Human and mouse perforin are processed in part through cleavage by the lysosomal cysteine proteinase cathepsin L

Summary Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4⁺ T cells play a critical role in protective immunity, and that CD4⁺ T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4⁺ T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4⁺ T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post‐T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4⁺ T cells marked by down‐regulation of CD62L. These cells can be isolated from intestine‐draining mesenteric lymph nodes (MLN) from day 14 post‐infection, but are rare or absent in MLN before this and in spleen at all times post‐infection. Among CD4⁺ CD62L^low MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4⁺ CD62L^low T‐cell migration to the large intestinal mucosa is dependent on the family of Gα_i‐coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4⁺ CD62L^low cell migration to the large intestinal mucosa during T. muris infection.     

Relationships between suicide and three economic factors in South Korea

The number of suicides in South Korea totaled 4840 in 1995 and 8569 in 1998; in Japan, suicides totaled 21,420 in 1995 and 31,755 in 1998. Suicide prevention is an important issue for both South Korea and Japan. In South Korea, factors related to the increase in suicides must be clarified, and specific suicide prevention measures must be promptly discussed in order to decrease the number of suicides. Therefore, this report examined suicide and unemployment rates and increased rates of mining and industrial production and of money supply in South Korea from 1990 to 2002. This report also discusses the relationships between suicide and unemployment rates and increased rates of mining and industrial production and increased rates of money supply during the same period.During the period studied, annual suicide rates ranged from 7.1 to 18.3 per 100,000 populations. Multiple regression analysis indicated that the suicide rate was clearly related to the unemployment rate, but the suicide rate was not related to increased rates of mining and industrial production and increased rates of money supply. Thus, when unemployment rates increase, relevant organizations and the community should pay close attention to the increase in suicide rates.     

Causative factors as cues for addressing the rapid increase in suicide in Mie Prefecture, Japan: comparison of trends between 1996-2002 and 1989-1995

The number of suicides in Japan has increased from approximately 22 000 per year from 1988 to 1997 to >30 000 per year since 1998. Likewise, the number of suicides has been increasing in Mie Prefecture. The purpose of the present study was to examine the incidence of and circumstances surrounding all suicide cases during 1996-2002 in Mie Prefecture and to compare the data with those from 1989 to 1995. In Mie Prefecture, the age-specific suicide rate during the second 7-year period included marked increases among men aged 50-59 and 60-69 years. Among women, the age-specific suicide rate increased with age during both 7-year periods. During the second period, psychiatric disorders as causative factors increased in all generations. They were especially important for women of the younger generation, whereas economic problems were the most common causative factor among men aged 40-64. Physical illness as a causative factor in suicide was high among the elderly, but among the other age groups this factor trailed behind economic difficulties for men and psychiatric disorders for women. To prevent suicide, social cooperation as well as a plenitude of visiting nurses and psychiatric care is required, and early detection and treatment are also important.     

Acute brainstem compression by intratumoral hemorrhages in an intracranial hypoglossal schwannoma

A 77-year-old female in the hospital was found tachycardic and hypothermic by a nurse, and the patient’s respiration subsequently ceased. Forensic autopsy revealed an intracranial cystic tumor that would have compressed the brainstem. On microscopic examination, the tumor was diagnosed as an Antoni A schwannoma growth, and recent multiple intratumoral hemorrhages in the intracranial schwannoma were observed, suggesting the sudden enlargement of the intracranial schwannoma due to intratumoral hemorrhaging. Accordingly, we diagnosed the cause of death as brainstem compression induced by the intratumoral hemorrhaging in the intracranial schwannoma. Meanwhile, a rhinopharyngeal tumor was also detected by the autopsy, which was compatible with an antemortem diagnosis of a dumbbell-shaped hypoglossal schwannoma.     

Antioxidant and Physicochemical Properties of Hydrogen Peroxide‐Treated Sugar Beet Dietary Fibre

The aim of the present work was to examine if hydrogen peroxide treatment of sugar beet fibre that aimed at improving its physicochemical properties would impair its antioxidant potential. Three different sugar beet fibres were obtained from sugar beet – non‐treated fibre (NTF) from sugar beet cossettes extracted with sulphurous acid, treated fibre (TF) from NTF treated with hydrogen peroxide in alkaline solution and commercially available Fibrex^®. The antioxidant activity of extractable and non‐extractable fibre fractions in ethanol/water mixture (80:20, v/v) of three fibre samples was estimated. Non‐extractable fractions obtained after alkaline treatment of investigated fibres were much higher in phenolic compounds and possessed higher antioxidant potential than extractable fractions. Ferulic acid was proven to be the dominant phenolic acid. Regarding both extractable and non‐extractable fractions, Fibrex^® had the highest antioxidant activity in chemical tests, while NTF was superior in comparison with TF. Based on the results of Caco‐2 cells‐based test, all non‐extractable fractions possessed potential for reactive oxygen species inhibition. Regarding the extractable fractions, only the TF manifested this effect.Copyright © 2016 John Wiley & Sons, Ltd.     

N-tert-butyl-alpha-phenylnitrone, a free radical scavenger with anticholinesterase activity does not improve the cognitive performance of scopolamine-challenged rats

Reversible inhibitors of acetylcholinesterase improve spatial learning and memory in animal models of cognitive impairment. Here we investigate if the beneficial effects of free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on cognitive performance could be explained by its recently discovered anticholinesterase activity. Morris water maze experiment was performed to examine the effect of PBN on the impairment of spatial learning and memory induced by the antagonist of cholinergic muscarinic transmission scopolamine. In situ hybridization histochemistry experiment was performed to study its effects on the induction of immediate early gene expression (c-fos, c-jun) by dopamine D1 receptor agonist SKF-82958 and on the augmentation of the SKF-82958-induced expression of these genes by scopolamine. In both experiments, the effects of PBN were compared to the effects of reversible anticholinesterase physostigmine. We found that physostigmine but not PBN significantly reversed the cognitive impairment in scopolamine-challenged rats, prevented the induction of c-fos and c-jun mRNAs by SKF-82958 and attenuated the augmentation of the SKF-82958-induced expression of these genes by scopolamine. The present experiments did not reveal a significant in vivo anticholinesterase activity of PBN.     

Sudden unexpected death in childhood due to eosinophilic myocarditis

A 12-year-old boy with no previous serious medical history experienced abdominal discomfort and chest pains for 5 days and suddenly died. The autopsy revealed diffuse and extensive infiltration of eosinophils into the myocardium, with poorly formed granulomas and few fibrotic changes. The necrotic change was so extensive that Charcot-Leyden crystals formed. The other visceral organs had no specific pathologic changes except for mild lymphocytic infiltration with an increase in goblet cells in the bronchial areas and eosinocytosis in the blood vessels. An initial viral infection. seemed to have caused subsequent eosinophil activation due to an allergic condition. Eosinophilic myocarditis is a rare cause of sudden death in apparently healthy children. Cardiac toxicity of eosinophils is, however, well established and dominates the ultimate prognosis of patients with complicated eosinophilia.