Magnetic resonance imaging detection of aortic and pulmonary artery wall thickening in the acute stage of takayasu arteritis. Improvement of clinical and radiologic findings after steroid therapy

Objective. Early diagnosis of Takayasu arteritis in the acute stage (prepulseless stage) is extremely difficult. Identification of a useful approach to detecting the initial changes of arteritis is therefore desirable. Methods. Careful clinical examination of a young woman with persistent fever and dry cough revealed faintly audible bruits at the cervical, supraclavicular, and abdominal regions. Aortographic features suggested thickening of the wall of the descending thoracic aorta. Magnetic resonance imaging (MRI) of this area was diagnostic. Results. MRI demonstrated involvement of the ascending aorta and right main pulmonary artery. Steroid therapy (prednisolone 60 mg/day) induced dramatic clinical and radiologic improvement in 2 months. Conclusion. This is the first report of MRI-documented reduction in the thickness of the walls of both the aorta and the pulmonary artery following steroid therapy.     

Synergy in antigen presentation by thyroid epithelial cells and monocytes from patients with graves'' disease

The present study was undertaken to examine the ability of thyrocytes from Graves' patients to present purified protein derivative (PPD) to autologous peripheral blood T cells. Normal human thyrocytes which were pre-cultured with interferon-gamma were able to induce the proliferation of T cells in response to PPD antigen, but unstimulated thyrocytes failed to do. Thyrocytes from Graves' patients on which HLA-DR antigens were expressed have an ability to induce the proliferation of T cells. Thyrocytes from Graves' patients which were pulsed with PPD antigen for 4 h were capable of stimulating proliferation of the T cells. However, the stimulation index of T cells co-cultured with thyrocytes and PPD were significantly lower than that of T cells co-cultured with monocytes and PPD. Sub-optimal numbers of monocytes which by themselves were unable to support T-cell proliferation synergistically augmented antigen presentation by thyrocytes. These results suggest that cellular interactions among thyrocytes, monocytes and T cells may perpetuate immune or autoimmune responses in thyroid tissues from Graves' patients.     

Qualitative and quantitative changes in normal aging and alzheimer''s disease

Qualitative changes in normal aging and Alzheimer's disease (AD) are as important as quantitative changes. Although qualitative changes do not co-vary with quantitative differences in every respect, quantitative changes, nevertheless, often accurately reflect qualitative changes. Moreover, the complementary use of each provides a more detailed characterization of brain changes with aging and AD. The quantitative and qualitative changes of choline acetyltransferase, as well as somatostatin-containing neurons and dendrites, in human cortex are described as examples of this.     

Conserved and divergent expression patterns of markers of axial development in the laboratory opossum,Monodelphis domestica

Background: Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short‐tailed opossum, a metatherian. Results: Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post‐coitus. Conclusions: Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176–1188, 2016. © 2016 Wiley Periodicals, Inc.     

Development of 2‐hour suicide intervention program among medical residents: First pilot trial

Aim: Suicide is associated not only with primary psychiatric disorders but also with physical disorders. Physicians' education on suicide prevention contributes to reducing suicide. Therefore, medical residents, who contact patients daily and who eventually become primary physicians in each specialty, might be the most appropriate candidates for intervention. In this article, we introduce our newly developed suicide intervention program among medical residents. Methods: We developed a 2‐hour suicide intervention program among medical residents, based on the Mental Health First Aid (MHFA), which had originally been developed for the public. The program contains a 1‐hour lecture and a 1‐hour role‐play session. As the first pilot trial, we conducted the program among 44 first‐year medical residents at a university hospital and evaluated its effectiveness. Changes in confidence, attitudes and behavior toward suicidal people were evaluated using self‐reported questionnaires before, immediately after, and 6 months after the program. Results: Participants' confidence and attitudes significantly improved after the program. The total mean score (standard deviation) of the Suicide Intervention Response Inventory improved from 18.4 (2.0) before the intervention to 19.4 (2.0) immediately after the intervention. However, the effectiveness was limited after 6 months. In the course of 6 months, the participants learned to apply the MHFA principles in their daily clinical practice. Conclusion: Our newly developed brief suicide intervention program demonstrating its effectiveness among medical residents should be modified in order to be more effective in the long term. The next trial with a control group ought to be conducted to evaluate our developed program.     

Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism

Objective A possible association between subclinical hypothyroidism and cardiovascular disease (CVD) has been reported. Monitoring of atomic‐bomb survivors for late effects of radiation exposure at the Radiation Effects Research Foundation has provided the opportunity to examine associations between subclinical hypothyroidism and metabolic CVD risk factors. The objective of the study was to evaluate associations between subclinical hypothyroidism and metabolic CVD risk factors, and a cluster of these factors. Design and participants This was a cross‐sectional study of 3549 subjects (mean age 70 years; 1221 men and 2328 women) between 2000 and 2003 comprising 306 subjects with subclinical hypothyroidism and 3243 control euthyroid subjects in Japan. Measurements We investigated associations between subclinical hypothyroidism and metabolic CVD risk factors such as hypertension, diabetes mellitus, dyslipidaemia and hyperuricaemia, and a cluster of these factors. Results Subclinical hypothyroidism was not significantly associated with either hypertension, diabetes mellitus or hyperuricaemia defined by taking into account the use of medications in both men and women, but in men it was associated with dyslipidaemia (P = 0·02). We observed a significantly increased odds ratio (OR) for the presence of three or more metabolic CVD risk factors in men with subclinical hypothyroidism after adjusting for age, body mass index (BMI), and smoking status [OR: 1·83, 95% confidence interval (CI): 1·13–2·94, P = 0·01]. The significant associations remained after an additional adjustment for atomic‐bomb radiation dose. Conclusions There appears to be a significant increase in a cluster of metabolic CVD risk factors among people with subclinical hypothyroidism.     

Generation Mechanism of Radical Species by Tyrosine-Tyrosinase Reaction

Alleviated melanin formation in the skin through inhibition of tyrosine-tyrosinase reaction is one of the major targets of cosmetics for whitening ability. Since melanin has a pivotal role for photoprotection, there are pros and cons of inhibition of melanin formation. This study applying electron spin resonance (ESR)-spin trapping method revealed that ^•H and ^•OH are generated through tyrosine-tyrosinase reaction. When deuterium water was used instead of H₂O, the signal of 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-H (a spin adduct of DMPO and ^•H) greatly decreased, whilst DMPO-OH (a spin adduct of DMPO and ^•OH) did not. Thus, it is suggested that ^•H was derived from H₂O, and ^•OH through oxidative catalytic process of tyrosine to dopaquinone. Our study suggests that tyrosinase inhibitors might contribute to alleviate the oxidative damage of the skin by inhibiting ^•OH generation via the enzyme reaction.     

Effect of SEA0400, a novel inhibitor of sodium-calcium exchanger, on myocardial ionic currents

The effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a newly synthesized Na(+)-Ca(2+) exchanger (NCX) inhibitor, on the NCX current and other membrane currents were examined in isolated guinea-pig ventricular myocytes and compared with those of 2-[2-[4-(4-nitrobenzyloxy) phenyl]ethyl]isothiourea (KB-R7943). SEA0400 concentration-dependently inhibited the NCX current with a 10 fold higher potency than that of KB-R7943; 1 microM SEA0400 and 10 microM KB-R7943 inhibited the NCX current by more than 80%. KB-R7943, at 10 microM, inhibited the sodium current, L-type calcium current, delayed rectifier potassium current and inwardly rectifying potassium current by more than 50%, but SEA0400 (1 microM) had no significant effect on these currents. These results indicate that SEA0400 is a potent and highly selective inhibitor of NCX, and would be a powerful tool for further studies on the role of NCX in the heart and the therapeutic potential of its inhibition.