Human malignant mesothelial cells: Variability of ultrastructural features in established and nude mice transplanted cell lines

The aim of this study was to determine, by transmission electron microscopy, the differentiation features of 21 human malignant mesothelioma cell lines (HMCLs) established from 13 specimens of 12 confirmed human malignant mesotheliomas, and of tumours induced in nude mice injected with 16 HMCLs. Fifty per cent of HMCLs showed typical mesothelial differentiation (long and slender microvilli, desmosomes, perinuclear intermediate filaments); 29 per cent did not show differentiation; and the remainder were poorly differentiated. Three human tumour specimens gave several different HMCLs; the cell lines obtained from a given tumour exhibited variable mesothelial differentiation. Eleven HMCLs were compared with the native tumour. Four were similar to the tumour and seven were less well differentiated, in most cases in relation to their microvilli. With six HMCLs, tumours induced in nude mice were less well differentiated than the corresponding cell lines, whereas with four HMCLs, tumours were equally or better differentiated. However, in most nude mice tumours, typical mesothelial microvilli were present. These results show that cell lines established from malignant mesothelioma may exhibit dedifferentiated features. However, while the variability in ultrastructural differentiation may result from the culture microenvironment, it could also be related to the state of differentiation, of the native tumour sample and to tumour cell heterogeneity.     

Complete Primary Sequences of Two λ Immunoglobulin Light Chains in Myelomas with Nonamyloid (Randall-Type) Light Chain Deposition Disease

We herein report on the first two primary sequences (BOU and RAC) of monoclonal light chains of the λ type responsible for nonamyloid λ light chain deposition disease. Both patients were affected with severe forms of myeloma complicated with renal failure. The pathological presentation typically featured Congo red-negative deposits along tubular basement membranes but differed somewhat from the typical “Randall-type” κ light chain deposition disease: they lacked the prominent glomerulosclerosis pattern often featuring nonamyloid κ deposits and were associated with cylinders or myeloma casts. Both protein sequences were deduced from those of the corresponding complementary DNAs in the bone marrow plasma cells. For each chain, products of three independent amplifications by polymerase chain reaction were sequenced and found to be identical. BOU and RAC λ mRNAs had a normal overall structure consisting of Vλ2 segments rearranged to Jλ2Cλ2 but displayed a number of unusual features within their primary sequences. These substitutions are likely responsible for changes in light chain conformation that promote their aggregation and deposition along renal tubule basement membranes.     

Comparative carcinogeniocities and reactivities of N-myristoyloxy-N-acetyl-2-aminofluorene and its 7-iodo derivative

Earlier studies showed that N-acetyl-2-aminofluorene (AAF) ismuch more carcinogenic than N-acetyl-2-amino-7-iodofluorene(AAIF). Subsequently it was found that substitution of C-8 ofguanine bases in DNA with AAF residues resulted in displacementof the guanine bases outside the DNA helix. This did not occurafter similar substitution with AAIF residues. As one approachto assessing the possible importance of this gross conformationaldifference to the carcinogenicity of AAF, the carcinogenic activitiesof two electrophilic esters, N-myristoyloxy-AAF and its 7-iododerivative, were compared by s.c. injection into male Fischerrats. On injection of a total of 64 µmol, each ester induceda high incidence of sarcomas, and the latent periods were similar.N-Myristoyloxy-AAIF was solvolyzed in aqueous media at aboutone-half the rate of N-myristoyloxy-AAF, and it was less than10% as reactive with native DNA as N-myristoyloxy-AAF. N-Myristoyloxy-AAFand N-myristoyloxy-AAIF were each less reactive than the correspondingacetoxy derivatives. These data suggest that the low carcinogenicityof AAIF as compared to that of AAF may not be associated withthe conformations of their adducts in the DNA. This differencein carcinogenicity may be related to differences in the ratesof metabolic activation and inactivation of these two amides.     

Survivin in Brain Tumors: An Attractive Target for Immunotherapy

Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors.     

Predictors of cervical coinfection with multiple human papillomavirus types.

Women infected with multiple human papillomavirus (HPV) types seem to be at higher risk of cervical intraepithelial neoplasia, although there is controversy about whether coinfections are associated with lower or higher grades of dysplasia. There is no established risk factor profile for infection with multiple HPV types. We analyzed data from a prospective cohort of 2,075 Brazilian women to identify determinants of HPV coinfection. Cervical specimens were collected for cytology and HPV DNA detection. Data on baseline and time-dependent putative risk factors were obtained by interview. Baseline predictors of HPV coinfection included younger age, greater number of recent sexual partners, a history of condyloma but not of other sexually transmitted diseases, and younger age at first sexual intercourse. In repeated measures analyses, there was a weak positive association between the number of sexual partners in the time interval between two study visits and the risk of coinfection. Our results suggest that the risk factor profile for HPV coinfection among HPV-infected women shares several similarities with risk factors for any HPV infection.     

