Health inequalities: bringing the hidden assumptions into the open.
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Health Promotion↗
Biomedical subjects
R Klein
Publications and source records attributed to R Klein.
A longitudinal study of autoantibodies against central nervous system tissue and gangliosides in connective tissue diseases.
Our objective was to investigate longitudinally, antibodies against central nervous tissue (anti-CNS) derived from bovine brain and gangliosides GM 1, GD1a, GD1b, and GT1b in 91 patients with connective tissue diseases (systemic lupus erythematosus, n = 38; mixed connective tissue disease, n = 16; primary Sjogren's syndrome, n = 7; progressive systemic sclerosis, n= 13; polymyositis/dermatomyositis, n=4; overlap syndrome, n = 5; undifferentiated connective tissue disease, n = 8). Anti-CNS and anti-ganglioside antibodies, measured by enzyme-linked immunosorbent assay, were found in 73% and 63% of patients, respectively. Anti-CNS positive sera were also reactive in Western blotting in 74% of cases and recognized up to 14 different polypeptides from 29 to 130 kDa. Anti-CNS and anti-ganglioside antibodies reflected only in a limited extent the disease activity. In 27 of 58 patients, anti-CNS antibodies remained positive independently of disease activity and antibody levels did not correlate with the phases of exacerbations. A total of 36 of 60 anti-CNS-positive patients, in contrast to two of 22 anti-CNS-negative patients, had major neuropsychiatric manifestations (P < 0.001). Anti-ganglioside antibodies were not significantly associated with neuropsychiatric manifestations. In conclusion, our longitudinal data suggest that anti-CNS antibodies may be an important marker for the diagnosis of cerebral involvement in connective tissue diseases, but the pathogenic role of these autoantibodies remains to be determined.
Adolescent↗
Detection of elastase from Pseudomonas aeruginosa in sputum and its potential role in epithelial cell permeability.
Most clinical strains of Pseudomonas aeruginosa produce elastase, a zinc metalloprotease that is implicated in the pathogenesis of infections related to these organisms. To better understand the physiologic role of this protease in the regulation of airway permeability, we developed a panel of specific monoclonal antibodies (mAb) against purified Pseudomonas elastase (PE) that do not react with either neutrophil elastase or porcine pancreatic elastase. These mAbs were used in a competitive enzyme-linked immunosorbent assay to determine the concentrations of PE in sputum samples from patients with pulmonary infections. Sputum from patients infected with P. aeruginosa showed a varying amount of PE, whereas others indicated no signals. We also found that the mAbs blocked the effect of PE on epithelial barrier function in vitro on the basis of measurement of transmonolayer electrical resistance of polarized epithelial cells as an index of paracellular permeability.
Adolescent↗
Arcus senilis and mortality in a population with diabetes.
PURPOSE: To estimate the prevalence of arcus senilis and its association with mortality in a diabetic population. METHODS: A cohort of persons with younger (n = 996) and older onset (n = 1,370) diabetes was examined. Mortality information was obtained from death certificates. RESULTS: Prevalence of arcus senilis increased with age and was higher in men than in women. In the younger onset group, it was also associated with a history of cardiovascular disease. As a risk factor for mortality after controlling for age and sex, arcus senilis was not associated with death from all causes, ischemic heart disease, or stroke. CONCLUSION: Arcus senilis provides no more information about mortality risk than age of the person.
Adult↗
Reproductive exposures, incident age-related cataracts, and age-related maculopathy in women: the beaver dam eye study.
PURPOSE: To evaluate the relationship of reproductive exposures and incident age-related cataract and maculopathy in women. METHODS: This was a population-based cohort study including all adults 43 to 84 years of age living in Beaver Dam, Wisconsin (a representative midwestern community) who were identified during a census in 1987 to 1988. They were evaluated initially in 1988 to 1990 and at follow-up in 1993 to 1995. Evaluations included medical histories and both fundus and lens photography. All procedures were done according to protocols that were the same at both examinations. All photographs were graded by trained observers using defined grading schemes. The severities of age-related cataracts and maculopathy were determined by grading of photographs. Information on hormone exposures was ascertained from structured interviews. RESULTS: After adjusting for age, the only significant finding for lens end points was a trend indicating a possible protective effect of increasing number of live births and incident posterior subcapsular cataract. There were no significant associations of any reproductive exposure with lesions of early or late age-related maculopathy. CONCLUSIONS: In these population-based data, there is little evidence of association of hormone exposures with incident age-related eye disease in women 5 years later. Longer follow-up of this population, whose mean age is approaching that of heightened incidence, may disclose significant relationships.
