Follicular lymphoma cell lines,an in vitro model for antigenic selection and cytokine-mediated growth regulation of germinal centre B cells

In the periphery, B cells differentiate in germinal centres (GCs) of secondary lymphoid organs. Isolated GC cells die quickly in vitro by apoptosis. Therefore, cell lines originating from follicular lymphomas, which are the malignant counterparts of GC B cells, would provide a stable in vitro model to study the immunobiology of GC B cells. We have established three novel human follicular lymphoma cell lines that were characterized with special reference to immunophenotypic features, response to B-cell receptor (BCR) triggering, response to cytokines and cytokine mRNA expression. One of the cell lines, HF-1A3, has a phenotype of a centrocyte. It expresses surface immunoglobulin G (sIgG) and dies by apoptosis following BCR cross-linking. Co-stimulation with interleukin-6 (IL-6), IL-15 or interferon-gamma (IFN-gamma) rescues HF-1A3 cells from BCR-induced apoptosis. The second cell line, HF-28, also represents phenotypically an IgG+ centrocyte. Ligation of its BCR leads to the cell-cycle arrest at G1 instead of apoptosis. HF-28 cells express both CD45RA and RO isoforms, which is unusual in B lymphocytes apart from plasma cells, thus suggesting a transition to plasma cell phenotype. The third cell line, HF-4.9, which phenotypically represents an sIgM+ centroblast, responds by proliferation to BCR cross-linking. These cell lines offer a unique in vitro model to study antigenic selection and cytokine-mediated growth regulation of human GC B cells.     

X-ray scattering in full-field digital mammography

Effects of x-ray scattering on full-field digital mammography are analyzed with the scattering model of Seibert and Boone [Med. Phys. 15, 567-575 (1988)]. A new method is introduced for the estimation of model parameters from measurements. It is shown that with breasts thinner than a certain threshold, removing the anti-scatter grid leads to an improved contrast-to-noise ratio with a smaller patient dose. A fast approximate algorithm is presented for determining the scattered field in a gridless digital mammogram.     

Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus

PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.     

Cognitive functioning in substance abuse and dependence: a population-based study of young adults

Aims   To investigate whether substance use disorders (SUDs) are associated with verbal intellectual ability, psychomotor processing speed, verbal and visual working memory, executive function and verbal learning in young adults, and to study the associations of SUD characteristics with cognitive performance.
Participants   A population-based sample ( n  = 466) of young Finnish adults aged 21–35 years.
Measurements   Diagnostic assessment was based on all available information from a structured psychiatric interview (SCID-I) and in- and out-patient medical records. Established neuropsychological tests were used in the cognitive assessment. Confounding factors included in the analyses were comorbid psychiatric disorders and risk factors for SUDs, representing behavioural and affective factors, parental factors, early initiation of substance use and education-related factors.
Findings   Adjusted for age and gender, life-time DSM-IV SUD was associated with poorer verbal intellectual ability, as measured with the Wechsler Adult Intelligence Scale–Revised (WAIS-R) vocabulary subtest, and slower psychomotor processing, as measured with the WAIS-R digit symbol subtest. Poorer verbal intellectual ability was accounted for by parental and own low basic education, whereas the association with slower psychomotor processing remained after adjustment for SUD risk factors. Poorer verbal intellectual ability was related to substance abuse rather than dependence. Other SUD characteristics were not associated with cognition.
Conclusions   Poorer verbal intellectual ability and less efficient psychomotor processing are associated with life-time alcohol and other substance use disorders in young adulthood. Poorer verbal intellectual ability seems to be related to parental and own low basic education, whereas slower psychomotor processing is associated with SUD independently of risk factors.     

Health-related services on the internet

The primary objective of this study is to evaluate a sample of health-related services available on the internet. In addition, types of new services and service qualities that may be required in the future were estimated. A registered nurse using a questionnaire containing items about usability, quality, and other characteristics related to the subject carried out an evaluation of 100 health-related internet sites, and the results were processed to determine average qualities and graphical presentations for the studied parameters. The services studied differed greatly from each other both in terms of content and quality. A general observation was that sites of larger organizations were, typically, both in terms of presentation and content, more sophisticated than sites of smaller producers. A typical characteristic was the superficiality of the information presented. In conclusion, the internet is an emerging medium for health-related information, and standards for the production and presentation of health content for the internet are still in development. However, even at this early stage, the internet represents a valuable source of information for those in need of health-related information for both health care professionals and consumers.     

Effects of α tocopherol and β carotene supplements on symptoms, progression, and prognosis of angina pectoris

Objective—To evaluate the effects of α tocopherol and β carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris.
Design—Placebo controlled clinical trial.
Setting—The Finnish α tocopherol β carotene cancer prevention study primarily undertaken to examine the effects of α tocopherol and β carotene on cancer.
Subjects—Male smokers aged 50-69 years who had angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795).
Interventions—α tocopherol (vitamin E) 50 mg/day, β carotene 20 mg/day or both, or placebo in 2 × 2 factorial design.
Main outcome measures—Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease).
Results—There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: α tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), α tocopherol and β carotene 1.02 (0.82 to 1.27), β carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo.
Conclusions—There was no evidence of beneficial effects for α tocopherol or β carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients.

Keywords: antioxidants;  angina pectoris;  prevention;  vitamin supplements     

Bayesian Latent Variable Collapsing Model for Detecting Rare Variant Interaction Effect in Twin Study

By analyzing more next‐generation sequencing data, researchers have affirmed that rare genetic variants are widespread among populations and likely play an important role in complex phenotypes. Recently, a handful of statistical models have been developed to analyze rare variant (RV) association in different study designs. However, due to the scarce occurrence of minor alleles in data, appropriate statistical methods for detecting RV interaction effects are still difficult to develop. We propose a hierarchical Bayesian latent variable collapsing method (BLVCM), which circumvents the obstacles by parameterizing the signals of RVs with latent variables in a Bayesian framework and is parameterized for twin data. The BLVCM can tackle nonassociated variants, allow both protective and deleterious effects, capture SNP‐SNP synergistic effect, provide estimates for the gene level and individual SNP contributions, and can be applied to both independent and various twin designs. We assessed the statistical properties of the BLVCM using simulated data, and found that it achieved better performance in terms of power for interaction effect detection compared to the Granvil and the SKAT. As proof of practical application, the BLVCM was then applied to a twin study analysis of more than 20,000 gene regions to identify significant RVs associated with low‐density lipoprotein cholesterol level. The results show that some of the findings are consistent with previous studies, and we identified some novel gene regions with significant SNP–SNP synergistic effects.