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Biomedical subjects

Y Hatta

Publications and source records attributed to Y Hatta.

At least 55 records · Page 3Linked to original sources

Effects of ceruletide on the dopamine receptor-adenylate cyclase system in striatum and frontal cortex of rats chronically treated with haloperidol.

Chronic treatment of rats with haloperidol decanoate (30 mg/kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [3H] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [3H] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 micrograms/kg IP twice a day for 5 days). [3H] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [3H] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol-induced increase of [3H] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 microM or 100 microM) or Gpp(NH)p (1 microM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p-stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

Selective killing of murine leukemic cells by adenosine triphosphate (ATP): a study of the value of autologous bone marrow transplantation.

To assess the value of adenosine triphosphate (ATP) for ex vivo purging of leukemic cells in autologous bone marrow transplantation, its biological effects on the murine leukemic cell lines (WEHI3B and L1210) and normal murine bone marrow hemopoietic stem cells (CFU-C and CFU-S) were studied. After treatment with 4 mM of ATP for 6 h, the number of viable WEHI3B cells decreased to less than 0.1% of that of the control. Furthermore, 3H-thymidine incorporations were also completely inhibited in both WEHI3B cells and L1210 cells. These phenomena were related to the concentration and exposure period of ATP. Treatment of bone marrow mononuclear cells with ATP under the same condition reduced the number of CFU-C, day 9 CFU-S and day 12 CFU-S to only 58.5 +/- 8.7%, 92.6 +/- 8.2% and 83.5 +/- 28.5%, respectively, with no change in the number of marrow nucleated cells. Although the effect of ATP is not entirely specific to leukemic cells, these findings provide evidence that ATP is useful for purging residual tumor cells in autologous bone marrow transplantation.

Adenosine Triphosphate↗

Inhibitory effects of the cholecystokinin antagonist loxiglumide on pancreatic exocrine secretion and pancreatic growth in conscious rats.

The effects of cholecystokinin (CCK) receptor antagonist Loxiglumide (CR 1505) on pancreatic exocrine secretion and growth stimulated by chronic bile-pancreatic juice diversion to the ileum were studied in conscious rats. Pancreatic secretion was measured each day at 0900 h for 7 d. Pancreatic flow and protein output were significantly increased 24 h after bile-pancreatic juice diversion. Protein output increased each successive day, reaching maximal values of 3.6-fold above basal by the 6th and 7th d of chronic bile-pancreatic juice diversion. Fluid output reached maximal values of approx. 3.5-fold above basal by the 3rd d of chronic bile-pancreatic juice diversion. Plasma CCK increased threefold above basal levels after 24 h of bile-pancreatic juice diversion and remained three- to fourfold above basal. Intragastric bolus infusion of CR 1505 (50 mg/kg) on the 7th d of chronic bile-pancreatic juice diversion inhibited pancreatic protein and fluid secretion by 80 and 75%, respectively, 60 min after administration and by 52 and 71%, respectively, 5 h later. Pancreatic wet wt after 7 d of chronic bile-pancreatic juice diversion was significantly increased by 56%, and this was completely suppressed by 50 mg/kg of CR 1505 given intragastrically every 12 h. These rests indicate that the rat with chronic bile-pancreatic juice diversion is a useful model to examine both potency and duration of the action of CCK receptor antagonists and show that CR 1505 inhibits pancreatic exocrine secretion and growth induced by endogenous CCK.

Animals↗

Microangiopathic hemolytic anemia in a graft-versus-host disease patient treated with cyclosporine A and prednisolone.

A 38-year-old male patient with chronic myelocytic leukemia in the first chronic phase underwent bone marrow transplantation (BMT) from an HLA identical sibling. He developed chronic graft-versus-host disease and his condition gradually deteriorated. Fourteen months after BMT, acute progressive anemia, thrombocytopenia, reticulocytosis, increased serum lactic dehydrogenase and increased serum bilirubin were revealed following treatment with cyclosporine A (240 mg/day i.v.), prednisolone (60 mg/day i.v.) and azathioprine (100 mg/day p.o.). Red blood cell fragmentations were also found microscopically. At that time, the serum cyclosporine A trough level was 1,300 ng/ml by the polyclonal antibody RIA method. These symptoms were resolved by discontinuation of cyclosporine A and administrations of aspirin, cilostazol, and dipyridamole as anti-platelet agents. We consider this phenomenon to be micro-angiopathic hemolytic anemia due to a serum high cyclosporine A level which resulted from the concomitant use of cyclosporine A with prednisolone.

