University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences

Abstract: Problem One immunoregulatory pathway receiving little attention is placental exosome release. In normal pregnancy, as factors linked with early immunomodulation decline, placental exosomes become critical in modulating T-cell activation, suppressing effector T cells by enhancing lymphocyte apoptosis and CD3-zeta loss. Method of study Placental exosomes were specifically isolated from the maternal peripheral circulation by a chromatographic/immunosorbent procedure. Exosomal suppression of T-cell signaling molecules on unfractionated T cells and T subsets was analyzed by Western immunoblot. The role of Fas ligand (FasL) was defined by use of Fas-blocking antibody. Results While exosomes of lymphoid origin could be demonstrated in all women, placenta-derived exosomes were only identified in pregnant patients. Placental exosomes suppressed T-cell expression of CD3-zeta and JAK3, while inducing SOCS-2. This downregulation of CD3-zeta was partially reversed by pre-incubating T cells with ZB4 antibody. Using T subsets, the level of CD3-zeta on CD8+ cells was inhibited 1.43-fold more than in CD4+ cells. On CD4+ CD25+ cells, CD3-zeta was not significantly inhibited. Conclusion Placental exosomes suppressed T-cell signaling components; however, while exosomal FasL is an important contributor, it does not appear to be the sole mediator. The additional expression of PD-L1 may explain immunoregulatory consequences of exosomes with low or absent FasL.

Steroid‐hormone receptors in breast cancer

Abstract: An obvious problem for the surgeon or oncologist treating breast cancer has been to identify the patients likely to respond to endocrine manipulation. Until recently, clinical factors such as previous response to hormone therapy, disease-free interval, age and menopausal status, and location of the dominant metastatic lesion were the principal criteria for selecting therapeutic regimens for these women. Recently, the measurement of steroid hormone receptors has become an important laboratory test. Progress during the last decade has shown that: the most reliable methods of determining estrogen receptors (ER) and progestin receptors (PR) are multipoint titration analysis using dextran-coated charcoal, and sucrose density gradient centrifugation; 55% to 65% of primary breast tumors contain more than 10 femtomole/mg cytosol protein of ER; 45% to 55% of metastatic breast tumors contain more than 10 fmol/mg cytosol protein of ER; ER are present more often in tumors of postmenopausal women compared with those of premenopausal women; benign breast lesions such as fibrocystic disease and fibroadenomas usually contain less than 10 fmol/mg cytosol protein of ER; 90% of male breast carcinomas contain ER; approximately 55% of women with breast tumors containing ER respond objectively to endocrine therapy, either additive or ablative; less than 3% of women with breast tumors lacking ER respond objectively to hormone therapy. In addition, it has been suggested that the absence of ER in a breast tumor correlates well with an increased response to cytotoxic chemotherapy; 45% to 60% of primary or metastatic breast tumors contain PR. Also, the presence of both ER and PR in a breast tumor indicates a 75% to 80% likelihood that the patient will respond to endocrine manipulation, either additive or ablative; it has been suggested that the presence of the 8 Svedberg form of ER in a breast tumor (as detected by sucrose gradient centrifugation) improves the accuracy of selecting the patient likely to respond to endocrine therapy; and there appears to be a relationship between the quantity of ER in a breast tumor and a patient's response to endocrine therapy. The incidence of response to hormone therapy increases with increasing ER levels.

Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline

Abstract: Purpose The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma.

The Role of Microvascular Damage in Photodynamic Therapy: The Effect of Treatment on Vessel Constriction, Permeability, and Leukocyte Adhesion

Abstract: Intravital microscopy of the rat cremaster muscle was used to evaluate changes in vessel constriction, vessel permeability, and leukocyte adhesion during and after photodynamic therapy (PDT). Animals were given Photofrin doses of 0–25 mg/kg i.v. 24 h before treatment. Cremaster muscles were exposed to 135 J/cm 2 light at 630 nm. Animals given 5 mg/kg Photofrin showed no vessel constriction or increase in vessel permeability to albumin. Doses of 10 and 25 mg/kg Photofrin caused a dose-related constriction of arterioles which was observed within the first minutes of illumination at the higher drug dose. After the initial constriction, arteriole response to PDT was biphasic in nature, with some vessels relaxing to nearly control levels while others remained fully constricted. Constriction of venules occurred only at the highest porphyrin dose studied (25 mg/kg) and was delayed in comparison to arteriole constriction. Photofrin doses which produced arteriole constriction also caused an increase in venule permeability to albumin, which occurred shortly after the start of light treatment and was progressive with time. Leakage began at specific sites along the venule wall but became uniform along the entire length of the venule by 1 h after treatment. Changes in the adherence of polymorphonuclear leukocytes to venule endothelium were also observed with PDT. Photofrin doses of 25 mg/kg and 45 J/cm 2 light were sufficient to cause polymorphonuclear leukocytes to become adherent to the vessel wall. A second group of animals was given indomethacin trihydrate to examine the involvement of cyclooxygenase products such as thromboxane in vessel response to PDT. Animals given 5 mg/kg indomethacin intraarterially 1 h before light treatment showed no constriction of arterioles or venules at all Photofrin and light doses studied. No increases in venule permeability to albumin were seen in this group of animals. This suggests that cyclooxygenase products including thromboxane are important in causing vessel constriction and changes in permeability during PDT. The initiating event which causes the release of these vasoactive agents remains unknown.