Low levels of follicle-stimulating hormone receptor-activation inhibitors in serum and follicular fluid from normal controls and anovulatory patients with or without polycystic ovary syndrome

In patients with normogonadotropic anovulation, either with or without polycystic ovary syndrome (PCOS), factors interfering with FSH action may be involved in arrested follicle development. The aim of this study is to assess whether factors inhibiting FSH receptor activation are elevated in serum or follicular fluid from anovulatory patients, as compared with regularly cycling women. For this purpose, a Chinese hamster ovary cell line, stably transfected with the human FSH receptor, has been applied. FSH-stimulated cAMP secretion in culture medium was measured in the presence of serum or follicular fluid. Chinese hamster ovary cells were stimulated with a fixed concentration of FSH (3 or 6 mIU/mL) to mimic FSH levels in serum or follicular fluid. Samples were added in concentrations ranging from 3-90% vol/vol to approach protein concentrations occurring in serum or follicular fluid. In the presence of 10% vol/vol serum from regularly cycling women (n = 8), FSH-stimulated cAMP production was inhibited to 42 +/- 2% (mean +/- SEM of 2 experiments, each performed in duplicate) of cAMP production in the absence of serum, whereas a similar cAMP level (up to 38 +/- 4% of the serum-free level) was observed at higher concentrations of serum (30-90% vol/vol). The inhibition of FSH-stimulated cAMP production in the presence of serum samples from normogonadotropic anovulatory patients, without (n = 13) or with (n = 16) PCOS, was similar to controls. Follicular fluid samples (n = 57) obtained during the follicular phase in 25 regularly cycling women and follicular fluid samples (n = 25) from 5 PCOS patients were tested in a slightly modified assay system. In the presence of 10 or 30% (vol/vol) follicular fluid, FSH-stimulated cAMP levels were decreased to 68 +/- 2% and 55 +/- 2% (mean +/- SEM of a single experiment in triplicate) of the cAMP levels in the absence of follicular fluid, respectively. There was no correlation between the degree of cAMP inhibition and follicle size, steroid content (androstenedione or estradiol concentrations), or menstrual cycle phase. Furthermore, no differences in inhibition were found, comparing PCOS follicles with size- and steroid content-matched follicles obtained during the normal follicular phase. It is concluded that inhibition of FSH receptor activation by proteins present in serum or follicular fluid is constant (60 and 40%, respectively) and independent from the developmental stage of the follicle, either during the normal follicular phase or in patients with normogonadotropic anovulation. Inhibition of FSH receptor activation may be of limited significance for normal and arrested follicle development.     

Influence of absorbable dusting powders on wound infection

OBJECTIVE: To investigate the lymphocyte subpopulations (T4, T8 and macrophages) and major histocompatibility (MHC) II antigens in patients with superficial bladder cancer before and after intravesical instillations of recombinant interferon-gamma (IFN-gamma). PATIENTS AND METHODS: Four intravesical weekly instillations of either 1.3 mg (20 patients, group A) or 0.7 mg (11 patients, group B) IFN-gamma were administered in 31 evaluable patients (28 men and three women, mean age 68.5 years). The CD4+, CD8+, CD68+ and HLA-DR antigens were detected immunohistochemically in tumours and a marker tumour before and after intravesical instillations. RESULTS: The median number of T4 lymphocytes increased from 15 per high-power field (HPF) to 27.5 in group A (P = 0.0029) and to 45 in group B (P = 0.0117). Macrophages increased from 6 cells/HPF to 15 cells/HPF in group A (P = 0.0029) and from 2 to 8.75 cells/HPF in group B (P = 0.0117). The T8 lymphocyte subpopulation decreased from 4 to 3 cells/HPF (P = 0.0231) in group A and from 5 to 2 cells/HPF (P = 0.0759) in group B. The median percentage of HLA-DR antigens increased from 1.5% to 18% in general, (P < 0.001), from 2.5% to 15% in group A (P = 0.0064) and from 0% to 20% in group B (P = 0.0077). The induction of HLA-DR antigens was statistically significant in those receiving the lower dose (from 0% before instillation to 20% afterward, P = 0.0277), while it was not with the higher dose (from 0% to 5%, P = 0.068). Irrespective of the dose of IFN used. T4 lymphocytes and macrophages increased significantly after treatment in patients in whom the tumour HLA-DR antigens were either up-regulated or remained stable. The median net increase in T4 cells was 17.5 and 30 cells/HPF for groups A and B, respectively (P = 0.0429). CONCLUSION: T4 lymphocytes, macrophages and HLA-DR antigens increased after intravesical IFN-gamma in patients with superficial bladder cancer, but T8 lymphocytes decreased. Irrespective of the drug dose used, patients with either upregulated or stable HLA-DR antigens after treatment showed the same pattern of changes in the lymphocyte subpopulations. The two doses generally had the same effect on the immunological variables assessed but the lower dose was more effective in inducing HLA-DR antigens and in increasing the number of T4 lymphocytes in the tumours.     

Cultural factors related to the peer review of teaching

Since 1994, the American Association for Higher Education Peer Review of Teaching Project has sought to popularize the notion that teaching is both a scholarly activity and community property to be shared with and critiqued by the larger academic community. In order to accomplish these goals, each of the three academic units at the twelve participating universities developed a pilot project that conformed to its own institutional, academic unit, and disciplinary culture. At a large Midwestern university, the academic units of mathematics, history, and nursing developed different projects. Each of these projects took account of the unit's specific culture, and this fact helps to account, in large part, for each project's success.     

Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic drugs

PURPOSE: We report an investigation into the distribution of proteoglycans (PGs) in normal, organ-cultured and dextran-treated human corneas. METHODS: Immunogold labeling was carried out at the electron microscope level to localize keratan sulphate (KS), chondroitin sulphate (CS), and heparan sulphate (HS) PGs. RESULTS: High levels of labeling for CS was found in the epithelium, endothelium, and keratocytes, with light labelling present in the basement membranes and the corneal stroma. Labeling for HS was present in the epithelium, endothelium, and keratocytes, with intense labeling present at the endothelium/Descemet's membrane interface and the epithelium/Bowman's layer interface. Large filaments were also observed in these regions in cuprolinic blue-stained specimens. Keratan sulphate was present at high levels in the stroma and the basement membranes with low levels present within the keratocytes, epithelium, and endothelium. The pattern of KS labeling along the collagen fibrils in the stroma sometimes showed evidence of periodicity. Organ-cultured corneas had extensive collagen-free "lakes," the interior of which immunolabeled positively for KS and showed staining with cuprolinic blue. The lakes were greatly reduced in the dextran-treated samples. CONCLUSION: This investigation determined the ultrastructural distribution of KS, CS, and HS PGs in human cornea and showed that organ culture is associated with a change in distribution of stromal PGs.     

Pin force measurement in a halo-vest orthosis, in vivo

Salmon calcitonin (sCT) is an example of one of the many bioactive peptides that require amidation of the carboxy terminus for full potency. We describe a method for the production of amidated sCT in the mammary gland of transgenic rabbits. Expression of a fusion protein comprising human alpha lactalbumin joined by an enterokinase cleavable linker to sCT was directed to the mammary gland under the control of the ovine beta lactoglobulin promoter. C-terminal amidation in vivo was achieved by extending the sCT by a single glycine residue that provides a substrate for endogenous amidating activity in the mammary gland. Full characterization of the released sCT demonstrated it to be equivalent to synthetic standard in terms of structure, purity, and potency.