Adult↗
A short questionnaire on visual function of older adults to supplement ophthalmic examination.
PURPOSE: To estimate frequency of self-reported visual dysfunction in specific life situations. METHODS: Performance-based measures of visual function were obtained during the 5-year follow-up examination of the Beaver Dam Eye Study cohort. During the subsequent yearly follow-up telephone call, four questions concerning visual abilities in specific situations were administered. RESULTS: Visual difficulties in everyday life situations were commonly reported by adults aged 48 to 91 years, with only 17% to 35% of persons reporting excellent or very good vision in the four specific situations related to visual function. Visual acuity, near vision, and contrast sensitivity measures do not reflect the visual difficulties encountered in common daily activities in our study population (Spearman correlation coefficients all less than 0.35). CONCLUSIONS: A few simple questions about visual function in common daily activities may give a clinician insights into patient complaints. It may be that environmental changes could improve self-reported visual function.
Activities of Daily Living↗
The preparation of copper-oxidized LDL for the measurement of oxidized LDL antibodies by EIA.
In the present study we try to define the optimal conditions for preparation of copper-oxidized low-density lipoprotein (oxLDL) to be used for the assay of oxLDL antibodies by enzyme immunoassay (EIA). Oxidation of LDL was monitored by measuring the formation of conjugated dienes at 234 nm and the generation of fluorescent products with emission at 430 nm when excitation is performed at 360 nm. The generation of immunogenic epitopes was evaluated by testing the reactivity of aliquots collected at different times during the oxidation process with human sera with high oxLDL antibody levels and with a purified human oxLDL antibody. The values of fluorescence emission at 430 nm correlated best with reactivity with oxLDL antibodies; strong reactivity was usually associated with values greater than 1.1 U. The time needed for fluorescence emission to reach maximum levels varied between 6 and 14 h for most LDL, but it was considerably longer in a few LDL preparations. The maximal reactivity of oxLDL with oxLDL antibodies was observed when the LDL oxidation reaction was stopped 4 or more hours after the fluorescence readings reached their peak. At this stage of the oxidation reaction, apolipoprotein B fragmentation and aggregation were observed as shown by Western blot analysis. The CV for 13 EIA runs of two reference oxLDL antibodies reacting with four different pools of standardized oxLDL prepared according to the stated guidelines was 14.5 and 3.9%, confirming the reproducibility of our oxidation conditions.
Antigen-Antibody Complex↗
The prevalence and 5-year incidence of ocular trauma. The Beaver Dam Eye Study.
PURPOSE: To describe the cumulative lifetime prevalence and 5-year incidence of ocular trauma and their relation to risk factors in a defined white adult population living in a small town. DESIGN: Population-based cross-sectional and follow-up study. PARTICIPANTS: Participants aged 43 to 86 years from the baseline Beaver Dam Eye Study that took place from 1988 through 1990 (n = 4926) and the follow-up study that took place from 1993 through 1995 (n = 3684). METHODS: Standardized interview at baseline and follow-up study. MAIN OUTCOME MEASURES: Cumulative lifetime prevalence and 5-year incidence of self-reported history of ocular trauma. RESULTS: The cumulative lifetime prevalence and 5-year incidence of ocular trauma was 19.8% (n = 972) and 1.6% (n = 57), respectively. A history of trauma in both eyes was reported in 15% of the prevalent cases and 8% of the incident cases. Sharp objects caused more than half of all injuries. Persons aged 43 through 54 years were 2.5 times more likely to have a lifetime history of ocular trauma than persons aged 75 and older (odds ratios [OR], 2.57; 95% confidence interval [CI], 2.0, 3.29). Males had four times the prevalence of females (OR, 4. 42; 95% CI, 3.79, 5.16). Almost one third of all males aged 43 through 54 years reported a history of ocular trauma in their lifetime. The higher risks in the 43 through 54 age group (OR, 1.60) and male gender (OR, 1.42) were not significant among incident cases. In multivariate analysis, blue collar (adjusted OR, 1.58; 95% CI, 1. 32, 1.89) and farm-related workers (adjusted OR, 1.32; 95% CI, 0.93, 1.87) had higher lifetime risks of ocular trauma compared with white collar workers. People with a history of fractures also had increased lifetime risks (adjusted OR, 1.30; 95% CI, 1.13, 1.52). A history of ocular trauma reported in the baseline examination was significantly associated with a higher risk of ocular trauma occurring again in the next 5 years (adjusted OR, 3.27; 95% CI, 1.76, 5.82), especially if both eyes had previous trauma (adjusted OR, 5.15; 95% CI, 2.03, 13.0). CONCLUSIONS: One fifth of white adult Americans more than 42 years of age residing in a small town reported ocular trauma in their lifetime. This group had a three times higher risk of experiencing ocular trauma again within 5 years.
