The pathogenic L392V mutation of presenilin 1 decreases the affinity to glycogen synthase kinase-3 beta

Determination of the effects of presenilin 1 (PSEN1) mutations, involved in autosomal dominant early-onset Alzheimer's disease (ADEOAD), on the interaction between PSEN1 and binding proteins is essential to determine which interactions are involved in Alzheimer's disease (AD) pathogenesis. The PSEN1 binding protein glycogen synthase kinase-3 beta (GSK-3 beta) has been considered as a key protein in AD pathogenesis since GSK-3 beta phosphorylates tau and hyperphosphorylated tau is a main component of neurofibrillary tangles associated to AD. We show here, using surface plasmonic resonance, that the pathogenic L392V mutation, identified in a large French ADEOAD pedigree including 39 affected members, leads to a decreased affinity to GSK-3 beta. We conclude therefore that the increase of affinity of PSEN1 to GSK-3 beta reported in previous studies is not a common effect of pathogenic mutations associated to ADEOAD.     

Numerical and Functional Characteristics of Lymphocyte Subsets in Centenarians

The immune system in the aged is a very interesting subject for study. In this study, analysis was extended to extrathymic T cells as well as NK cells and conventional T cells (i.e., thymus-derived T cells) in terms of their constitution and function in both healthy and unhealthy centenarians. Middle-aged persons were used as controls. Healthy and unhealthy centenarians showed lower levels in the proportion and absolute number of lymphocytes. The major change in the constitution of lymphocyte subsets was increased levels in the proportion of NK cells (CD56⁺/CD57⁺) and extrathymic T cells (CD3⁺CD57⁺). Inversely, conventional T cells decreased in proportion and function (i.e., proliferative response to mitogen). Although NK cells increased in centenarians, NK activity by whole lymphocytes and the purified NK fraction decreased. The difference between healthy and unhealthy centenarians was small in all parameters, the only difference being a lower level of expression of CD56 antigens on CD57⁺ T cells in unhealthy centenarians. These results indicate that there is a major shift in lymphcyte population from conventional T cells to NK cells and extrathymic T cells with aging. Concerning the age-associated increases in CD56⁺ T and CD57⁺ T cells, these cells correspond to NK1⁺ T cells in mice.     

Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples

A growing shortage of cadaveric donors has prompted expansion of the criteria for acceptable living donors. Because of this, ABO-incompatible kidney transplantation has been carried out. To remove anti-A and/or anti-B antibodies, the recipients received one or two sessions of double filtration plasmapheresis (DFPP) and three or four sessions of immunoadsorption prior to transplantation until the anti-A IgG/IgM titers and/or anti-B IgG/IgM titers decreased to 1:16 or less. Our immunosuppressive protocol involved treatment with the drugs methylprednisolone, cyclosporine, azathioprine, anti lymphocyte globulin and deoxyspergualin. The patient survival was 98% at 1 month, 98% at 3 months, 94% at 6 months, and 92% at 1-5 years. Graft survival was 92% at 1 month, 88% at 3 months, 85% at 6 months, 81% at 1 year, and 76% at 5 years. Both DFPP and/or immunoadsorption eliminated anti-ABO antibodies from ABO-incompatible kidney transplant recipients effectively and safely. The results of the ABO-incompatible kidney transplantation were acceptable and not different from those of ABO-compatible cases.     

A survey on the vaccination practice for perinatal hepatitis B virus infection at a clinic in Okinawa, Japan

The prevalence of hepatitis B (HB) virus carrier mothers and the HB immunization rate at a clinic in Okinawa prefecture were investigated. The prevalence of HB virus carrier mothers during 1981-1985, 1986-1994 and 1995-1997 were 3.5%, 2.3% and 1.1% respectively. According to the national prevention program, passive-active immunoprophylaxis with HB immune globulin (HBIG) and HB vaccine was carried out for 12 infants born to HB virus carrier mothers positive for HBe antigen (high risk infants) and for 24 infants born to carrier mothers negative for HBe antigen (low risk infants) since 1986. The immunization rate of high risk infants and low risk infants were 100.0% and 91.7%, respectively. A follow up system for the prevention program and assessment of vaccination schedule will be necessary to improve HB immunization rate of low risk infants in the future.     

Diagnosis of neonatal hemochromatosis with MR imaging and duplex Doppler sonography

Neonatal hemochromatosis is a rare congenital disorder which affects both fetuses and newborns. It is characterized by hepatocellular failure, often appearing on the first day of life in the form of coagulopathy, hypoalbuminemia, hypoglycemia, and jaundice. Most of the affected infants die early in life, and definitive diagnosis has often been made only by post-mortem evaluation. With the help of MRI, plus increasing awareness of the disorder, diagnosis is now often made early, even in utero. Duplex Doppler sonography does not provide information on siderosis but shows abnormalities in the liver or blood-flow patterns associated with liver disease. Received: 24 September 1998; Revised: 23 November 1998; Accepted: 27 January 1999     

Cell proliferation effect of lactoferrin in human endometrial stroma cells

The aim of this study was to evaluate the effect of lactoferrin (LF) on the proliferation of human endometrial stroma cells. In addition, we compared the effect of LF, oestradiol and epidermal growth factor (EGF) on the proliferation of human endometrial stroma cells. Human endometrial tissue was obtained from patients with a normal menstrual cycle in the proliferative phase and the stroma cells were isolated and cultured in vitro. When LF was added to the culture medium, the rate of cell proliferation increased significantly in comparison to controls (P < 0.01). The enhanced rate of proliferation induced by LF was neutralized by the addition of anti-LF monoclonal antibody. The effect of LF on cell proliferation at a concentration of 100 ng/ml was similar to that of 10 nmol/l oestradiol, but less than that of 10 mg/ml EGF. When LF was added in combination with either oestradiol or EGF, no additive effects on cell proliferation were observed. Based on the present results, it is suggested that LF has a potential biological effect in the proliferation of human endometrium.     

Transplantable urothelial cell sheets harvested noninvasively from temperature-responsive culture surfaces by reducing temperature

Augmentation cystoplasty using gastrointestinal flaps may induce severe complications such as lithiasis, urinary tract infection, and electrolyte imbalance. The use of viable, contiguous urothelial cell sheets cultured in vitro should enable us to avoid these complications. Transplantable urothelial cell sheets were obtained by utilizing a temperature-responsive cell culture method, and then examined by immunostaining and electron microscopy. Canine urothelium was produced on the surfaces of temperature-responsive culture dishes covalently bonded with the thermally sensitive polymer, poly(N-isopropylacrylamide). Stratified urothelial cell sheets were cultured and then harvested intact without enzymatic treatment from these dishes by reducing the temperature. Histological structure and cell-to-cell junctions were compared between these urothelial cell sheets and those harvested with dispase. All urothelial cell sheets were harvested from the bonded surfaces by reducing the culture temperature without the need for dispase. Electron microscopy revealed well-developed microridge, microvilli, and cell junction complexes. Conversely, these same cell features were destroyed by dispase treatment. Immunoblotting revealed that dispase fragmented occludin, whereas it remained unchanged in the intact urothelial cell sheets. Novel urothelial cell sheets obtained by culture on temperature-responsive culture surfaces were successfully harvested much less destructively than with dispase. This technology should prove useful in urinary tract tissue engineering in the near future.