ZTTA,a Prolyl Endopeptidase Inhibitor,Potentiates the Arginine-Vasopressin-Induced Incorporation of [14C]Leucine in Rat Amygdaloid and Cortical Slices

Pharmaceutical Research -     

ULTRASTRUCTURAL STUDY OF LYMPHOCYTIC INTERACTION WITH HEPATOCYTES AND ENDOTHELIAL CELLS IN ACUTE NON-A, NON-B HEPATITIS

In the liver biopsy specimens of all six patients with acute non-A, non-B hepatitis, the lymphocytic interaction with hepatocytes and sinusoidal endothelial cells was observed by electron microscopic study. Lymphocytes were in a close contact with damaged hepatocytes and interrupted endothelial cells, and the microvilli on the surface of these damaged hepatocytes were degenerated and lost. These findings pointed out the possibility that the lymphocyte may play one of the important roles in hepatocytic damage and endothelial cell damage in acute non-A, non-B hepatitis.     

Antibodies to GAD in Japanese patients classified as Type 2 diabetes at diagnosis. High titre of GAD Ab is a predictive marker for early insulin treatment--report of west Japan (Kyushu, Yamaguchi, Osaka) study for GAD Ab(+) diabetes.

AIM: We evaluated the prevalence of GAD Ab in Japanese Type 2 diabetic patients treated with oral hypoglycaemic agents (OHA) and/or diet and followed GAD Ab(+) patients to assess the usefulness of GAD Ab as a marker for future insulin treatment prospectively. METHODS: A total of 2658 Japanese Type 2 diabetic patients treated by OHA and/or diet were randomly selected between April 1996 and December 1998. The clinical characteristics at entry were assessed and patients were followed for 1-3 years. RESULTS: The overall prevalence of GAD Ab among Type 2 diabetic patients was 2.0%. Forty-five had a history of diabetes of < or = 5 years (short history) while those with duration > 5 years (long history) totalled nine. Among them, 47% of patients with a short history did not require insulin in the follow-up period. However, none of those with a long history required insulin treatment within 2 years. Comparison of patients based on GAD titre in those with short history showed that 33% of patients in the high-titre group (> or = 20 U) required no insulin treatment in the first year of follow-up. In contrast, this proportion was 80% in the first and 67% in the second year in the low-titre group (< 20 U). CONCLUSIONS: The prevalence of GAD Ab in Japanese patients with a short and long history of diabetes was 2.8% and 0.9%, respectively. The presence of GAD Ab in Japanese Type 2 diabetic patients with a short history of diabetes is a marker for early insulin treatment.     

Movement of fluorescein monoglucuronide in the rabbit cornea. Diffusion in the stroma and endothelial permeability

The movement of fluorescein monoglucuronide, a fluorescent metabolite of fluorescein, was studied in the rabbit cornea in vitro and in vivo. A stromal strip was exposed to fluorescein monoglucuronide, and the diffusion rate and the distribution in the stroma were measured every hr for 24 hr. The diffusion coefficient was 0.94 +/- 0.11 (+/- S.D.) X 10(-6) cm2/sec, and the saline/stroma distribution ratio was in a range of 0.67 to 0.69. The concentration of fluorescein monoglucuronide in the anterior chamber and the cornea was measured every hr for 8 hr following intravenous administration. The endothelial permeability was 4.7 +/- 1.0 X 10(-4) cm/min, and the aqueous/cornea distribution ratio was 0.56 +/- 0.05. It appears that the corneal endothelial permeability in the living eye determined hitherto from systemic administration of fluorescein is most likely the permeability to fluorescein monoglucuronide.     

Epidemiology and primary prevention of thyroid cancer.

The purpose of this review is to provide an account of our present knowledge about the epidemiology of nonmedullary thyroid carcinoma, to discuss the effects of environment, lifestyle and radiation on the risk of developing thyroid cancer, and to discuss aspects on primary prevention of the disease. In areas not associated with nuclear fallout, the annual incidence of thyroid cancer ranges between 2.0-3.8 cases per 100,000 in women and 1.2-2.6 per 100,000 in men, women of childbearing age being at highest risk. Low figures are found in some European countries (Denmark, Holland, Slovakia) and high figures are found in Iceland and Hawaii. Differences in iodine intake may be one factor explaining the geographic variation, high iodine intake being associated with a slightly increased risk of developing thyroid cancer. In general, lifestyle factors have only a small effect on the risk of thyroid cancer, a possible protective effect of tobacco smoking has been recently reported. Because of the (small) increase in risk of thyroid cancer associated with iodination programs, these should be supervised, so that the population does not receive excess iodine. The thyroid gland is highly sensitive to radiation-induced oncogenesis. This is verified by numerous reports from survivors after Hiroshima and Nagasaki, the Nevada, Novaja Semlja and Marshal Island atmospheric tests, and the Chernobyl plant accident, as well as by investigations of earlier medical use of radiation for benign diseases in childhood. These reports are summarized in the review. There appears to be a dose-response relation for the risk of developing cancer after exposure to radioactive radioiodine. The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. Thus, the incidence of thyroid cancer in children in the Belarus area was less than 1 case per million per year before the Chernobyl accident, increasing to a peak exceeding 100 per million per year in certain areas after the accident. It is a social obligation of scientists to inform the public and politicians of these risks. All nuclear power plants should have a program in operation for stockpiling potassium iodide for distribution within 1-2 days after an accident.     

Eradication of Epstein-Barr virus episome and associated inhibition of infected tumor cell growth by adenovirus vector-mediated transduction of dominant-negative EBNA1.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), a latent viral protein consistently expressed in infected proliferating cells, is essentially required in trans to maintain EBV episomes in cells. We constructed a mutant (mt) EBNA1 and examined whether it exerted dominant-negative effects on maintenance of the viral episome thereby leading to abrogation of EBV-infected tumor cell growth. Using lymphocyte and epithelial cell lines converted with neomycin-resistant recombinant EBV (rEBV) as models, adenovirus vector-mediated transduction of mtEBNA1, but not LacZ, brought about rapid and striking reductions in rEBV-derived wild-type EBNA1 levels and viral genomic loads in converted lines of three major viral latencies. This outcome was further validated at the single-cell level by cellular loss of G418 resistance and viral signals in situ. The mtEBNA1 transduction significantly impaired growth of naturally EBV-harboring Burkitt lymphoma cells in vitro and in vivo, largely in association with the eradication of viral episomes. Expression of mtEBNA1 per se caused no detectable cytotoxicity in EBV-uninfected cells. These results indicate that mtEBNA1 can act as a dominant-negative effector that efficiently impedes the EBV-dependent malignant phenotypes in cells regardless of viral latency or tissue origin. The mutant will afford an additional therapeutic strategy specifically targeting EBV-associated malignancies.