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R Klein

Publications and source records attributed to R Klein.

At least 73 records · Page 4Linked to original sources
PubMed2001

Cataract and hearing loss in a population-based study: the Beaver Dam studies.

PURPOSE: Cataract and hearing loss are each common at older ages and together may influence the ability to function independently and affect the sense of well-being. For these reasons, we sought to estimate the risk factors for comorbidity of age-related cataract and hearing loss. METHODS: A cross-sectional evaluation of a population-based cohort of older adults was conducted in Beaver Dam, Wisconsin, for presence of age-related cataract and hearing loss. The study evaluation included taking standardized medical histories, measuring blood pressures, and obtaining blood specimens. Standardized photographs, which were graded according to well-defined protocols to assess the presence of nuclear, cortical or posterior subcapsular cataract, were taken. Audiometric testing was performed according to well-defined study protocols. RESULTS: Any type of cataract in combination with hearing loss in either ear was frequent, occurring in 27.8% of the population overall and increasing consistently with age. Nuclear and posterior subcapsular cataract in combination with hearing loss occurred more often in men. Lifestyle factors that were associated with at least one cataract-hearing loss end point in at least one sex were history of heavy drinking and smoking. CONCLUSIONS: In this community, older adults appear to be at high risk of cataract and hearing loss. Although risk is strongly associated with age, some elective exposures appear to influence risk. It is possible that modification of certain lifestyle habits may alter these risks.

Age Factors↗
PubMed2001

Risk factors for age-related macular degeneration: Pooled findings from three continents.

OBJECTIVE: To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of population-based eye disease prevalence data. PARTICIPANTS: There were 14,752 participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME MEASURES: AMD diagnosis was made from masked grading of stereo macular photographs. Final classification of AMD cases was agreed by consensus between study investigators. RESULTS: AMD prevalence was strongly age related. Overall, AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years. Prevalence of neovascular AMD (NV) increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these age groups. There were no significant gender differences in the prevalence of NV or GA. Subjects in the Rotterdam population had a significantly lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only risk factor consistently associated with any form of AMD in all sites separately and in pooled analyses over the three sites. CONCLUSIONS: These combined data from racially similar communities across three continents provide strong and consistent evidence that tobacco smoking is the principal known preventable exposure associated with any form of AMD.

Adult↗
PubMed2001

Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye Study.

OBJECTIVE: To evaluate incident cataract after a 5-year interval with respect to medication use. DESIGN: Population-based incidence study. MAIN OUTCOME: Incident cataract judged from standard photographs. SETTING: Study subjects were adults 43 to 86 years of age in 1988 to 1990 and again in 1993 to 1995. All participants were examined and interviewed, and photographs were taken. All procedures and grading were done by protocols at both examinations. All medications in current use, prescribed as well as over-the-counter, were brought to the examination site, and the names were recorded at that time. RESULTS: There were 678 drug preparations (active ingredients) being used at the baseline examination. Significantly lower incidences of nuclear cataracts 5 years later occurred in those who took thiazide diuretics (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.63, 1.00) and aspirin (OR = 0.76, 95% CI 0.61, 0.95) at the baseline examination. There were significantly more incident cortical cataracts in those taking oral steroids (OR = 2.59, 95% CI 1.45, 4.62), amitriptyline (OR = 2.03, 95% CI 1.09, 3.79), oral hypoglycemic agents (OR 2.06, 95% CI 1.23, 3.44), and insulin (OR = 3.38, 95% CI 1.61, 7.08). There were significantly more incident posterior subcapsular cataracts in those taking potassium-sparing diuretics (OR = 2.13, 95% CI 1.42, 3.18) and oral hypoglycemic agents (OR = 2.89, 95% CI 1.57, 5.33). Considering past use with never and current use did not alter the patterns of associations. We were not able to separate the effects of antihypertensive or diuretic agents from that of hypertension. However, hypoglycemic agents were no longer associated with any cataract type after stratifying by diabetes status. CONCLUSIONS: Although many different medications were being used at the baseline examination in the Beaver Dam Eye Study cohort, few were associated with incident cataract. However, with the high frequency of use of medications and the possibility that effects of current exposure may occur in the future, it is reasonable to follow this and other older cohorts for the development of cataract.

Adult↗
PubMed2001

Changes in visual acuity in a population over a 10-year period : The Beaver Dam Eye Study.

