Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland.

Background: The prevalence of sporadic and familial idiopathic pulmonary fibrosis (IPF) cases in Finland was evaluated according to the revised recommendations of the American Thoracic Society.

Methods: All Finnish pulmonary clinics (n=29) were included in the primary screening. Hospital data bases were used to identify patients with the diagnosis "alveolitis fibroticans idiopathica" (J84.

Gender influence on vasoactive hormones at rest and during a 70 degrees head-up tilt in healthy humans.

To evaluate the influence of age and gender on the neuroendocrine control of blood pressure in normal subjects, a 13-min 70 degrees head-up tilt (HUT) was applied after 3 h of recumbency to 109 healthy men and women aged 23-50 yr (age group I) and 51-77 yr (age group II). We found that age and gender had a significant influence on plasma norepinephrine (PNE) concentration at baseline and in the upright position. PNE was significantly higher in older men compared with the younger men and women of both age groups, suggesting a divergent age-related activation of the sympathetic nervous system between genders at baseline as well as during a sustained orthostatic challenge.

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.

Perinatal risk factors for hay fever--a study among 2550 Finnish twin families.

Previous studies have suggested that perinatal factors influence the risk for asthma but population studies on perinatal factors and risk for hay fever are few. We studied the effect of perinatal factors on the risk for hay fever among adolescent twins by a questionnaire study involving five consecutive nation-wide birth cohorts of 16-year-old twins and their parents. The risk for parent-reported, doctor-diagnosed hay fever in the adolescents associated with several perinatal characteristics was assessed with logistic regression analysis among individuals and by a discordant pair analysis.

Single region linkage analyses of asthma: description of data sets.

Linkage (genotypic) data from the 5q31-33 candidate region for asthma were contributed to Genetic Analysis Workshop 12 by members of the International Consortium on Asthma Genetics (COAG). Data came from five independent studies sampled from five countries. Genotypic data for a total of 26 markers were available, although the number of markers typed in each data set varied.

Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women?

Objective: Postmenopausal hormone replacement therapy (HRT) has been associated with reduced risk of cardiovascular disease; however, the mechanisms remain obscure, and it is not known whether this applies to regimens containing both estrogen and progestin. One possibility is that estrogen would act via enhancement of cardiac autonomic regulation.

Design: In this prospective, controlled study of 6-months duration, 22 osteoporotic, postmenopausal women in the intervention group were treated with combined estradiol hemihydrate corresponding to estradiol 2 mg and norethisterone acetate 1 mg with or without clodronate (HRT group).

Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased occurrence of cardiac valve abnormalities. However, the prevalence of cardiac abnormalities in patients with a uniform genotype of ADPKD has not been previously reported. We performed M-mode and color Doppler echocardiography on 109 patients from 16 families with polycystic kidney disease type 1 (PKD1).

Heart rate variability and its determinants in patients with severe or mild essential hypertension.

How cardiac autonomic nervous control is related to the severity of essential hypertension in patients receiving long-term antihypertensive therapy is not well known. The aim of this study was to examine heart rate variability (HRV), a non-invasive measure of cardiac autonomic function, in patients with long-term and medically treated mild and severe essential hypertension and healthy control subjects, and to assess the clinical determinants of HRV in these patients. Thirty-four patients with severe essential hypertension (SEHT) and 29 with mild essential hypertension (MEHT) as well as healthy age- and sex-matched control subjects were studied.

A second-generation association study of the 5q31 cytokine gene cluster and the interleukin-4 receptor in asthma.

We have analyzed a dense set of single-nucleotide polymorphisms (SNPs) and microsatellites spanning the T-helper cytokine gene cluster (interleukins 3, 4, 5, 9, and 13, interferon regulatory factor-1, colony-stimulating factor-2, and T-cell transcription factor-7) on 5q31 and the gene encoding the interleukin-4 receptor (IL4R) on 16p12 among Finnish families with asthma. As shown by haplotype pattern mining analysis, the number of disease-associated haplotype patterns differed from that expected for the 129Q allele polymorphism in IL13 for high serum total immunoglobulin (Ig) E levels, but not for asthma. The same SNP also yielded the best haplotype associations.

Role of major histocompatibility complex class III genes in recurrent spontaneous abortions.

Increased parental Human Leukocyte Antigen (HLA) sharing has been repeatedly reported in recurrent spontaneous abortions (RSA). Parental HLA sharing increases the chance of feto-maternal histocompatibility and potentially affects maternal allo-recognition of the fetus. However, strong linkage disequilibrium across the whole Major Histocompatibility Complex (MHC) region makes it difficult to interpret parental HLA sharing conclusively.

A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population.

The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries.

Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region.

Asthma is a common, complex human disease. Gene discovery in asthma has been complicated by substantial etiological heterogeneity, the possibility of genes of small effect and the concomitant requirement for large sample sizes. Linkage to asthma phenotypes has been investigated most intensively in the 5q chromosomal region, although results have been inconsistent across studies and all studies have had modest sample sizes.

Normal values for the Pelli-Robson contrast sensitivity test.

Purpose: To define normal values for the Pelli-Robson contrast sensitivity test in different age groups.

Setting: University Eye Clinic of Kuopio, Kuopio, Finland.

Methods: Contrast sensitivity was measured with the Pelli-Robson contrast sensitivity test in 87 persons (60 women and 27 men) with a mean age of 34.

The functionally important IL-10 promoter polymorphism (-1082G-->A) is not a major genetic regulator in recurrent spontaneous abortions.

Enhanced secretion of anti-inflammatory Th2 cytokines is a characteristic feature in normal physiological pregnancy. In recurrent spontaneous abortions (RSA), however, defective production of interleukin-10 (IL-10) and other Th2 cytokines has been shown in humans. Association studies have shown that a base exchange polymorphism (guanine-->adenine) at position -1082 of the IL-10 promoter is associated with differential IL-10 production.

Effect of conscious sedation on cardiac autonomic regulation during colonoscopy.

Background: Colonoscopy is associated with cardiovascular events including hypotension, hypertension, and myocardial ischemia. The pathogenetic mechanisms of these cardiovascular events are unknown, but there is evidence that the autonomic nervous system may play a role. Conscious sedation is often used to relieve the inconvenience caused by the procedure.

Late correlative imaging findings of previous acute infective spondylitis.

Purpose: To evaluate late correlative imaging findings in relation to clinical outcome in persons with previous acute infective spondylitis, the authors performed bone and leukocyte scintigraphy (planar and SPECT imaging) and magnetic resonance imaging of the spine in nine patients (two men, seven women; mean age, 66 years; age range, 57 to 84 years) 3.1 years (range, 0.9 to 6.

The IL9R region contribution in asthma is supported by genetic association in an isolated population.

Interleukin 9 (IL9) is involved in mast cell maturation and the enhancement of IgE production by B cells. Furthermore, linkage data in human and mice have suggested that IL9 may contribute to asthma. Since our genetic analysis of the 5q cytokine cluster did not support a genetic role for the IL9 gene, we became interested in the IL9 receptor gene (IL9R) in the pseudoautosomal region.

A first trial of retrospective collaboration for positional cloning in complex inheritance: assay of the cytokine region on chromosome 5 by the consortium on asthma genetics (COAG).

The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy.

Cardiac adrenergic innervation within the first 3 months after acute myocardial infarction.

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri-infarcted myocardium. On the contrary, the concept of re-innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re-innervation occuring several months after myocardial infarction, the extent and time scale of re-innervation are only poorly known.

Cardiac adrenergic denervation in patients with non-Q-wave versus Q-wave myocardial infarction.

In spite of smaller infarct size and better preserved left ventricular function the long-term prognosis after a non-Q-wave infarction is not better than after a Q-wave infarction. In fact, the risk of sudden cardiac death is higher in patients with a non-Q-wave infarction than in patients with a Q-wave infarction. One possible reason for postinfarction arrhythmias is cardiac adrenergic denervation resulting from myocardial infarction.

Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28.

Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers.

A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with a disease-associated susceptibility allele.

A susceptibility gene for psoriasis, a chronic skin disorder, resides in chromosome 6p near the HLA-C locus. Sequencing of the region has allowed the identification of a new gene, HCR. We found that HCR is highly polymorphic with at least 12 coding variants.

Conscious sedation and cardiorespiratory safety during colonoscopy.

Background: Cardiorespiratory events during colonoscopy are common. The effect of sedative premedication on cardiorespiratory parameters during colonoscopy has not been studied in controlled, prospective trials.

Methods: One hundred eighty patients undergoing colonoscopy were divided into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group).

Inversion of the roles of the nucleophile and acid/base catalysts in the covalent binding of epoxyalkyl xyloside inhibitor to the catalytic glutamates of endo-1,4-beta-xylanase (XYNII): a molecular dynamics study.

X-Ray crystal structures have revealed that 2, 3-epoxypropyl-beta-D-xyloside reacts with endo-1,4-beta-xylanase (XYNII) by forming a covalent bond with Glu86. In contrast, 3, 4-epoxybutyl-beta-D-xyloside forms a covalent bond with Glu177. In the normal enzyme reaction Glu86 acts as the catalytic nucleophile and Glu177 as the acid/base catalyst.