α-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer’s disease

The gene encoding α-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer’s disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that α-T-catenin is expressed in human brain, and like other α-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Aβ deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n>700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.     

Free and conjugated estrogens and androgens in stallion semen

The steroid content of semen from a total of 11 mature fertile stallions was studied during two breeding seasons and one winter. The levels of free and conjugated substrates (testosterone and androstenedione), and products (estradiol and estrone), of aromatase were measured by radioimmunoassay with a validated method. The results were seasonally and monthly highly variable with characteristic peaks. The concentrations of free and conjugated estrogens were always higher in the gel-free ejaculate than in the gel except in one subfertile stallion used as comparison. Furthermore, the steroid production and the maximal resulting aromatase activity, estimated by the estrogens/androgens ratio, peaked in April-May and June. The breeding season (spring and summer) presents a clear estrogenic profile with estrogens/androgens ratios higher in contrast to the nonbreeding period (autumn and winter). The involvement of estrogens in the regulation of reproduction and equine spermatogenesis is discussed, and estrogens production and thus equine aromatase is proposed as a strong marker of testicular endocrine function.     

Use of a local fasciocutaneous flap for treatment of exposed vascular grafts to the dorsalis pedis artery

Exposed or infected peripheral vascular grafts pose a significant challenge to the vascular surgeon. Although graft removal and extraanatomic bypass is feasible in selected circumstances, this procedure is generally not applicable for bypass to the pedal vessels. Preservation of patent grafts is almost always required for limb salvage. We present a case report of an exposed vein graft to the dorsalis pedis artery. We conclude that a local fasciocutaneous flap is an excellent treatment option, and describe the procedure in detail.     

Effects of human amniotic fluid and membrane in the treatment of Achilles tendon ruptures in locally corticosteroid-induced Achilles tendinosis: An experimental study on rats

BackgroundTo determine the effects of human amniotic fluid and membrane in the treatment of Achilles tendon ruptures, 72 tendons of 36 Wistar rats were injected with betamethasone sodium phosphate.MethodsBy the end of fourth week, both tendons were tenotomized and repaired, then the samples were divided into three groups. The first group was left untreated after suturing. Human amniotic fluid was injected to the second and amniotic fluid and membrane were both administered to the third group. Twenty-four tendons were scored at the end of the first week, and 24 at the end of the second week histopathologically, and 24 biomechanically at the end of the third week.ResultsThere was a significant statistical difference only between the histopathological results of Groups 2 and 3 at the first week.ConclusionsHuman amniotic membrane and fluid do not add anything to the healing process of Achilles tendon ruptures in the early phase.     

Lupus anticoagulants, thrombosis and the protein C system.

Although lupus anticoagulants (LAs) are immunoglobulins that inhibit procoagulant reactions in vitro, these molecules are associated with thrombosis in vivo. We and others have hypothesized that this may be due to selective targeting of the activated protein C (APC) anticoagulant pathway. Populations of antibodies that interact with protein C or protein S in ways that inhibit their activity are obvious candidates for such pathological molecules. However, it is less clear how populations that appear to bind to membrane surfaces might target the APC anticoagulant complex selectively. Studies now show that the membrane requirements of the APC anticoagulant complex are significantly different from those of the procoagulant reactions. The most dramatic difference is the requirement for the presence of phosphatidylethanolamine (PE) in the membrane for optimal APC function. The inhibitory activity of at least some LAs is enhanced by the presence of PE, but the anti-APC activity is enhanced even more, resulting in the plasma from these patients clotting faster than normal when APC is present. Structure-function studies have been undertaken to understand the PE dependence of this reaction better. Chimeric proteins in which all or part of the Gla domain of protein C has been replaced by the homologous region of prothrombin have been prepared. Unexpectedly, the PE dependence resides primarily in the C-terminal half of the Gla domain. Using liposomes of various composition, we found both the presence of the PE head group and unsaturation of the fatty acid chains are required for optimal inactivation of factor Va. It is hoped that a better understanding of the biochemistry of these reactions, combined with the use of the chimeric proteins described, will permit us to design better assays for the identification of pathologic LAs.     

Utility and complications of permanent venous access devices (PVAD) in oncological treatments. Follow-up of 100 cases.

BACKGROUND: Permanent venous access devices (PVAD) are nowadays routinely implanted and used with some morbidity for the oncological treatments. The adequate timing of implantation based on the number of treatments, the survival rate and the complications has not yet been well estimated. METHODS: A hundred permanent venous access devices placed in oncological patients were followed-up prospectively. RESULTS: No mortality was seen due to the surgical act. A 11% morbidity rate was noted, largely due to infections, with 6 patients needing a second surgery. On average, 6 chemotherapy cycles were done after placing of the permanent venous access device. CONCLUSIONS: Due to these results and an average survival rate of 10.7 months, we suggest the placing of a permanent venous access device early in the management of oncological patients requiring chemotherapy cycles, so as to increase the comfort of the patient and to safeguard his peripheral venous system.     

Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170-kDa protein detected by photoaffinity labeling.

Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit increased specific and saturable binding of vinblastine. To identify the molecules that bind vinblastine, membrane vesicles from multidrug-resistant cells were exposed to two analogs of vinblastine, N-(p-azido-[3,5-3H]benzoyl)-N'-(beta-aminoethyl)vindesine and N-(p-azido-[3-125I]salicyl)-N'-(beta-aminoethyl)vindesine, that could be photoactivated. Our studies show the specific labeling of a 150- to 170-kDa protein in membrane vesicles from two independently selected multidrug-resistant KB cell lines, which was not seen in drug-sensitive parental or revertant cell lines. The labeling of the high molecular weight protein was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at about 1 microM. Photolabeling was also inhibited by 100 microM vincristine or 100 microM verapamil but not by 100 microM colchicine or 100 microM dexamethasone. The data suggest that the 150- to 170-kDa protein may play an important role in the multidrug-resistance phenotype.     

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency

Journal of Clinical Immunology - NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are...