Amino acids and peptides. V. Synthesis of amino acid derivatives containing a sulfonamide bond.
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Biomedical subjects
Publications and source records attributed to M Maeda.
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The effect of caerulein on insulin response to graded amounts of glucose from the isolated perfused rat pancreas was investigated in the presence or absence of an amino acids mixture. Caerulein at a concentration of 0.1 ng/ml which is a submaximal concentration for an effect on exocrine pancreatic secretion potentiated insulin responses to glucose concentrations less than 200 mg/dl, but produced no further increase when added to a glucose stimulus over a 200 mg/dl. However, in the presence of amino acids the insulin response to 200 mg/dl glucose was significantly potentiated by the stimulation of 0.1 ng/ml caerulein. The effectiveness of caerulein as an insulinotropic agent depended on the glucose concentration only when amino acids were present. These results indicate that caerulein, at a concentration which stimulate pancreatic exocrine secretion, has a synergistic effect on insulin response to glucose and amino acids and therefore raises the possibility that endogenously released CCK may contribute to the entero-insular axis.
A reproducible model of diabetic state was produced by resecting more than 90% of the pancreatic tissue in Wistar strain male rats. Five rats with diabetic state after the resection received islet transplantation into the liver through the portal vein. All these five rats showed normoglycemia one week after the injection and it lasted about six months. A morphometric analysis using 1190 serial sections of the control rat pancreas showed that the islet distribution accorded satisfactorily with Weibull and gamma distribution, when an islet was regarded as a sphere in the three dimensional space. The estimated value of radius and number of the islets was 0.0155 mm and 131.2/mm3, respectively, whereas volume fractions of the islet tissue in the splenic and gastric segments, and parabiliary and duodenal segments were estimated at 1.45 and 0.98%, respectively. The mean half of the largest diameter of the isolated islets under dissecting microscope reached to 0.080 mm and 500 isolated islets account for about 14% of volume fraction in a whole pancreas. As the remnant pancreas possibly had approximately five percent of islet volume, the transplanted animal contained about 19% of islet volume as compared to the control animal. It could be concluded that transplantation of 500 islets controlled diabetes in the rat with subtotal pancreatectomy. But the transplanted rats eventually became diabetic about six months after the transplantation possibly because of insufficient volume of implanted islets.
Ligation and section of the main and accessory pancreatic ducts were performed in adult mongrel dogs. Four weeks after the procedure we carried out total pancreatectomy in six duct-ligated dogs, and an attempt was made to prepare the graft of islets from the highly scarred pancreas of the duct-ligated dogs by means of a newly developed collagenase perfusion method. We succeeded to normalize the high fasting glucose level which occurred after the total pancreatectomy in three of six dogs through the autotransplantation of the procured graft. However, insulin secretion was severely depressed in transplanted animals. Two of the three dogs showed high plasma glucose levels 15 and 20 weeks after the transplantation, respectively. Histological examination of the spleen revealed well preserved islets with good immunocytochemical insulin staining in one transplanted dog whose plasma glucose level was controlled for about five months. No pancreatic exocrine tissue was detected in the histological sections of the spleen in the transplanted dogs and in a transplanted control dog.
The inhibitory effect of nicardipine, a calcium antagonist, on the antigen- and anti-IgE-induced histamine release from basophilic leucocytes of patients with bronchial asthma was examined. The agent significantly inhibited both antigen-stimulated and anti-IgE-induced histamine release from basophils (the maximum percent inhibition was 57.8 +/- 7.2% and 56.0 +/- 8.8%, respectively). Pre-incubation of basophils with nicardipine for periods of up to 120 min did not alter the inhibitory effect. These results suggest that nicardipine modifies the histamine release from basophils which closely participate in an attack of bronchial asthma.
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Successful intrasplenic islet autotransplantation in dogs requires an islet cell mass considerably greater than what might be expected based on studies of subtotal pancreatectomy. Grafts of marginal function ultimately fail, suggesting severe limitations in the capacity of an islet graft to adapt. Accommodation was tested in established intrasplenic grafts by either chronically stressing the graft with mild carbohydrate intolerance induced by exogenous corticosteroids or chronically suppressing the graft with exogenous insulin. After these manipulations, insulin output into the portal vein in response to intravenous (i.v.) glucose was measured and compared with that of normal dogs and dogs receiving islet autografts with no further treatment with either steroids or insulin. Transplanted islets tolerated the two manipulations well in that neither exogenous steroid nor insulin led to failure of the graft as a consequence of either stress or protracted diminished demand. The major determinant of successful islet grafting is the endocrine competence of the initial graft. If that competence is provided at the outset, the graft can adapt to a considerable range of demand for insulin secretion.
Industrial micro-robots are now being applied to hazardous jobs or tedious jobs. These in-house micro-robots (MELFA, RM-501, Mitsubishi Electric Inc.) were used to make a collection system of waste scintillator solution on the experimental basis. Newly developed were hands, vial holders and a system soft ware, and satisfactory results have been obtained.
