A CASE OF HODGKIN’S DISEASE EXHIBITING ERYTHRODERMIA PROBABLY DUE TO ALLERGIC REACTION TO VINCA ALKALOIDS

症例は58歳の男性。Hodgkin病の診断確定後，MOPP療法を開始したところ紅皮症の発現および好酸球増加を認めた。しかし，VCRとVDSをetoposideに変更すると紅皮症の発現はみられなくなり，治療の継続が可能となり寛解した。本例における紅皮症は，臨床経過からvinca alkaloid剤に対するアレルギー反応によると考えられた。VCR,VDSの主な副作用は血液障害，神経障害であるが，VDSにより紅皮症を生じた例の報告はまだない。化学療法には，複数の薬剤が同時に使われる場合が多く，副作用出現時にその原因薬剤の同定はしばしば困難である。したがって，薬剤の副作用についての症例の集積が重要と考えられる。A 58 year-old man with Hodgkin’s disease exhibited erythrodermia due to allergic reaction to vincristine sulfate (VCR) and vindesine sulfate (VDS). However, chemotherapy could be continued by changing VCR and VDS to etoposide without allergic symptom. Clinical observation strongly suggested that erythrodermia was due to the use of vinca alkaloids in this patient. Hematological and neurological side effects have been well known for VDS and VCR, but erythrodermia has not yet been reported as being caused by these agents. It is often difficult to difference drugs as a cause of an allergic reaction when several drugs are used together. Therefore, it is important to collect all the cases showing the effects of drugs

Age-Related Declines in the Ability to Modulate Common Input to Bilateral and Unilateral Plantar Flexors During Forward Postural Lean

Aging can impair an ability to lean the body forward to the edge of the base of support. Here, we investigated, using a coherence analysis, common inputs to bilateral and unilateral plantar flexor muscles to test a hypothesis that the age-related impairment would be related to strong synchronous bilateral activation and reduced cortical control of these muscles. Healthy young (n = 14) and elderly adults (n = 19), who were all right-foot dominant, performed quiet standing task and tasks that required the subjects to lean their body forward to 35 and 75% of the maximum lean distance. The electromyogram was recorded from the bilateral medial gastrocnemius (MG) and soleus (SL) muscles. We analyzed delta-band coherence, that reflects comodulation of muscle activity, between the bilateral homologous muscles (MG-MG and SL-SL pairs). The origin of this bilateral comodulation is suggested to be the subcortical system. Also, we examined beta-band coherence, that is related to the corticospinal drive, between the unilateral muscles (MG-SL pair) in the right leg. Results indicated that the bilateral delta-band coherence for the MG-MG pair was significantly smaller in the 75% forward lean than quiet standing and 35% forward lean tasks for the young adults (quiet: p = 0.036; 35%: p = 0.0011). The bilateral delta-band coherence for the SL-SL pair was significantly smaller in the 75% forward lean than 35% forward lean task for the young adults (p = 0.027). Furthermore, the unilateral beta-band coherence was larger in the forward lean than quiet standing task for the young adults (35%: p < 0.001; 75%: p = 0.029). Contrarily, the elderly adults did not demonstrate such changes. These findings suggest the importance of decreasing the synchronous bilateral activation and increasing the unilateral cortical control of the plantar flexor muscles for the successful forward postural lean performance, and that aging impairs this modulatory ability

マルトース発酵関連遺伝子のクローニングと染色体位置の決定（第２報）

Maltose fermentation activator protein, MAL63 homologue, MAL63 (NCYC1006), was cloned from S. cerevisiae NCYC1006. This yeast strain is top-fermenting yeast, and ferments maltose very well. Laboratory yeast S. cerevisiae YNN27 ferments maltose very poorly, however, the transformant with MAL63 (NCYC1006) could ferment maltose very well. Genome sequencing by a next generation sequencer revealed the chromosomal location of MAL63 (NCYC1006). These typical chromosomal structures are conserved among top-fermenting yeast strains and bottom-fermenting yeast strain