PURPOSE: To describe the change in visual acuity in a 10-year period. DESIGN: Population-based cohort study. PARTICIPANTS: Included 3684 persons 43 to 86 years of age at the time of a baseline examination in 1988 to 1990, living in Beaver Dam, Wisconsin, at a follow-up examination in 1993 to 1995 and/or 1998 to 2000. METHODS: Best-corrected visual acuity was measured, after refraction, with logarithm of the minimum angle of resolution charts using a modification of the Early Treatment Diabetic Retinopathy Study protocol. MAIN OUTCOMES MEASURES: Doubling of the visual angle and incidence of visual impairment. RESULTS: The change in the mean number of letters read correctly over the 10-year period varied in the right eye from -0.9 (standard deviation [SD] = 5.5) and in the left eye from -1.2 (SD = 6.6) in people between 43 and 54 years of age to -11.0 (SD = 20.0) in the right eye and -12.6 (SD = 20.4) in the left eye in people 75 years of age or older (n = 184) at baseline. Over the 10-year period, 5.9% of the population had impaired vision (20/40 or worse in the better eye) develop, 0.8% had severe visual impairment (20/200 or worse in the better eye) develop, 4.8% had doubling of the visual angle, and 3.9% had improved vision. People who were 75 years of age or older at baseline were 15.0 times (95% confidence interval [CI], 10.9-20.6; P < 0.001) as likely to have impaired vision develop, 9.3 times (95% CI, 6.5-13.3; P < 0.001) as likely to have doubling of the visual angle, and 19.8 times as likely (95% CI, 8.4-46.4; P < or = 0.001) to have severe visual impairment develop than people younger than 75 years of age at baseline. For the 82 persons 75 years of age or older, currently residing in a nursing or group home at follow-up, they were 2.6 times (95% CI, 1.45-4.52) as likely to have impaired vision develop, 1.6 times (95% CI, 0.47-5.62) as likely to have severely impaired vision develop, and 3.6 times (95% CI, 1.96-6.78) as likely to have had a doubling of the visual angle than those not residing in a nursing or group home at follow-up. CONCLUSIONS: These data provide precise population-based estimates of the 10-year incidence of loss of vision over a wide spectrum of ages and show that decreased visual acuity in people 75 years of age after 10 years is a common finding, especially in those who are admitted to nursing or group homes.

Adult↗
PubMed2001

Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo.

The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal lobes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with severely downregulated kinase activity. We demonstrate that EphA4 is required for CST formation as a receptor for which it requires an active kinase domain. In contrast, the formation of the AC is rescued by kinase-dead EphA4, suggesting that in this structure EphA4 acts as a ligand for which its kinase activity is not required. Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts.

Animals↗
PubMed2001

Excitatory Eph receptors and adhesive ephrin ligands.

Ephrins are cell surface associated ligands for Eph receptor tyrosine kinases and are implicated in repulsive axon guidance, cell migration, topographic mapping and angiogenesis. During the past year, Eph receptors have been shown to associate with glutamate receptors in excitatory neurons, suggesting a role in synapse formation or function. Moreover, ephrin/Eph signaling appears to regulate neural stem cell proliferation and migration in adult mouse brains. The mode of action of ephrin/Ephs has been expanded from repulsion to adhesion and from cell surface attachment to regulated cleavage.

Animals↗
PubMed2001

Standardisation and decay data of 177Lu and 188Re.

The activity values of 177Lu and 188Re standard sources were measured using the 4pibeta-gamma-coincidence method and by liquid scintillation counting. The X- and gamma-ray emission probabilities per disintegration were determined by means of photon spectrometry with calibrated Ge and Si(Li) detectors and using the pertinent activity values. The half-lives were measured with ionization chambers, yielding T(1/2)(177Lu) = 6.646(5) d and T(1/2)(188Re) = 0.70848(9) d.

Absorptiometry, Photon↗
PubMed2001

Coupling Met to specific pathways results in distinct developmental outcomes.

Receptor tyrosine kinases (RTKs) mediate distinct biological responses by stimulating similar intracellular signaling pathways. Whether the specificity of the response is determined by qualitative or quantitative differences in signaling output is not known. We addressed this question in vivo by replacing the multifunctional docking sites of Met, the receptor for hepatocyte growth factor, with specific binding motifs for phosphatidylinositol-3 kinase, Src tyrosine kinase, or Grb2 (Met(2P), Met(2S), and Met(2G), respectively). All three mutants retained normal signaling through the multiadaptor Gab1, but differentially recruited specific effectors. While Met(2G) mice developed normally, Met(2P) and Met(2S) mice were loss-of-function mutants displaying different phenotypes and rescue of distinct tissues. These data indicate that RTK-mediated activation of specific signaling pathways is required to fulfill cell-specific functions in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Medulloblastoma displays distinct regional matrix metalloprotease expression.

