C4A deficiency in children and adolescents with recurrent respiratory infections

Increased susceptibility to recurrent viral and bacterial respiratory infections in children and young adults is not well understood. To evaluate the role of complement factor C4 in the defense against respiratory infections, we studied complement factor C4 allotypes C4A and C4B and copy numbers of C4A and C4B genes in 84 children and young adults with recurrent acute otitis media, sinusitis, or pneumonia and in 74 healthy controls. The occurrence of C4A gene deficiency was significantly higher in patients compared with controls (26% vs 14%, p = 0.048). Girls predominated in the group of patients with C4A deficiency (73% girls and 27% boys, p = 0.004). The lectin pathway of complement was more often functionally impaired in patients with C4A deficiency than in patients with no C4A deficiency (41% vs 13%, p = 0.033). Classical and alternative pathways were normal in individuals with C4 null alleles. C4A deficiency is 1 of the minor defects of the innate immunity that may predispose children and young adults to recurrent respiratory infections. C4 gene testing should be added to the list of investigations when the cause for recurrent acute otitis media, maxillary sinusitis, or pneumonia in children and young adults is sought.     

Cardiovascular disease occurrence in two close but different social environments

Background  

Cardiovascular diseases estimate to be the leading cause of death and loss of disability-adjusted life years globally. Conventional risk factors for cardiovascular diseases only partly account for the social gradient. The purpose of this study was to compare the occurrence of the most frequent cardiovascular diseases and cardiovascular mortality in two close cities, the Twin cities.     

Inheritance of intrahepatic cholestasis of pregnancy in one kindred

Hirvioja M-L, Kivinen S. Inheritance of intrahepatic cholestasis of pregnancy in one kindred
Clin Genet 1993: 43: 315–317. © Munksgaard, 1993
We report three sisters with intrahepatic cholestasis of pregnancy (ICP) and the pedigree of the family, including six: generations. ICP was observed in five successive generations; most of the patients also had cholelithiasis. The uniform expression, the complete penetrance of the trait and the direct parent-to-child transmission support the Mendelian dominant mode of inheritance. Determination of HLA A, B and C haplotype was made in five ICP patients, without any findings of HLA type common to everyone. X-linked inheritance cannot be excluded in this study.     

Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms

CYP1A2 is involved in the metabolism of several widely used drugs and endogenous compounds, and in the activation of procarcinogens. Both genetic and environmental factors influence the activity of this enzyme. The current knowledge regarding factors influencing the activity of CYP1A2 is summarized in this review. Substrates, inhibitors and inducers of CYP1A2 activity, as well as phenotyping probes, are discussed. The functional significance and clinical importance of CYP1A2 gene polymorphisms are reviewed and interethnic differences in the distribution of CYP1A2 variant alleles and haplotypes are summarized. Finally, future perspectives for the possible clinical applications of CYP1A2 genotyping are discussed.     

MicroRNA microarrays on archive bone marrow core biopsies of leukemias—Method validation

Due to availability of bone marrow core biopsies (CB) in many pathology laboratories, we evaluated the quality and the biological information of the miRNA profiling using 9 acute lymphoblastic leukemia (ALL) and 9 chronic myeloid leukemia (CML) matched CB and bone marrow aspirates (BA). Technical replicates showed reproducible results across platforms and clustered together in hierarchical clustering analysis; and matched samples showed similar biological content having common differentially expressed miRNAs against the same control samples. We showed, that CBs, which have underwent decalcification in addition to formalin-fixation, are suitable for miRNA profiling.     

Campylobacter jejuni isolates in Finnish patients differ according to the origin of infection

Background

Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria.

Results

C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni -infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter -infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics.

Conclusion

These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.     

Prognostic impact of CD31-positive microvessel density in follicular lymphoma patients treated with immunochemotherapy

BackgroundTumour-infiltrating mast cells (MCs) can remodel tumour microenvironment and growth by suppressing immune responses and potentiating angiogenesis. Furthermore, accumulation of MCs in follicular lymphoma (FL) correlates with unfavourable prognosis after immunochemotherapy. Here we investigated whether tumour vascularity is associated with MC content and outcome in FL patients treated with immunochemotherapy.Patients and methodsMicrovessel density (MVD) and MC content were determined immunohistochemically from pretreatment samples of 95 FL patients using CD31, CD34 and mast cell tryptase antibodies. Gene expression data from a separate set of 24 FL patients were analysed for comparison. All patients were treated with the combination of rituximab (R) and cyclophoshamide-doxorubicin–vincristine–prednisone (CHOP) chemotherapy.ResultsIncreased CD31+ MVD correlated positively with the number of tumour infiltrating MCs and CD34+ vessels, and negatively with the outcome. Overall survival and progression-free survival were significantly better among patients with low CD31+ MVDs. In multivariate analyses, CD31+ MVD had prognostic value independently of Follicular Lymphoma Prognostic Index but not of MC content. Consistent with the immunohistochemical data, high CD31/PECAM1 mRNA levels were associated with adverse outcome. Conversely, a positive prognostic impact of VEGF mRNA expression on the outcome was found.ConclusionVascularity is associated with MC content and outcome in R-CHOP-treated FL patients.     

Annual injection of vitamin D and fractures of aged bones

Summary In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people, an annual intramuscular injection of ergocalciferol (150,000–300,000 IU) was given to two series of aged subjects: first to 199 (45 male) of 479 subjects (110 male) aged more than 85 years who were living in their own home, and second to 142 (29 male) of 320 (58 male) subjects aged 75–84 and living in a home for aged people. This prospective series was divided into treatment groups according to month of birth. These injections were given annually from September to December in the years 1985–1989, two to five times to each participant. The fracture rates, laboratory values, vitamin D levels, possible side effects, and mortality were followed until October 1990. A total of 56 fractures occurred in the 341 vitamin D recipients (16.4%) and 100 in 458 controls (21.8%) (P=0.034). The fracture rate was about the same in both outpatient and municipal home series. Fractures of the upper limb were fewer in the vitamin D recipients, 10/341=2.9% (P=0.025), than in the controls, 28/458=6.1%, during the follow-up. A similar result was obtained in fractures of ribs, 3/341=0.9% and 12/458=2.6%, respectively. Fractures of the lower limbs occurred almost as frequently, 31/341=9.1%, among the vitamin D recipients as among the controls, 49/458=10.7%. The fracture rate was higher in females (22.2%) than in males (9.5%). The fractures were fewer in the vitamin D recipients only in females. No significant differences were found in total mortality, or due to any group of diseases, between the two treatment groups. No deleterious effects of the vitamin D injections were seen. The authors recommend the supplementation of vitamin D in aged people, at least in northernmost latitudes (e.g., as an annual intramuscular injection).