Adult↗

[Pulmonary function and exercise tolerance in patients treated with bone marrow transplantation (BMT)].

We assessed pulmonary function and exercise tolerance in 10 BMT patients. Their underlying disorders were as follows; chronic myeloid leukemia 5 cases, acute lymphoblastic leukemia 2 cases, aplastic anemia, acute myeloid leukemia and non-Hodgkin's lymphoma one case each. Their mean age was 26 +/- 9 years old. When the patients were healthy and free of serious complications and anemia, arterial blood gas examination, pulmonary function tests and incremental treadmill exercise test were examined repeatedly. Although %VC and FEV1.0% kept within normal range, PaO2 at rest, %DLCO, VO2max, VO2max/kg and O2-pulsemax remained low at one year after BMT. There were significant correlations between VO2max and O2-pulsemax [r = 0.955 (p < 0.001)], %VC [r = 0.758 (p < 0.02)], VE/VO2max [r = -0.749 (p < 0.02)] and delta SaO2/VO2/kg [r = -0.731 (p < 0.02)], suggesting that exercise intolerance in BMT patients may be based on both cardiac and gas exchange abnormalities. To evaluate cardiac dysfunction, we compared exercise parameters obtained at an exercise level of 75% predicted heart rate max in five age-matched normal subjects to those in six BMT patients who did not demonstrate desaturation during exercise. As a result, the mean values of VO2max/kg and O2-pulse/m2 in BMT patients were significantly lower than those in normal subjects, suggesting that cardiac dysfunction may be due to insufficiency of stroke volume during exercise. It is concluded that exercise intolerance in BMT patients may be mainly due to cardiac dysfunction.

Adolescent↗

[Histological evaluation of intra-arterial infusion and systemic chemotherapy of pancreatic carcinomas].

Histological analyses of 16 autopsies of pancreatic carcinoma [9 cases after intra-arterial infusion chemotherapy (IAC), and 7 cases of systemic chemotherapy (SC)] were performed. Histological effects of chemotherapy (Shimosato) were seen in 15 cases, but less than 5 Grade II a. cases of IAC and 4 cases of SC showed Grade IIa, 3 cases of IAC and 3 cases of SC showed Grade I. The ratio of Grade IIa was almost the same in IAC and SC. But histologically, anaplastic change, sarcomatous change and Bizarre cells, immunohistologically positive to anti-EMA and Vimentin antibody, were dominant in IAC. And clinically, serum tumor markers (CEA, CA19-9) were fewer in almost all the cases in IAC. These results may suggest that the anti-tumor effect of IAC was greater than the histological appearance.

Adenocarcinoma↗

[Changes in collagen and non-collagen protein metabolisms in rat acute pancreatitis induced by ethionine].

Collagen and non-collagen protein metabolisms in rat acute pancreatitis induced by ethionine were investigated with an incorporation study of 3H-proline to those proteins. Enhanced collagen metabolism, which may provide a basis for parenchymal cells regeneration, was observed in the initial phase of acute pancreatitis. This phenomenon was followed by the increase of non-collagen protein metabolism, and histologically mitosis of pancreatic acinar cell was detected concomitantly. Thereafter the enhancement of collagen metabolism continued to the convalescent phase of acute pancreatitis and this change was thought to be related to the resolution and the elimination of excess of collagenous materials and simultaneous increase of non-collagen protein synthesis, which may result in the maturation of acinar cell, was observed. It was thus assumed that the restoration from acute pancreatitis was initiated by the enhanced collagen metabolism with following parenchymal cell regeneration, and was finished by the maturation of acinar cells.

