Improved insulin release from a bioartificial pancreas using mesh-reinforced polyvinyl alcohol hydrogel tube: immobilization of islets in agarose gel.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M Imamura
Publications and source records attributed to M Imamura.
Invisible axion search in 139La M1 transition.
Explore the source record for details and available documents.
Journal Article↗
Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice.
BACKGROUND: Cholecystokinin is thought to be an important factor regulating the growth of human pancreatic cancers. The study was designed to evaluate the effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of human pancreatic cancer. METHODS: Human gastrointestinal cancer xenografted tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two pancreatic cancers) were transplanted into nude mice. The mice were given CR1505 at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and the tumor volumes before and after treatment were compared. In vitro effects of CR1505 were assessed by measuring the DNA synthesis (3H-thymidine incorporation). RESULTS: CR1505 inhibited the growth of the two pancreatic cancer lines but did not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreatic cancer-specific inhibitory effect of CR1505 was retarded by exogenously administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by oral administration of the trypsin-inhibitor camostate (FOY-305) in both pancreatic cancer lines. CONCLUSIONS: These results suggest that CR1505 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative effect may not necessarily be dependent on its cholecystokinin-antagonism but may be mediated through the proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.
Animals↗
Fluorocyclopropyl quinolones. 1. Synthesis and structure-activity relationships of 1-(2-fluorocyclopropyl)-3-pyridonecarboxylic acid antibacterial agents.
A series of 1-(2-fluorocyclopropyl)-3-pyridonecarboxylic acids has been prepared. These derivatives are characterized by having a fluorine atom at the 2-position on the cyclopropane ring as the N1 substituent and consist of both cis and trans stereoisomers. Structure-activity relationship studies indicate that the cis derivatives are more potent against Gram-positive bacteria than the corresponding trans counterparts, but the difference in potency against most Gram-negative bacteria is much smaller. The inhibitory effect of compounds 4, 5, 26, 27, 38, and 39 on supercoiling activity of DNA gyrase obtained from E. coli KL-16 correlated with their MICs against the same strain and also depend on their (26, 27, 38, 39) stereochemistry. Introduction of a fluorine atom on the cyclopropyl group resulted in the reduction of lipophilicity compared with the corresponding nonfluorinated quinolones.
Anti-Infective Agents↗
[A case of acute suppurative thyroiditis associated with thyroid papillary carcinoma].
A sixty-one-year-old female was admitted to our hospital in October 1988 because of fever and a right neck mass associated with redness and tenderness. The size of the thyroid mass had gradually increased over 3 months. Two masses were detected in the thyroid by ultrasonography and MRI. She has positive thyroid autoantibodies, high CRP levels and high erythrocyte sedimentation rates. While she had normal white blood cell counts, massive neutrophils were obtained from her thyroid mass by aspiration biopsy, indicating acute suppurative thyroiditis. However, we could not find any bacteria to cause suppurative thyroiditis either in the blood or in thyroid aspirates. Serum levels of thyroid hormone were slightly elevated but she did not complain of any thyrotoxic symptoms. Radioactive iodine uptake (RAIU) of the thyroid gland was markedly decreased (2%/24h). Following treatment with antibiotics, her inflammation and symptoms immediately improved, and pus spontaneously ran from the collapsed thyroid mass. Then serum thyroid hormone levels and RAIU were normalized and the right thyroid mass disappeared. She was discharged in December 1988. There were no signs of recurrence of suppurative thyroiditis until now. She received a pharyngo-esophageal barium examination in search of the route of infection 4 times, but no fistula was revealed. However, as her left thyroid mass consistently remained thereafter, an operation of the left thyroid mass was performed in December 1989. The histologic examination of the resected thyroid revealed the coexistence of encapsulated follicular adenoma, minute papillary carcinoma and chronic thyroiditis. There are few reports of such a case having a combination of suppurative thyroiditis, thyroid cancer and chronic thyroiditis observed in an elderly female.
Acute Disease↗
Relation of epidermal growth factor receptor concentration to growth of human esophageal cancer cell lines.
