Changes in bone turnover during tibolone treatment

OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period.     

Identification, characterization and biological activity of oxytocin receptor in the developing human penis

Although abnormalities of the male external genitalia (MEG) are a relatively common problem, little is known concerning the molecular mechanisms that finely regulate penile development. We report here the expression of the oxytocin receptor (OTR) gene by real-time RT-PCR in human fetal tissues (11th-12th week of gestation), including the MEG. The developing penis expressed a very high level of OTR mRNA, only a half log(10) unit lower than fetal central nervous system, used as a positive control. The OTR protein is also highly expressed (western, immunohistochemistry and binding studies) and immunolocalized both in the mesenchymal body and in the surrounding blood capillaries, which will later constitute penile trabeculae and sinusoids. Binding studies using [125I]oxytocin antagonist ([125I]OTA) in cultured human fetal penile smooth muscle cells (hfPSMC) revealed the presence of specific OTR with a high capacity and affinity for oxytocin (OT) and for OTA. Increasing concentrations of OT dose-dependently induced intracellular Ca2+ mobilization. Furthermore, OTR mediated an increase in the proliferation and the migration of hfPSMC. In conclusion, we demonstrate that in the developing human MEG, OTR is highly expressed and might be involved in coordinating timely and appropriate proliferation and migration of the penile cells. Thus, OTR might represent an additional target for investigating human fetal MEG organogenesis.     

Familial adenomatous polyposis coli: five novel mutations in exon 15 of the adenomatous polyposis coli (APC) gene in Italian patients. Mutations in brief no. 225. Online

Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain-terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction-single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.     

Heterogeneous Subcellular Morphology of Lung Adenocarcinoma Cells: Identification of Different Cytotypes on Cytological Material

We performed an electron microscopic study of cytologic material from 20 cases of primary lung adenocarcinoma (pleural effusion, 13 cases; fine needle aspiration biopsy, 7 cases). Ultrastructural characteristics related to secretory and storing activity of adenocarcinoma cells were evaluated semi-quantitatively. Data analysis identified three basic cell types (secretory, well or poorly differentiated; storing; and indifferent). We could classify our cases in five groups of pure or mixed cytotypes. Our results demonstrated a subcellular morphological heterogeneity manifested by the presence of different basic cell types: secretory, storing or indifferent features (or both); and different secretory and storage products in the same cell. This heterogeneity of lung adenocarcinoma cells suggests that the neoplasm could arise from a single cell type capable of differentiating along different lines. Cases lacking secretory differentiation seemed to be characterized by more aggressive biologic behavior. A clear correlation between the ultrastructural cytotypes identified and the clinical and prognostic data on the patients was not observed. This may be due to the fact that 75% of the patients were in clinical stage III at the time of diagnosis; also, in this series only five cases did not have characteristics that indicated secretory activity.     

Screening for cognitive impairment in older adults attending an eye clinic

PURPOSE: We conducted a cross-sectional study examining potentially modifiable factors associated with cognitive impairments (mild or severe) in older whites, African Americans and Hispanics attending an outpatient eye clinic. METHODS: In-clinic interviews and physical examinations assessed social, demographic and health information from 100 consecutive Hispanic, African-American and white adults aged > or = 55. Our primary outcome was presence of any cognitive impairment (mild or severe) using the St. Louis University Mental Status Examination (SLUMS) scale. RESULTS: Of the 100 subjects, 65 screened positive for cognitive impairments on the SLUMS cognitive instrument: 46 with mild cognitive impairment and 19 with severe impairment (possible dementia). African-American and Hispanic adults (nonwhites) were significantly more likely to have cognitive impairment compared to white adults (OR 2.80: 95% CI = 1.05-7.44), independent of age, years of education and systolic blood pressure. Subjects with diabetes also had increased odds of cognitive impairments (OR 3.28, 95% CI = 1.21-8.90) even after adjusting for relevant confounders. There was a nonsignificant trend between visual acuity impairment and cognitive impairment (p = 0.059). CONCLUSIONS: Sixty-five percent of adults aged > or = 55 attending the eye clinic screened positive for cognitive impairments, with higher rates among nonwhites and adults living with diabetes.     

From rafts to crafts: membrane asymmetry in moving cells

Many important biological events, including the leukocyte-mediated immune response, wound repair, axon guidance and developmental patterning, involve persistent cell movement towards a directional signal, a process termed chemotaxis. Establishment of functional and spatial cell polarity is an absolute requirement for this response. We propose that redistribution of specific membrane microdomains, termed rafts, during cell migration is a pivotal step in achieving polarity. On the one hand, partitioning of molecules into rafts might help to localize proteins at the front or the rear of moving cells, and on the other hand, rafts might function as platforms for local activation and coordination of the signaling pathways involved in cell migration.