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(8, 9). Unlike the cysteine-rich sterol/steroid-binding proteins in serum vitamin D-binding protein/albumin (9) and vitamin D/steroid receptor protein (10) families, which are confined prinicipally to the extracellular domain and nucleus, respectively, IDBP is a relatively abundant, cysteine-poor protein concentrated in, but not confined to, the cytoplasmic compartment of cells (11). However, like these other sterol/steroidbinding proteins (8,9), IDBP has been shown preferentially to bind 25-hydroxylated vitamin D metabolites (12). In the current report we have greatly expanded the vitamin D metabolite-IDBP binding studies to define more clearly which structural modifications of the vitamin D molecule are important for either enhancing or reducing ligand binding to IDBP extracted from NWP cells. We also document the IDBP binding potential of a much more extensive panel of molecules in an attempt to define additional classes of small, lipid-soluble signaling molecules which may interact with IDBP. Although we were previously able to enrich vitamin D metabolite binding activity in extracts of NWP cells (13), attempts to purify IDBP to homogeneity were unsuccessful. Here we report the purification and structural identification of the NWP IDBP as a member of the hsp-70 family of proteins and demonstrate the sterol/steroid binding properties of hsp-70-like proteins. D Sterols, Steroids, 3 H]Hydroxyvitamin D 3 (25-[ 3 H]OHD 3 ; specific activity, 181 Ci/mmol) and MATERIALS AND METHODS Vitamin

Urine sampling via a centralized national laboratory was efficient and cost-saving. Iodine deficiency in Israeli SAC and PW is a serious public-health concern. A national program of salt iodization and iodine supplementation of PW should be urgently considered.

ORMAL pubertal development and fertility depend on the intricate interplay of hypothalamic, pituitary, and gonadal factors. Crucial in this respect are normal secretory patterns of follicle-stimulating hormone and luteinizing hormone. These hormones stimulate the production of estrogen and ovulation in women and the production of testosterone and spermatogenesis in men. Secreted from common gonadotroph cells, the hormones are heterodimers composed of a common a -subunit and a specific b -subunit, each encoded by a separate gene. Specificity of action depends on the recognition of these hormones by specific receptors on the surface of gonadal cells.Various genetic defects of the hypothalamic-pituitary-gonadal axis that cause hypogonadism have been identified. 1 At the level of the hypothalamus, secretion of gonadotropin-releasing hormone is disturbed by mutations in the KAL gene, 2 leading to Kallmann's syndrome, and in the DAX-1 gene, 3 causing X-linked adrenal hypoplasia and hypogonadotropic hypogonadism. At the pituitary level, mutations in the gene for the b -subunit of luteinizing hormone 4 cause hypogonadotropic hypogonadism, and at the gonadal level, loss-of-function mutations in the genes that encode the receptors for folliclestimulating hormone and luteinizing hormone cause hypergonadotropic hypogonadism. 5,6 Specifically, mutations in the gene for luteinizing hormone receptors result in Leydig-cell hypoplasia and undermasculinization in genetic males, 5,7,8 whereas mutations in the gene for follicle-stimulating hormone receptors cause primary gonadal failure and hypergonadotropic hypogonadism in genetic females. 6 Two female patients with follicle-stimulating hor-N mone deficiency caused by mutations in the gene for the b -subunit of follicle-stimulating hormone have been described. One presented with primary amenorrhea and infertility, 9 and the other with delayed puberty. 10 In this report, we describe a man with impaired secretion of follicle-stimulating hormone caused by a homozygous mutation in the gene for the b -subunit of follicle-stimulating hormone, as well as two asymptomatic heterozygous male members of his family. METHODS SubjectsThe proband was referred to our center at the age of 18 years for evaluation of delayed puberty. He reported normal erections and ejaculatory orgasms. He had a prepubertal physique and underdeveloped muscles. He was 178 cm tall (69th percentile) and weighed 59 kg. He had pubic hair (Tanner stage 4), scant axillary hair, and no facial hair. No breast tissue was palpated. The scrotum was thin, and two small, soft testicles (testicular volume, 1 to 2 ml) were palpated. There was no family history of consanguinity, infertility, or delayed puberty.Laboratory studies revealed low serum testosterone and follicle-stimulating hormone concentrations and high serum luteinizing hormone concentrations (Table 1). Serum thyrotropin, prolactin, and cortisol concentrations were normal. Chromosomal analysis revealed a 46,XY karyotype. After intravenous administration of 100 µg of gon...

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BackgroundOne of the major challenges health care systems face in modern time is treating chronic disorders. In recent years, the increasing occurrence of multiple chronic disorders (MCC) in single individuals has compounded the complexity of health care. In 2008, it was estimated that worldwide as many as one quarter of the population between the ages of sixty five to sixty nine suffered from two or more chronic conditions and this prevalence rose with age. Clinical guidelines provide guidance for management of single disorders, but not for MCC. The aim of the present study was the study of the prevalence, distribution and impact of MCC in a large Israeli health system.MethodsWe performed a cross-sectional study of MCC in the Maccabi Healthcare System (MHS), Israel’s second largest healthcare service, providing care for approximately two million people. Data regarding chronic conditions was collected through electronic medical records and organizational records, as was demographic and socioeconomic data. Age and sex specific data were compared with previously published data from Scotland.ResultsTwo thirds of the population had two or more chronic disorders. This is significantly higher than previously published rates. A correlation between patient age and number of chronic disorders was found, as was a correlation between number of chronic disorders and low socioeconomic status, with the exception of children due to a high prevalence of learning disabilities, asthma, and visual disturbances.DiscussionMCC is very prevalent in the MHS population, increases with age, and except for children is more prevalent in lower socioeconomic classes, possibly due to the a combination of the structure of the Israeli universal insurance and requirements of the ministry of education for exemptions and benefits. A higher than previously reported prevalence of MCC may be due to the longtime use of use of integrated electronic medical records.ConclusionsTo effectively deal with MCC health care systems must devise strategies, including but not limited to, information technologies that enable shared teamwork based on clinical guidelines which address the problem of multiple, as opposed to single chronic disorders in patients.

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