Large Ulceration of the Oropharynx Induced by Methotrexate-Associated Lymphoproliferative Disorders

We present a case of a 67-year-old Japanese man with a serious oropharyngeal ulceration that at first seemed to be destructive malignant lymphoma or oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete regression of the disease was observed, confirming our diagnosis

Speech Correction Class at Izushi Primary School ―History and recent problems―

Fifteen years have passed since the speech correction class was established at Izushi Primary School in Okayama. Of the 2252 children who studied in this class, 737 finished the curriculum. This class has played an important role in the education and rehabilitation of speech handicapped school children. The author introduced the history of this class and presented the recent problems

Rheb (Ras Homologue Enriched in Brain)-dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Activation Becomes Indispensable for Cardiac Hypertrophic Growth after Early Postnatal Period

Cardiomyocytes proliferate during fetal life but lose their ability to proliferate soon after birth and further increases in cardiac mass are achieved through an increase in cell size or hypertrophy. Mammalian target of rapamycin complex 1 (mTORC1) is critical for cell growth and proliferation. Rheb (Ras homologue enriched in brain) is one of the most important upstream regulators of mTORC1. Here, we attempted to clarify the role of Rheb in the heart using cardiac-specific Rheb-deficient mice (Rheb(−/−)). Rheb(−/−) mice died from postnatal day 8 to 10. The heart-to-body weight ratio, an index of cardiomyocyte hypertrophy, in Rheb(−/−) was lower than that in the control (Rheb(+/+)) at postnatal day 8. The cell surface area of cardiomyocytes isolated from the mouse hearts increased from postnatal days 5 to 8 in Rheb(+/+) mice but not in Rheb(−/−) mice. Ultrastructural analysis indicated that sarcomere maturation was impaired in Rheb(−/−) hearts during the neonatal period. Rheb(−/−) hearts exhibited no difference in the phosphorylation level of S6 or 4E-BP1, downstream of mTORC1 at postnatal day 3 but showed attenuation at postnatal day 5 or 8 compared with the control. Polysome analysis revealed that the mRNA translation activity decreased in Rheb(−/−) hearts at postnatal day 8. Furthermore, ablation of eukaryotic initiation factor 4E-binding protein 1 in Rheb(−/−) mice improved mRNA translation, cardiac hypertrophic growth, sarcomere maturation, and survival. Thus, Rheb-dependent mTORC1 activation becomes essential for cardiomyocyte hypertrophic growth after early postnatal period

p38α Mitogen-Activated Protein Kinase Plays a Critical Role in Cardiomyocyte Survival but Not in Cardiac Hypertrophic Growth in Response to Pressure Overload

The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, to heart failure is poorly understood. The mitogen-activated protein kinase p38α is a key component of stress response pathways in various types of cells. In this study, we attempted to explore the in vivo physiological functions of p38α in hearts. First, we generated mice with floxed p38α alleles and crossbred them with mice expressing the Cre recombinase under the control of the α-myosin heavy-chain promoter to obtain cardiac-specific p38α knockout mice. These cardiac-specific p38α knockout mice were born normally, developed to adulthood, were fertile, exhibited a normal life span, and displayed normal global cardiac structure and function. In response to pressure overload to the left ventricle, they developed significant levels of cardiac hypertrophy, as seen in controls, but also developed cardiac dysfunction and heart dilatation. This abnormal response to pressure overload was accompanied by massive cardiac fibrosis and the appearance of apoptotic cardiomyocytes. These results demonstrate that p38α plays a critical role in the cardiomyocyte survival pathway in response to pressure overload, while cardiac hypertrophic growth is unaffected despite its dramatic down-regulation