Matrix metalloproteases (MMPs) play an important role in tissue remodeling and neoangiogenesis during tumor progression. Little is known about the presence and regional distribution of MMPs in medulloblastomas. Based on immunohistochemical, immunocytochemical and zymographical analysis is the present study illustrates the differential pattern of MMP expression for the medulloblastoma compared to that of glioma and ependymoma. In 10 examined medulloblastoma tumors gelatinase-A was strongly expressed by clusters of tumor cells. Gelatinase-B was, similar to glioma and ependymoma, predominantly found around endothelial cells. The DAB signal for macrophage metalloelastase was seen around macrophages and matrilysin was expressed by single tumor cells. Stromelysin-1 protein was detected in medulloblastoma but not in glioma or ependymoma. From the presented data it follows that each tumor entity might display its own characteristic MMP expression pattern.

Astrocytoma↗
PubMed2001

Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to kill transformed cells. We have studied the expression and functionality of the TRAIL apoptotic pathway in Ewing's sarcoma. We demonstrate that tumors from patients with Ewing's sarcoma express receptors TRAIL-R1 and -R2. Using a panel of nine Ewing's sarcoma cell lines TRAIL could induce apoptosis in seven cell lines. Preincubation with interferon-gamma rendered the two resistant cell lines sensitive. TRAIL was the most potent inducer of apoptosis when compared to Fas ligand or TNF. TRAIL-mediated apoptosis could be inhibited by various caspase-inhibitors. No difference in the surface expression of TRAIL-receptors was observed between sensitive and resistant cell lines. Also, all cell lines had similar levels of expression of Flice-like inhibitory protein (FLIP) on immunoblot. However, the two resistant cell lines had only very low level expression of caspase 8 on RNA and protein level. In summary, we show that Ewing's sarcoma expresses receptors for TRAIL, and that cells are exquisitely sensitive to TRAIL-mediated apoptosis. These results may warrant clinical trials with TRAIL in Ewing's sarcoma once the safety of TRAIL for humans has been established.

Apoptosis↗
PubMed2001

L-tryptophan contaminant 'peak E' induces the release of IL-5 and IL-10 by peripheral blood mononuclear cells from patients with functional somatic syndromes.

In 1989, the development of eosinophilia myalgia syndrome (EMS) was observed in some patients after the intake of l-tryptophan containing several contaminants, including 1,1'-ethylidenebis[l-tryptophan] ('peak E'). Since l-tryptophan has been taken particularly by individuals suffering from functional somatic syndromes (FSS), such as fibromyalgia syndrome (FMS), we put forward the hypothesis that EMS may have developed preferentially in patients with FSS as an allergic reaction towards the contaminant peak E. We therefore studied the immunological reactivity towards l-tryptophan and peak E in these individuals (n = 12) and compared these data with those obtained in 12 healthy controls and 12 patients with other chronic disorders. Peripheral blood mononuclear cells (PBMC) were cultured for 7 days with pure l-tryptophan and peak E. Supernatant fluids were collected at day 7. The type 2 cytokines IL-4, IL-5 and IL-10, and the type 1 cytokines IL-2 and IFN-gamma, were determined by a double sandwich ELISA. PBMC from seven of the 12 FSS patients, but only three of the 24 controls, produced cytokines after incubation with peak E (P < 0.05). Interestingly, six of the seven FSS patients reacting with peak E produced IL-5 and/or IL-10. In contrast, PBMC from only one patient with other chronic disorders and one healthy control secreted type 2 cytokines in response to peak E. The observed heightened type 2 reactivity towards the more immunogenic contaminant 1,1'-ethylidenebis[l-tryptophan] in FSS patients may therefore be taken as an additional argument for our concept that EMS may have developed as a kind of drug-induced allergic disease.

Adult↗
PubMed2001

Antiphosphatidylserine antibodies are elevated in normal tension glaucoma.

The two main entities of open-angle glaucoma are primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Both diseases may be associated with autoimmune processes. Therefore, IgG and IgM antibodies to phospholipids (APL) and their subspecies cardiolipin (ACL), phosphatidylserine (APS) and beta2-glycoprotein (beta2GP) were determined in 43 NTG patients, 40 POAG patients and 40 healthy controls in a prospective study. The most prominent observation was the increase in APS concentrations in NTG patients (IgG 20.6 +/- 2.7 U/ml, IgM 24.4 +/- 3.4 U/ml) compared with POAG patients (IgG 8.8 +/- 1.2 U/ml, IgM 11.0 +/- 1.7), and controls (IgG 7.7 +/- 1.3 U/ml, IgM 12.8 +/- 1.5 U/ml). APS may be important due to their binding specificity to phosphatidylserine molecules which become accessible during apoptosis; this in turn may lead to local thrombosis.

Aged↗
PubMed2001

Measures of obesity and age-related eye diseases.

