colorectal cancer patients was performed and correlation of PCNA expression with clinicopathological findings and DNA ploidy pattern was studied. PCNA labeling rate (PCNA LR) was estimated in the advancing margin of the tumor and ranged from 23.8% to 77.9%. There was a significant difference in lymphatic vessel invasion, liver metastasis and Dukes' stage between the groups with high (> 48.7) and low (< 48.7) PCNA LR (P < 0.05). No differences were seen in tumor size, histological type, lymph node metastasis or DNA ploidy pattern. In patients with younger age, infiltration to neighboring organs, a high degree of venous invasion, and peritoneal dissemination, the frequency of high PCNA LR tended to be higher (P < 0.1). The results above suggest that a high proliferative activity as defined by evaluation of the PCNA LR at the advancing margin of the tumor may be one of the parameters of malignant potential and helpful as a predictor of liver metastasis in colorectal cancer.

Antibodies, Monoclonal

Inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on compound 48/80-induced gastric mucosal lesions in rats.

We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on rat gastric mucosal lesions induced by compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of disodium cromoglycate (DSCG: a mast cell stabilizer), LY171883 (a peptidoleukotriene antagonist) and cimetidine (a histamine H2 receptor antagonist). Subcutaneous administration of C48/80 (1 mg/kg) once daily for four consecutive days produced extensive gastric lesions in the fundic mucosa. DS-4574 (20, 50 and 100 mg/kg/day, oral) and DSCG (200 mg/kg/day, intraperitoneal) treatment markedly inhibited formation of these mucosal lesions, but LY171883 (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did not. Moreover, DS-4574 and DSCG significantly suppressed both hyperhistaminemia and histamine release from rat peritoneal mast cells induced by C48/80. These results indicate that the inhibitory effect of DS-4574 on gastric lesions induced by C48/80 may be related to its mast cell stabilizing action, but to neither its antisecretory nor its peptidoleukotriene antagonistic activity.

Acetophenones

Carcinoembryonic antigen levels of peripheral and draining venous blood in patients with colorectal cancer. Correlation with survival.

Correlations between preoperative carcinoembryonic antigen (CEA) levels of peripheral (p-CEA) and draining blood (d-CEA), the CEA gradient between d-CEA and p-CEA (d-p CEA gradient) levels, and survival after resection of cancer lesions were examined in 94 patients with colorectal cancer. Survival rates of patients with normal p-CEA and d-CEA levels and d-p CEA gradient levels (less than 5 ng/ml) were significantly better than those of patients with abnormal levels (greater than or equal to 5 ng/ml), and the 5-year survival rates were, respectively, 62%, 69%, and 72% in the former and 42%, 41%, and 35% in the latter. The differences in the 5-year survival rates between patients with normal and abnormal d-p CEA gradient, d-CEA, and p-CEA levels were 37%, 28%, and 20%, respectively. Furthermore, the positive rates of d-CEA levels (64%) and d-p CEA gradient levels (48%) were higher than that of p-CEA levels (36%). However, some significant differences in background variables also were found between the respective groups of patients with normal and abnormal p-CEA and d-CEA levels and d-p CEA gradient levels. These results suggest that patients with poor prognoses are examined more effectively by determining their d-p CEA gradient and d-CEA levels than their p-CEA levels, and that CEA may be expressed as a quantitative sum total of various pathophysiologic variables of patients with colorectal cancer but not as an independent prognostic variable.

Carcinoembryonic Antigen

Effect of DS-4574, a novel peptidoleukotriene antagonist with mast cell stabilizing action, on acute gastric lesions and gastric secretion in rats.

DS-4574 is a peptidoleukotriene antagonist with mast cell stabilizing activity. In the present study, we studied the effects of this compound on gastric secretion and various acute gastric lesions in rats. Intraduodenal administration of DS-4574 at doses of 5 to 10 mg/kg significantly and dose-dependently inhibited gastric acid secretion in pylorus-ligated rats, but a further increase in the dose up to 50 mg/kg did not cause any further inhibition. Shay ulceration in response to pylorus ligation was dose-dependently prevented by DS-4574 (10-25 mg/kg, i.d.). Water-immersion restraint stress- and aspirin-induced gastric ulcers were also significantly prevented in a dose-related manner by oral pretreatment with DS-4574 (10-50 mg/kg). The lower doses of DS-4574 (1-10 mg/kg, p.o.) significantly and dose-dependently protected the gastric mucosa against the necrotizing action of either absolute ethanol or concentrated hydrochloric acid, indicating that this compound possesses a potent gastroprotective activity. These antiulcer and gastric protective effects of DS-4574 were more potent than those of cimetidine used as a reference drug. These findings suggest that DS-4574 is useful for peptic ulcer therapy, as well as for the therapy of various allergic diseases, including asthma.

Animals

Ouabain-insensitive, vanadate-sensitive K(+)-ATPase of rat distal colon is partly similar to gastric H+,K(+)-ATPase.

