Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP) in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP) were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB) phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.</p

Two Cases of Unilateral Ashy Dermatosis

Ashy dermatosis is a typically asymptomatic disease of unknown origin that causes symmetrical gray spots to appear on the trunk and extremities. We report 2 cases of ashy dermatosis with unilateral distribution. To our knowledge, only 5 cases of ashy dermatosis with unilateral lesion have been reported so far. Case 1: an 11-year-old woman presented with asymptomatic slate-gray pigmented plaques on the left trunk and left upper arm. The skin biopsy specimen demonstrated a mild lymphohistiocytotic infiltrate in the upper dermis with epidermal and dermal melanosis. Q-Switched ruby laser did not improve such lesions. Case 2: a 21-year-old man was referred to our hospital because of asymptomatic slate-gray pigmented plaques on the left trunk and left upper arm. Histopathological findings were compatible with a mild lymphocytic infiltration with melanin incontinence in the upper dermis. The mechanism that governs unilateral distribution of ashy dermatosis, including in our cases, remains unclear

An Alternative Approach to Atopic Dermatitis: Part I—Case-Series Presentation

Atopic dermatitis (AD) is a complex disease of obscure pathogenesis. A substantial portion of AD patients treated with conventional therapy become intractable after several cycles of recurrence. Over the last 20 years we have developed an alternative approach to treat many of these patients by diet and Kampo herbal medicine. However, as our approach is highly individualized and the Kampo formulae sometimes complicated, it is not easy to provide evidence to establish usefulness of this approach. In this Review, to demonstrate the effectiveness of the method of individualized Kampo therapy, results are presented for a series of patients who had failed with conventional therapy but were treated afterwards in our institution. Based on these data, we contend that there exist a definite subgroup of AD patients in whom conventional therapy fails, but the ‘Diet and Kampo’ approach succeeds, to heal. Therefore, this approach should be considered seriously as a second-line treatment for AD patients. In the Discussion, we review the evidential status of the current conventional strategies for AD treatment in general, and then specifically discuss the possibility of integrating Kampo regimens into it, taking our case-series presented here as evidential basis. We emphasize that Kampo therapy for AD is more ‘art’ than technology, for which expertise is an essential pre-requisite

An Alternative Approach to Atopic Dermatitis: Part II—Summary of Cases and Discussion

In the first part of this Review, we presented case-series where Kampo treatment was introduced for those atopic dermatitis (AD) patients who had failed with conventional therapy, in an attempt to prove that there exists a definite subgroup of AD patients for whom Kampo treatment is effective. In this second part, we will first provide the summary of the results for 140 AD patients we treated in 2000. The results suggest that Kampo treatment is effective for more than half of AD patients who fail with conventional therapy. In the Discussion, we will examine the evidential basis for conventional AD therapy and discuss how Kampo treatment should be integrated into the guidelines for AD therapy. We contend that Kampo treatment should be tried before systematic immunosuppressive agents are considered. As each Kampo treatment is highly individualized, it should be regarded more as ‘art’ than technology, and special care should be taken to assess its efficacy in clinical trial

Bullous Pemphigoid IgG Induces BP180 Internalization via a Macropinocytic Pathway

Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell–extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein–tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG–induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG–induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis

18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit