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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 145 records · Page 8Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Depletion forces in colloidal mixtures

Depletion forces are accounted for by a contraction of the description of colloidal mixtures based on the integral equations theory of simple liquids. The applicability of this treatment is illustrated for binary mixtures of hard spheres, in the bulk and near a hard wall. The Asakura and Oosawa potential is obtained as the dilute limit of our equations. At higher concentrations the depletion potential has an oscillatory behavior and becomes more long ranged. If charge is put on the small particles there are energy-driven depletion forces in addition to those of entropic origin, which result in repulsive interaction at contact.

Journal Article↗
PubMed2000

Moderate alcohol consumption and hearing loss: a protective effect.

OBJECTIVE: To determine if moderate alcohol consumption is associated inversely with hearing loss in a large population based study of older adults. DESIGN: Cross-sectional population based cohort study. Data are from the 1993-1995 examinations for the population based Epidemiology of Hearing Loss Study (EHLS) (n = 3571) and the Beaver Dam Eye Study (BDES) (n = 3722). SETTING: Midwestern community of Beaver Dam, Wisconsin. PARTICIPANTS: Residents of Beaver Dam aged 43 to 84 in 1987-1988 were eligible for the BDES (examinations in 1988-1990 and 1993-1995). During 1993-1995, this same cohort was eligible to participate in the baseline examination for the EHLS. MEASUREMENTS: Hearing thresholds were measured by pure tone air and bone conduction audiometry (250-8000 Hz.). History of alcohol consumption in the past year, heavy drinking (ever), medical history, occupation, noise exposure, and other lifestyle factors were ascertained by a questionnaire that was administered as an interview. RESULTS: In multiple logistic regression analyses controlling for potential confounders, moderate alcohol consumption (>140 grams/week) was inversely associated with hearing loss (PTA(.5,1,2,4 > 25 dB HL); odds ratio [OR] = .71, 95% confidence interval [CI] = .52, .97; where PTA is pure tone average). A similar association was found for moderate hearing loss (PTA(.5,1,2,4 > 40 dB HL); OR = 0.49, 95% CI = 0.32, 0.74). Alcohol consumption was associated inversely with the odds of having a low frequency hearing loss (OR = 0.61) or a high frequency hearing loss (OR = 0.60). These findings did not vary significantly by age or gender. There was an increase in the odds of having a high frequency hearing loss (OR = 1.35, 95% CI = 1.04, 1.75), in those with a history of heavy drinking (> or =4 drinks/day). Including cardiovascular disease or its related factors did not significantly attenuate the protective effect. CONCLUSIONS: There is evidence of a modest protective association of alcohol consumption and hearing loss in these cross-sectional data. This finding is in agreement with a small body of evidence suggesting that hearing loss is not an inevitable component of the aging process.

Aged↗
PubMed2000

Cost-utility of one-time colonoscopic screening for colorectal cancer at various ages.

OBJECTIVE: One-time colonoscopy has been recommended as a possible colorectal cancer (CRC) screening strategy. Because the incidence of colorectal neoplasia increases with age, the effectiveness and cost of this strategy depend on the age at which screening occurs. The purpose of this study was to investigate the age-dependent cost-utility of one-time colonoscopic screening. METHODS: We constructed a computer simulation model of the natural history of colorectal neoplasia. This model was used to compare the cost-utility of no screening and age-based strategies employing one-time colonoscopic screening (age ranges evaluated: 45-49, 50-54, 55-59, and 60-64 yr). RESULTS: We determined that one-time colonoscopic screening in men age <60 yr and in women age <65 yr dominates never screening and screening at older ages. For both sexes, one-time colonoscopic screening between 50 and 54 yr of age is associated with a marginal cost-utility of less than $10,000 per additional quality-adjusted life-year compared to screening between 55 and 60 yr of age. One-time colonoscopic screening between 45 and 49 yr of age is either dominated (women) or associated with a marginal cost-utility of $69,000/per quality-adjusted life-year (men) compared to screening between 50 and 54 yr of age. The marginal cost-utility of one-time colonoscopic screening is relatively insensitive to plausible changes in the cost of colonoscopy, the cost of CRC treatment, the sensitivity of colonoscopy for colorectal neoplasia, the utility values representing the morbidity associated with the CRC-related health states, and the discount rate. CONCLUSIONS: One-time colonoscopic screening between 50 and 54 yr of age is cost-effective compared to no screening and screening at older ages in both men and women. Screening in men between 45 and 49 yr of age may be cost-effective compared to screening between 50 and 54 yr of age depending on societal willingness to pay.

Age Factors↗
PubMed2000

Improved 2000-meter rowing performance in competitive oarswomen after caffeine ingestion.

