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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 199 records · Page 11Linked to original sources
PubMed1999

Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. METHODS: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. MAIN OUTCOME MEASURES: Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). RESULTS: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. CONCLUSION: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.

Aged↗
PubMed1999

Botulinum toxin injection to improve tracheoesophageal speech after total laryngectomy.

Total laryngectomy patients, after undergoing a tracheoesophageal puncture (TEP), may have poor TEP speech because of hypertonicity or spasm of the pharyngoesophageal segment (PES). Conventional treatment options include speech therapy, PES dilation, pharyngeal neurectomy, and myotomy. Botulinum toxin injection into the PES has recently been reported to be effective for this disorder. However, data accumulated were based primarily on subjective analyses. This prospective investigation used both qualitative and quantitative measures to assess the effects of videofluoroscopy-guided botulinum toxin injection on TEP voice quality in laryngectomees with PES dysfunction. Patients underwent voice analyses, tracheal air pressure measures, and barium swallows before and after botulinum toxin injection. Seven of 8 patients had significant voice quality improvement, and tracheal air pressures normalized in 6 of 8 patients after injection. Videofluoroscopic botulinum toxin injection into the PES is efficacious, safe, and cost-effective and should be considered as a first-line therapy for the treatment of laryngectomees with poor quality TEP speech caused by PES dysfunction.

Adult↗
PubMed1999

EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains.

Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with "reverse" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Essential role for TrkB receptors in hippocampus-mediated learning.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate both short-term synaptic functions and long-term potentiation (LTP) of brain synapses, raising the possibility that BDNF/TrkB may be involved in cognitive functions. We have generated conditionally gene targeted mice in which the knockout of the trkB gene is restricted to the forebrain and occurs only during postnatal development. Adult mutant mice show increasingly impaired learning behavior or inappropriate coping responses when facing complex and/or stressful learning paradigms but succeed in simple passive avoidance learning. Homozygous mutants show impaired LTP at CA1 hippocampal synapses. Interestingly, heterozygotes show a partial but substantial reduction of LTP but appear behaviorally normal. Thus, CA1 LTP may need to be reduced below a certain threshold before behavioral defects become apparent.

Animals↗
PubMed1999

The prevalence of age-related maculopathy by geographic region and ethnicity.

The prevalence of age-related maculopathy (ARM) varies considerably in different locations and racial/ethnic groups around the world. At present there are insufficient data to determine whether it is likely that these differences in prevalence, especially for the early forms of ARM are due to variations in genetic and environmental factors or due to variations in age of the cohorts and methods used to ascertain and define ARM. In three population-based studies of whites living in Beaver Dam, Wisconsin, Blue Mountains, Australia, and Rotterdam, The Netherlands, in which similar methods of ascertainment and classification were used to detect and define ARM, late ARM was present in 1.2%, 1.4%, and 1.2% of the population less than 86 years of age, respectively. While data from clinical studies suggest that late ARM associated with choroidal neovascularization is rare in blacks compared with whites, some epidemiological studies suggest that late ARM may be similar in blacks and whites. There are still too few data from various ethnic/racial groups around the world and too few population-based data in older Hispanic and Asian populations to make meaningful comparisons. There is a need for further research into the distribution of ARM and its possible causes using similar methodologies to ascertain and define the disease. Further insights will be gained when genotypes associated with ARM are discovered.

Demography↗
PubMed1999

Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety.

The glucocorticoid receptor (Gr, encoded by the gene Grl1) controls transcription of target genes both directly by interaction with DNA regulatory elements and indirectly by cross-talk with other transcription factors. In response to various stimuli, including stress, glucocorticoids coordinate metabolic, endocrine, immune and nervous system responses and ensure an adequate profile of transcription. In the brain, Gr has been proposed to modulate emotional behaviour, cognitive functions and addictive states. Previously, these aspects were not studied in the absence of functional Gr because inactivation of Grl1 in mice causes lethality at birth (F.T., C.K. and G.S., unpublished data). Therefore, we generated tissue-specific mutations of this gene using the Cre/loxP -recombination system. This allowed us to generate viable adult mice with loss of Gr function in selected tissues. Loss of Gr function in the nervous system impairs hypothalamus-pituitary-adrenal (HPA)-axis regulation, resulting in increased glucocorticoid (GC) levels that lead to symptoms reminiscent of those observed in Cushing syndrome. Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety.

Adrenal Glands↗
PubMed1999

Hepatocyte growth factor, a versatile signal for developing neurons.

Here we summarize recent findings on the biology of hepatocyte growth factor (HGF, also known as scatter factor), focusing on its effects on developing neurons. HGF is both a chemoattractant and a survival factor for embryonic motor neurons. In addition, sensory and sympathetic neurons and their precursors respond to HGF with increased differentiation, survival and axonal outgrowth. The broad spectrum of HGF activities and its observed synergy with other neurotrophic factors suggest that the major role of HGF is to potentiate the response of developing neurons to specific signals.