Acute Disease↗

[Development of pancreatic exocrine function including intestinal negative feedback regulation using oral trypsin inhibitor in rats].

To investigate the development of pancreatic exocrine function and intestinal negative feedback regulation with aging in rats, we measured pancreas weight, content of amylase and trypsinogen in the rat pancreas and plasma CCK concentrations, activity of amylase and trypsin in the small intestine at an hour after oral administration of trypsin inhibitor (TI), and also examined amylase secretory response to CCK-8 in the rat pancreatic acini at various ages in vitro. As a result, amylase content per pancreas weight increased with the age and amylase activity in the small intestine at al ages showed a significant increase in TI group compared to controls. Plasma CCK concentrations were elevated after administration of TI at all ages. Amylase release from pancreatic acini stimulated by CCK-8 responded poorly on days 7, then gradually increased with age, showing a biphasic dose response curve with maximal response of 10(-10) M of CCK-8 from 14-day-old to 66-day-old. The results indicated that the mechanism of pancreatic secretory response to TI already might exist at the stage of sucking rat and secretory response to CCK-8 in vitro showed a low response, and developed with age.

Administration, Oral↗

[A case of neuroleptic malignant syndrome developed in liver cirrhosis patient addicted to alcohol].

A 55-year-old man with addiction of alcohol was admitted to our hospital with hematoemesis. After admission, the rupture of esophageal varices was observed and it was treated with endoscopic injection sclerotherapy. On the 3rd hospital day, the patient showed alcohol withdrawal syndrome and therefore haloperidol was administered intramuscularly and intravenously. After a half day of this treatment, high fever, diaphoresis, hypotension, tachycardia, muscular rigidity and tremor developed. With the laboratory data including high serum levels of CK, LDH, GOT and GPT, neuroleptic malignant syndrome (NMS) was suspected. Regardless of intensive care, hepatic failure, DIC and acute renal failure promptly developed, and he died on the 11th hospital day. Neuroleptics may cause serious side effects, such as NMS, when the physical status of patients was deteriorated. Especially in exhausted patient such as our case, even the small dose of neuroleptics caused NMS within short term. Thus, it seemed to be important for clinicians to pay attention to choice of neuroleptics.

Adult↗

[Serum and ascitic phospholipase A2 activities and their heat stabilities in taurocholate induced rat acute pancreatitis].

Serum and ascitic phospholipase A2 (PLA2) activities in rat acute pancreatitis induced by sodium taurocholate (TCA) were investigated with special reference to their heat stabilities and were compared to those in serum of carrageenan induced granuloma in rats. PLA2 activity was measured by previously reported radiochemical method and was separated into two forms, heat stable and labile PLA2, based on the stability to preincubation at 55 degrees C for 5 minutes. While a heat stable PLA2 predominantly increased in ascitic fluid, the elevations of both heat stable and labile PLA2 activities in serum were observed in TCA induced pancreatitis. On the other hand, serum PLA2, which was mainly composed of heat labile form, elevated with the increase of leukocyte count in carrageenan induced granuloma rats. These facts suggested that serum PLA2 activity might increase in acute inflammatory changes other than in pancreatic diseases. And it is assumed that PLA2 derived from extrapancreatic origins as well as pancreatic secretory PLA2 may also contribute to high PLA2 level in acute pancreatitis, because pancreatic secretory PLA2 was generally accepted to be heat stable.

Acute Disease↗

[Collagen metabolism in ethionine induced rat chronic pancreatic injury].

Under low choline diet, chronic pancreatic injury was induced by the intraperitoneal administration of ethionine of 10 mg/100 g body weight, 3 times a week for sequential 8 weeks in rats and histological changes, pancreatic hydroxyproline and collagenase activity were studied. Histologically, acute inflammatory changes were observed mainly in the early days, and infiltration of fibroblastoid cells was increased on the 28th day. Then, fat droplets deposition became remarkable. Though hydroxyproline concentration increased gradually after the injection of ethionine and showed maximal level on the 28th day when the slight fibrosis was noticed, it was decreased on the 56th day when collagenous tissue was replaced by fat droplets. On the other hand, collagenase activity showed two peaks, in the early phase and on the 56th day, and it showed bottom level on the 28th day. Collagen synthesis relatively dominated over degradation on the 28th day. It is suggested that the unbalance of collagen metabolism between synthesis and degradation may result in fibrosis.

