Cancers take their Toll--the function and regulation of Toll-like receptors in cancer cells

Cancer could be deemed as an abnormal and uncontrolled tissue repair process. Therefore, it would not be surprising that factors that function in the tissue repair process, such as cytokines, chemokines, growth factors and Toll-like receptor (TLR) ligands, as well as growth signals for compensatory proliferation, would also be key factors in regulating and enhancing cancer progression. The TLR pathways, which play a critical role in tissue repair, are also key regulators in cancer progression as well as chemoresistance. TLRs serve as cell surface sensors that can initiate pathways leading to proliferation and chemoresistance; as well as mediators that are able to regulate the infiltrating immune cells to provide further support for cancer progression.     

Trend in Incidence and Case Fatality of Meningococcal Disease over 16 Years in Northern Denmark

 The incidence and case fatality rates of meningococcal disease were assessed in the county of Northern Jutland, Denmark, during the 16-year period from 1980 to 1995. A total of 320 patients were identified from the Meningococcal Research Database, which comprises information from the following sources: (i) the Department of Public Health, to whom notification of meningococcal disease is obligatory; (ii) the Regional Hospital Discharge Registry; and (iii) the register of the regional department of clinical microbiology. In order to assess prognostic indicators assessable at admission, information was collected for each patient from hospital records regarding contacts, symptoms and signs on arrival, laboratory data, and course of disease. The mean incidence was 4.3 cases per 100 000 persons per year (range, 2.7–7.7). The incidence increased slightly during the period studied. Overall, the case fatality rate was 9.7%, with a significant rise occurring during the period (P=0.016) and a peak occurring in 1992. Advanced age (≥50 years), seizures, impaired consciousness, and skin bleeding on arrival at hospital were predictors of death.     

Evaluation of Histo-Blood Group ABO Genotyping in a Danish Population: Frequency of a Novel O Allele Defined as O2

Traditional blood group ABO serology is based on immunoreactivity with the carbohydrate determinants A, B and H antigens. Recent advances at the DNA level of the ABO genes have provided a molecular genetic model for the ABO polymorphism. This genetic model has to date only been tested on a limited basis. The present study was initiated to evaluate the universality of the proposed genetic model on a larger group of serologically defined ABO phenotypes. Three hundred healthy Danish blood donors were analysed (A: 50, B: 50, AB: 50, O: 150) by PCR amplification followed by diagnostic restriction enzyme cutting. In all cases A, B, and AB at least one allele of correctly predicted status was found. However, in O phenotype individuals, 11 out of 150 carried one allele discordant to the proposed genetic model. This novel O allele (3.7% allele frequency) was further characterized by diagnostic restriction enzyme analysis in two positions divergent between A and B alleles and by DNA sequencing of the two major exons. The novel O allele is termed O² as it typed as B in nucleotide position 526 and as A in positions 703, 796, and 803, in contrast to the most predominant O allele termed O¹, which types as A in all 4 positions. The structural defect in the O² allele appears to be an additional substitution at nucleotide position 802. The results clearly demonstrate that with the addition of the two distinctly different O alleles, O¹, O², the previously proposed molecular genetic basis of the ABO polymorphism is quite valid. More importantly the determined characteristics of these two O alleles have practical implications in ABO genotyping, because it establishes within the limits of the number of samples tested that ABO genotypes can be assessed directly by non-allele specific PCR amplification and restriction enzyme analysis.     

The incidence of asthma in young adults

STUDY OBJECTIVES: Longitudinal data on adult asthma are sparse. The objectives of this study were to determine the incidence of asthma and to establish the risk factors for the development of asthma in subjects who were 12 to 41 years old over an 8-year period. DESIGN: From birth cohorts over the period 1953 to 1982 in The Danish Twin Registry, 19,349 subjects with no history of asthma, as determined by a questionnaire-based survey in 1994, answered a follow-up questionnaire in 2002. The subjects were regarded as incident asthma cases when answering "yes" to the question "Do you have, or have you ever had asthma?" in 2002, and "no" to the same question in 1994. RESULTS: A total of 838 cases (4.3%) of new asthma were identified in 2002. The incidence rates of asthma were 4.5 and 6.4 per 1,000 person-years, respectively, among male and female subjects. For all ages, the probability of adult-onset asthma was greater for female subjects (odds ratio [OR], 1.49; p < 0.001), and for both sexes there was a slow decline in probability with increasing age. There was a positive association between increasing body mass index (BMI) and risk of adult-onset asthma applying to both sexes (OR, 1.05 per unit; p < 0.001). Furthermore, positive associations were found between incident asthma and a history of hay fever (OR: male subjects, 4.2; female subjects, 3.7; p < 0.001), eczema (OR: male subjects, 3.5; female subjects, 2.0; p < 0.001), and both (OR: male subjects, 6.9; female subjects, 8.0; p < 0.001). CONCLUSIONS: There is a continuing high incidence of asthma past childhood that is most pronounced among female subjects. Increasing levels of BMI are associated with a greater likelihood of developing asthma for both sexes. A substantial portion of cases of adult asthma is preceded by upper airway allergic symptoms and/or eczema, thus indicating a shared pathogenesis.