The relation between the concentration of epidermal growth factor (EGF) receptor and the effects of EGF on cell proliferation were studied using 16 newly established human esophageal cancer cell lines. According to 125I-EGF binding assay, the amount of EGF receptor was found to vary from 6 x 10(4) to 1.2 x 10(7) (sites/cell). Changes in EGF-stimulated tyrosine-specific protein kinase activity almost paralleled changes in the number of EGF receptors per cell. Amplification of EGF receptor gene was detected in only one cell line. Under monolayer culture conditions, we found three types of growth responses of esophageal cell lines to EGF; growth in 5 cell lines was inhibited and that in 4 cell lines was stimulated while that in the other 7 cell lines remained unaffected. Relation was observed between the number of EGF receptors per cell and the growth response to EGF. On the other hand, cell lines whose growth was inhibited by EGF in monolayer culture were stimulated by EGF in soft agar culture, though the opposite was not necessarily true.
Cell Division↗
Loss of 17p, mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas.
We analyzed mutations of the p53 gene by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing through all coding exons and exon-intron junctions in 32 cases with esophageal squamous cell carcinoma. Mutations were detected in 15 of 32 (47%) tumor samples, in which G:C to T:A transversions were rather frequent (33%). Previously, we reported deletion of chromosome 17p where the p53 gene is located in 45% of Japanese esophageal squamous cell carcinoma, and here the relationship between mutation of the p53 gene and loss of 17p was analyzed. Mutations were observed in 12 of 16 patients with loss of 17p, whereas only 2 of 11 without loss were positive for mutations, suggesting that mutations of the p53 gene were closely associated with a 17p deletion. Furthermore, we immunohistochemically analyzed the expression of p53 protein in esophageal squamous cell carcinoma tumor tissues using a monoclonal antibody. Five of 6 tumors with missense mutations of the p53 gene were positively stained, while in tumors with nonsense mutations or without mutations of the p53 gene staining was very weak or negative. These results suggest a good correlation between mutations and abnormal expression of the p53 gene.
Aged↗
Prognostic significance of cell culture in carcinoma of the oesophagus.
The prognostic significance of the potential of cells to grow in tissue culture was studied in 50 patients with oesophageal cancer. The ability of cell lines to grow from resected oesophageal specimens was determined; from 50 patients, 21 cell lines were established (42 per cent). The patients were divided into two groups on this basis: group 1, from whom cancer cells could be grown as continuous cell lines and group 2, from whom cell lines could not be established. The cumulative survival rate of patients in group 1 was significantly lower than that of those in group 2 (P < 0.05). There was also a significantly higher incidence of lymph node metastases in group 1 (P < 0.05). These results suggest that the potential of cancer cells for growth is a useful long-term prognostic indicator for patients with oesophageal carcinoma.
Aged↗
Monoclonal gammopathy (IgA: lambda) after autologous T-cell-depleted bone marrow transplantation in a patient with non-Hodgkin's lymphoma.
We report a case study of a patient suffering from T-lymphoblastic lymphoma, for whom autologous T-cell-depleted bone marrow transplantation was carried out. Low-dose cyclosporin A (CsA) was administered just after autologous bone marrow transplantation (ABMT) for induction of autologous graft-versus-host disease. Three months later, the lymphoma relapsed with marked monoclonal gammopathy of the immunoglobulin A type, which had not been seen before ABMT. It is suggested that the regrowth of the lymphoma cells was related to the maturation of B cells or the secretion of immunoglobulins from plasma cells, associated with some cytokines produced under the condition of an abnormal immunological circumstance after ABMT plus CsA.
Adult↗
Bone metastasis as a prognostic factor in breast cancer patients with liver metastasis given OK-432-combined adoptive immunotherapy via the hepatic artery.
