Activation of the receptor protein tyrosine kinase EphB4 in endometrial hyperplasia and endometrial carcinoma

Background: Members of the Eph family of tyrosine kinases have been implicated in embryonic pattern formation and vascular development; however, little is known about their role in the adult organism. We have observed estrogen-dependent EphB4 expression in the normal breast suggesting its implication in the hormone-controlled homeostasis of this organ. Since the endometrium is a similarly hormone dependent organ and endometrial carcinoma is thought to result from estrogenic stimulation, we have investigated EphB4 expression in normal human endometrium and during its carcinogenesis. Patients and methods: EphB4 expression was analyzed immunohistochemically in 26 normal endometrium specimens, 15 hyperplasias and 102 endometrioid adenocarcinomas and correlated with clinical and prognostic tumor characteristics. Results: In normal endometrial tissue no EphB4 protein was detected. Strikingly, we observed a drastic increase (P <0.0001) in the number of EphB4 protein-expressing glandular epithelial cells in the majority of hyperplasias and carcinomas. Moreover, we found a statistically highly significant positive correlation between EphB4 expression and post-menopausal stage of the patient (P = 0.007). Conclusions: These findings indicate that in the endometrium, EphB4 is an early indicator of malignant development and, thus, EphB4 may represent a potent tool for diagnosis and therapeutic interventio

Recent Decisions

CHOICE OF LAW--WRONGFUL DEATH--GOVERNMENTAL-INTEREST ANALYSIS DETERMINES LAW APPLICABLE TO MEASURE OF DAMAGES IN CLAIMS ARISING FROM FOREIGN Air CRASH John Edison Drake =============== EUROPEAN COMMUNITIES--FREE MOVEMENT OF WORKERS--COURT OF JUSTICE SETS GUIDELINES FOR USE BY MEMBER STATES OF THE PUBLIC POLICY EXCEPTION IN ARTICLE 48 Heidi A. Rohrbach ================ TAX TREATIES--UNITED STATES MAY USE THE INTERNAL REVENUE CODE SUMMONING AUTHORITY TO OBTAIN DOMESTIC INFORMATION SOLELY TO AID A FOREIGN DOMESTIC TAX INVESTIGATION PURSUANT TO A TAX TREATY John R. Hellinger ============== TREATY INTERPRETATION--WARSAW CONVENTION-- PASSENGERS UNDERGOING SEARCH PREREQUISITE TO BOARDING ARE ENGAGED IN OPERATIONS OF EMBARKING Elizabeth Graeme Brownin

Staphylococcus aureus Small Colony Variants in Prosthetic Joint Infection

Background. Small colony variants of Staphylococcus aureus tend to persist despite antimicrobial therapy, especially when involved in implant-associated infections. Methods. We analyzed 5 cases of hip prosthesis-associated infections due to small colony variants, including their course prior to identification of the pathogen. Biopsy investigations included microbiological examination and, in 1 case, transmission electron microscopy to detect intracellular bacteria in nonprofessional phagocytes. A treatment concept was elaborated on the basis of a published algorithm and patients were managed accordingly. Results. The patients' mean age was 62.2 years. All patients experienced treatment failures prior to isolation of small colony variants, despite as many as 3 surgical revisions and up to 22 months of antibiotics. Transmission electron microscopy performed on biopsy specimens from periprosthetic tissue revealed intracellular cocci in fibroblasts. All prostheses were removed without implanting a spacer, and antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5 cases. Conclusions. In the case of a poor response to adequate antimicrobial and surgical treatment in implant-associated staphylococcal infections, small colony variants should be considered and actively sought. In our case series, a 2-stage exchange without implantation of a spacer combined with antimicrobial therapy for an implant-free interval of 6-8 weeks was associated with successful outcome, with a mean follow-up of 24 month

Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast

Summary Background: Axl, a member of a family of receptor tyrosine kinases characterized by an extracellular domain resembling cell adhesion molecules and an intracellular conserved tyrosine kinase domain has been reported to induce cell proliferation and transformation. In mice, axl is expressed in the normal mammary gland and over-expressed in aggressive mammary tumors. Patients and methods: We have investigated the expression of axl immunohistochemically in 23 normal human breast samples and in 111 consecutive breast carcinomas. Expression of axl was correlated with tumour characteristics (lymph node involvement, stage, grade) and immunohistochemical expression of ER, PR, Ki-67 and c-erbB-2. Results: In normal tissue, axl localizes to the membrane of breast epithelial cells. Axl protein shows membrane associated staining in high correlation (P = 0.004) with the expression of the estrogen receptor (ER). Axl expression was found in a subset of breast carcinomas and was also correlated with high significance (P < 0.0001) with the presence of ER. Conclusion: Our results suggest that axl may serve as a mediator of estrogen stimulation preventing the completion of the breast epithelial life cycle and that estrogen induced axl expression may give a survival signal to cancerous cells, preventing them from dying through apoptosi

A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound

MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of OCT compound used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that OCT compound also interferes with protein quantification assays, and that the presence of OCT compound impacts the quantification of extracted sphingolipids by LC-ESI-MS/MS. We developed and validated a simple and inexpensive method that removes OCT compound from OCT compound-embedded tissues. Our results indicate that removal of OCT compound from cryopreserved tissues does not significantly affect the accuracy of sphingolipid measurements with LC-ESI-MS/MS. We used the validated method to analyze sphingolipid alterations in tumors compared with normal adjacent uninvolved lung tissues from individuals with lung cancer and to determine the long-term stability of sphingolipids in OCT compound-cryopreserved normal lung tissues. We show that lung cancer tumors have significantly altered sphingolipid profiles and that sphingolipids are stable for up to 16 years in OCT compound-cryopreserved normal lung tissues. This validated sphingolipidomic OCT compound-removal protocol should be a valuable addition to the lipid biologist\u27s toolbox. Keywords: biorepository; cancer, ceramide; lipidomics; lung adenocarcinoma; lung squamous cell carcinoma; mass spectrometry; non-small cell lung cancer. Copyright © 2020 Rohrbach et al

Grazing Endophyte Infested Tall Fescue and Changes in Bovine Blood Components and Gain

Tall fescue (Festuca arundinacea) is utilized on more than 15 million ha of pasture in the eastern USA and over 80% of the plants in this area are infested with the endophyte Neotyphodium coenophialum. Tall fescue toxicosis results from consumption of the infested (E+) grass host and is an important problem that causes considerable economic loss to producers. However, the agronomic attributes of tall fescue make it an attractive forage because of its ability to withstand cool temperatures, drought, poor soil conditions and intensive defoliation. There is need to understand mechanisms of animal physiology that are affected by the alkaloids produced by the endophyte/grass association. Blood serum samples were collected from steers (Bos taurus) grazing either E+ or endophyte free (E-) tall fescue in spring and summer during three consecutive years and were related to animal performance. Consistent and significant changes associated with E+ tall fescue were noted for daily gain, prolactin, albumin/globulin ratio, alanine aminotransferase, cholesterol, creatinine, globulin, total bilirubin, total serum protein, copper, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, and eosinophils. Thus, repeatable changes that occur in serum biochemical and blood cellular values of cattle grazing E+ tall fescue were identified and will aid in understanding the pathogenesis of the toxicosis