Synthetic neuromedin C stimulates exocrine pancreatic secretion in dogs and rats

We have examined the effect of neuromedin C on exocrine pancreatic secretion both in vivo and in vitro, and compared its bioactivity with those of related peptides. In anesthetized dogs, neuromedin C caused a dose-dependent initial reduction of pancreatic blood flow and an increase in secretin-stimulated exocrine pancreatic secretion, and had almost the same potency as gastrin-releasing peptide (GRP) in decreasing pancreatic blood flow. A potent stimulatory effect on exocrine pancreatic secretion was found in conscious dogs accompanied by a significant elevation in the circulating cholecystokinin (CCK) levels. In isolated rat pancreatic acini, amylase was released dose-dependently in response to neuromedin C. This study demonstrates that neuromedin C (a smaller molecular form of GRP) possesses potent bioactivity on exocrine pancreas and suggests that two factors may be involved in the mechanism by which this peptide effects exocrine secretion, namely; direct stimulation on acinar cells and stimulation of CCK release.     

Non-Hodgkin's lymphoma in patients under twenty years of age. A clinicopathological study.

A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma.     

Clinical cytogenetic studies on patients with cleft lip and/or cleft palate--2. Chromosome analysis of twins

Development of DNA diagnosis on the monocular level for patients with cleft lip and/or palate may be expected in the near future. The necessary condition for this is to confirm the heredity, elucidate the mode of inheritance and decide on the regional mapping etc. The authors tried a chromosome analysis on a pair of monozygotic twins with cleft lip and palate by using high-resolution banding techniques (about 700 bands). However, chromosome aberration was not confirmed. Therefore, the relation between this congenital anomaly and the chromosome aberration could not be confirmed. In this paper the authors discussed about this problem.     

Effect of beraprost sodium on peripheral circulation insufficiency in rats and rabbits

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.     

A study on the ability of leukocytes in the cervical mucus of pregnant women to produce superoxide anions using the histochemical nitroblue tetrazolium reduction test

We performed the histochemical nitroblue tetrazolium (NBT) reduction test for leukocytes in cervical mucus and peripheral blood in women in pregnancy to investigate the leukocyte functions in the uterine cervix during pregnancy. The results were as follows. (1) With regard to leukocytes in cervical mucus, the proportion of NBT positive leukocytes was significantly highest in women in the third trimester and was higher in pregnant women than in non-pregnant women. (2) With regard to leukocytes in peripheral blood, the ability of leukocytes to reduce NBT in pregnant women was significantly greater than that of leukocytes in non-pregnant women. These results suggest that the bactericidal activity of leukocytes in cervical mucus during pregnancy is probably more accelerated than that of leukocytes during non-pregnancy.     

FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.     

Efficient detection of deletions induced by a single treatment of mitomycin C in transgenic mouse gpt delta using the Spi(-) selection.

Transgenic rodent mutation assays permit the detection and molecular analysis of various types of gene mutations, such as base changes and frameshifts, in a number of tissues. It is reported, however, that deletion mutations are not efficiently detected by the assays, in particular those using lambda phage shuttle vectors. Recently, a new transgenic mouse model, i.e., gpt delta, has been developed to selectively detect some types of deletions by Spi(-) selection. Spi(-) selection has an advantage over the other selections to preferentially identify deletions because only lambda phages deficient in both the red and gam gene functions are allowed to form phage plaques. In this study, we examined whether in vivo deletions induced by the treatment of mitomycin C (MMC) are detectable by the Spi(-) assay in the mouse model. The mice were treated with MMC (0.5, 1.0, 2.0, and 4.0 mg/kg, single intraperitoneal injection) and sacrificed 14 days after the dosing. The treatment at 4.0 mg/kg approximately doubled the mutant frequency of Spi(-) in the bone marrow, i.e., 2.52 x 10(-6) vs. 1.31 x 10(-6). The molecular analyses using polymerase chain reaction (PCR) and DNA sequencing indicated that seven Spi(-) mutants at 4.0 mg/kg group had deletions with molecular sizes from 0.8 kilo basepairs (kb) to 8.5 kb, whereas no such deletions were observed in the Spi(-) mutants in the control group. The results suggest that deletions induced by MMC in the bone marrow are efficiently detectable by Spi(-) selection and also that the molecular analyses are useful to evaluate the significance of a marginal increase in mutant frequency in the transgenic rodent mutation assays.