世界卫生组织与热带病防治

简述世界卫生组织之缘起、架构、工作、人事及各区域分署等,及其热带病,例如疟疾、血吸虫、丝虫病、登革热、黑热病、麻风及锥虫病的防治状况。     

Career Outcomes of Graduates of R25E Short-Term Cancer Research Training Programs

The efficacy of short-term cancer research educational programs in meeting its immediate goals and long-term cancer research career objectives has not been well studied. The purpose of this report is to describe the immediate impact on, and the long-term career outcomes of, 499 medical students and graduate students who completed the Cancer Research Experiences for Students (CaRES) program at the University of Alabama at Birmingham (UAB) from 1999 to 2013. In summer 2014, all 499 program alumni were located and 96.4 % (481 of 499) agreed to complete a longitudinal tracking survey. About 23 % of CaRES alumni (110 of 499) have published at least one cancer-related paper. Overall 238 cancer-related papers have been published by CaRES alumni, one third of this number being first-authored publications. Nearly 15 % (71 of 481 respondents) reported that their current professional activities include cancer research, primarily clinical research and outcomes research. Of these 71 individuals, 27 (38 %) have completed their training and 44 (62 %) remain in training. Of all respondents, 58 % reported that they administered care to cancer patients and 30 % reported other cancer-related professional responsibilities such as working with a health department or community group on cancer control activities. Of the 410 respondents not currently engaged in cancer research, 118 (29 %) stated intentions to conduct cancer research in the next few years. Nearly all respondents (99.6 %) recommended CaRES to today’s students. Challenging short-term educational cancer research programs for medical students and graduate health professional students can help them refine and solidify their career plans, with many program alumni choosing cancer research careers.     

A mono-sited transferrin from a representative deuterostome: the ascidian Pyura stolonifera (subphylum Urochordata)

An iron-binding protein has been found in the plasma of Pyura stolonifera. This protein has a molecular weight of about 41,000 +/- 2,000 and binds 1 mol iron/mol protein. The absorption maxima are lambda = 280 and lambda = 429 nm (E429/E280 = 0.044). Bicarbonate is bound concomitantly with high affinity and is necessary for optimal color formation at lambda = 429 nm. The protein showed a negligible exchange of iron with human apotransferrin under physiologic conditions over two hours. Upon incubation with rat reticulocytes, the protein reacts with membrane receptors for transferrins, and the protein, with its iron, is transported intracellularly where the iron is incorporated into heme. The 59Fe protein, after intravenous injection, disappears rapidly from the plasma and is excreted largely in the urine, with a substantial fraction present in the kidney and another large fraction present in the gut. These findings established the protein as a "transferrin" and support the concept that the larger transferrin molecule in vertebrates, with two iron-binding sites, resulted from a gene duplication.     

Genetic heterogeneity in familial hyperinsulinism [published erratum appears in Hum Mol Genet 1998 Sep;7(9):1527]

Familial hyperinsulinism (HI) is a disorder characterized by dysregulation of insulin secretion and profound hypoglycemia. Mutations in both the Kir6.2 and sulfonylurea receptor (SUR1) genes have been associated with the autosomal recessive form of this disorder. In this study, the spectrum and frequency of SUR1 mutations in HI and their significance to clinical manifestations of the disease were investigated by screening 45 HI probands of various ethnic origins for mutations in the SUR1 gene. Single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses of genomic DNA revealed a total of 17 novel and three previously described mutations in SUR1 . The novel mutations comprised one nonsense and 10 missense mutations, two deletions, three mutations in consensus splice-site sequences and an in- frame insertion of six nucleotides. One mutation occurred in the first nucleotide binding domain (NBF-1) of the SUR1 molecule and another eight mutations were located in the second nucleotide binding domain (NBF-2), including two at highly conserved amino acid residues within the Walker A sequence motif. The majority of the remaining mutations was distributed throughout the three putative transmembrane domains of the SUR1 protein. With the exception of the 3993-9G-->A mutation, which was detected on 4.5% (4/88) disease chromosomes, allelic frequencies for the identified mutations varied between 1.1 and 2.3% for HI chromosomes, indicating that each mutation was rare within the patient cohort. The clinical manifestations of HI in those patients homozygous for mutations in the SUR1 gene are described. In contrast with the allelic homogeneity of HI previously described in Ashkenazi Jewish patients, these findings suggest that a large degree of allelic heterogeneity at the SUR1 locus exists in non-Ashkenazi HI patients. These data have important implications for genetic counseling and prenatal diagnosis of HI, and also provide a basis to further elucidate the molecular mechanisms underlying the pathophysiology of this disease.      

Measured haplotype analysis of the angiotensin-I converting enzyme gene

Linkage and segregation analysis have shown that circulating angiotensin-I converting enzyme (ACE) levels are influenced by a major quantitative trait locus that maps within or close to the ACE gene. The D variant of a 287 bp insertion/deletion (I/D) polymorphism in intron 16 of the gene is associated with high ACE levels and may also be related to increased risk of cardiovascular disease. Multiple variants that are in linkage disequilibrium with the I/D polymorphism have been described, but it is unknown if any of these are directly implicated, alone or in combination with as yet undiscovered variants, in the determination of ACE levels. An analysis of 10 polymorphisms spanning 26 kb of the ACE gene revealed a limited number of haplotypes in Caucasian British families due to strong linkage disequilibrium operating over this small chromosomal region. A haplotype tree (cladogram) was constructed with three main branches (clades A-C) which account for 90% of the observed haplotypes. Clade C is most likely derived from clades A and B following an ancestral recombination event. This evolutionary information was then used to direct a series of nested, measured haplotype analyses that excluded upstream sequences, including the ACE promoter, from harbouring the major ACE-linked variant that explains 36% of the total trait variability. Residual familial correlations were highly significant, suggesting the influence of additional unlinked genes. Our results demonstrate that a combined cladistic/measured haplotype analysis of polymorphisms within a gene provides a powerful means to localize variants that directly influence a quantitative trait.      

Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in human immunodeficiency virus-infected persons

Anemia, thrombocytopenia, and neutropenia have been observed in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. To investigate whether red cells (RBCs) of patients with human immunodeficiency virus infection were coated with IgG and/or complement (C3), blood samples of 239 patients were tested. The prevalence of a positive direct antiglobulin test on RBCs was 16.7 percent. By use of an enzyme-linked antiglobulin test (ELAT) to measure more accurately the number of IgG molecules per RBC in a group of 67 patients, 30 of the 67 individuals were observed to have increased numbers (mean, 155) compared to normal controls and to patients with hypergammaglobulinemia due to multiple myeloma or chronic liver disease. Hemoglobin level was correlated with the number of IgG molecules per RBC (p = 0.008), but no correlation could be demonstrated between those numbers and serum immunoglobulin (p = 0.10) or circulating immune complexes (p = 0.38). Our results with ELAT suggest that some AIDS patients may have specific binding of IgG on the surface of their RBCs, rather than nonspecific uptake; further clinical correlations are necessary to confirm these findings.