BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.

After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.     

Enhancement of spontaneous killer cytotoxicity by soluble factor

Two-stage stimulation of SK activity of normal human peripheral blood lymphocytes by soluble factors was demonstrated. The first stage was initiated by factors present in supernatant derived from normal B-LCL cultures. Only cell lines which could induce SK activity in culture in an MLR-type reaction had the capacity to produce the active factor. Supernatant factor required adherent cells to cause SK augmentation. The interaction of adherent cells plus supernatant factor resulted in the production of a second soluble factor which stimulated an increase in SK activity in responding lymphocyte populations. This second stage involved a different soluble factor which acted directly on the non-SK, Fc-negative lymphocyte population, and within 3 hr. Data obtained using antisera to interferon (IF) indicated that IF is a component of the second soluble factor, and not of the supernatant factor derived from the B-LCL.     

Studies on the incidence of dementia: the European perspective.

Dementing diseases, the most common of which are Alzheimer's disease and vascular dementia, are highly prevalent in Europe. To progress further in the search for the etiology of these diseases, incidence studies are needed. Comparison of the data of such studies will be important; the question of whether they produce comparable and interpretable data is therefore critical. We discuss the methodologic differences between earlier and more recent studies conducted in Europe that may account for some of the variation in the incidence rates of the dementia they report. Issues to be explored in the current European studies on the incidence of dementing diseases are also described.     

Tuberculosis in children: a 13-year follow up of 1714 patients in a Belgian home care centre

From May 1970 to September 1983, 1714 children with different forms of primary tuberculosis were referred to the paediatric home care centre (Enfants soignés au Foyer, E.S.F.) of the Brussels University Hospital St.-Pierre. They were subdivided in five groups: asymptomatic (33%), symptomatic (28%), dubious tuberculous infections (35%), high-risk contacts (3%) and unestablished diagnosis (1%). They were aged from 10 days to 19 years, and 82% of them were migrants of low socio-economic level. Fifty percent of the symptomatic infections, mainly pulmonary, appeared in children under 3 years of age. An adult source of contamination was identified in 33% of the case (48% of the symptomatic children). Diagnosis was based on tuberculin screening with a 2IU intradermal test. Gastric aspirates yieldedMycobacterium tuberculosis in 15% of our patients, 11% of them showing resistance to one or more tuberculostatic drugs. Treatment was given to 1359 patients with excellent results. Therapy was shortened during the last 2 years of the study from 12 to 6 months for the asymptomatic patients and from 12 to 9 months for the symptomatic infections. Few complications were observed. Tuberculosis remains a serious cause of morbidity particularly in migrant children. Correct diagnosis and treatment of the disease is very important.