Coronary ostium occlusion by coronary cusp displacement in Williams syndrome

Williams syndrome is a contiguous gene deletion syndrome resulting from a heterozygous deletion on chromosome 7q11.23, and is characterized by distinctive facial features and supravalvular aortic stenosis (SVAS). This syndrome rarely presents unpredictable cardiac death, and yet, as illustrated in the present case, it is still not possible to predict it, even on close monitoring. We herein describe the case of a 6‐year‐old Japanese girl with Williams syndrome, who had sudden cardiac collapse due to cardiac infarction after pharyngitis. Cardiac failure followed a critical course that did not respond to catecholamine support or heart rest with extracardiac mechanical support. Although marked coronary stenosis was not present, the left coronary cusp abnormally adhered to the aortic wall, which may synergistically cause coronary ostium occlusion with SVAS. Altered hemodynamic state, even that caused by the common cold, may lead to critical myocardial events in Williams syndrome with SVAS.     

A case of angioimmunoblastic T-cell lymphoma with interstitial shadow which disappeared after injection of hydrocortisone]

A case of angioimmunoblastic T-cell lymphoma (AITL) was reported. A 56-year-old woman was admitted because of high fever and systemic lymphademopathy. Her chest X-ray on admission showed mediastinal and bilateral hilar lymphademopathy (BHL) and interstitial shadows in both lower lung fields. Chest CT scan revealed thickening of interlobular septum and bronchovascular bundles. There was a remarkable elevation in serum soluble interleukin-2 receptor. A biopsy of cervical lymph nodes for histopathological examination revealed AITL. After intravenous injection of 200mg of hydrocortisone for 7 days, the interstitial shadows and BHL disappeared. It was suspected that interstitial shadow was caused by pulmonary infiltration of AITL.     

Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlling primary B cells and their cognate T-cell help

In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses. We previously reported an L22 monoclonal antibody with which human primary resting B cells in the mantle zones of lymphoid follicles are well-defined. Proteomics analyses enabled identification of an L22 antigen as Alox5, which was highly expressed by naive and memory B cells surrounding germinal centers. Cellular growth of mantle cell lymphoma cells also seemed to depend on Alox5. Alox5(-/-) mice exhibited weak antibody responses specific to foreign antigens at the initial and recall phases. This was probably attributable to the low number of follicular and memory B cells and the functional loss of interleukin-21-mediated responses of follicular B cells. Moreover, Alox5(-/-) mice could not fully foster the development of follicular B helper T (Tfh) cells even after immunization with foreign antigens. Further experiments indicated that Alox5 affected mortality in experimentally induced enterocolitis in germ-prone circumstances, indicating that Alox5 would endow immunologic milieu. Our results illustrate the novel role of Alox5 in adaptive humoral immunity by managing primary B cells and Tfh cells in vivo.     

Ca2+ entry channels involved in contractions of rat aorta induced by endothelin-1, noradrenaline,and vasopressin

Endothelin-1 (ET-1) has been shown to activate three types of Ca2+ channel, namely two Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC), and that these channels can be discriminated by Ca2+ channel blockers such as LOE 908 (a blocker of NSCC-1 and NSCC-2) and SK&F 96365 (a blocker of NSCC-2 and SOCC). This study pharmacologically compared Ca2+ entry channels involved in contractions of rat thoracic aorta without endothelium induced by ET-1, noradrenaline (NA), or arginine-vasopressin (AVP). These agonists-induced contractions of aortic rings without endothelium and increases in the intracellular free Ca2+ concentration ([Ca2+]i) of cultured aortic smooth muscle cells were abolished by removal of extracellular Ca2+. A blocker of L-type voltage-operated Ca2+ channel (VOCC), nifedipine had no effect on the responses to ET-1, but it suppressed the responses to NA and AVP to 70% and 65% of control responses, respectively. LOE 908 partially suppressed the nifedipine-resistant responses to ET-1 and AVP, but not those to NA. SK&F 96365 also partially suppressed the nifedipine-resistant responses to ET-1 and AVP, whereas it abolished the responses to NA. LOE 908 in combination with SK&F 96365 abolished the nifedipine-resistant responses to either of the agonists. These results show that the contraction of rat aorta involves different Ca2+ entry channel depending on agonists: (a) NSCC-1, NSCC-2, and SOCC for ET-1; (b) VOCC and SOCC for NA; and (c) VOCC, NSCC-1, NSCC-2, and SOCC for AVP.     

Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice

We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) has antidepressive-like activity. The aim of the present study was to examine (i) whether caffeic acid, a major metabolite of rosmarinic acid, also has antidepressive-like activity, and (ii) whether these substances inhibit either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity. Rosmarinic acid (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each significantly reduced the duration of immobility in the forced swimming test in mice. In contrast, neither substance, at doses that produced a significant reduction in the immobile response in the forced swimming test, affected spontaneous motor activity. These results indicate that, like rosmarinic acid, caffeic acid also possesses antidepressive-like activity. In neuropharmacological studies, neither rosmarinic acid (10 x (-9)-10 x (-3) M) nor caffeic acid (10 x (-9)-10 x (-3) M) affected either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity in the mouse brain. These results suggest that both caffeic acid and rosmarinic acid may produce antidepressive-like activity via some mechanism(s) other than the inhibition of monoamine transporters and monoamine oxidase.     

Effects of Ca(2+) influx through nonselective cation channel on noradrenaline-induced mitogenic responses

We have recently shown that noradrenaline induces extracellular Ca(2+) influx through nonselective cation channel (NSCC) in Chinese hamster ovary cells expressing alpha(1A)-adrenoceptors (CHO-alpha(1A)). Moreover, this NSCC is sensitive to (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908) and resistant to 1-[b-(3-[4-Methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride (SK&F 96365). In the present study, we characterized the effects of extracellular Ca(2+) influx through NSCC on noradrenaline-induced mitogenic responses and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) of CHO-alpha(1A) using LOE 908 and SK&F 96365. Noradrenaline induced a mitogenic response in CHO-alpha(1A). LOE 908 completely inhibited the noradrenaline-induced mitogenesis, whereas SK&F 96365 did not inhibit it. The IC(50) value of LOE 908 for noradrenaline-induced mitogenesis was similar to that for the noradrenaline-induced increase in intracellular free Ca(2+) concentration ([Ca(2+)](i)). Noradrenaline stimulated ERK1/2 activity. The magnitude of noradrenaline-induced ERK1/2 activity in the absence of extracellular Ca(2+) was 40% of that in the presence of extracellular Ca(2+). LOE 908 partially (60%) inhibited the noradrenaline-induced ERK1/2 activity, whereas SK&F 96365 did not inhibit it. The IC(50) value of LOE 908 for noradrenaline-induced ERK1/2 activity was similar to that for the noradrenaline-induced increase in [Ca(2+)](i). Collectively, these results demonstrate that extracellular Ca(2+) influx through LOE 908-sensitive and SK&F 96365-resistant NSCC may be essential for noradrenaline-induced mitogenesis in CHO-alpha(1A). Moreover, the noradrenaline-induced ERK1/2 activity involves two distinct pathways, one dependent on extracellular Ca(2+) influx through NSCC, whereas the other is independent of the influx.