Adult↗
Redetermination of the total internal conversion coefficient of the 279 keV transition following the decay of 203Hg
A new measurement of the total internal conversion coefficient of the 279 keV transition following the decay of 203Hg resulted in alpha = 0.2250(12).
Journal Article↗
Eph receptors and ephrin ligands. essential mediators of vascular development.
The molecular and cellular mechanisms governing vascular development are still poorly understood. Prominent among the intercellular signals that control the initial establishment of the vascular network (termed vasculogenesis) and the subsequent remodeling process (called angiogenesis) are soluble ligands that signal through receptor tyrosine kinases (RTKs). Recent reports have added cell-bound ephrin ligands and their cognate Eph RTKs to the list of key players in vascular development.
Animals↗
Sequential occurrence of primary sclerosing cholangitis and autoimmune hepatitis type III in a patient with ulcerative colitis: a follow up study over 14 years.
In 1983, a female patient born in 1963 presented with symptoms of ulcerative colitis and typical clinical and histological signs of primary sclerosing cholangitis (PSC). At this time only pANCA were positive while other marker antibodies for autoimmune liver disorders could not be detected. In summer 1987 the clinical picture changed and was replaced by laboratory and histological signs typical of autoimmune hepatitis (AIH). Thus, IgG levels increased considerably and cholestatic enzymes became normal. For the first time, anti-liver-pancreas antibodies (LP), a diagnostic marker for AIH type III could be detected. In the following years several relapses occurred also induced by repeated discontinuation of immunosuppressive therapy. Symptoms of colitis persisted but signs of cholestasis remained absent for the following ten years. In 1997, colitis exacerbated again and colectomy had to be performed together with liver transplantation. Surprisingly, histology of the explanted liver now showed the typical features of PSC stage III/IV while the significant criteria for AIH were now lacking. Thus, progression to cirrhosis was, probably, mainly induced by the biliary destructive and fibrotic process although biochemical and serological data were clearly indicative of an autoimmune, i.e. AIH-related manifestation.
Adult↗
Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities.
To directly compare biological activities of the neurotrophins NT4 and BDNF in vivo, we replaced the BDNF coding sequence with the NT4 sequence in mice (Bdnfnt4-ki). Mice expressing NT4 in place of BDNF were viable, in contrast with BDNF null mutants, which die shortly after birth. Although the Bdnfnt4-ki/nt4-ki and wild-type Bdnf+/+ alleles yielded similar levels of NT4 and BDNF proteins, NT4 supported more sensory neurons than BDNF and promoted functional synapse formation in cultured hippocampal neurons. Homozygous Bdnfnt4-ki/nt4-ki mice showed reduced body weight, infertility and skin lesions, suggesting unique biological activities of NT4 in vivo. The distinct activities of NT4 and BDNF may result partly from differential activation of the TrkB receptor and its down-stream signals.
Animals↗
The archaeal halophilic virus-encoded Dam-like methyltransferase M. phiCh1-I methylates adenine residues and complements dam mutants in the low salt environment of Escherichia coli.