Animals↗
PubMed1999

Overlapping but distinct specificities of anti-liver-kidney microsome antibodies in autoimmune hepatitis type II and hepatitis C revealed by recombinant native CYP2D6 and novel peptide epitopes.

Anti-liver-kidney microsome antibodies (anti-LKM) occur in autoimmune hepatitis (AIH) type II and in a subset of patients with hepatitis C. Anti-LKM1 in AIH are directed against cytochrome P4502D6 (CYP2D6), but conflicting data exist concerning the specificity of anti-LKM in hepatitis C. The aim of this study was to evaluate binding specificities of anti-LKM antibodies in both diseases using novel test antigens as well as their inhibitory capacity on CYP2D6 enzyme activity. Sera from 22 patients with AIH type II and 17 patients with hepatitis C being anti-LKM-positive in the immunofluorescence test were investigated for binding to native recombinant CYP2D6 and liver microsomes by ELISA and immunoblotting, and to synthetic peptides covering the region 254-339 (254-273, 257-269, 270-294, 291-310, 307-324, 321-339, 373-389) as well as the novel peptide 196-218 by ELISA. Furthermore, all sera were tested for inhibition of CYP2D6-dependent bufuralol 1'-hydroxylase activity. Twenty of the 22 AIH type II sera (91%) and nine of the 17 hepatitis C sera (53%) were positive for CYP2D6 by ELISA and/or immunoblotting. The previously described major peptide epitope comprising CYP2D6 amino acids 257-269 was recognized by 16 of the 22 AIH sera but by only one hepatitis C serum. A further epitope, 196-218, could be defined for the first time as another immunodominant epitope for AIH because it was recognized by 15 of the 22 AIH (68%) but only three of the 17 hepatitis C sera (18%). With the exception of the peptide 254-273, the other peptides showed no significant reactivity. Analysing the inhibitory properties of anti-LKM antibodies it emerged that 95% of AIH sera and 88% of hepatitis C sera inhibited enzyme function. These data indicate that anti-LKM antibodies in AIH and hepatitis C react with CYP2D6, as shown by their inhibitory activity, and that besides the known epitope 257-269 a further immunodominant epitope exists on CYP2D6 which is recognized by sera from patients with AIH II but hardly by sera from patients with hepatitis C.

Adolescent↗
PubMed1999

[Are morphologic changes in skeletal muscles of patients with malignant hyperthermia diagnostically useful?].

Malignant Hyperthermia (MH) represents a functional myopathy triggered by volatile anesthetics and depolarizing muscle relaxants, and leading to metabolic disturbances of intracellular Calcium homeostasis. Central-Core-like-structures (CCLS) were recently described as central defects in enzyme-histochemical stains and well correlated to the autosomal-dominant MH-predisposition. We studied the correlation of a MH-predisposition with specific myopathological signs. Skeletal muscles of suspected MH-individuals were histochemically stained by SDH-, NADH-, COX-, Gomori-Trichrome-, ATPase-, Acid Phosphatase-, Oil-red O- und PAS-stain und evaluated without knowing MH-diagnosis by the in-vitro-contracture test. Out of 118 patients (30% MHS ["susceptible"], 63% MHN [normal], 7% MHE ["equivocal"]) 19% revealed pathological findings corresponding to CCLS. 45% of these findings were associated with MHS/MHE. With HE-staining internal nuclei were not specific, but increased with the probability of MHS/MHE from 24% to 80%. Central Cores were correlated in 100% with MHS/MHE (4 out of 118 patients). CCLS were found with about similar frequency in skeletal muscle of MHS/MHE and MHN individuals. Internal nuclei were, however, not specifically, associated with MHS. In contrast, Central Cores correlated significantly with MHS/MHE diagnosis. In conclusion, histopathological findings in skeletal muscle seem to be a reliable marker for MH-predisposition only with Central Cores.

Adolescent↗
PubMed1999

Associations of performance-based and self-reported measures of visual function. The Beaver Dam Eye Study.