Animals↗

[Changes of the urinary excretions of hydroxyproline and fibronectin fragment in acute pancreatitis].

Urinary excretions of hydroxyproline and fibronectin fragment (FN fragment) were serially investigated in the patients with acute pancreatitis or acute exacerbation of chronic pancreatitis. While urinary excretion of FN fragment showed the maximal level on the first day of admission, high levels of urinary hydroxyproline were observed on the second to fifth day. As to the changes in the individuals, peak level of urinary FN fragment always preceded that of hydroxyproline. And it was assumed that the elevation of FN fragment excretion on the early phase of pancreatitis reflected tissue damages of pancreas itself and complicated organs, and following elevation of hydroxyproline showed enhanced collagen metabolism induced by acute inflammation and tissue damage. According to the severity of pancreatitis, urinary excretion of FN fragment on the first day increased, and it was therefore suggested that urinary FN fragment would be one of the parameters for the assessment of the severity of acute pancreatitis.

Acute Disease↗

[The effectiveness of CDDP in metastatic adenocarcinoma with unknown origin].

A 28-year-old man with inoperable metastatic adenocarcinoma in the retroperitoneum was referred to our hospital for a further evaluation for its origin. The tumor was measured 80 x 107 mm by abd. U.S. and showed papillary adenocarcinoma, histologically. Chemotherapy with intravenous administration of CDDP at the dose of 80 mg/m2 for 6 times at 2-3 week intervals was started, and CDDP concentration of binding-form and free-form in serum and urine were measured in time course. The tumor has reduced for 29 weeks after the discontinuance of CDDP. Free-CDDP, which was thought to have an anticancerous effect, immediately went up high levels in serum and rapidly excreted to urine, while total-CDDP in serum remained in high concentration for more than 10 weeks. Thus it was suggested that anticancerous effect of CDDP could not be contributed only to free-CDDP and the mechanism of CDDP will be clarified by the elucidation of metabolism of both free and total CDDP, especially in the tumor tissue.

Adenocarcinoma↗

[Studies on heat stability of phospholipase A2 in human serum].

Heat stability of human serum phospholipase A2 (PLA2) was investigated comparing to those of porcine pancreatic PLA2 (p-PLA2) and PLA2 in human duodenal aspirate. PLA2 activity was measured by radiochemical method using phosphatidylcholine as a substrate. While the activities of PLA2 in duodenal aspirate and p-PLA2 solution were not influenced by the heat treatment of 55 degrees C, PLA2 activity in normal human serum was remarkably decreased by the preincubation at 55 degrees C for only 5 minutes. From the result of preincubation temperature, serum PLA2 activity began to decrease at 50 degrees C and the decrease of PLA2 activity was remarkable above 55 degrees C of preincubation temperature. As a conclusion, PLA2 in human serum was consisted of heat labile and stable form, and latter was thought to be derived from pancreas. Thus serum PLA2 level should be assessed with consideration of incubation temperature of PLA2 assay and whether pretreatment of heating was done or not.

Animals↗

[Successful ATG and bolus methylprednisolone therapy towards severe aplastic anemia with splenomegaly].

A 22-year-old female patient with severe aplastic anemia was treated by ATG.bolus methylprednisolone therapy. After the therapy, anemia and thrombocytopenia began to recover within a month. The frequency of blood transfusion decreased thereafter. Since anemia due to splenomegaly was certified, bolus methylprednisolone therapy was performed in good response. Suppressor T-cells towards hemopoiesis were confirmed in this case, and hemopoietic potential was augmented by ATG.bolus methylprednisolone therapy. In spite of discontinuation of any therapy in 1986, she is being in good health more than five years.

Adult↗