Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

Abeta-degrading endopeptidase,neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology

Metabolism of amyloid-beta peptide (Abeta) is closely associated with the pathology and etiology of Alzheimer's disease (AD). Since neprilysin is the only rate-limiting catabolic peptidase proven by reverse genetics to participate in Abeta metabolism in vivo, we performed detailed immunohistochemical analysis of neprilysin in mouse brain using neprilysin-deficient mice as a negative control. The aim was to assess, at both the cellular and subcellular levels, where Abeta undergoes neprilysin-dependent degradation in the brain and how neprilysin localization relates to Abeta pathology in amyloid precursor protein (APP)-transgenic mice. In hippocampus, neprilysin was present in the stratum pyramidale and stratum lacunosum-moleculare of the CA1-3 fields and the molecular layer of the dentate gyrus. Confocal double immunofluorescence analyses revealed the subcellular localization of neprilysin along axons and at synapses. This observation suggests that after synthesis in the soma, neprilysin, a type II membrane-associated protein, is axonally transported to the terminals, where Abeta degradation is likely to take place. Among various cell types, GABAergic and metabotropic glutamate 2/3 receptor-positive neurons but not catecholaminergic or cholinergic neurons, expressed neprilysin in hippocampus and neocortex, implying the presence of a cell type-specific mechanism that regulates neprilysin gene expression. As expected, Abeta deposition correlated inversely with neprilysin expression in TgCRND8 APP-transgenic mice. These observations not only support the notion that neprilysin functions as a major Abeta-degrading enzyme in the brain but also suggest that down-regulation of neprilysin activity, which may be caused by aging, is likely to elevate local concentrations of Abeta at and around neuronal synapses.     

Efficacy of postoperative adjuvant therapy for stage ilia breast cancer: Futraful vs futraful+tamoxifen for er-positive patients and futraful vs futraful + adriamycin for er-negative breast cancer

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located throughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage IIIa breast cancer. Patients with estrogen receptor-positive [ER( + )] breast cancer were treated with two types of regimens, ie, cyclophosphamide + adriamycin + fluorouracil (CAF; 2 cycles) + Futraful (FT) or CAF (2 cycles) + FT + tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER( + ) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation. The 5-year survival rate was 77.2% for the CAF + FT group and 74.6% for the CAF + FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF + FT + TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF + FT + TAM group was significantly higher than that for the corresponding patients in the CAF + FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF + FT+TAM group than in the CAF + FT group). Patients with estrogen receptor-negative [ER( -)] breast cancer were treated with two types of regimens, ie, CAF + FT or CAF + FT + adriamycin (ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478 (93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF + FT group and 63.0% for the CAF + FT + ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF + FT and CAF + FT + ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF + FT+ADR group than in the CAF + FT group.     

Endovascular treatment of ruptured dissecting aneurysms aimed at occlusion of the dissected site by using Guglielmi detachable coils

OBJECT: Surgical or endovascular occlusion of the parent artery proximal to an aneurysm has been recommended for treatment of dissecting aneurysms of the intracranial posterior circulation. However, dissecting aneurysms may rupture even after proximal occlusion because distal progression of thrombus is necessary to occlude the dissecting aneurysm completely, and this may be delayed by the presence of retrograde flow. In this article the authors present their experience in treating six patients with ruptured dissecting aneurysms. METHODS: The authors report on six patients with a ruptured dissecting aneurysm in the posterior fossa who were successfully treated by endovascular occlusion of the aneurysm by using Guglielmi detachable coils. The procedure was particularly aimed at occluding the dissected site. CONCLUSIONS: At the present time, endovascular occlusion of the dissected site is a safe, minimally invasive, and reliable treatment for dissecting aneurysms when a test occlusion is tolerated and adequate collateral circulation is present.     

Hormone receptors and obesity in Japanese women with breast cancer

Summary An association between hormone receptors in primary breast cancer and obesity determined prior to mastectomy was investigated in 128 Japanese women. The following criteria for obesity were used: (1) weight 60 kg (132 lbs), (2) weight kg/height cm–105 1.3, (3) weight lbs/height in 2.30, (4) body surface area 1.56 m². In view of the 4 criteria, tumor estrogen receptor (ER) values 4 fmol/mg were observed in obese patients more often than in nonobese patients, though the difference was not statistically significant. The same tendency was observed in the postmenopausal subgroup, 62 patients, especially in the 36 patients more than 5 years beyond menopause. However, there was still no statistical difference between obese and nonobese patients because the number of subjects was small. The same tendency was observed in the case of progesterone receptor (PgR) (6 fmol/mg) as observed in the case of ER. Address for reprints: Dr. Keijiro Kuno, Department of Surgery, Cancer Institute Hospital, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo, Japan 170     

Quantitative ultrastructure of physiologically identified premotoneuron terminals in the trigeminal motor nucleus in the cat

Little is known about the ultrastructure of synaptic boutons contacting trigeminal motoneurons. To address this issue, physiologically identified premotor neurons (n = 5) in the rostrodorsomedial part of the oral nucleus (Vo.r) were labeled by intracellular injections of horseradish peroxidase (HRP) in cats. The ultrastructure of 182 serially sectioned axon terminals from the five neurons was both qualitatively and quantitatively analyzed. In addition, the effects of the glycine antagonist strychnine, GABA(A) antagonist bicuculline, NMDA antagonist 2-amino-5-phosphonovalerate (APV), and non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on Vo.r-induced postsynaptic potentials in trigeminal motoneurons (n = 11) were examined to evaluate potential signaling substances of the premotor neurons. Labeled boutons made synaptic contacts with either jaw-closing or -opening motoneurons. All the boutons contained pleomorphic vesicles, and most formed a single symmetric synapse either on the somata or on primary dendrites. Morphometric analyses indicated that bouton volume, bouton surface area, apposed surface area, total active zone area, and mitochondrial volume were not different between boutons on jaw-closing and -opening motoneurons. Vesicle number and density, however, were higher for boutons on jaw-closing motoneurons. The five morphological parameters were positively correlated with bouton volume. Vesicle density was the exception, which tending to be negatively correlated. Intravenous infusion of strychnine or bicuculline suppressed Vo.r-induced inhibitory postsynaptic potentials (IPSPs) in jaw-closing motoneurons. Abolition of Vo. r-induced excitatory postsynaptic potentials in jaw-opening motoneurons with APV and CNQX unmasked IPSPs. The present results suggest that premotor neurons in the Vo.r are inhibitory and that positive correlations between the ultrastructural parameters associated with synaptic release and bouton size are applicable to the interneurons, as they are in primary afferents.