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Y Kitsukawa

Publications and source records attributed to Y Kitsukawa.

At least 19 recordsLinked to original sources
PubMed1994

Thapsigargin defines roles of Ca2+ in initial, sustained, and potentiated stimulation of pepsinogen secretion.

The roles of Ca2+ in agonist-induced pepsinogen secretion from guinea pig chief cells remain unclear. We used cholecystokinin octapeptide (CCK-8) or secretin alone or with thapsigargin (TG) to clarify these roles. TG releases Ca2+ from intracellular stores by inhibiting microsomal Ca(2+)-adenosinetriphosphatase (ATPase), thereby depleting intracellular Ca2+ (Cai2+) stores. In most cells TG also causes Ca2+ influx. In the present study, with an extracellular Ca2+ concentration ([Ca2+]o) of 1.5 mM, CCK-8 (0.1 microM) caused a rapid increase in pepsinogen secretion; however, the rate decreased with time. With [Ca2+]o = 0, the initial increase was similar but later secretion was abolished, suggesting that Ca2+ influx was important for sustained secretion. With [Ca2+]o = 1.5 mM, TG (0.1 microM) caused a 2.7-fold sustained increase in in Cai2+ concentration ([Ca2+]i) and a ninefold sustained increase in pepsinogen secretion. With [Ca2+]o = 0, TG caused a transient 66% increase in [Ca2+]i and a 50% increase in pepsinogen secretion. The time course of TG-induced pepsinogen secretion correlated with the time course of TG-induced increases in [Ca2+]i. These data demonstrated that Ca2+ influx itself was a potent stimulant of pepsinogen secretion. We further focused on the roles of increasing [Ca2+]i from Cai2+ stores. With or without extracellular Ca2+ (Cao2+) present, addition of CCK-8 (0.1 microM) 10 min after TG caused no further increase in [Ca2+]i, demonstrating depletion of the inositol 1,4,5-trisphosphate-sensitive pool. The Ca(2+)-mobilizing agent CCK-8 caused no pepsinogen secretion 10 min after TG preincubation, demonstrating that mobilization of Ca2+ from intracellular stores was important in the rapid initial phase stimulation of pepsinogen secretion caused by CCK-8. In contrast, preincubation with TG had no effect on pepsinogen secretion by secretin, an agent that increases adenosine 3',5'-cyclic monophosphate. A 6-min preincubation with TG potentiated the subsequent stimulation of pepsinogen secretion caused by secretin in the presence of Cao2+ where [Ca2+]i remained elevated. However, TG-induced potentiations of secretin-stimulated pepsinogen secretion was abolished once [Ca2+]i had returned to the basal level in the absence of Cao2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Gastric smooth muscle cells possess two classes of endothelin receptors but only one alters contraction.

Endothelin (ET)-like immunoreactivity and ET binding sites are widely distributed in the gastrointestinal tract, and ET causes contraction of stomach muscle strips. To determine whether ETs could interact with gastric smooth muscle cells directly and alter function, we measured binding of 125I-ET-1, 125I-ET-2, and 125I-ET-3 to dispersed gastric smooth muscle cells from guinea pig and their abilities to alter cell length. Each ligand bound in a time- and temperature-dependent manner, which was specific and saturable. Analysis of the dose-inhibition curves of both ET-1 and ET-3 for binding of each ligand indicated the presence of two classes of receptors, one class (ETA receptor) with a high affinity for ET-1 and ET-2 but a low affinity for ET-3, and the other (ETB receptor) with a high affinity for ET-1, ET-2, and ET-3. The ligands were rapidly internalized by both receptors; however, it was greater with ETA receptors. ET-1 stimulated muscle contraction (50% effective concentration approximately 2 nM), whereas ET-3 did not stimulate contraction or cause relaxation. These results demonstrate that gastric smooth muscle cells possess two classes of ET receptors. One type (ETA) has a high affinity for ET-1 and ET-2 and a low affinity for ET-3, and receptor occupation results in rapid ligand internalization and muscle contraction; the other type (ETB) has a high affinity for ET-1, ET-2, and ET-3, and receptor occupation results in a lesser degree of ligand internalization than the ETA receptor and does not alter contractile behavior.

Animals↗
PubMed1992

Effect of ingestion of eicosapentaenoic acid ethyl ester on carrageenan-induced colitis in guinea pigs.

The effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E) on colitis was investigated using a guinea pig model. The technique for preparing a degraded carrageenan with a molecular weight of about 30,000 from commercial iota-carrageenan was first refined. When this degraded carrageenan was fed to guinea pigs, localized ulcerations occurred in the cecum with infiltration of numerous mononuclear phagocytes. Oral administration of 300 mg.kg-1.day-1 of EPA-E for 3 weeks significantly prevented the development of colitis. The amounts of prostaglandin E2, thromboxane B2, and leukotriene B4 released from the cecal mucosa were also measured. The release of prostaglandin E2 and thromboxane B2 was significantly decreased in the animals fed EPA-E compared with those given olive oil or a vehicle alone. In addition, there was a positive correlation between the amounts of these eicosanoids and the degree of ulcer formation. However, there was no difference in the amount of leukotriene B4 among various experimental groups of animals. Furthermore, EPA-E feeding induced a significant decrease in the level of arachidonic acid and a significant increase in that of EPA in peritoneal macrophages. These results suggest that EPA has a prophylactic effect on the development of carrageenan-induced colitis, which may be ascribed in part to reduced eicosanoid production.

Animals↗
PubMed1990

Anaesthesia, not surgical stress, induces increases in serum concentrations of reverse triiodothyronine and thyroxine during surgery.

Effects of anaesthesia on serum concentrations of thyroid hormones during and soon after abdominal surgery were examined in 29 patients undergoing cholecystectomy (n = 22) or removal of gastric cancer (n = 7). They were given one of the following anaesthetics in combination with nitrous oxide in oxygen: epidural bupivacaine, enflurane, pentazocine, ketamine, halothane, epidural bupivacaine and enflurane. Regardless of type of anaesthesia, T3 decreased significantly during and after surgery. T4 and rT3 increased markedly when either enflurane or halothane was given but not with the other anaesthetic agents; they then decreased toward pre-surgical levels after surgery. There was no correlation between changes in rT3 and those in cortisol or free fatty acids. TSH fluctuated little. These results show that the increases in rT3 and T4 during and soon after surgery are due not to surgical trauma but to inhalational anaesthetics such as enflurane and halothane.

Abdomen↗
PubMed1990

Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer.

To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer.

Combined Modality Therapy↗
PubMed1989

Clinical trial with surgery and intraperitoneal hyperthermic perfusion for peritoneal recurrence of gastrointestinal cancer.

To treat six patients with peritoneal recurrence after radical operation for gastrointestinal cancer, an intraperitoneal hyperthermic perfusion (IPHP), combined with surgical resection of recurrent tumors, intestinal by-pass anastomosis, or both, was carried out. Immediately after complete resection of the intraperitoneal recurrent tumors, a 2- to 3-hour IPHP was performed under hypothermic general anesthesia at about 32 degrees C, using a perfusate containing 10 micrograms/ml or 20 micrograms/ml of mitomycin C (MMC) warmed at the inflow temperature of 46.6 degrees C to 46.9 degrees C. The apparatus used for IPHP was designed for intraperitoneal perfusion as a closed circuit. Although five of the six patients had a malignant peritoneal effusion at the time of admission, the effusion disappeared soon after IPHP, and no cancer cell was present in the lavage from Douglas' pouch. The other patient had a recurrent tumor at the anastomotic region after low anterior resection for rectal cancer and complete resection of the recurrent tumor, combined with IPHP, was carried out. One patient with a recurrent gastric cancer died of hepatic metastasis and cancerous pleuritis 5 months after this treatment, and the other five are in good health 12.8 +/- 5.1 months after IPHP. On the other hand, five patients with intra-abdominal recurrent gastric cancer, who received only surgical treatment within the same period of time, died 3.0 +/- 2.1 months after the surgery. Postoperatively, in the six patients with IPHP, transitory hepatic dysfunction, hypoproteinemia, and thrombocytopenia occurred. These results show that IPHP using MMC combined with surgery is a safe, reliable treatment for patients with peritoneal recurrence of gastrointestinal cancer.

Adult↗
PubMed1986

[Study of metabolism in critically ill patients by indirect calorimetry].

