Interaction of the estrogen receptors with the Fas ligand promoter in human monocytes.

The predominance of autoimmune diseases among women suggests that estrogen may modulate immune function. Monocytes and macrophages are important in initiating, maintaining, and resolving inflammatory responses through cell-signaling molecules, which control immune cell survival. One important mechanism of cell survival is mediated by the Fas/Fas ligand (FasL) system.

Vaginal intraepithelial neoplasia: treatment by carbon dioxide laser and risk factors for failure.

Objective: To evaluate the effectiveness of CO(2) laser ablation of vaginal intraepithelial neoplasia (VAIN) and to define prognostic factors.

Study Design: Medical records of 24 patients with VAIN II or III, treated by CO(2) laser ablation from 1990 to 1998 were reviewed. The grade, location, and focality of the lesions, the age, follow-up period and menopausal status of the patients, the power and duration of laser ablation, the presence of concurrent cervical or vulvar neoplasia or previous hysterectomy were evaluated as possible prognostic factors.

Combined immunocytochemistry and FISH: an improved method to study engraftment of accessory bone marrow stromal cells.

In aplastic anaemia (AA), correction of bone marrow (BM) stromal function may contribute to the outcome of bone marrow transplantation (BMT). Engraftment of BM stromal cells is rarely observed, but engraftment of accessory cells (macrophages and T cells) may be important. We have improved a method of combined immunocytochemistry and FISH described by van Tol et al.

Cryomyolysis in the management of uterine fibroids: technique and complications.

Uterine fibroids are common benign tumors of the uterus and a major public health problem. Between 20 and 25% of women over 35 years of age are estimated to have fibroids. Three subtypes of fibroids are recognized depending on their relationship to the myometrium, namely, submucosal, subserosal and intramural.

The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hot spot.

Paroxysmal nocturnal hemoglobinuria (PNH) may arise during long-term follow- up of aplastic anemia (AA), and many AA patients have minor glycosylphosphatidylinositol (GPI) anchor-deficient clones, even at presentation. PIG-A gene mutations in AA/PNH and hemolytic PNH are thought to be similar, but studies on AA/PNH have been limited to individual cases and a few small series. We have studied a large series of AA patients with a GPI anchor-deficient clone (AA/PNH), including patients with minor clones, to determine whether their pattern of PIG-A mutations was identical to the reported spectrum in hemolytic PNH.

Mechanical unfolding of a titin Ig domain: structure of unfolding intermediate revealed by combining AFM, molecular dynamics simulations, NMR and protein engineering.

The mechanical unfolding of an immunoglobulin domain from the human muscle protein titin (TI I27) has been shown to proceed via a metastable intermediate in which the A-strand is detached. The structure and properties of this intermediate are characterised in this study. A conservative destabilising mutation in the A-strand has no effect on the unfolding force, nor the dependence of the unfolding force on the pulling speed, indicating that the unfolding forces measured in an AFM experiment are those required for the unfolding of the intermediate and not the native state.

Phase I study of perillyl alcohol in patients with refractory malignancies.

We treated 21 patients in a dose-finding and pharmacokinetic study of the monoterpene perillyl alcohol with the drug given orally in 3 divided doses on a chronic basis. The average number of days that patients remained on study was 48 (range 11-172). Fatigue and low-grade nausea were dose limiting.

Regulation of Fas ligand expression by estrogen in normal ovary.

Objective: The clinical significance of the Fas/Fas ligand (FasL) system in hormone-sensitive carcinomas such as breast and ovary has been reported. However, only a few studies have investigated the potential hormonal regulation of its expression. In this study, we evaluated the expression of FasL in normal ovarian tissue during the normal female reproductive cycle with the goal of identifying potential hormones that can regulate FasL expression.

Detection of telomerase-positive circulating epithelial cells in ovarian cancer patients.

The aim of this study is the detection of circulating tumor cells in peripheral blood of ovarian cancer patients. We applied immunomagnetic beads coated with an epithelial or leukocyte-specific antibody to isolate epithelial cells from peripheral blood and we measured their telomerase activity. Both enrichment methods showed high sensitivity and specificity to isolate ovarian tumor cells from peripheral blood.

Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells.