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Human T-cell leukemia virus (HTLV)-infected cell lines derived from adult T-cell leukemia (ATL) express constitutively the receptor for Interleukin-2 (IL-2-R) and the associated antigen (Tac antigen). In contrast, the same antigen is transiently expressed by normal T-cells only after immune stimulation. Recently, it was reported that the constitutively expressed Tac antigen on ATL cells and cell lines was not down-regulated or modulated by anti-Tac antibody. Since the antigen was modulated on normal mitogen- or alloantigen-stimulated T-cells, we postulated that the regulation of IL-2-R may be abnormal on ATL cells; the synthesis of IL-2-R is continuously stimulated in these cells. A unique HTLV/ATLV(-) cell line (YT) derived from a child with acute lymphoblastic leukemia was found to express low levels of Tac antigen that could be enhanced by various stimuli, including conditioned medium (CM) derived from normal lymphocytes, but not by lectins (PHA, Con A). Of particular interest, the exposure of YT cells to CM from ATL cell lines with helper phenotype revealed the presence of factor(s) (ATL-derived factor, ADF) that augmented the synthesis and expression of IL-2-R/Tac antigen on YT cells and promoted YT cell growth. CM from HTLV(-) leukemia cell lines lacked both IL-2-R augmenting activity and a growth promoting activity. Immunoaffinity-purified IL-2 and recombinant gamma interferon also lacked IL-2-R augmenting activity. Moreover, the physicochemical analysis with Fast protein liquid chromatography (FPLC) revealed that ADF was quite different in pI point from the IL-2-R augmenting activity in CM from normal lymphocytes. These results suggested that ADF is a unique product of HTLV(+) cells. The possible relationship between ADF production, HTLV infection, and the abnormal expression of IL-2-R is suggested, and these abnormalities may be advantageous for the leukemogenesis and abnormal growth of ATL.
A new method for preparation of viable islet cells from the normal pancreas is introduced. After total pancreatectomy, the pancreatic duct is cannulated and perfused with Hanks' balanced salt solution (HBSS) containing 0.2% collagenase at 37 degrees C for 30-45 minutes. The gland is then chopped and dissociated by shaking in a water bath. The cell suspension is filtered through steel mesh and washed with cold HBSS by centrifugation. By this method, collagenase is applied preferentially into the acinar tissue and the islet yield is greatly enhanced with decreased acinar contamination. Estimation of insulin and amylase in pancreatic tissue and islet rich cell suspension (graft) indicates a 57% islet recovery and a six-fold enrichment in islet concentration. Graft prepared by this method is autotransplanted into totally pancreatectomised dogs and normoglycemia is achieved in ten of 13 animals.
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Interleukin 2 (IL 2) receptor (IL 2-R) is constitutively expressed on T cell lines established from the patients with adult T cell leukemia (ATL), which is a human T cell leukemia lymphoma virus (HTLV-1)(+) T4(+)-leukemia endemic in Japan, the United States, and other countries. Many of these cell lines continuously produce an acidic lymphokine, ATL-derived factor (ADF), which preferentially induces the synthesis and expression of IL 2-R on a sensitive HTLV-1(-) non-T cell line (YT). The induced IL 2-R was characterized by the binding of 125I-IL 2 and flow cytometry by using fluoresceinated anti-human IL 2-R monoclonal antibodies (anti-Tac). Scatchard analysis with 125I-IL 2 showed ADF induced high-affinity receptor sites on YT cells. To test the possibility that ADF produced by HTLV-1(+) T cells is involved in the abnormal expression of IL 2-R, we studied the effect of ADF on an HTLV-1(+) IL 2-dependent T cell line (ED) in which the beta-chain gene of the T cell antigen receptor (T beta) was rearranged. Unlike IL 2-independent HTLV-1(+) cell lines that constitutively expressed Il 2-R, the IL 2-R expression on ED cells declined in the absence of crude IL 2 or recombinant IL 2. When either ADF or recombinant IL 2 was added to the culture of ED cells, there was a dose-dependent enhancement of IL 2-R expression in 24 hr. ADF and IL 2 showed a synergism in the IL 2-R induction, and both factors were needed to induce the maximal receptor expression in these T cells. The lack of IL 2 production by ADF-treated YT, as well as ED cell line suggested IL 2 may not be involved in the IL 2-R induction by ADF. Northern blot hybridization with human IL 2-R cDNA probe showed the increase of IL 2-R mRNA in YT cells after ADF-treatment. ADF also enhanced IL 2-R expression of a rat T cell line transformed by HTLV-1(TARS-1), as demonstrated with anti-rat IL 2 receptor monoclonal antibodies (ART-18). An ADF-like IL 2-R-inducing factor was also detected in the conditioned medium of two HTLV-1(+) rat T cell lines (TARL-2 and TART-1), which constitutively expressed a higher number of Il 2-R than TARS-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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