Werner Syndrome

Werner syndrome is a premature aging disease caused by the mutation in the WRN gene. The cloning andcharacterization of the WRN gene and its product allows investigators to study the disease and the human aging process atmolecular level. This review summarizes the recent progresses on various aspects of the WRN research including functionalanalysis of the protein, interactive cloning, complexes formation, mouse models, and SNPs (single nucleotidepolymorphisms). These in depth investigations have greatly advanced our understanding of the disease and elucidated futureresearch direction for Werner syndrome and the human aging process.     

Colchicine-induced Inhibition of Fat Globule Development in Hepatocytes of Rats Injected with Ethionine

To examine the effect of colchicine on ethionine induced fatty liver, adult female rats were starved overnight and then injected i.p. with 1 g kg ethionine at 11th hour of fasting; then a half of the rats were also injected i.p. with 2.5 mg kg colchicine twice at 3 and 6 h after the single administration of ethionine. Similarly, fasted control rats were injected i.p. with vehicle alone at the above times. All of the rats were sacrificed after a 20 h fast, and the hepatocytes in periportal areas were observed ultra-structurally. In addition, total lipids in the liver tissue were extracted and determined biochemically. Although similar significant increases of triglyceride were observed in the liver tissue of all ethionine-injected rats, the hapatocytes in the group treated with both chemicals had fewer cytoplasmic fat globules (CFG) than those in the group treated with ethionine only. On the other hand, the diameters of markedly increased membrane-bound lipid particles (MLP) in the double treated group were distributed mainly in the range 0.2–0.4 μm, compared with those (0.1-0.2 μm) in the other groups. These findings indicate that colchicine inhibits the development of CFG in ethionine injured hapatocytes. Acta Pathol Jpn 39: 281∼288, 1989.     

Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood

It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature.     

Induction of histidine decarboxylase in type 2 T helper lymphocytes treated with anti-CD3 antibody

Inflammation Research -     

Hormonal modulation of glomerular function

Glomeruli contain receptors for many hormones. Binding of angiotensin II (ANG II) or antidiuretic hormone (ADH) to glomerular mesangial cells elicits a contractile response. Other hormones induce synthesis of cyclic nucleotides (cAMP, cGMP). Glomeruli also synthesize several prostaglandins, renin, and ANG II. Micropuncture studies in Munich-Wistar rats have examined the effects of vasoactive drugs and hormones on the filtration process. Several vasodilators increase renal plasma flow in the dog and rat, but GFR remains relatively unchanged due to an offsetting fall in the ultrafiltration coefficient (Kf). Vasoconstrictor substances such as ANG II and norepinephrine cause declines in renal plasma flow and Kf, but GFR remains constant due to an increase in the transcapillary hydraulic pressure gradient. Antidiuretic peptides and parathyroid hormone also reduce Kf. Glomerular mesangial cells may regulate Kf by contracting and reducing glomerular capillary surface area. ANG II and ADH directly stimulate mesangial cell contraction in vitro. Other hormones appear to cause contraction by inducing local ANG II synthesis. These hormonal pathways are implicated in the pathogenesis of altered glomerular function in diverse forms of renal injury.     

HIV/AIDS surveillance in Japan, 1984-2000

The HIV/AIDS surveillance system in Japan, which began collecting data on the number of AIDS patients in 1984 and the number of HIV-infected persons in 1987, has played an important role in monitoring the trend and magnitude of Japan's HIV/AIDS epidemic and its distribution across various population subgroups. However, the system lacks any personal identifiers, making it impossible to eliminate duplication or to track cases for disease progression. It also does not permit the identification of the residence of HIV-infected persons because the residence of only the reporting physician is documented under the New Infectious Diseases Control Law, effective since April 1, 1999. The number of people with HIV/AIDS in Japan continues to grow. Among youth, sexually transmitted diseases, induced abortion, and sexual activities have shown a marked increase since the mid-1990s. Behavioral risk of infection for both injection drug users (IDUs) and men who have sex with men (MSM) remains alarmingly high. Accurate monitoring of infection rates is critical to the planning and evaluation of treatment, care and prevention programs. Japan should restructure its HIV/AIDS surveillance system to more accurately monitor the HIV/AIDS epidemic and related risk behaviors.     

Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism

BACKGROUND. Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS. The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS. The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.