Trophoblast rejection, which is characterized by increased apoptosis, is mediated by T helper (Th)-1, or proinflammatory, cytokines, whereas Th-2, or anti-inflammatory, cytokines confer immune protection and facilitate implantation. We investigated the role of both types of cytokines on the expression and function of the Fas/Fas ligand (FasL) apoptotic pathway in trophoblast cells. First-trimester human trophoblast primary-culture cells as well as A3 and HTR/8 trophoblast cell lines were treated with proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNFalpha) and with the anti-inflammatory cytokines interleukin (IL)-6 and IL-10.

Hormonal regulation of apoptosis and the Fas and Fas ligand system in human endometrial cells.

The process of apoptosis is responsible for normal cellular turnover in numerous tissues throughout the body. The endometrial layer of the uterus shows steroid-dependent cyclic changes in structure and function. After a proliferative and secretory phase, steroid support is withdrawn and the uterine epithelium is shed.

Ezrin, a membrane-cytoskeletal linking protein, is highly expressed in atypical endometrial hyperplasia and uterine endometrioid adenocarcinoma.

We previously demonstrated that ezrin transcription was required for in vitro invasion and was involved in the acquisition of metastatic potential in endometrial cancer cells. In order to determine the functional role of ezrin in endometrial cancer, we examined ezrin protein expression in 20 cancerous and 33 non-cancerous tissues by immunohistochemistry and Western blot analysis. The specimens included 20 uterine endometrioid adenocarcinomas (UEC), seven simple endometrial hyperplasias (sH), seven complex endometrial hyperplasias (cH), seven atypical endometrial hyperplasias (aH), and 12 samples of normal endometrium (NE).

Ovarian epithelial carcinoma tyrosine phosphorylation, cell proliferation, and ezrin translocation are stimulated by interleukin 1alpha and epidermal growth factor.

Background: Ezrin is a member of the ezrin, radixin, and moesin family. These proteins are membrane-actin cross-linking proteins. Furthermore, ezrin is an important signal transduction protein that undergoes phosphorylation and translocation on stimulation by growth factors.

Correction of stromal cell defect after bone marrow transplantation in aplastic anaemia.

Defects in stromal cell function have been demonstrated in a number of aplastic anaemia (AA) patients. Here we have studied a patient with severe AA and abnormal stromal cell function who underwent bone marrow transplantation (BMT). The objective of this study was to investigate the timing and the mechanism of correction of the stromal defect after transplantation.

Stereoisomers of Mono-, Di-, and Triruthenium(II) Complexes Containing the Bridging Ligand 1,4,5,8,9,12-Hexaazatriphenylene and Studies of Their Photophysical Properties.

A combination of synthetic methods involving mononuclear precursors of predetermined chirality {Delta- or Lambda-[Ru(pp)(2)(CO)(2)](2+); pp = 2,2'-bipyridine or 1,10-phenanthroline} and chromatographic techniques has allowed the isolation of the meso (DeltaLambda) and rac (DeltaDelta/LambdaLambda) diastereoisomers of the dinuclear complexes [{Ru(pp)(2)}(2)(&mgr;-HAT)](4+) {HAT = 1,4,5,8,9,12-hexaazatriphenylene}. The enantiomers of the rac forms have been separated, and characterization of all species has been achieved by NMR and CD studies. Additonally, the homochiral (Delta(3)/Lambda(3)) and heterochiral (Delta(2)Lambda/Lambda(2)Delta) diastereoisomers of the trinuclear complexes [{Ru(pp)(2)}(3)(&mgr;-HAT)](6+), and the enantiomers of both forms, have been isolated and identified.

NMR studies and semi-empirical energy calculations for cyclic ADP-ribose.

A possible pH-dependent conformational switch was investigated for cyclic ADP-ribose. NMR signals for the exchangeable protons were observed in H2O at low temperature, but there was no direct evidence for the protonation of N-3 at neutral pH that has previously been postulated. MNDO calculations indicated that pH dependent 31P chemical shift changes are attributable to protonation of the phosphate adjacent to the N-1 of adenine, and not due to trans-annular hydrogen bonding with a protonated N-3.

Design, synthesis and characterisation of a peptide with oxaloacetate decarboxylase activity.

