Pseudoxanthoma elasticum diagnosed 25 years after the onset of cardiovascular disease.

A 63-year-old man who had experienced cerebral infarction and myocardial infarction at an early age, and repeatedly underwent coronary angioplasty was admitted to our hospital for cardiac evaluation. A coronary angiography showed complex multi-vessel disease with significant stenosis in all major vessels and coronary-artery bypass grafts. A funduscopic examination to evaluate hypertensive and diabetic changes revealed angioid streaks. Therefore, a skin biopsy was performed despite the absence of characteristic skin lesions. Histopathologic examinations revealed calcification and fragmentation of elastic fibers. Therefore, he was finally diagnosed as having pseudoxanthoma elasticum 25 years after the onset of cardiovascular disease.     

What is artificial endocrine pancreas？ Mechanism and history

The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocrine pancreas is now available in Japan： STG-22 （Nikkiso Co. Ltd., Japan）. In the insulin infusion algorithm, insulin is infused on the basis of its proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices.     

Decomposition of dextran sulfate sodium under alkaline, acidic, high temperature and high pressure conditions

The pathogenic mechanisms responsible for inflammatory bowel disease (IBD) are poorly understood. In an IBD animal model, the oral administration of polysaccharides such as dextran sulfate sodium (DSS) induced colitis, which exhibited several clinical and histological features similar to IBD. However, pathogenic factors in the development of colitis remain unclear, as do the chemical properties of DSS. Therefore, we investigated the chemical properties of DSS in this study. DSS reacted under 1 N acidic or alkaline conditions, and the reactants were analyzed using size exclusion and ion chromatography. The reactants were also analyzed in terms of metachromasia as a peculiarity of sulfated polysaccharides. DSS was depolymerized to a Mr 2500 moiety under acidic, but not under alkaline conditions. Sulfate was depleted from DSS under alkaline conditions (30%), but less so under acidic conditions (10%). In addition, autoclave treatment induced depolymerization to a Mr 1800 moiety and depleted the sulfate. This depolymerized DSS under acidic conditions has as many sulfates as a native DSS molecule with a Mr of 5000, exhibiting metachromasia as a peculiarity of sulfated polysaccharides. Therefore, these Mr 2500 or 1800 DSS molecules may be useful in investigating the mechanisms of DSS-induced colitis.     

Aurora A overexpression induces cellular senescence in mammary gland hyperplastic tumors developed in p53-deficient mice

Aurora A mitotic kinase is frequently overexpressed in various human cancers and is widely considered to be an oncoprotein. However, the cellular contexts in which Aurora A induces malignancy in vivo are still unclear. We previously reported a mouse model in which overexpression of human Aurora A in the mammary gland leads to small hyperplastic changes but not malignancy because of the induction of p53-dependent apoptosis. To study the additional factors required for Aurora A-associated tumorigenesis, we generated a new Aurora A overexpression mouse model that lacks p53. We present evidence here that Aurora A overexpression in primary mouse embryonic fibroblasts (MEFs) that lack p53 overrides postmitotic checkpoint and leads to the formation of multinucleated polyploid cells. Induction of Aurora A overexpression in the mammary glands of p53-deficient mice resulted in development of precancerous lesions that were histologically similar to atypical ductal hyperplasia in human mammary tissue and showed increased cellular senescence and p16 expression. We further observed DNA damage in p53-deficient primary MEFs after Aurora A overexpression. Our results suggest that Aurora A overexpression in mammary glands is insufficient for the development of malignant tumors in p53-deficient mice because of the induction of cellular senescence. Both p53 and p16 are critical in preventing mammary gland tumorigenesis in the Aurora A overexpression mouse model.     

Efficiency of Using Frozen-Thawed Testicular Sperm for Multiple Intracytoplasmic Sperm Injections

Purpose: To compare fertilization and pregnancy rates of fresh and frozen-thawed testicular sperm injections (TESE-ICSI). Methods: Sperm collected from the testes of 28 azoospermic patients by an open testicular biopsy technique was used for initial ICSI or cryopreserved. Results: Fresh-sperm ICSI treatment (28 cycles) resulted in a 58.1% fertilization rate and a 32.1% clinical pregnancy rate per embryo transfer, while frozen-thawed sperm (24 subsequent cycles) had rates of 54.5 and 29.2%, respectively. The PR was lower using frozen-thawed sperm from nonobstructive azoospermia patients (9.1%) than from obstructive azoospermia patients (46.2%). PR declined to 0% upon the fourth ICSI attempt. Conclusions: Fertilization, embryo cleavage, and pregnancy rates were unaffected by fresh or frozen-thawed sperm use. A 57.1% cumulative clinical PR was achieved using the latter. The PR was significantly lower using frozen-thawed sperm from nonobstructive azoospermia patients than from obstructive azoospermia patients.     

Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene.

We report a case of familial frontotemporal dementia and parkinsonism characterized by early onset with mental retardation. The patient died at the age of 54; neuronal loss was severe in the frontal and temporal cortices, globus pallidus, substantia nigra, red nucleus and dentate nucleus. Anti-tau-positive fibrillary changes were observed in neurons and glia in these regions. Although the patient had 2 novel point mutations of the tau gene, P301P (CCG to CCA) and an intron 10+11-splice site (T to C), exon trapping analysis indicated that the latter was pathogenic.