The outcome in 31 patients with liver metastases from breast cancer given OK-432-combined adoptive immunotherapy via the hepatic artery was analyzed. Patients received intraarterial OK-432, a streptococcal preparation, followed by the transfer of autologous lymphocytes cultured with autologous tumor extract and interleukin-2 for 9-13 days. Liver lesions were evaluable in 11 of the 12 patients with bone metastasis (group A) and in 16 of the 19 patients without bone metastasis (group B). Complete response (CR) in the liver was attained in 8 patients in group A, but in only 1 in group B (p < 0.01). In group A, radiological features of all metastatic foci of bone improved after CR in the liver. Moreover, the median survival time (MST) of group A (20 months) was longer (p = 0.06) than that of group B patients with extra-hepatic metastasis (n = 12; MST = 6 months), while group B patients with liver metastasis alone (n = 7) showed a MST similar to that of group A. Thus, loco-regional immunotherapy via the hepatic artery was found to be useful in controlling both liver and bone metastasis from breast cancer. Moreover, in breast cancer patients with liver metastasis, bone metastasis appears to be a prognostic factor associated with good response to this immunotherapy.
Adult↗
The induction of murine tumor infiltrating lymphocytes (TIL) by interleukin-2 or T cell growth factor.
Mice were injected in the foot pad with either 5 x 10(5) syngeneic plasmacytoma (MOPC104E) or fibrosarcoma cells (Meth A). Lymph nodes containing tumor cells were harvested 14 days later and cultured. In the presence of recombinant interleukin-2 (r-IL-2) predominantly tumor cells proliferated. Culture with T cell growth factor (TCGF) resulted in the growth of lymphoid cells. Concanavalin A (Con A) had only a modest effect on elimination of tumor cells in the culture. Tumor-infiltrating lymphocytes (TIL) prepared from the lymph nodes showed specific tumor-neutralizing activity when grown in the presence of TCGF. In vitro examination revealed that Meth A cells could not be lysed by TIL, while TIL from MOPC tumors showed tumor specific activity. This study may explain negative results in human trials with TIL induced by IL-2 alone.
Animals↗
Low serum apolipoprotein A-I level in patients with vasospastic angina.
The serum lipid and lipoprotein levels in 15 patients with vasospastic angina were compared with those in 33 patients with no angiographic coronary stenosis and no vasospastic angina after intracoronary acetylcholine infusion. The serum level of apolipoprotein A-I in patients with vasospastic angina (112 +/- 6 mg/dl) was significantly lower (p < 0.05) than that in patients without vasospasm (128 +/- 4 mg/dl). However, there were no differences between the two groups in the serum levels of cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein A-II, and apolipoprotein B. Thus apolipoprotein A-I may play some role in the prevention of vasospastic angina.
Adult↗
Role of secretin in negative feedback regulation of postprandial pancreatic secretion in dogs.
BACKGROUND: A negative feedback regulation of pancreatic exocrine secretion has been observed in fasting rats, pigs, and humans, but this phenomenon could not be found in fasting dogs. The aims of the present study were to investigate whether or not postprandial pancreatic secretion is regulated by a negative feedback mechanism and to determine if the mechanism is mediated by secretion and/or cholecystokinin (CCK) in dogs. METHODS: In eight dogs prepared with gastric and Herrera's pancreatic cannulas, pancreatic juice was collected for 3 hours after feeding a mixed meal to measure volume, bicarbonate, and trypsin output. Peripheral venous blood was obtained to determine plasma immunoreactive secretin and CCK levels. Four groups of experiments were performed while pancreatic juice was diverted from the duodenum: (1) diversion of pancreatic juice alone, (2) intraduodenal infusion of fresh pancreatic juice while pancreatic juice was diverted, (3) intraduodenal infusion of 150 mg/h of trypsin and 300 mg/h of chymotrypsin, and (4) intraduodenal infusion of 0.1 mol/L NaHCO3. RESULTS: Pancreatic secretion during diversion of pancreatic juice was significantly greater than that obtained while pancreatic juice was returned. Diversion-induced pancreatic hypersecretion was significantly suppressed by intraduodenal administration of pancreatic proteases, but it was not influenced significantly by 0.1 mol/L NaHCO3. The suppression by either pancreatic juice or proteases paralleled the decrease in plasma secretin response, whereas the CCK response remained unchanged. The inhibitory effect of pancreatic proteases on pancreatic secretion was blocked by a physiological dose of exogenous secretin, 0.06 clinical U.kg-1.h-1. CONCLUSIONS: In dogs, postprandial pancreatic secretion is controlled by a negative feedback mechanism mediated mainly by the release of secretin, but not by CCK.