The synthesis of Oxaldie-3, a synthetic 31-residue peptide with oxaloacetate decarboxylase activity, is described. Biophysical characterisation by gel filtration, CD and NMR spectroscopy indicated that the peptide adopted a folded structure in solution. Oxaldie-3 was an efficient catalyst at concentrations as low as 2 microM, 100-fold lower than the previously described Oxaldie-2, which relied on aggregating alpha-helices for activity.

The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines.

A 2.4-kb truncated L-plastin promoter was inserted either 5' to the LacZ gene (Ad-Lp-LacZ) or 5' to the cytosine deaminase (CD) gene (Ad-Lp-CD) in a replication-incompetent adenoviral vector backbone. Infectivity and cytotoxicity experiments with the LacZ and CD vectors suggested that the L-plastin promoter-driven transcriptional units were expressed at much higher levels in explants of ovarian cancer cells from patients and in established ovarian or bladder cancer cell lines than they were in normal peritoneal mesothelial cells from surgical specimens, in organ cultures of normal ovarian cells, or in the established CCD minimal deviation fibroblast cell line.

Bcl-2 and Bcl-x expression in the CD34+ cells of aplastic anaemia patients: relationship with increased apoptosis and upregulation of Fas antigen.

Aplastic anaemia (AA) is a syndrome of haemopoietic failure involving increased apoptosis in stem cells. AA CD34+ cells often have upregulated Fas antigen, but this does not explain the increased apoptosis in all patients. To examine whether abnormal expression of the apoptotic modulators Bcl-2 and Bcl-x is involved in increased apoptosis in the CD34+ cells of patients, we examined cells from 19 AA patients and 18 normal controls by triple staining for CD34, Bcl-2 or Bcl-x, together with 7-amino actinomycin D to determine viability or with staining for Fas antigen.

Psammoma bodies in cervicovaginal smears.

Objective: To estimate the prevalence of psammoma bodies in routine cervical cytology specimens and describe clinical diagnoses associated with them in pre- and postmenopausal women.

Methods: We identified all reports that contained psammoma bodies from a retrospective review of 34,816 cytology reports over 4 consecutive years from the computerized pathology database at Yale New-Haven Medical Center. Slides were reviewed to confirm and qualify psammoma bodies.

Synthesis, analysis and rearrangement of novel unnatural glucosinolates.

As part of a structure activity study to examine the interaction of glucosinolates with leaf surfaces, a number of glucosinolates were synthesised bearing novel side chain functionalities. These included 7-carboxyheptyl, heptyl, and naphthyl side chains. For the carboxyheptyl glucosinolate, a novel intramolecular rearrangement reaction was observed during the final deprotection step, which generated an ester attached to the C-3 of glucose.

B-lymphotropic viruses in a novel tropical splenic lymphoma.

Peripheral blood from patients with a novel tropical splenic lymphoma, characterized by splenomegaly and circulating naïve CD5-negative villous B lymphocytes, has been screened for evidence of an association with the B-lymphotropic viruses, Epstein--Barr virus (EBV), hepatitis C virus (HCV) and human herpesvirus 8 (HHV8). No increased prevalence of EBV, HCV and HHV8 was demonstrated using serological and molecular techniques, compared with a geographical, age-matched control group. However, lymphoma patients had markedly raised EBV antibody levels without a concomitant increase in the rate of detection of viral genomes in the peripheral blood.

Cystic pelvic pathology presenting as falsely elevated post-void residual urine measured by portable ultrasound bladder scanning: report of 3 cases and review of the literature.

Dedicated portable ultrasound devices generally offer a rapid, noninvasive, largely operator-independent means of assessing post-void residual urine (PVR) volume. In most published series, PVR measured by portable ultrasound correlates well with catheterized urine volume. We report 3 cases in which follow-up of falsely elevated PVR measurements on ultrasound resulted in comparatively low catheterized volumes.

Characterization of cerebral white matter damage in preterm infants using 1H and 31P magnetic resonance spectroscopy.

The biochemical characteristics of white matter damage (WMD) in preterm infants were assessed using magnetic resonance spectroscopy (MRS). The authors hypothesized that preterm infants with WMD at term had a persisting cerebral lactic alkalosis and reduced N-acetyl aspartate (NAA)/ creatine plus phosphocreatine (Cr), similar to that previously documented in term infants weeks after perinatal hypoxiaischemia (HI). Thirty infants (gestational age 27.