A case-control study of stillbirths at a teaching hospital in Zambia, 1979-80: antenatal factors

A total of 266 mothers of stillborn babies (cases) and 266 mothers of live-born babies (controls), matched for parity, were studied in an attempt to define the causes of the stillbirths. Altogether, 16% of mothers in the former group were over 35 years old, compared with 9% in the latter; in addition, 16% of cases had a history of past perinatal death, compared with only 2.4% among the controls.     

Determination of left ventricular ejection fraction by visual estimation during real-time two-dimensional echocardiography

It has been shown that the measured reduction in the cross-sectional area of the left ventricle (LV), as viewed in the short axis, closely approximates its ejection fraction (EF). We assessed the reliability of using two-dimensional echocardiography (2DE) to visually estimate the EF during real-time viewing, without the need of digitizers, planimetry, or calculations. Twenty-five adult hospitalized patients with either suspected or known cardiac disease were evaluated prospectively. Each patient also had gated nuclear angiography during the same admission, and 14 had cardiac catheterization with left ventriculography. The EF was determined by 2DE using a visual estimate of the percent area reduction of the LV cavity in the short-axis view at the level of the papillary muscles. All 2 DE studies were read by two or more blinded reviewers, with a value for the EF to the nearest 2.5% determined by consensus. These values correlated closely to the values determined in all 25 patients with gated nuclear angiography (r = 0.927) and the 14 patients who had left ventriculography (r = 0.935). We believe that this method of visually estimating the LVEF will enable echocardiographers to easily use 2 DE for a reliable and instantaneous assessment of ventricular function, without the need of sophisticated analytical equipment.     

Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis

Tea, one of the most widely consumed beverages worldwide, has been shown to have anti-cancer activity in various cancers including colon cancer. It has been demonstrated that overexpression of the inducible isoform of cyclooxygenase (COX-2) occurs during colon tumorigenesis and inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) is chemopreventive. To determine whether the anti-cancer effect associated with green tea impacted COX-2 expression levels, human colorectal cancer cell lines HT-29 and HCA-7, were treated with (-)-epigallocatechin-3-gallate (EGCG), the most abundant and effective polyphenol of green tea. EGCG significantly inhibited constitutive COX-2 mRNA and protein overexpression. The inhibitory effects of EGCG on signaling pathways controlling COX-2 expression were examined. We observed that EGCG down regulated the ERK1/2 and Akt pathways in colon cancer cells. The effect of EGCG on COX-2 expression resulted in decreased COX-2 promoter activity via inhibition of nuclear factor kappaB (NF-kappaB) activation. EGCG also promoted rapid mRNA decay mediated through the COX-2 3'untranslated region (3'UTR). In conclusion, these data suggest that inhibition of COX-2 is a mechanism for the anti-proliferative effect of green tea and emphasizes the role that dietary factors have as anti-cancer agents.     

The psychological costs of inadequate cervical smear test results: three-month follow-up

We have previously shown that upon receipt of inadequate cervical smear test results, women have elevated levels of state anxiety and concern about their test results, similar to those of women receiving abnormal smear test results. The current paper reports data on the psychological impact three months after receiving an inadequate smear test result. Two groups of women who initially received a normal test result (n=184) or either a first or non-consecutive inadequate smear test result (n=140) responded. Women with initially received inadequate smear test results no longer had higher state anxiety than women who received normal test results. However, women who initially received inadequate smear test results were still more concerned about their test results and less satisfied with the information they had received about these initial test results, even after receiving normal results from repeat cervical smear tests. Concern was strongly predicted by dissatisfaction with information provided about inadequate smear test results. These results underscore the need to improve communication about inadequate cervical smear test results.     

Agonist-induced cell surface trafficking of an intracellularly sequestered D1 dopamine receptor homo-oligomer

The role of oligomerization in D1 dopamine receptor trafficking to the cell surface was examined using conformationally distinct variants of this receptor. Substitution of the highly conserved aspartic acid (Asp103) in transmembrane domain 3 resulted in a constitutively active receptor, D103A, that did not bind agonists or antagonists but trafficked to the cell surface as oligomers. Coexpression of D103A with the wild-type D1 receptor in human embryonic kidney 293t cells resulted in inhibition of cell surface expression of the D1 receptor because of receptor oligomerization, causing intracellular retention of both proteins. Rescue of the intracellularly retained oligomer could be achieved only by membrane-permeable full and partial agonists, which resulted in cell surface expression of the D1 receptor, whereas cell-permeable antagonists and cell impermeable agonists had no effect. Cell surface fluorescence resonance energy transfer studies of cells coexpressing D103A and D1 revealed no signal before agonist treatment but a robust signal after agonist treatment, indicating that the intact D1/D103A oligomer reached the cell surface only after agonist treatment but not under basal conditions. This suggests that rescue of the retained D1/D103A oligomer to the cell surface was a result of an agonist-induced change in the conformation of D1, permitting cell surface trafficking of the D1/D103A receptor oligomeric complex from the endoplasmic reticulum.     

Phospholipase C-beta3 and -beta1 form homodimers, but not heterodimers, through catalytic and carboxyl-terminal domains

Phospholipase C-beta (PLC-beta) isoenzymes are key effectors in G protein-coupled signaling pathways. Prior research suggests that some isoforms of PLC-beta may exist and function as dimers. Using coimmunoprecipitation assays of differentially tagged PLC-beta constructs and size-exclusion chromatography of native PLC-beta, we observed homodimerization of PLC-beta3 and PLC-beta1 isoenzymes but failed to detect heterodimerization of these isoenzymes. Size-exclusion chromatography data suggest that PLC-beta3 and PLC-beta1 form higher affinity homodimers than PLC-beta2. Evidence supportive of limited PLC-beta monomer-homodimer equilibrium appears at < or =100 nM. Further assessment of homodimerization status by coimmunoprecipitation assays with differentially tagged PLC-beta3 fragments demonstrated that at least two subdomains of PLC-beta3 are involved in dimer formation, one in the catalytic X and Y domains and the other in the G protein-regulated carboxyl-terminal domain. In addition, we provide evidence consistent with the existence of PLC-beta homodimers in a whole-cell context, using fluorescent protein-tagged constructs and microscopic fluorescence resonance energy transfer assays.     

NCCN Task Force Report: Bone Health and Cancer Care

Higher incidences of osteoporosis and osteopenia are found in cancer patients, particularly in women receiving aromatase inhibitors or with chemotherapy-induced ovarian failure, or in men with prostate cancer and androgen deprivation therapy. Therefore, management of long-term bone health is emerging as an important aspect of comprehensive cancer care. Patients with cancer typically have a number of additional risk factors for osteoporosis that should prompt screening, regardless of patient age or sex. Maintaining bone health requires a broad knowledge base, including understanding underlying bone metabolism and how it is affected by both cancer itself and the drugs used to treat cancer, the effect of chemotherapy-induced menopause on bone health, bone markers and imaging techniques used to assess bone health, therapeutic strategies to maintain bone health, and treatment of bone metastases, including surgery for pathologic fractures. Multiple members of the healthcare team may need to be involved in education and care of the patient. This report summarizes discussion of these and other issues regarding bone health and cancer care from the NCCN Bone Health and Cancer Care Task Force meeting in early 2006.