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Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.

A case of pheochromocytoma was discovered incidentally during long-term hemodialysis for chronic renal failure due to acquired cystic kidney disease. A 52-year-old male patient was examined for weight loss of 3 kg during over a period of 3 months. Abdominal computed tomography (CT) revealed a left adrenal mass (3.0 cm in size). Plasma adrenaline and noradrenaline were increased to 521 pg/ml and 1,341 pg/ml, respectively, and the metoclopramide provocative test was positive. Further, in the scintiscan using 123I-metaiodobenzylguanidine (MIBG), an accumulation of the radionuclide in the left adrenal tumor region was confirmed. The patient is currently under observation and conservative treatment due to the possible occurrence of arterial hypotension after resection of the tumor and to lesser possibility of the malignancy.

A 35-year-old man was admitted because of significant hepatic dysfunction with mild splenomegaly and intra-abdominal lymphadenopathy of unknown cause. Infectious mononucleosis was suggested by subsequently detected high fever, pharyngotonsillitis and cervical lymphadenopathy, but IgM to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) showed dual positivity. A definite diagnosis of EBV-induced infectious mononucleosis was established 3 months later on the basis of seroconversion to Epstein-Barr nuclear antigen (EBNA)-IgG positivity and reduced CMV-IgM titer with persistently negative CMV-IgG. This case highlights the initial diagnostic difficulties of EBV-induced infectious mononucleosis particularly in older patients, due to concomitant abnormal humoral immunity and unusual initial manifestations such as significant liver injury and extensive intra-abdominal lymphadenopathy.

A 51-year-old man on hemodialysis was studied with Tc-99m MIBI and I-123 scintigraphy for the assessment of a parathyroid mass. Although the results for the parathyroid detection were negative, bone structure was incidentally visualized with Tc-99m MIBI. Bone scintigraphy with Tc-99m MDP and marrow scintigraphy with In-111 chloride did not indicate a high bone turnover or marrow hyperplasia.

The first successful treatment by plasma exchange of acute renal failure and disseminated intravascular coagulation, as well as liver and central nervous system damage, was achieved in two patients with severe multiorgan damage associated with extensive muscle tissue damage caused by heatstroke and/or electrical injury. Substances derived from damaged muscle tissue, such as myoglobin and enzymes, were efficiently removed by a cellulose acetate membrane filter. Improvement of consciousness, disturbance, coagulation disorder, and renal failure were observed. The disorders associated with extensive rhabdomyolysis seem to be a promising indication for this therapy. Plasma exchange with a membrane filter is useful for treatment of patients with renal failure, being readily connected on-line with conventional dialysis.