Inhibition of bone turnover by milk intake in postmenopausal women

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59.3 (SD 3.3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, -3.2 pg/ml (P=0.0054); for crosslinked telopeptide of type I collagen, -624 pg/ml (P<0.0001); for propeptide of type I procollagen, -5.5 ng/ml (P=0.0092); for osteocalcin, -2.8 ng/ml (P=0.0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.     

Symposium on obesity and asthma �CNovember 2, 2006

Asthma and obesity are frequently associated, and obesity has been considered a factor contributing to both an increase in severity of asthma and to its development. The present document summarizes the proceedings of a symposium held in Montreal, Quebec, on November 2, 2006, under the auspices of the Réseau en santé respiratoire du Fonds de la recherche en santé du Québec in collaboration with the McGill University – Strauss Severe Asthma Program, Université Laval (Quebec City) and Université de Montréal. It includes an overview of the various aspects of the relationships between asthma and obesity with regard to animal models; genetic, hormonal and physiological determinants; influence of comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and psychological features; and management of asthma in the obese population.     

Is the volume-outcome relation still an issue in the era of PCI with systematic stenting? Results of the greater Paris area PCI registry.

AIMS: In acute myocardial infarction (AMI), primary percutaneous transluminal angioplasty (PTCA) is the preferred option when it can be performed rapidly. Because of the limited access to high PTCA volume centres in some areas, it has been suggested that PTCA could be performed in low-volume centres on AMI patients. Little data exist on the validity of this strategy in modern era PTCA. METHODS AND RESULTS: The Greater Paris area comprises 11 million inhabitants and accounts for 18% of the French population. In 2001, the hospital agency of the Greater Paris area set up a registry of all PTCAs performed in this region. Data from 2001 and 2002 was analysed. Hospitals performing <400 PTCAs per year were classified as low-volume. A case-control analysis (propensity score) compared in-hospital mortality in low- and high-volume centres. A total of 37 848 angioplasty procedures were performed in 44 centres during the study period; 24.7% were performed in low-volume centres. A non-statistically significant trend towards reduced in-hospital mortality was noted in high-volume centres as opposed to low-volume centres: 2.01 vs. 2.42%, P = 0.057. In-hospital mortality rates were significantly different in the sub-group of emergency procedures: 6.75% in high- vs. 8.54% in low-volume centres, P = 0.028. No difference was noted between low- and high-volume centres in non-emergency procedures (0.62 vs. 0.62%, P = 0.99). CONCLUSION: In the era of modern stenting, a clear inverse relationship exists between hospital PTCA volume and in-hospital mortality after emergency procedures. Tolerance of low-volume thresholds for angioplasty centres with the purpose of providing primary PTCA in AMI should not be recommended, even in underserved areas.     

Creation and testing of the Geriatric Self-Efficacy Index for Urinary Incontinence

OBJECTIVES: To report on the content development, construct validity, and reliability testing of the Geriatric Self-Efficacy Index for Urinary Incontinence (GSE-UI).
DESIGN: Prospective cohort study.
SETTING: Six UI outpatient clinics in Quebec, Canada.
PARTICIPANTS: Community-dwelling incontinent men and women aged 65 and older.
MEASUREMENTS: Thirty-eight items were generated using a literature search and interdisciplinary panel of experts. Item reduction was achieved through field-testing with 75 older men and women with UI attending an information session. The final 20-item draft, measuring older adults' level of confidence in preventing urine loss, was administered to a new group of consecutive patients 1 week before and at the time of their first visit to the UI clinic to enable evaluation of test–retest reliability. A 3-day voiding diary, quantifying the frequency of UI, and the Incontinence Quality of Life questionnaire were used to test construct validity.
RESULTS: One hundred sixteen of 300 eligible patients (39%) participated (mean age±standard deviation 74±6, range 65–87). The GSE-UI items showed normal distributions and no ceiling effects. Self-efficacy scores ranged from 16 to 193 (mean 104±41, possible range 0–200) and correlated positively with quality of life scores ( r =0.7, P <.001) and negatively with UI severity ( r =−0.4, P <.001). Internal consistency for the GSE-UI was 0.94 (Cronbach alpha). Initial test–retest reliability of the 20 items using intraclass correlations ranged from 0.50 to 0.86.
CONCLUSION: The GSE-UI will enable measurement of whether a person's confidence in their ability to prevent urine loss is an important mechanism contributing to improvements in UI.