Indirect calorimetry was performed in 48 postsurgical critically ill patients including those with multiple organ failure. The patients were divided into two groups, organ failure group (OF group) and postsurgical control group (C group), according to the presence of postsurgical organ failure and severe infection. The following results were obtained. The ratio of energy expenditure to basal energy expenditure, reflecting a degree of hypermetabolism, was 1.44 +/- 0.38 in OF group and 1.26 +/- 0.23 in C group respectively. The change in respiratory quotient by caloric intake was greater in OF group than in C group, indicating that it is more important to maintain an adequate intake for the prevention of increased respiratory work and excess lipogenesis in OF group. When nitrogen intake as amino acids was sufficient (0.1-0.2 g/kg/day), nitrogen balance could be maintained around 0 by a caloric intake being equal to measured energy expenditure. A positive correlation was observed between arterial ketone body ratio reflecting energy charge in hepatocytes and respiratory quotient, indicating that in patients with impaired mitochondrial function in hepatocytes as shown by a decrease in ketone body ratio, glucose cannot be utilized effectively. These results let us conclude that calorimetry is indispensable in the management of critically ill patients and that adequate energy intake should be cautiously determined according to the calorimetry.

Calorimetry↗
PubMed1985

Long-term survivors of colorectal cancer with unresectable hepatic metastases.

Five patients with colorectal cancer and unresectable synchronous liver metastases have survived for over five years at this writing. Four of the five had multiple metastases over both lobes, as diagnosed preoperatively, and the other had multiple metastases in the right lobe not evident preoperatively. The primary foci were excised completely in four patients. For one patient with multiple metastases limited to the right lobe, the postoperative cancer chemotherapy prescribed was intravenous mitomycin C (MMC; 12 mg) and oral ftorafur (a derivative of 5-FU) for a total dose of 291 gm over 63 weeks. The remaining four patients underwent postoperative intra-arterial infusion therapy with the average total dose of 20.5 mg of MMC plus 5600 mg of 5-FU; subsequently, they received protracted chemotherapy with oral ftorafur of 354 gm as an average, with little or no side effects. In these four patients, duration of intra-arterial treatment was an average of 3.2 weeks, and the subsequent oral treatment continued for an average of 85 weeks. Recent hepatic echography and CEA determinations show these patients to be free from intrahepatic metastasis.

Administration, Oral↗
PubMed1984

[Preclinical studies of intra-arterial chemotherapy using mitomycin C microspheres].

Heated albumin microspheres 45 +/- 8 microns dia. containing 5% mitomycin C were infused into rabbit femoral artery to assess the depot effects. MMC levels were measured in the muscle and VX -2 tumor tissues fed by the femoral artery as well as in the drainage vein blood. Furthermore, the histologic changes in the VX -2 tumor and the MMC microspheres entrapped in the arterioles were surveyed microscopically. Drug concentration in the case of MMC microspheres was maintained at high levels in both tissue and venous blood over 4 hours, but in the rabbits infused conventional MMC, drug levels decreased below the assay limitation 2 hours after injection. The microscopic findings 2 weeks later revealed necrotic VX -2 tumor tissue as well as the MMC microspheres remaining in the arterioles .

Animals↗
PubMed1983

Continued in vitro and in vivo release of an antitumor drug from albumin microspheres.

Heated albumin microspheres with an average diameter of 45 +/- 8 microns and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor.

Animals↗
PubMed1983

Clinical evaluation of prolonged chemotherapy combined with induction of hepatic drug-metabolizing enzymes as an adjuvant for treating patients with gastric cancer.

A clinical trial of a protracted adjuvant cancer chemotherapy was carried out on 207 patients with operable gastric cancer, from April, 1977, in the First Department of Surgery, Chiba University Hospital and two closely related hospitals. These patients were given intravenously 0.4 mg/kg and 0.2 mg/kg of mitomycin C on the day of operation and the next day, respectively, and then 16 mg/kg intravenously of Futraful (FT-207) daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 12 mg/kg, for 24 to 36 months after discharge. Two mg/kg of phenobarbital and 30 mg/kg of glutathione were administered randomly to half the number of patients (induction group) to induce hepatic drug-metabolizing enzymes. Significantly higher levels of serum 5-Fluorouracil (5-FU) released from FT-207 were found in the induction group than in the controls. Five-year overall survival rates in the induction and control groups revealed no difference. However, the survival rates in Stage III patients in the induction group were significantly superior in the 3-5 postoperative years, compared to those in the Stage III of the control group, while Stage I, II and IV patients apparently received no benefit from this induction treatment.