OBJECTIVE: To compare body mass index with waist-to-hip ratio as correlates of age-related eye disease. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants of the Beaver Dam Eye Study at 5-year follow-up examinations. METHODS: Body mass index was computed from weight and height, and waist-to-hip ratio was computed from measurements all done at the 5-year examination. Presence of ocular lesions was based on gradings of standard photographs of the retina and lens. MAIN OUTCOME MEASURES: Presence of early and late age-related maculopathy and nuclear, cortical, and posterior subcapsular cataracts. RESULTS: In women, early age-related maculopathy was significantly associated with both body mass index and waist-to-hip ratio. The relationship between waist-to-hip ratio and late age-related maculopathy was of borderline significance. When analyzed as continuous measures, waist-to-hip ratio was more strongly associated with nearly every outcome compared to body mass index. In men, there was little difference between body mass index and waist-to-hip ratio as correlates of age-related eye diseases. The reason for differences between men and women is not clear, but is unlikely to be due to current exposure to estrogen. CONCLUSIONS: In women in our analyses, waist-to-hip ratio is more strongly associated with age-related eye disease than is body mass index. When adiposity is considered as a risk factor itself, or as a confounder of risk factors for age-related ocular disease, waist-to-hip ratio may be the better measure to use in women.

Adult↗
PubMed2001

Oral administration of Lactobacillus induces cardioprotection.

OBJECTIVES: Our goal was to investigate the potential of oral administration of Lactobacillus to induce cardioprotection against ischemia-reperfusion injury in rat hearts, and to determine whether this protection is associated with myocardial catalase activation and heat shock protein 70 expression. DESIGN: Lactobacillus was administered orally to rats on a daily basis, from 1 to 21 days before global ischemia. Global ischemia was produced by full-stop flow in isolated Langendorff-perfused rat hearts for 20 minutes and was followed by reperfusion. Similarly, saline was administered to control animals. RESULTS: Lactobacillus significantly reduced reperfusion tachyarrhythmia and improved functional recovery of the ischemic rat hearts. These cardioprotective effects were associated with reduction of norepinephrine release at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70 kd heat stress protein at ischemia and reperfusion (p < 0.05). CONCLUSIONS: Oral administration of Lactobacillus produces marked cardioprotection against ischemia-reperfusion injury. This effect is attributed to activation of the cellular defense system, manifested by activation of the antioxidant pathway, and by expression of protective proteins. Norepinephrine is involved in this process. The results of this study suggest that Lactobacillus, which is generally considered safe, could serve as a basis for the development of a new agent for preventive therapy of various ischemic heart syndromes.

Administration, Oral↗
PubMed2001

The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism.

The discoidin domain receptor 2 (DDR2) is a member of a subfamily of receptor tyrosine kinases whose ligands are fibrillar collagens, and is widely expressed in postnatal tissues. We have generated DDR2-deficient mice to establish the in vivo functions of this receptor, which have remained obscure. These mice exhibit dwarfism and shortening of long bones. This phenotype appears to be caused by reduced chondrocyte proliferation, rather than aberrant differentiation or function. In a skin wound healing model, DDR2-/- mice exhibit a reduced proliferative response compared with wild-type littermates. In vitro, fibroblasts derived from DDR2-/- mutants proliferate more slowly than wild-type fibroblasts, a defect that is rescued by introduction of wild-type but not kinase-dead DDR2 receptor. Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation.

Animals↗
PubMed2001

Rapid typing of Borrelia burgdorferi sensu lato species in specimens from patients with different manifestations of Lyme borreliosis.

To further investigate the pathogenic potential of different Borrelia burgdorferi genospecies, specimens from 27 patients with different manifestations of Lyme borreliosis were analyzed by PCR and reverse line blotting (RLB). In samples from Lyme arthritis patients, B. burgdorferi sensu stricto was predominantly identified, while in patients with neuroborreliosis or acrodermatitis, Borrelia garinii and Borrelia afzelii, respectively, were exclusively detected. The results demonstrate that PCR-RLB is a valuable tool for epidemiological and pathogenetic studies of Lyme borreliosis.

Adult↗
PubMed2001

Is the pulse rate useful in assessing risk of diabetic retinopathy and macular oedema? The Wisconsin Epidemiological Study of Diabetic Retinopathy.

AIM: To describe the relation between pulse rate and incident diabetic retinopathy. METHODS: Population based cohort study of people with diabetes. Resting pulse rate was measured in 30 second intervals. Diabetic retinopathy was evaluated from masked gradings of fundus photographs. RESULTS: People with higher pulse rates were more likely to have 4 year progression of retinopathy, progression to proliferative retinopathy, and incident macular oedema than those with lower pulse rates. However, these associations were attenuated after controlling for blood pressure, glycosylated haemoglobin, and other risk factors. CONCLUSION: Pulse rate may be a clinical indicator of overall risk of diabetic retinopathy, but is not independently associated with the condition.

Adult↗