The genome of the archaeal virus phiCh1, infecting Natrialba magadii (formerly Natronobacterium magadii), is composed of 58.5 kbp linear ds DNA. Virus particles contain several RNA species in sizes of 100-800 nucleotides. A fraction of phiCh1 genomes is modified within 5'-GATC-3' and related sequences, as determined by various restriction enzyme digestion analyses. High performance liquid chromatography revealed a fifth base, in addition to the four nucleosides, which was identified as N6-methyladenosine. Genetic analyses and subsequent sequencing led to the identification of a DNA (N6-adenine) methyltransferase (mtase) gene. The protein product was designated M.phiCh1-I. By the localization of the most conserved motifs (a DPPY motif occurring before FxGxG), the enzyme was placed within the beta-subgroup of the (N6-adenine) methyltransferase class. The mtase gene of phiCh1 was classified as a 'late' gene, as determined by measuring the kinetics of mRNA and protein expression in N. magadii during the lytic cycle of phiCh1. After infection of cells, M.phiCh1-I mRNA and protein could be detected in lower amounts than in the situation of virus induction from lysogenic cells. Consequently, only about 5% of the phiCh1 progeny genomes after infection of N. magadii carry the M.phiCh1-I methylation in contrast to 50% of virus genomes generated by induction of phiCh1-lysogenic N. magadii cells. Heterologous expression of the mtase from a halophile with 3 M cytoplasmic salt concentration showed an unexpected feature: the protein was active in the low environment of Escherichia coli and was able to methylate DNA in vivo. Interestingly, it seemed to exhibit a higher sequence specificity in E. coli that resulted in adenine methylation exclusively in the sequence 5'-GATC-3'. Additionally, expression of M.phiCh1-I in dam- E. coli cells led to a complete substitution of the function of M. Dam in DNA mismatch repair.
Amino Acid Sequence↗
Short stature in competitive prepubertal and early pubertal male gymnasts: the result of selection bias or intense training?
OBJECTIVES: To determine whether high-volume, high-impact physical training in prepubertal and early pubertal male gymnasts is associated with reduced statural and segmental growth and reduced serum insulin-like growth factor-I (IGF-I) and increased cortisol (C) levels. STUDY DESIGN: Height, sitting height, leg length, and segmental lengths (humerus, radius, femur, and tibia) and breadths (biacromial and bi-iliac), diet, serum IGF-I, testosterone, and C were measured in competitive male gymnasts and normoactive children (Tanner stage < or = 2) every 3 to 4 months over an 18-month period. RESULTS: At baseline, gymnasts (n = 31) were 0.7 years older than members of the control group (P <.05, n = 50) but were no different in terms of biologic maturity. Age-adjusted z scores showed that the gymnasts were shorter than members of the control group (-0.5 +/- 0.2 SD, P <.05) because of reduced leg length (-0.8 +/- 0.2 SD, P <.001) but not sitting height. Segmental lengths and bi-iliac breadth age-adjusted z scores were also reduced in the gymnasts (P ranging <.05 to <.001). No difference was detected for serum IGF-I or C. After 18 months of follow-up, no differences were found for rates of change in height, sitting height or leg length, segmental lengths, IGF-I, or C between those gymnasts and control subjects who remained prepubertal and early pubertal (gymnasts n = 18; control group n = 35). However, the magnitudes of baseline differences in anthropometric measures (z scores) persisted throughout the study. CONCLUSION: Short stature in these competitive male gymnasts was due to a reduced leg length but not sitting height. The lack of a difference in growth rates, IGF-I, and diet over the 18-month period indicates that the short stature reported in male gymnasts is due to selection bias rather than gymnastics training.
Adolescent↗
Lens thickness and five-year cumulative incidence of cataracts: The Beaver Dam Eye Study.
PURPOSE: To evaluate whether lens thickness is related to incidence of cataracts. METHODS: Lens thickness was measured from slit-lamp photographs of the lens at the time of the prevalence evaluation in the Beaver Dam Eye Study. Incident cataract was determined by grading standard slit-lamp and retroillumination photographs of the lens at the baseline and five-year follow-up examinations. Medical history was obtained and blood pressures, height and weight were measured according to protocol. RESULTS: Lens thickness was positively associated with incident nuclear cataract and inversely associated with incident cortical cataract after accounting for age, sex, diabetes status, hypertension, heavy drinking and cigarette smoking. CONCLUSIONS: Lens thickness is related to incidence of cataracts. Mechanisms to explain these relationships require further laboratory and epidemiologic investigation.
Adult↗
Hypereosinophilia induced by high-dose intratumoral and peritumoral mistletoe application to a patient with pancreatic carcinoma.