Animals↗
Purification and characterization of carbonyl reductases from bovine liver cytosol and microsome. The cytosolic enzyme has a novel 3 alpha/17 beta-hydroxysteroid dehydrogenase activity.
1. Carbonyl reductase, which is distributed in both cytosolic and microsomal fractions in bovine liver, were purified to homogeneity on 12.5% sodium dodecylsulfate-polyacrylamide gel electrophoresis and shown to have molecular weights of 32 kDa and 68 kDa, respectively. 2. Both carbonyl reductases can catalyze the reduction of many carbonyl compounds including ketone, quinones and aldehyde with relatively low Km values. 3. From the absorption spectrum result, microsomal carbonyl reductase closely resembles cytochrome P-450 reductase. 4. Cytosolic carbonyl reductase is a novel enzyme which can act on both testosterone and androsterone at low concentration.
17-Hydroxysteroid Dehydrogenases↗
Prostaglandin E2 production by hepatic macrophages and peripheral monocytes in liver cirrhosis patients.
We analyzed PGE2 production in primary-cultured human hepatic macrophages (HHM phi) and peripheral monocytes (MO) from patients with and without liver cirrhosis, and correlated PGE2 production with the patients' liver function. Serum choline esterase (ChE) levels were used as an indicator of liver function. PGE2 production in both HHM phi and MO from cirrhotic patients was significantly lower than in HHM phi and MO from non-cirrhotic patients. PGE2 production in cirrhotic HHM phi was inversely correlated with ChE levels, whereas PGE2 production in cirrhotic MO showed no obvious correlation. In conclusion, both HHM phi and MO might contribute to the pathophysiology of liver cirrhosis via attenuated PGE2 production. Furthermore, HHM phi activity appears to be more strongly affected by the chronic pathological changes observed in the cirrhotic liver.
Cells, Cultured↗
Confirmation of the reported 330-keV electron line in e++Th interactions using the positron emitter 82Sr.
Explore the source record for details and available documents.
Journal Article↗
Measurements of 10Be and 26Al production cross sections with 12 GeV protons by accelerator mass spectrometry.
Explore the source record for details and available documents.
Journal Article↗
Hyperthermic enhancement of cytotoxicity and increased uptake of cis-diamminedichloroplatinum(II) in cultured human esophageal cancer cells.
Thermal enhancement of cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP) has been well recognized and applied clinically to chemotherapy of various malignancies, but its fundamental mechanism remains to be elucidated. In order to obtain a clue to this mechanism, we analyzed the effect of hyperthermia on the uptake and subsequent distribution of [195mPt]CDDP in two lines of esophageal cancer cells (KYSE-150 and KYSE-170) established from clinical patients. First, we observed a significant increase in [195mPt]CDDP uptake by both types of cells at increasingly higher temperatures. The incorporated CDDP was distributed between the nucleus and the cytosol at a ratio of approximately 3:1, and the ratio remained the same at various temperatures. The CDDP was found in all four molecular fractions, i.e., DNA, RNA, protein, and TCA-soluble, with a slight preference for DNA at higher temperatures. Enhancement of cytotoxicity required simultaneous, and not sequential, treatments with CDDP and hyperthermia; hyperthermia after CDDP treatment increased the efflux of CDDP from the cells, and rather reduced the cytotoxicity of CDDP. These results suggest that thermal enhancement of the cytotoxicity of CDDP is caused mainly by acceleration of the drug entry into the cell, probably due to increased permeability, and a consequent increase in the amount of CDDP binding to DNA. This mechanism gives support for clinical trial of simultaneous treatment with CDDP and hyperthermia.
Carcinoma, Squamous Cell↗