Acute effects of adaptive servo ventilation on hemodynamics, coronary flow, and flow reserve in a patient with idiopathic dilated cardiomyopathy

Adaptive servo ventilation (ASV) is reported to be effective for the treatment of heart failure. We treated a patient with idiopathic dilated cardiomyopathy using ASV and assessed the effects on hemodynamics, coronary flow, and flow reserve before and after ASV therapy. This case suggests that ASV might decrease myocardial oxygen demand, which was represented by the decreased resting coronary flow velocity (the improvement of coronary flow velocity reserve) on ASV.     

Effect of VA-045, a novel apovincaminic acid derivative,on closed head injury-induced neurological dysfunction in aged rats

Abstract

Objective: The strength–duration time constant (SDTC) is a measure of axonal excitability and it can provide information about Na⁺ channel function. In this study, we sought to examine the changes in the SDTCs of motor and sensory fibers of the median nerve in patients taking colchicine, which affects axoplasmic flow and may result in axonal neuropathy.

Methods and results: The SDTCs of motor and sensory fibers of 29 patients who had been taking colchicine were measured following stimulation of the right median nerve at the wrist. The results were compared with ten healthy age-matched subjects. No significant differences were found between the groups.

Conclusions: The lack of any effect on the SDTC by colchicine might have been due to the fact that axonal degeneration caused by colchicine affects the Na⁺–K⁺ ATP pump or that it affects internodal channels other than nodal channels.     

New-onset psychiatric disorders after corticosteroid therapy in systemic lupus erythematosus: an observational case-series study

The objective of this study was to clarify the incidence, clinical characteristics, and courses of new-onset psychiatric manifestations after corticosteroid therapy in patients with systemic lupus erythematosus (SLE), including possible ways of differentiating between corticosteroid-induced psychiatric disorders (CIPDs) and central nervous system manifestations of SLE (CNS-SLE). We prospectively followed for 8 weeks 139 consecutive episodes in 135 in-patients who had a non–CNS-SLE flare treated with corticosteroids. Psychiatric events were evaluated once a week using DSM-IV criteria. We then conducted a post hoc etiological analysis of any newly developed psychiatric events during this follow-up period. In the 8 weeks of corticosteroid administration, new psychiatric events occurred in 20 (14.4 %) of the 139 episodes. The mean dosage of corticosteroids administered was prednisolone at 0.98 (range 0.24–1.39) mg/kg/day. Of the 20 psychiatric events, 14 (10.1 %) were suitable for the strict definition of CIPDs, accompanied by mood disorders in 13 (depressive in 2, manic in 9, and mixed in 2) and psychotic disorder in one. Two (1.4 %), both presenting delirium, were diagnosed as CNS-SLE on the basis of evidence of abnormal CNS findings even before psychiatric manifestations, all of which improved in parallel with these patients’ recoveries through augmentation of immunosuppressive therapy. The other four events (2.9 %) could not be etiologically identified. This study suggests that corticosteroid therapy triggers CIPDs and CNS-SLE in patients with SLE. Delirium may be suggestive of CNS-SLE, while mood disorders may be more suggestive of CIPDs. Electroencephalographic abnormalities may possibly be predictive of CNS-SLE.     

Specific Expression of Apolipoprotein A-IV in the Follicle-Associated Epithelium of the Small Intestine

Background

Peyer’s patches (PPs), which are covered by specialized follicle-associated epithelium (FAE) including M cells, play a central role in immune induction in the gastrointestinal tract. This study is to investigate a new molecule to characterize PPs.

Methods

We generated a monoclonal antibody (mAb 10-15-3-3) that specifically reacts to the epithelium of PPs and isolated lymphoid follicles. Target antigen was analyzed by immunoprecipitation and mass spectrometry. Localization and expression of target antigen were evaluated by immunofluorescence, in situ hybridization and real-time PCR.

Results

Immunoprecipitation and mass spectrometry revealed that mAb 10-15-3-3 recognized apolipoprotein A-IV (ApoA-IV), a well-known lipid transporter; this finding was confirmed by the specific reactivity of mAb 10-15-3-3 to cells transfected with the murine ApoA-IV gene. Immunofluorescence using mAb 10-15-3-3 showed intestinal localization of ApoA-IV, in which strong expression of the ApoA-IV protein occurred throughout the entire intestinal epithelium during developing period before weaning but was restricted to the FAE in adult mice. In support of these findings, in situ hybridization showed strong expression of the ApoA-IV gene throughout the entire intestinal epithelium during developing period before weaning, but this expression was restricted to the FAE predominantly and the tips of villi to a lesser extent in adult mice. Deficiency of ApoA-IV had no effect on the organogenesis of PP in mice.

Conclusions

Our current results reveal ApoA-IV as a novel FAE-specific marker especially in the upper small intestine of adult mice.     

