The development of anti-glomerular basement membrane nephritis in two children with Alport's syndrome after renal transplantation: characterization of the antibody target

Two children with Alport's syndrome are described, who developed anti-glomerular basement membrane (GBM) antibody-mediated nephritis after renal transplantation. The reactivity of antibodies in their serum with collagenase-solubilized normal GBM was examined by SDS-PAGE with one- and two-dimensional immunoblotting. The specificity was compared with that of antibodies present in serum from a patient with Goodpasture's syndrome, and a mouse monoclonal antibody (MCA-P1), directed against the Goodpasture antigen. All reacted in a similar way with collagenase-solubilized GBM. Since abnormalities in the composition of the GBM are present in Alport's syndrome, it is proposed that differing antigen composition of GBM in the host compared with the donor kidney, together with transplant rejection, may have provoked the development of post-transplant anti-GBM antibodies.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.      

Comparison of antigenic targets involved in antibody-mediated membranous glomerulonephritis in the mouse and rat

Membranous glomerulonephritis in the mouse can be induced by a single injection of an antiserum against homologous, pronase-digested, renal tubular antigens (TAPron). In indirect immunofluorescence studies on normal mouse and rat kidneys it has now been found that the antiserum reacts strongly with the visceral epithelia of the mouse in a homogeneous pattern, while a faint granular staining is seen in the rat glomerulus against a homogeneous background. After injection in rats, a classic passive Heymann nephritis could be induced. By immunoprecipitation of radiolabeled rat renal brush borders (BB) it could be shown that anti-TAPron antisera contain antibodies to 330-kd and 90-kd BB proteins expressed by rat glomeruli. With the use of two monoclonal antibodies specific for the 330- and 90-kd proteins the homogeneous binding observed in rat and mouse glomeruli could be related to the 90-kd antigen, whereas the coarse irregular staining observed in rat glomeruli was only related to the 330-kd antigen. Immunoglobulins eluted from glomeruli of rats bound to rat glomeruli and reacted only with the 330-kd protein. They did not bind to mouse glomeruli. Discrete localization in coated pits, multivesicular bodies, and endoplasmic reticulum of the visceral epithelia was seen in immunoelectron-microscopy. The results presented thus demonstrate that immune deposits induced in the rat by anti-TAPron antibodies are related to antibodies specific for the 330-kd antigen, ie, the classic Heymann antigen. By contrast, immune deposits observed in the mouse are related to antibodies specific for a 90-kd protein.     

Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function

Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(−/−) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein.     

Knowledge of cardiovascular disease prevention: an analysis from two New England communities.

BACKGROUND: Cardiovascular disease (CVD) mortality has been decreasing in the United States, possibly due in part to educational programs about CVD prevention. This study investigates CVD risk-reduction knowledge among demographic subgroups in two New England cities and how the level of knowledge changed in these subgroups over time. METHODS: Six independent cross-sectional surveys including a series of open-ended recall CVD knowledge questions were conducted biennially from 1981 to 1993 as part of the outcome evaluation for the Pawtucket Heart Health Program. We constructed a raw CVD knowledge score and then created an analysis of variance model with knowledge score as the dependent variable and explanatory variables including demographics, survey, and city. RESULTS: CVD prevention knowledge improved significantly over time in both cities and in every demographic subgroup, increasing rapidly from 1981 to about 1988 and then plateauing between 1988 and 1993. Adjusted knowledge scores were higher for people born in the United States, women, more educated individuals, and those who spoke English at home. The increase in knowledge over time came mainly from an increase in the identification of physical inactivity, and blood cholesterol/high fat diet as CVD risk factors, while there was a decrease in the identification of overweight and blood pressure. CONCLUSIONS: In order to assure that reductions in CVD morbidity and mortality will be sustained, national educational efforts which stress behavior change skills as well as knowledge must continue. These programs should focus particularly on higher risk subgroups, and risk factors such as weight reduction and blood pressure control should be special priorities.