Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding

BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial biopsies taken from women suffering breakthrough bleeding (BTB) under different exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne with BTB were divided into four groups: combined-continuous hormone therapy (HT) (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were using the Mirena intrauterine levonorgestrel-releasing system for contraceptive purposes, with menstrual diaries for classification into four groups (amenorrhea, infrequent, regular and prolonged). Control biopsies from Melbourne were included in the study. Endometrial samples were immunostained for VEGF and blood vessel localization using an antibody to CD34. RESULTS: Results showed that BVD was significantly reduced in the progestin-only treated group compared with the other three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had significantly reduced BVD compared with controls. Considerable heterogeneity was observed in VEGF immunostaining within and between individual samples with no major differences between HT or Mirena. CONCLUSION: These results provide strong evidence that unopposed progestins reduce endometrial BVD and that there is no link between VEGF immunostaining and BVD or BTB.     

Low IgG2 and polysaccharide response in a T cell receptor expression defect

B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens.     

Phenotypically different cells with heterogeneous nuclear ribonucleoprotein A2/B1 overexpression show similar genetic alterations

Immunocytochemical studies have revealed that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/ B1 in exfoliated epithelial cells is a potentially useful marker of early lung cancer. This study analyzed the correlation of hnRNP A2/B1 expression with molecular alterations in phenotypically different epithelial cells of paraffin-embedded pulmonary tissues. Sections from 20 human subjects were analyzed immunohistochemically for expression of hnRNP A2/B1. Normal-appearing, hyperplastic, and malignant epithelial cells with and without hnRNP A2/B1 expression (n = 78) were microdissected and assessed for microsatellite alterations (MA) and loss of heterozygosity (LOH) (n = 14 markers) as well as for clonality. Results showed that (1) hnRNP A2/B1 immunoreactive cells contained a significantly higher frequency of MA and LOH than did comparable cells that lacked detectable hnRNP A2/B1; (2) over 80% of MA and LOH seen in hnRNP A2/B1 immunoreactive normal-appearing and hyperplastic cells persisted in malignant cells; (3) preliminary analysis of methylation status of the androgen receptor gene in non-neoplastic cells was suggestive of hnRNP A2/B1-expressing cells being of clonal origin; and (4) cells with cytoplasmic hnRNP A2/B1 immunoreactivity had a 3-fold higher frequency of MA and LOH than did cells with nuclear hnRNP A2/B1 immunoreactivity. These findings suggest that phenotypically different respiratory epithelial cells with hnRNP A2/B1 overexpression might be clonally derived, and that the subcellular localization of hnRNP A2/B1 might be an important factor associated with tumor progression.     

Altered monocyte function in uremia

Uremia appears to suppress immune function predisposing patients to infections. When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive. Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid. Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes. Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes. Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia. The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls. Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia.     

Control of a Candida glabrata prosthetic endovascular infection with posaconazole.

A 63-year-old man with a history of cirrhosis of the liver developed Candida glabrata fungemia after undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement. Treatment with oral fluconazole was initially effective, but when the patient became neutropenic, subsequent blood cultures grew C. glabrata and a thrombus developed, which partially occluded the stent. Despite treatment with fluconazole, blood cultures remained positive for C. glabrata. Treatment with posaconazole resulted in clinical improvement and the patient had only intermittently positive fungal cultures for 6 weeks. A CT scan showed resolution of the inferior vena cava thrombus. Subsequently, the patient developed hepatocellular carcinoma and hepatic encephalopathy and became noncompliant with posaconazole. Blood cultures again became positive for C. glabrata. The patient died a few weeks after the diagnosis of hepatocellular carcinoma, but the cause of death was believed to be worsening liver dysfunction, not C. glabrata infection. Posaconazole had controlled the infection for about 3 months prior to his death. In conclusion, posaconazole may be a useful option in the management of prosthetic endovascular infections caused by C. glabrata.     

Visual motion perception from stimulation of the human medial parieto-occipital cortex

Summary Visual phenomena evoked by direct electrical stimulation of extrastriate cortex were observed in 30 epileptic patients as part of a presurgical investigation. An incremental sequence of low-level bipolar stimulation trains was delivered at medial and lateral pairs of contacts of stereotaxically-implanted multilead intracerebral electrodes in parietal, occipital and posterior temporal regions. Diffusion of stimulus afterdischarges was monitored by electrodes in temporal and frontal lobes and by the non-stimulated contacts of the stimulated electrode. Localized stimulations evoked few visual phenomena. The strongest anatomo-perceptual correlation was found for stimulation in the medial parieto-occipital fissure which evoked visual motion phenomena in all three patients stimulated in that region. The evoked motion perceptions were not associated with eye movements or any particular localization of the epileptic focus. These perceptions were only evoked once outside of the medial PO region at the 61 sites examined. The results suggest that the medial parieto-occipital region is closely linked to the human visual motion processing system.