Eight competitive oarswomen (age, 22 +/- 3 years; mass, 64.4 +/- 3.8 kg) performed three simulated 2,000-m time trials on a rowing ergometer. The trials, which were preceded by a 24-hour dietary and training control and 72 hours of caffeine abstinence, were conducted 1 hour after ingesting caffeine (6 or 9 mg á kg-1 body mass) or placebo. Plasma free fatty acid concentrations before exercise were higher with caffeine than placebo (0.67 +/- 0.34 vs. 0.72 +/- 0.36 vs. 0.30 +/- 0.10 mM for 6 and 9 mg á kg-1 caffeine and placebo, respectively; p <.05). Performance time improved 0.7% (95% confidence interval [CI] 0 to 1.5%) with 6 mg á kg-1 caffeine and 1. 3% (95% CI 0.5 to 2.0%) with 9 mg á kg-1 caffeine. The first 500 m of the 2,000 m was faster with the higher caffeine dose compared with placebo or the lower dose (1.53 +/- 0.52 vs.1.55 +/- 0.62 and 1. 56 +/- 0.43 min; p =.02). We concluded that caffeine produces a worthwhile enhancement of performance in a controlled laboratory setting, primarily by improving the first 500 m of a 2,000-m row.

Adult↗
PubMed2000

Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET.

OBJECTIVE: To investigate prospectively abnormalities of brain glucose utilisation in relation to major or minor neuropsychiatric symptoms in systemic lupus erythematosus (SLE). METHODS: Positron emission tomography (PET) using F-18-labelled fluorodeoxyglucose was performed in 28 patients with SLE. Patients were classified as having severe neuropsychiatric manifestations (seizures, focal neurological deficits, acute confusional states, mood disorders) (n=12), or mild neuropsychiatric manifestations (headache, reactive depression, cognitive dysfunction, anxiety disorders) (n=11) and five patients without signs of central nervous system (CNS) involvement. Ten clinically and neurologically healthy volunteers served as controls. In 26 patients magnetic resonance imaging (MRI) was performed and autoantibodies against CNS tissue, ribosomal P protein and cardiolipin were measured. In 14 patients follow up PET scans were performed after a mean (SD) period of 11.6 (9.5) months. RESULTS: PET scans showed hypometabolism in at least one brain region in all patients with severe or mild CNS symptoms (100%) as compared with patients without cerebral symptoms (40%) (p<0.0025). Parieto-occipital regions were most commonly affected (96%), followed by parietal regions (32%). In contrast, MRI images were abnormal in only 11 of 22 patients (50%) with neuropsychiatric symptoms and in one of four patients (25%) without symptoms. In 12 of 14 patients examined in follow up PET scans persistence, improvement or worsening of cerebral symptoms were associated with unchanged, decreased or increased brain hypometabolism, respectively. No significant correlation was found between PET or MRI findings and autoantibody profiles. CONCLUSIONS: PET imaging represents a sensitive tool to detect manifest or subclinical CNS involvement in SLE and PET findings correlate well with the clinical course of disease.

Adolescent↗
PubMed2000

A new method of long-term preventive cardioprotection using Lactobacillus.

Potential long-term cardioprotection was investigated in an extensive experimental study. Lactobacillus cultivation components (LCC) were administered intravenously in anesthetized rats 1, 7, and 21 days before global ischemia (GI). GI was produced by full stop flow in isolated Langendorff-perfused hearts for 20 min and was followed by reperfusion. Control animals were injected with saline. LCC reduced reperfusion tachyarrhythmia significantly and improved functional recovery of the ischemized rat heart. These beneficial effects were associated with reduction of release of norepinephrine (NE) and prostacyclin at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70-kDa heat stress protein (HSP-70) at ischemia and reperfusion (P < 0.05). This cardioprotection was documented up to 21 days after a single injection of LCC. Thus Lactobacillus cultivation components are new nontoxic materials that produce marked long-term cardioprotection against ischemia-reperfusion damage. This effect is attributed to an activation of the cellular defense system, manifested by activation of the antioxidant pathway and by expression of protective proteins. NE is involved in this process, and the data also suggest a role for prostacyclin in this model of cardioprotection. The potential of LCC and related compounds working through similar mechanisms in the prevention and therapy of various ischemic heart syndromes should be explored.

Adenosine Triphosphate↗
PubMed2000

Familial idiopathic dilatation of the right atrium with complete atrio-ventricular block: a new syndrome?

Familial occurrence of idiopathic dilatation of the right atrium is extremely rare. This is the first description of a family in which 2 siblings had a syndrome of idiopathic dilatation of the right atrium associated with complete atrio-ventricular block. The family workup did not show other family members to be affected, and the question we raise is whether or not this might be a new syndrome.

Adolescent↗