Clinical Trials as Topic↗
PubMed1983

[Studies on biodegradable microspheres containing mitomycin C].

For the purpose of enhancing antitumor effects, we prepared heated albumin microspheres containing an antitumor drug, mitomycin C. The biodegradable MMC microspheres which have an average diameter of 45 +/- 8 mum contain approximately 10% of MMC and release in vitro approximately 20% of the MMC over 3-day period. The microspheres were injected into albino rabbit femoral artery of the hind leg into which a VX-2 tumor had been implanted. Peripheral blood levels of MMC were reduced as compared to the conventional MMC group, within 60 minutes after injection. Subsequently in the MMC-microsphere administered rabbits, the level was higher than in the conventional MMC administered group. The survival of VX-2 tumor-bearing rabbits prolonged markedly with MMC microspheres.

Animals↗
PubMed1982

[Immunologic studies on the patients with gastrointestinal cancer--with particular reference to correlation between T lymphocyte and macrophage].

Correlation of monocyte with T lymphocyte or IgG-FcR+ T lymphocyte was studied in 57 gastrointestinal cancer patients and 24 healthy volunteers as control. In 24 volunteers, no correlation was found between them. Forty gastrointestinal cancer patients with curative tumor showed pre-and postoperatively a close correlation between monocyte and T lymphocyte, but there was little correlation, both pre-and postoperatively, between monocyte and IgG-FcR+ T lymphocyte. Seventeen patients with recurrent and/or inoperable gastrointestinal cancer, had a reverse correlation of monocyte with IgG-Fc R+T lymphocyte. It was suggested from these data that mononuclear phagocyte system (monocyte), which fulfils its function as an antigen presentation, has an intimate relationship, both directly and indirectly, to T lymphocyte.

Adult↗
PubMed1981

Further investigations of immunoreactive carcinoembryonic antigen (CEA) in colorectal cancer patients--with particular emphasis on the correlation between immunoreactive CEA levels in tissue, feces and blood.

Immunoreactive carcinoembryonic antigen (IR-CEA) levels in colorectal cancer and mucosal tissues, feces and blood were measured in 14 colorectal cancer patients to study the correlation. IR-CEA levels in colorectal cancer tissues were about 30 times higher than those in colonic mucosal tissues. The correlation coefficient between IR-CEA levels in the tumor tissue and serum was 0.654 (p less than 0.02). We assumed that the total tumor IR-CEA levels were the product of the tumor IR-CEA level, by the estimated tumor weight. The correlation coefficient between the serum IR-CEA level and total tumor IR-CEA level was 0.750 (p less than 0.001). When the patients were divided into two groups with more and less a total tumor IR-CEA level of 65,000 ng, respectively, the statistical difference in serum IR-CEA levels was p less than 0.001. The differences in fecal IR-CEA levels between these two groups, however, are statistically insignificant (p less than 0.3). We assumed that there was a positive correlation between the IR-CEA levels in blood and tumor from the consideration that circulating IR-CEA originates from the metabolic imbalance of its production in colorectal cancer tissues over its degradation in the liver. Moreover, it is essential to consider that the fecal IR-CEA levels may be influenced by the following three factors: the intraluminal direct release of CEA from tumor, no degradation process of CEA in the gut lumen, and the intraluminal transport rate of colonic contents.

Aged↗
PubMed1981

Comparative efficacy of antitumor treatment for liver metastases from colorectal cancer.

A retrospective study of 37 colorectal cancer patients with synchronous liver metastases was made. Of these patents, 6 who had undergone primary tumor removal were treated with considerable success by hepatic arterial infusion of 5-FU and mitomycin C. Ten patients who underwent primary tumor excision were treated by oral chemotherapy using fluorinated pyrimidines. These patients survived about 23 months. On the other hand, 12 patients after primary tumor removal without cancer chemotherapy survived for about 10 months. Six patients without antitumor treatment for both primary tumor and hepatic metastasis survived about 5.2 months. The overall results of this study suggest that intrahepatic arterial infusion is of practical importance for hepatic metastases from colorectal cancer and that oral chemotherapy is indeed effective for selected patients.

Adult↗