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。     

Oral disease in the elderly in long-term hospital care

OBJECTIVE: To obtain baseline information on the prevalence of oral problems and disease in institutionalized elderly in a Scottish hospital.
DESIGN: A cross-sectional clinical investigation with complementary microbiological studies as appropriate. SUBJECTS AND METHODS: A cohort of 147 elderly in five long-term care wards; collection of demographic data; clinical examination to determine: i) the dental, and denture status and associated lesions such as Candida-associated denture stomatitis and angular cheilitis, ii) oral mucosal disease; swabs as appropriate for microbiology.
MAIN OUTCOME MEASURES: Dental status, root caries prevalence; denture status and hygiene, and associated disease; oral mucosal health.
RESULTS Median period of institutionalization of 147 patients was 15 months and 65% were aged 80 years or more; the majority were significantly mentally impaired; 52% wore complete dentures, 9% were partially dentate, 19% possessed partial or incomplete dentures; 20% were neither dentate nor had dentures. Of 80 patients who verbalired their complaints, 35% complained of dry mouth and 45% had denture-related problems, principally discomfort. The commonest oral finding was a coated tongue (56%); angular cheilitis was present in 25%, and Candida-associated denture stomatitis in 19%; none had oral ulcers.
CONCLUSIONS: There was considerable unmet dental need with significant oral disease and poor levels of oral and denture hygiene in this target group; both dental and medical professionals should act in concert to deliver curative as well as preventative dental care for the elderly living in institutions to improve their quality of life.     

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.     

Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expanding CAG repeat coding for polyglutamine in the huntingtin protein. Recent data have suggested the possibility that an N-terminal fragment of huntingtin may aggregate in neurons of patients with HD, both in the cytoplasm, forming dystrophic neurites, and in the nucleus, forming intranuclear neuronal inclusion bodies. An animal model of HD using the short N-terminal fragment of huntingtin has also been found to have intranuclear inclusions and this same fragment can aggregate in vitro . We have now developed a cell culture model demonstrating that N-terminal fragments of huntingtin with expanded glutamine repeats aggregate both in the cytoplasm and in the nucleus. Neuroblastoma cells transiently transfected with full-length huntingtin constructs with either a normal or expanded repeat had diffuse cytoplasmic localization of the protein. In contrast, cells transfected with truncated N-terminal fragments showed aggregation only if the glutamine repeat was expanded. The aggregates were often ubiquitinated. The shorter truncated product appeared to form more aggregates in the nucleus. Cells transfected with the expanded repeat construct but not the normal repeat construct showed enhanced toxicity to the apoptosis- inducing agent staurosporine. These data indicate that N-terminal truncated fragments of huntingtin with expanded glutamine repeats can aggregate in cells in culture and that this aggregation can be toxic to cells. This model will be useful for future experiments to test mechanisms of aggregation and toxicity and potentially for testing experimental therapeutic interventions.      

Ethnic variation of Fc gamma receptor polymorphism in Sami and Norwegian populations

Receptors for the Fc domain of IgG (Fc gammaR) play a critical role in linking cellular and humoral immunity. The various Fc gammaR genotypes may contribute to differences in infectious and immune-related diseases in various ethnic populations. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and differ ethnically from the Norwegians. The distribution of various immune-related diseases has been reported to differ between Sami and Norwegians. This is the first study to evaluate the distribution of Fc gammaR polymorphisms in a Sami population. Two hundred Samis were genotyped for polymorphisms in the Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genes. The genotype and allele frequencies were compared with those of 272 healthy Norwegians. The Sami and Norwegian Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genotypes differed significantly. The Samis had higher frequencies of the Fc gammaRIIa-H/H131, Fc gammaRIIIa-F/F158 and Fc gammaRIIIb-NA1/NA1 genotypes. The Fc gammaR genotypes were non-randomly distributed in both populations. These findings may be important for the prevalence of autoimmune and infectious diseases in the two populations.     

Fcgamma receptor polymorphisms in populations in Ethiopia and Norway

Seventy-seven healthy Ethiopians were genotyped for polymorphisms in the immunoglobulin G Fc receptors (FcgammaR) FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb, including the SH allele. The genotype and allele frequencies were compared with those of 96 healthy Norwegians. Ethiopians had higher frequencies of the SH-FcgammaRIIIb (P = 0.001), FcgammaRIIIa-158 V (P = 0.026) and FcgammaRIIIb-Na2 (P = 0.046) alleles. The genotype distributions of FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb, however, did not differ significantly from those of the Norwegians. The data were also compared with those reported from studies on other ethnic groups. The variation of different polymorphisms both within and between ethnic groups may influence differences in the incidence rates of infectious and autoimmune diseases.     

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.