Mutations of histone demethylase genes encoded by X and Y chromosomes, Kdm5c and Kdm5d, lead to noncompaction cardiomyopathy in mice.

Mammalian X and Y chromosomes evolved from a pair of autosomes. Although most ancestral genes have been lost from the Y chromosome, a small number of ancestral X-Y gene pairs are still present on the sex chromosomes. The KDM5C and KDM5D genes, which encode H3K4 histone demethylases, are a surviving ancestral gene pair located on the X and Y chromosomes, respectively. Mutations in KDM5C cause X-linked intellectual disability in human males, suggesting functional divergence between KDM5C and KDM5D in the nervous system. In this study, to explore the functional conservation and divergence between these two genes in other organs, we generated female mice lacking Kdm5c (homozygous X5c- X5c- females) and male mice lacking both Kdm5c and Kdm5d (compound hemizygous X5c- Y5d- males). Both X5c- X5c- females and X5c- Y5d- males showed lower body weights and postnatal lethality. Histological examination of the hearts showed prominent trabecular extension and a thin layer of compacted myocardium in the left and right ventricles, indicating noncompaction cardiomyopathy. However, hemizygous males lacking either Kdm5c or Kdm5d showed no signs of noncompaction cardiomyopathy. These results clearly demonstrate that the function of Kdm5c and Kdm5d in heart development is conserved.

[Effect of an educational admission program for patients at the conservative phase of chronic kidney disease (CKD)].

PURPOSE: We have been conducting a 1-week educational admission program for patients at the conservative phase of chronic kidney disease (CKD) since 2006. In this study we evaluated the effect of the program. METHODS: We retrospectively reviewed 469 patients who could be followed for 12 months after a 1-week educational admission program for CKD out of a total of 700 patients who attended the program between October 2006 and April 2012. We compared the rates of decrease in renal function before and after the program. In addition, we divided the patients into two groups of diabetic nephropathy and non-diabetic nephropathy. We compared the rate of decrease in renal function in each group. RESULTS: The rate of decrease in renal function 12 months after discharge was improved compared with that 6 months before admission. (before: 0.316 mL/min/1.73 m2/month; after: 0.001 mL/min/1.73 m2/month.) The rate of decrease in renal function 6 months before admission of the diabetic nephropathy group was 72.3 times faster than that of the non-diabetic nephropathy group. However, the rate of decrease in renal function 12 months after admission was improved in both groups. CONCLUSION: It was revealed that the educational admission program is effective for preserving the renal function on patients at the conservative phase of CKD.

[Case of lupus nephritis complicated with hemophagocytic syndrome].

A 27-year-old woman was referred to our hospital because of pancytopenia and nephritic syndrome in November, 2008. The findings of physical and laboratory examinations showed systemic lupus erythematosus (SLE). Diffuse proliferative lupus nephritis(group IV-G(A))was confirmed by renal biopsy. After combined therapy with prednisolone, intravenous cyclophosphamide pulse and mizoribine, proteinuria decreased from 13.0 g/day to 2.0 g/day and the serum complement level recovered to the normal level. However, she visited our hospital again for management of bleeding tendency in July 2009. She was diagnosed as hemophagocytic syndrome (HPS), with pancytopenia, high ferritin, high LDH level and hemophagocytosis in the bone marrow. She was treated effectively with steroid pulse therapy, but relapsed with HPS after two weeks. Although her child caught a cold, the case did not show any sign or symptom of infection, such as the common cold. However, we diagnosed her HPS as infection-associated hemophagocytic syndrome (IAHS) because she was not in the active phase of SLE at the onset of hemophagocytosis and the laboratory findings showed elevation of her serum ferritin and LDH. Therefore, we considered that her infectious sign may have been concealed by immunosuppressive therapy with prednisolone for SLE. It is very difficult to distinguish between IAHS and autoimmune-associated hemophagocytic syndrome (AAHS)in autoimmune diseases, but the differential diagnosis is necessary to treat the HPS. Here, we report an important case of HPS complicated with SLE. This case may attract interest particularly in the management of HPS-complicated autoimmune disease. Therefore, we report it with a review of the literature.