Periostin is essential for cardiac healingafter acute myocardial infarction

Acute myocardial infarction (AMI) is a common and lethal heart disease, and the recruitment of fibroblastic cells to the infarct region is essential for the cardiac healing process. Although stiffness of the extracellular matrix in the infarct myocardium is associated with cardiac healing, the molecular mechanism of cardiac healing is not fully understood. We show that periostin, which is a matricellular protein, is important for the cardiac healing process after AMI. The expression of periostin protein was abundant in the infarct border of human and mouse hearts with AMI. We generated periostin−/− mice and found no morphologically abnormal cardiomyocyte phenotypes; however, after AMI, cardiac healing was impaired in these mice, resulting in cardiac rupture as a consequence of reduced myocardial stiffness caused by a reduced number of α smooth muscle actin–positive cells, impaired collagen fibril formation, and decreased phosphorylation of FAK. These phenotypes were rescued by gene transfer of a spliced form of periostin. Moreover, the inhibition of FAK or αv-integrin, which blocked the periostin-promoted cell migration, revealed that αv-integrin, FAK, and Akt are involved in periostin signaling. Our novel findings show the effects of periostin on recruitment of activated fibroblasts through FAK-integrin signaling and on their collagen fibril formation specific to healing after AMI

Histochemical Nature of Eosinophilic Globules in Pheochromocytoma of Adrenal Medulla

Eosinophilic globules were observed in 7 out of 11 cases of pheochromocytoma of the adrenal medulla. All of these globules were present in the cytoplasm, and were round and eosinophilic, measuring 3 μm to 30 μm in diameter. These globules were periodic acid Schiff (PAS) -positive with and without diastase predigestion, phosphotungstic acid hematoxylin (PTAH) positive, acid fuchsin positive, and autofluorescent under ultraviolet illumination. These findings were very similar to the eosinophilic globules of yolk sac tumor, hepatocellular carcinoma, Kaposi\u27s sarcoma, and alpha-l-antitrypsin deficiency in light microscopy and histochemistry. They were not stained with Grimelius\u27s method for argyrophil reaction, and Fontana-Masson\u27s method for argentaffin reaction. It might be suggested that eosinophilic globules in pheochromocytoma of the adrenal medulla were not related to the chromaffin secretory granules and these globules were glycoprotein

Comparison of Count Normalization Methods for Statistical Parametric Mapping Analysis Using a Digital Brain Phantom Obtained from Fluorodeoxyglucose-positron Emission Tomography

Objective(s): Alternative normalization methods were proposed to solve the biased information of SPM in the study of neurodegenerative disease. The objective of this study was to determine the most suitable count normalization method for SPM analysis of a neurodegenerative disease based on the results of different count normalization methods applied on a prepared digital phantom similar to one obtained using fluorodeoxyglucose-positron emission tomography (FDG-PET) data of a brain with a known neurodegenerative condition.Methods: Digital brain phantoms, mimicking mild and intermediate neurodegenerative disease conditions, were prepared from the FDG-PET data of 11 healthy subjects. SPM analysis was performed on these simulations using different count normalization methods. Results: In the slight-decrease phantom simulation, the Yakushev method correctly visualized wider areas of slightly decreased metabolism with the smallest artifacts of increased metabolism. Other count normalization methods were unable to identify this slightly decreases and produced more artifacts. The intermediate-decreased areas were well visualized by all methods. The areas surrounding the grey matter with the slight decreases were not visualized withthe GM and VOI count normalization methods but with the Andersson. The Yakushev method well visualized these areas. Artifacts were present in all methods. When the number of reference area extraction was increased, the Andersson method better-captured the areas with decreased metabolism and reduced the artifacts of increased metabolism. In the Yakushev method, increasing the threshold for the reference area extraction reduced such artifacts.Conclusion: The Yakushev method is the most suitable count normalization method for the SPM analysis of neurodegenerative disease

Analysis of mRNA expression for steroidogenic enzymes in the remaining adrenal cortices attached to adrenocortical adenomas.