The scaffold protein JLP plays a key role in regulating ultraviolet B‐induced apoptosis in mice

The ultraviolet B (UVB) component of sunlight can cause severe damage to skin cells and even induce skin cancer. Growing evidence indicates that the UVB‐induced signaling network is complex and involves diverse cellular processes. In this study, we investigated the role of c‐Jun NH₂‐terminal kinase‐associated leucine zipper protein (JLP), a scaffold protein for mitogen‐activated protein kinase (MAPK) signaling cascades, in UVB‐induced apoptosis. We found that UVB‐induced skin epidermal apoptosis was prevented in Jlp knockout (KO) as well as in keratinocyte‐specific Jlp KO mice. Analysis of the repair of UVB‐induced DNA damage over time showed no evidence for the involvement of JLP in this process. In contrast, UVB‐stimulated p38 MAPK activation in the skin was impaired in both Jlp KO and keratinocyte‐specific Jlp KO mice. Moreover, topical treatment of UVB‐irradiated mouse skin with a p38 inhibitor significantly suppressed the epidermal apoptosis in wild‐type mice, but not in Jlp KO mice. Our findings suggest that JLP in skin basal keratinocytes plays an important role in UVB‐induced apoptosis by modulating p38 MAPK signaling pathways. This is the first study to show a critical role for JLP in an in vivo response to environmental stimulation.     

Relation of circulating interleukin-6 to left ventricular remodeling in patients with reperfused anterior myocardial infarction

BACKGROUND: During the remodeling process after myocardial infarction (MI), the expression of proinflammatory cytokines is enhanced in the myocardium. However, only a few clinical studies have been conducted on cytokine involvement in left ventricular (LV) remodeling after MI. HYPOTHESIS: Circulating proinflammatory cytokines may be involved in LV remodeling in patients with reperfused MI. METHODS: We studied 25 patients with acute anterior MI who had undergone coronary reperfusion therapy, and 10 normal control subjects with no cardiac disease. In all patients, LV ejection fraction, end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) were determined using left ventriculography at the acute phase and 6 months after onset. The delta EDVI and delta ESVI were calculated as the value of LV volume reduction, suggesting LV reverse remodeling. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were measured using enzyme-linked immunosorbent assay. RESULTS: Serum levels of IL-6 and TNF-alpha at the acute phase were significantly higher in patients with MI than in control subjects (both p < 0.05). The IL-6 levels correlated well negatively with delta EDVI (r = 0.779, p = 0.039), whereas no correlation was found for TNF-alpha. According to multivariate analysis, IL-6 at the acute phase was a significant independent predictor for LV remodeling after reperfused MI (p = 0.007). CONCLUSIONS: Circulating IL-6 levels correlated closely with LV geometric changes during the remodeling process in patients with reperfused MI. Our study addresses the usefulness of another marker for LV remodeling after MI.     

Progressive Cytopenia Developing during Treatment of Cryptococcosis in a Patient with HIV Infection and Bone Marrow Cryptococcal Infection

Cytopenia is a common complication in patients with human immunodeficiency virus (HIV) infection. Identifying the cause is demanding because of the wide range of possible diagnoses. We herein report an HIV-infected patient with disseminated cryptococcosis involving multiple organs including the blood, brain, lungs, and bone marrow, who developed progressive pancytopenia after initiation of anti-fungal treatment with liposomal amphotericin-B (L-AMB) and flucytosine (5FC). The pancytopenia persisted despite early 5FC discontinuation. A bone marrow biopsy revealed cryptococcal infiltration and the blood examination findings recovered quickly after resuming L-AMB. Thus, this HIV-infected patient''s pathological findings and clinical course suggested that the primary cause of the pancytopenia was bone marrow cryptococcosis.     

Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia

Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.     

Soluble interleukin-2 receptor level on day 7 as a predictor of graft-versus-host disease after HLA-haploidentical stem cell transplantation using reduced-intensity conditioning

In the present study, we analyzed the kinetics of serum soluble interleukin-2 receptor (sIL-2R) using data from 77 patients undergoing HLA-haploidentical transplantation using reduced-intensity conditioning (RIC), who were at an advanced stage or at high risk for relapse, to clarify the usefulness of sIL-2R as a biomarker of acute graft-versus-host disease (GVHD). Anti-T-lymphocyte globulin and methylprednisolone were used as GVHD prophylaxis. While the median sIL-2R in 38 patients not developing GVHD was suppressed at levels <740 U/ml, sIL-2R in 25 patients developing severe GVHD peaked on day 11 (1,663 U/ml), and thereafter decreased to <1,000 U/ml after day 30. The occurrence of GVHD was not limited to times of high sIL-2R level, but occurred at any time point on the sIL-2R curve. Most patients developing GVHD, however, experienced a higher sIL-2R level early in their transplant course. The combination of RIC and glucocorticoids sufficiently suppressed sIL-2R levels after HLA-haploidentical transplantation. In a multivariate analysis to identify factors associated with GVHD, day 7 sIL-2R >810 U/ml was the only factor significantly associated with the occurrence of severe GVHD (p = 0.0101).