A membrane fraction from rat distal colon contained both ouabain-sensitive and -insensitive K(+)-ATPase activities, which were measured under Na(+)-free conditions. About 38% of the ouabain-insensitive K(+)-ATPase activity was inhibited by vanadate. It was determined whether the ouabain-insensitive, vanadate-sensitive K(+)-ATPase in the colon is similar or identical to gastric H+,K(+)-ATPase. This colonic K(+)-ATPase activity was inhibited completely by monoclonal antibody HK4001, which inhibits the hog gastric H+,K(+)-ATPase activity but not Na+,K(+)-ATPase or Ca(2+)-ATPase. The colonic ATPase activity was inhibited partly by SCH 28080, which is a specific reversible inhibitor of gastric H+,K(+)-ATPase. The colonic ATPase activity was stimulated by low concentrations of K+ (its half-maximal stimulating concentration was 1 mM) and inhibited by high concentrations of K+ (its half-maximal inhibiting concentration was 10 mM), indicating that high and low K+ affinity sites are present in the colonic enzyme as in gastric H+,K(+)-ATPase and that this enzyme is not fully operative under normal physiological conditions. Two other monoclonal antibodies, which inhibit the gastric H+,K(+)-ATPase activity, did not inhibit the colonic K(+)-ATPase activity. The present results suggest that the colonic ouabain-insensitive K(+)-ATPase is partly similar but not identical to the gastric H+,K(+)-ATPase.

Adenosine Triphosphatases

[Cushing's syndrome found during long-term glucocorticoid treatment of rheumatoid arthritis in an elderly woman].

A 69-year-old female patient had been treated with glucocorticoid for eight years because of rheumatoid arthritis. She showed characteristic Cushingoid features such as central obesity, moon face, and fragility of skin and vessels. She was disabled because of spinal compression fracture and muscle weakness. The blood pressure was 186/100 mmHg and the laboratory tests revealed serum K: 2.8 mEq/l, WBC: 15, 510/mm3, total cholesterol: 310 mg/dl. These suggested that she had iatrogenic Cushing's syndrome. After discontinuation of glucocorticoid, however, the serum cortisol level remained high. This fact prompted us to conduct further examinations for Cushing's syndrome. Oral dexamethasone administration did not suppress the plasma cortisol level and a left adrenal adenoma was found on abdominal CT scan. Because of the presence of bleeding diathesis, operation for adenoma was contraindicated. Though we tried to treat her with metyrapone, trilostane or opeprim (OP'-DDD), we had to abandon specific treatment because of severe side effects such as acute adrenal dysfunction and gastrointestinal problems. Decrease in the endogenous cortisol level after metyrapone treatment caused exacerbation of symptoms of rheumatoid arthritis. This is a peculiar case in which the long-term administration of glucocorticoid for rheumatoid arthritis might have concealed Cushing's syndrome, and conversely the increased intrinsic adrenal steroid hormone might have suppressed the activity of the rheumatoid arthritis.

Aged

[Establishment of an experimental model with a high frequency of liver metastasis and recurrence from gastric VX2 cancer: histological analysis of the developmental process of primary and metastatic cancer lesions].

An experimental model with a high frequency of liver metastases and recurrence was established by the non-resection and resection of gastric cancer lesions induced with implanting VX2 cancer cells into the stomach of 35 rabbits. The frequency of liver metastases was 0% on Days 7 and 14, 40% on Day 21 and 60% on Day 28 in the non-resection group. In the resection group, primary lesions were resected on Days 7, 10 and 14, and the metastases were found in all the animals 14 days after the resection on Day 14, though they did not occur in every animal 18 and 21 days after the resection on Days 10 and 7. The metastatic lesions were found in the peri-lobular area, accompanied by cancer emboli in the interlobular veins. Vascular invasion was found in almost all (90%) the primary lesions of animals with liver metastases or recurrence. These results suggest that hepatic micrometastases occur between 10 and 14 days after implantation, and that vascular invasion plays an important role in the formation and extension of liver metastases or recurrence. They also suggest that this model is utilized as a useful tool for studying many aspects of liver metastases or recurrence in gastric cancer.

Animals

[Optimal dose of midazolam as premedicant for combined spinal and epidural anesthesia with midazolam sedation].

Sixty patients who underwent simple total hysterectomy under combined spinal and epidural anesthesia with midazolam sedation, were the subjects of a randomized double-blind comparison of intramuscular midazolam 4, 4.5 and 5 mg, and a dose determined by body weight as premedicants. Similar changes in arterial pressure and heart rate were observed. Furthermore sedation and the value of pulse oximetry on arrival were the same. Besides half the patients were amnesic during the procedure of regional approach. However the dose of premedicant was inversely correlated with the maintenance dose. The reduction of pulse oximetry reading on the induction was smaller, while the requirement of vasopressor occurred earlier following the larger dose of premedicant. In spite of the slower induction, the fall of pulse oximetry reading did not decrease. One hour after incision, the reduction of PaO2 was not dose related. In addition count of leucocyte and the level of blood glucose were unchanged. Premedicant determined by body weight was not correlated with the induction dose and amnesic effect. Our findings suggest midazolam 5 mg intramuscularly is the more preferable dose, but careful attention on arterial pressure is required.