OBJECTIVE: To describe and compare performance-based and self-reported measures of visual function and to evaluate how each varied with age and how the performance-based measures were associated with the responses to self-reported questions about visual function. DESIGN: Population-based epidemiologic study. PARTICIPANTS: Adults participating in the first follow-up of the Beaver Dam Eye Study (n = 3,722). MAIN OUTCOME MEASURES: Performance-based measures of vision including current binocular, best-corrected and near visual acuities, sensitivity to light as measured by an automated perimeter, contrast sensitivity, and self-reported measures from a standardized interview. RESULTS: All performance-based and self-reported visual functions decreased with increasing age (p < 0.0001 for each). On average, women did more poorly than men on all the performance-based measures (p < 0.0001 for each), and on some of the self-reported measures. For both genders, correlations among the performance-based measures ranged from 0.38 to 0.67. In general, individuals reporting good visual function or little difficulty with visual tasks scored better on performance-based measures compared to individuals whose questionnaire responses reflected limited visual function. Overall, about 39% of drivers reported that their vision caused them to limit their night driving. Correlations of performance-based with self-reported measures of visual function were greater for best-corrected, binocular and near visual acuity compared to correlations of visual sensitivity to light and contrast sensitivity. There were 1,285 persons whose best-corrected acuity was better than their current binocular acuity and there were 97 people with visual impairment considering only current binocular acuity whose vision improved to better than 20/40 after refraction. CONCLUSIONS: Performance-based and self-reported measures of visual function were consistently and inversely related to age. Performance-based measures were, in general, more highly correlated between themselves than were self-reported measures. Self-reported visual functions were significantly positively correlated with all performance-based measures, but correlations were moderate. While high contrast measures are usually used in clinical settings and in many studies, the data suggest that in assessing function it is appropriate to measure several different aspects of vision, both performance-based and self-assessed. Our data give some indication of the impact these visual functions have on daily life as reflected by night driving and on near and distant visual acuity. New refractive corrections would likely improve the visual acuity in many older adults.

Adult↗
PubMed1999

High prevalence of antibodies to calreticulin of the IgA class in primary biliary cirrhosis: a possible role of gut-derived bacterial antigens in its aetiology?

BACKGROUND: In a preliminary study we showed that antibodies to the endoplasmic reticulum protein calreticulin (CR) occur in primary biliary cirrhosis (PBC) and autoimmune hepatitis type 1 (AIH). Since anti-CR antibodies have also been found in patients with infectious diseases, we investigated their prevalence and immunoglobulin classes in patients with various hepatic and intestinal diseases, hoping to get some information on a possible relationship between an infectious trigger and the induction of a certain class of anti-CR antibodies. METHODS: Sera were tested for anti-CR antibodies of the IgA, IgG, and IgM class by Western blotting, using CR isolated from human liver: in autoimmune liver diseases (primary biliary cirrhosis (PBC) (n = 86) and autoimmune hepatitis (AIH) type 1 (n = 57)), alcoholic liver cirrhosis (ALC) (n = 32), viral liver infections (acute hepatitis A (n = 8), acute hepatitis B (n = 20), and chronic hepatitis C (n = 28)), and intestinal diseases (Crohn disease (CD) (n = 30), acute yersiniosis (n = 26)). Sera from 100 healthy individuals served as negative controls. RESULTS: The most prominent finding was the high prevalence of anti-CR antibodies of the IgA class and the similarity in the anti-CR antibody class pattern in PBC (IgA, 62%; IgG, 43%; IgM, 55%) and yersiniosis (IgA, 62%; IgG, 39%; IgM, 42%). Class IgA anti-CR antibodies also occurred frequently in ALC (IgA, 44%; IgG, 41%; IgM, 19%). In contrast, in AIH anti-CR antibodies were predominantly of class IgG (IgA, 28%; IgG, 60%; IgM, 33%). In hepatitis A anti-CR antibodies were absent. In the other diseases they had a low prevalence and were mostly of class IgG (acute hepatitis B: IgA, 0%; IgG, 15%; IgM, 0%; chronic hepatitis C: IgA, 7%; IgG, 21%; IgM, 0%; CD: IgA, 13%; IgG, 20%; IgM, 13%). Of the healthy individuals 7% had anti-CR antibodies exclusively of class IgG. CONCLUSIONS: The high prevalence of anti-CR antibodies of class IgA in patients with PBC and yersiniosis as well as in alcoholic liver disease reflects a reactivity of the gut-associated immune system and could imply that a still undefined gut-derived bacterial (?) agent may trigger PBC.

Antigens, Bacterial↗
PubMed1999

Postoperative suction drainage of the axilla: for how long? Prospective randomised trial.

OBJECTIVE: To define the correct time to remove the drain after axillary dissection for carcinoma of the breast. DESIGN: Prospective randomised trial. SETTING: Two public hospitals, Israel. SUBJECTS: 90 women who required axillary dissection for carcinoma of the breast. INTERVENTIONS: 42 were randomised to have the drain removed on postoperative day 3, and 48 to keep the drain in until discharge had decreased to less than 35 ml/24 hours. MAIN OUTCOME MEASURES: Formation of seromas or wound infections, need to reinsert the drain, and duration of hospital stay. RESULTS: Early removal of the axillary drain was associated with a significantly higher incidence of seromas (9/42 compared with 2/48, p = 0.02) unless the total amount of fluid drained during the first three postoperative days was less than 250 ml. CONCLUSION: Drains should be removed after axillary dissection only when the daily amount of fluid discharged is low, unless the drainage during the first three days is less than 250 ml.