DESIGN AND METHODS: We have recently demonstrated that the adrenal cortices attached to aldosterone-producing adenoma (APA) contained microscopic subcapsular micronodules suggestive of active aldosterone production. In this study, we used in situ hybridization to investigate the mRNA expression of steroidogenic enzymes in the adrenal cortices attached to cortisol-producing adenoma (CPA) and clinically silent adenoma (non-functioning adenoma; NFA), in addition to APA. RESULTS: Microscopic subcapsular micronodules, which were several hundreds of micrometers in size and spheroid in shape, were observed in the cortices attached to CPA and NFA, as well as APA, at high frequency. Most of the cortical nodules in zona fasciculata to zona reticularis showed a suppressed steroidogenesis in the cortices attached to adenoma, but some expressed intensely all necessary steroidogenic enzyme mRNAs for cortisol synthesis. CONCLUSIONS: It is thus necessary to keep in mind, on the occasion of subtotal adrenalectomy, that lesions with the potential to later develop into functional adrenocortical nodules may be present in other parts of the ipsilateral or contralateral adrenal cortices

Spatial Frequency-Based Analysis of Mean Red Blood Cell Speed in Single Microvessels: Investigation of Microvascular Perfusion in Rat Cerebral Cortex

BACKGROUND: Our previous study has shown that prenatal exposure to X-ray irradiation causes cerebral hypo-perfusion during the postnatal development of central nervous system (CNS). However, the source of the hypo-perfusion and its impact on the CNS development remains unclear. The present study developed an automatic analysis method to determine the mean red blood cell (RBC) speed through single microvessels imaged with two-photon microscopy in the cerebral cortex of rats prenatally exposed to X-ray irradiation (1.5 Gy). METHODOLOGY/PRINCIPAL FINDINGS: We obtained a mean RBC speed (0.9±0.6 mm/sec) that ranged from 0.2 to 4.4 mm/sec from 121 vessels in the radiation-exposed rats, which was about 40% lower than that of normal rats that were not exposed. These results were then compared with the conventional method for monitoring microvascular perfusion using the arteriovenous transit time (AVTT) determined by tracking fluorescent markers. A significant increase in the AVTT was observed in the exposed rats (1.9±0.6 sec) as compared to the age-matched non-exposed rats (1.2±0.3 sec). The results indicate that parenchyma capillary blood velocity in the exposed rats was approximately 37% lower than in non-exposed rats. CONCLUSIONS/SIGNIFICANCE: The algorithm presented is simple and robust relative to monitoring individual RBC speeds, which is superior in terms of noise tolerance and computation time. The demonstrative results show that the method developed in this study for determining the mean RBC speed in the spatial frequency domain was consistent with the conventional transit time method

Akt1 in Osteoblasts and Osteoclasts Controls Bone Remodeling

Bone mass and turnover are maintained by the coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts, under regulation of many systemic and local factors. Phosphoinositide-dependent serine-threonine protein kinase Akt is one of the key players in the signaling of potent bone anabolic factors. This study initially showed that the disruption of Akt1, a major Akt in osteoblasts and osteoclasts, in mice led to low-turnover osteopenia through dysfunctions of both cells. Ex vivo cell culture analyses revealed that the osteoblast dysfunction was traced to the increased susceptibility to the mitochondria-dependent apoptosis and the decreased transcriptional activity of runt-related transcription factor 2 (Runx2), a master regulator of osteoblast differentiation. Notably, our findings revealed a novel role of Akt1/forkhead box class O (FoxO) 3a/Bim axis in the apoptosis of osteoblasts: Akt1 phosphorylates the transcription factor FoxO3a to prevent its nuclear localization, leading to impaired transactivation of its target gene Bim which was also shown to be a potent proapoptotic molecule in osteoblasts. The osteoclast dysfunction was attributed to the cell autonomous defects of differentiation and survival in osteoclasts and the decreased expression of receptor activator of nuclear factor-κB ligand (RANKL), a major determinant of osteoclastogenesis, in osteoblasts. Akt1 was established as a crucial regulator of osteoblasts and osteoclasts by promoting their differentiation and survival to maintain bone mass and turnover. The molecular network found in this study will provide a basis for rational therapeutic targets for bone disorders