UNLABELLED: A patient with inoperable adenocarcinoma of the pancreas was treated with intraperitumoral and peritumoral injections of a Viscum album L. extract containing 5,700 ng/mL mistletoe lectin, mainly mistletoe lectin 1 (Abnobaviscum Quercus 2) for 5 weeks (1 injection per week). After the third injection (day 22), a marked eosinophilia was observed (1,800 per microliter) that rose to 3,268 per microliter after the fifth injection (day 42). Furthermore, histology performed on day 28 revealed accumulation of eosinophils in ductal lesions and adjacent stroma in addition to the features of ductal adenocarcinoma. In order to investigate whether eosinophilia correlated with immunological features, we analyzed cytokine production of peripheral blood mononuclear cells (PBMC) from this patient after stimulation with antigens known to "unmask" an individual's predisposition for defined immunoreactions, namely purified protein derivative (PPD) as a stimulator of T-helper (TH1)1-cells and tetanus toxoid (TT) as an activator of TH2-cells. PBMC of the patient showed a strong proliferation and production of interleukin (IL)-5 and IL-10 after incubation with TT indicating a type-2 response. Simultaneously, PBMC were induced to proliferate and produce interferon gamma (IFN-gamma) by incubation with PPD suggesting also a type-1 response. These data would readily explain the eosinophilia because eosinophils are effector cells of type-2 reaction but also require type-1 cytokines. Although the overall clinical course of the patient was rapidly progressive, temporary stabilization of the patient's general condition during mistletoe treatment was observed. It is, however, still an open question whether this transient benefit was due to the induction of eosinophilia by a type-2 response. CONCLUSION: Before high-dose intratumoral and peritumoral treatment with a Viscum album L. extract containing mistletoe, lectin 1 can be associated with hypereosinophilia and strong production of TH1 as TH2 cytokines as well.
Adenocarcinoma↗
Immunoadsorption onto protein A induces remission in severe systemic lupus erythematosus.
BACKGROUND: Reduction of pathological autoantibodies and circulating immune complexes can be useful in the treatment of autoimmune disease. Plasmapheresis has been shown to reduce autoantibody levels in systemic lupus erythematosus (SLE), but its effect on patients' outcome was not better compared with conventional immunosuppression in the past. AIM OF THE STUDY: Immunoadsorption as a selective extracorporeal immunoglobulin elimination technique was evaluated as rescue therapy in patients suffering from SLE. METHODS: Eight patients with severe, therapy-resistant SLE underwent immunoadsorption onto protein A sepharose without concomitant immunosuppressants. RESULTS: Remission of the disease was achieved in seven patients. Therapy had to be stopped in one patient because of side-effects. The best results were obtained when immunoadsorption was carried out daily, without supplementary intravenous immunoglobulin therapy. Oral cyclophosphamide for 3-6 months during follow-up was used to suppress relapse. Autoantibodies and circulating immune complexes were effectively eliminated regardless of their IgG subclass. CONCLUSION: Immunoadsorption onto protein A might be used as an extracorporeal treatment option in SLE when other therapies are ineffective.
Administration, Oral↗
Enhancement of 2000-m rowing performance after caffeine ingestion.
PURPOSE: To investigate the effect of caffeine ingestion on short-term endurance performance in competitive rowers. METHODS: In this randomized double-blind crossover study, eight competitive oarsmen (peak oxygen uptake [VO2peak] 4.7+/-0.4 L x min(-1), mean +/- SD) performed three familiarization trials of a 2000-m rowing test on an air-braked ergometer, followed by three experimental trials at 3- to 7-d intervals, each 1 h after ingesting caffeine (6 or 9 mg x kg(-1) body mass) or placebo. Trials were preceded by a standardized warm-up (6 min at 225+/-39 W; 75+/-7.7% VO2peak). RESULTS: Urinary caffeine concentration was similar before ingestion (approximately 1 mg x L(-1)) but rose to 6.2+/-3.6 and 14.5+/-7.0 mg x L(-1) for the low and high caffeine doses, respectively. Plasma free fatty acid concentration before exercise was higher after caffeine ingestion (0.29+/-0.17 and 0.39+/-0.20 mM for 6 and 9 mg x kg(-1), respectively) than after placebo (0.13+/-0.05 mM). Respiratory exchange ratio during the warm-up was also substantially lower with caffeine (0.94+/-0.09 and 0.93+/-0.06 for the low and high dose) than with placebo (0.98+/-0.12). Subjects could not distinguish between treatments before or after the exercise test. Both doses of caffeine had a similar ergogenic effect relative to placebo: performance time decreased by a mean of 1.2% (95% likely range 0.4-1.9%); the corresponding increase in mean power was 2.7% (0.4-5.0%). Performance time showed some evidence of individual differences in the effect of caffeine (SD 0.9%; 95% likely range 1.5 to -0.9%). CONCLUSIONS: Ingestion of 6 or 9 mg x kg(-1) of caffeine produces a worthwhile enhancement of short-term endurance performance in a controlled laboratory setting.
Caffeine↗