Axilla↗
PubMed1999

Serum carotenoids and tocopherols and incidence of age-related nuclear cataract.

BACKGROUND: It is not known whether the protective effects of antioxidants on cataract observed in experimental animals are relevant to age-related opacities in humans. OBJECTIVE: The relations of serum carotenoids and tocopherols to the incidence of age-related nuclear cataract were investigated in a random sample of 400 adults, 50-86 y of age, in the Beaver Dam Eye Study. DESIGN: Nuclear opacity was assessed by using lens photographs taken at baseline (in 1988-1990) and follow-up (in 1993-1995). Nonfasting concentrations of individual carotenoids and alpha- and gamma-tocopherol, were determined from serum obtained at baseline. A total of 252 persons were eligible for incident cataract, of whom 57 developed nuclear cataract in at least one eye. Results were adjusted for age, smoking, serum cholesterol, heavy drinking, adiposity, and, in the tocopherol models, dietary linoleic acid intake. RESULTS: Only serum tocopherol (the sum of alpha- and gamma-tocopherol, in micromol/mmol cholesterol) was associated with cataract. For total serum tocopherol, persons in tertile 3 had a lower risk of cataract than persons in tertile 1 [odds ratio (OR): 0.4; 95% CI: 0.2, 0.9; P = 0.03 for linear trend]. Although serum carotenoids were not significantly associated with nuclear cataract, marginal inverse associations with lutein (OR: 0.3; 95% CI: 0.1, 1.2; P = 0.13 for linear trend) and cryptoxanthin (OR: 0.3; 95% CI: 0.1, 1.3; P = 0.11 for linear trend) were suggested in people < or = 65 y of age. CONCLUSIONS: Findings were compatible with the possibility that nuclear cataract may be linked inversely to vitamin E status, but neither strongly supported nor negated the hypothesized inverse association of nuclear cataract with serum carotenoids.

Age Factors↗
PubMed1999

Primary intracerebral Hodgkin's disease: report of a case with Epstein-Barr virus association and review of the literature.

A case of primary intracerebral Hodgkin's disease (HD) without dural attachment in a 54-year-old immunocompetent patient is described. The infiltrate was located superficially in the occipital lobe and corresponded to the histologic type of nodular sclerosis. A typical immunohistochemical profile (membrane and cytoplasmic staining with dotlike Golgi enhancement of CD30, moderate cytoplasmic staining of CD15 in the Golgi area, membrane staining of CD20 of <10% of blastic cells, CD45RB negative) and in addition Epstein-Barr virus (EBV) latent membrane protein was detectable in Reed-Sternberg cells. Staging revealed no other organ sites of involvement. After combined surgery, postoperative radiotherapy, and chemotherapy, there are no signs of recurrence or systemic disease on follow-up for >1 year. To the authors' best knowledge, an association of EBV with primary central nervous system HD has not been demonstrated before.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Utility valuations for outcome states of colorectal cancer.

OBJECTIVE: Utilities for the outcome states of colorectal cancer (CRC) must be measured to evaluate the cost-utility of screening and surveillance strategies for this disease. We sought to measure utilities for stage-dependent outcome states of CRC. METHODS: We identified persons who had previously undergone removal of colorectal adenoma. We conducted individual interviews in which these participants were presented with stage-dependent outcome states and were asked to assess utilities for them using the standard gamble technique. RESULTS: A total of 90 participants were interviewed; nine were excluded, leaving 81 for analysis. We obtained the following utility valuations: stage I rectal or stage I/II colon cancer (mean 0.74, median 0.75); stage III colon cancer (mean 0.67, median 0.75); stage II/III rectal cancer without ostomy (mean 0.59, median 0.60), stage II/III rectal cancer with ostomy (mean 0.50, median 0.55), stage IV rectal or colon cancer (mean 0.25, median 0.20). These valuations were statistically different from each other. CONCLUSIONS: We measured utilities for stage-dependent outcome states of CRC in a sample of persons who had previously undergone removal of colorectal adenoma. We found that our participants were able to differentiate between the presented outcome states and assigned lower utility to increasingly morbid states. Our results show that stage-dependent morbidity is an important consideration in CRC and should be incorporated into any decision analysis model evaluating the cost-effectiveness of CRC screening or surveillance.

Adenoma↗
PubMed1999

Eph receptors and ephrins: effectors of morphogenesis.

Eph receptor tyrosine kinases and their ligands, the ephrins, appear to lie functionally at the interface between pattern formation and morphogenesis. We review the role of Eph and ephrin signalling in the formation of segmented structures, in the control of axon guidance and cell migration and in the development of the vasculature. We address the question of how the specificity of response is achieved and discuss the specificity of ephrin-Eph interactions and the significance of structural domains in Eph receptors.

Animals↗