Adult

[The effect of age and gender on the effect of midazolam as intramuscular premedicant].

This study was designed to quantify the appropriate dose of midazolam relating to age and gender for intramuscular premedication. Three hundred and eighty-six consecutive patients (15-83 years) received midazolam (2.5-5.5 mg) with atropine 30 minutes prior to surgery. The perioperative effects of midazolam on arterial pressure as well as heart rate, SpO2 and amnesic effects of regional anesthesia were evaluated in patients divided to 10-year age intervals. Reduction of arterial pressure correlated with preanesthetic values (r = 0.515, P less than 0.01). Especially in those over 60 years, we observed significant reductions. Besides, compared with the males, the reduction was smaller in females. On the arrival at the operating room, this reduction recovered slightly, but preanesthetic hypertension was still attenuated effectively. After age 70, the SpO2 was lower, while the amnesic effect during regional anesthesia was significantly prominent. Amnesic effect correlated more with the dose than the dosage determined by body weight. Younger female patients required larger dosage determined by body weight than the corresponding male. As age increases, dose adjustment should be made mostly on the basis of age, and its adjustment on the basis of body weight should be made with great caution. In this study, we determined the appropriate dose of midazolam, 5 mg for those males younger than 60 years and females below 50 years, and 3-3.5 mg for those older than 80 years.

Adolescent

Colorectal cancer patients with high risk of hematogenous metastasis: correlation with CEA levels in peripheral and draining venous blood during the period of operation.

Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood during the period of operation, and pre- and post-operatively detected hematogenous metastases were examined in 78 patients with colorectal cancer. The metastases were found in 28 patients (HM group), but not found in the other 50 patients (non-HM group). The mean values (43 and 198 ng/ml) and positive rates (61 and 96%) greater than 5 ng/ml of p- and d-CEA levels in the HM group were significantly higher than those (6 and 14 ng/ml, and 22 and 48%, respectively) in the non-HM group. The differences (mean 184 ng/ml and positive rate 49%) of d-CEA levels between both groups were more significant than those (39 ng/ml and 30%) of p-CEA levels. The mean value (155 ng/ml) and positive rate (82%) greater than 5 ng/ml of the gradient between d- and p-CEA levels (d-p CEA gradient) in the HM group were significantly higher than those (8 ng/ml and 34%) in the non-HM group. These results suggest that patients with a high risk of hematogenous metastases are more effectively checked by the determination of d-CEA levels and d-p CEA gradient than of p-CEA levels, and that they are patients with positive d-CEA and d-p CEA gradient levels.

Carcinoembryonic Antigen

Liver metastases induced by implantation of VX2 cancer into the gastrointestine.

An experimental model with a high frequency of spontaneous liver metastases was induced by implantation of VX2 cancer cells into the gastrointestinal walls of 36 rabbits, and the developmental process of primary cancer lesions and metastases was examined histologically. Gastric and colonic cancer lesions showed similar growth patterns in both primary and metastatic lesions: the average diameter of primary lesions enlarged from 0.7-0.8 cm on Day 7 to 2.4-2.8 cm on Day 28. The frequency and average diameter of liver metastases were 25% and microscopically certificated levels on Day 14, 25% and 3 mm on Day 21, and 50% and 8 mm on Day 28 in the gastric wall-implantation group. They were, respectively, 20% and microscopically recognized levels on Day 14, 40% and 2 mm on Day 21, and 80% and 9 mm on Day 28 in the colonic wall-implantation group. Thus, the frequency and diameter of the metastases increased in parallel with the primary cancer growth. Liver metastases occurred only in animals with vascular invasion in primary lesions, though none of the animals with the invasion always showed the metastases. These results suggest that vascular invasion of cancer cells in the primary lesions may be a premise of liver metastases, and that this experimental model may be utilized as a useful tool for studying many aspects of the pathogenesis and/or therapy of the spontaneous liver metastases in gastrointestinal cancer.

Animals

Angiotensin converting enzyme inhibitors suppress the vascular renin-angiotensin system of spontaneously hypertensive rats.

The effects of angiotensin converting enzyme (ACE) inhibitors on the release of angiotensin II (Ang II) from isolated mesenteric arteries of spontaneously hypertensive rats (SHRs) were examined. Delapril, enalapril, and captopril suppressed Ang II release in a dose-dependent manner. After oral treatment with delapril (10 mg/kg/day), enalapril (10 mg/kg/day), and captopril (50 mg/kg/day) for 1 week, the blood pressure of SHRs was significantly reduced in the three groups and 54%, 46%, and 36% decreases in basal Ang II release were observed, respectively, compared with control. However, low-dose captopril (10 mg/kg/day) had no effect on blood pressure or basal Ang II release. These results provide clear evidence that ACE inhibitors suppress vascular renin-angiotensin activity of SHRs, and the possible contribution of the tissue renin-angiotensin system to spontaneous hypertension is suggested.

Angiotensin II

Converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats.

To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.

Angiotensin II

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