PubMed Health⌕ Search

Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 91 records · Page 5Linked to original sources
PubMed2001

The NEI-VFQ-25 in people with long-term type 1 diabetes mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

OBJECTIVES: To examine the association of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) overall and specific scale scores with visual acuity, diabetic retinopathy, and other characteristics, in a cohort of persons with type 1 diabetes. DESIGN: Population-based cohort study. SETTING: An 11-county area in southern Wisconsin. PARTICIPANTS: Six hundred two persons with diabetes whose conditions were diagnosed when they were younger than 30 years and who were currently taking insulin participated in baseline, 4-year, 10-year, and 14-year follow-up examinations. MAIN OUTCOME MEASURES: An interview that consisted of the 25-item NEI-VFQ was completed. Visual acuity was measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol and the presence and severity of retinopathy and macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the ETDRS retinopathy severity scheme. RESULTS: Univariate analyses revealed that the total NEI-VFQ-25 score was lower in persons who were older, had a longer duration of diabetes, higher glycosylated hemoglobin, were in renal failure, had a history of cardiovascular disease, hypertension, or amputation of a lower limb, had poorer visual acuity, more severe diabetic retinopathy, macular edema, glaucoma, cataract, abnormalities in tactile sensation or temperature sensitivity, smoked more total pack-years, led a more sedentary lifestyle, and had poor peak expiratory flow. In multivariate analyses, while controlling for the physical and mental component scores from the Medical Outcomes Survey 36-Item Short-Form Health Survey as measures of comorbidity, lower total NEI-VFQ-25 scores were independently associated with poorer visual acuity, more severe retinopathy, older age, history of loss of tactile sensation, and more total pack-years of cigarettes smoked. CONCLUSIONS: In this cross-sectional study, the 25-item NEI-VFQ seems to be strongly associated with vision, independent of severity of retinopathy and other complications associated with type 1 diabetes. It may be a useful measure of health-related quality of life as it relates to vision in epidemiological studies and clinical trials in persons with diabetes.

Adolescent↗
PubMed2001

Medication use and the 5-year incidence of early age-related maculopathy: the Beaver Dam Eye Study.

OBJECTIVE: To evaluate incident early age-related maculopathy (ARM) after a 5-year interval with respect to medication use. DESIGN: Population-based incidence study. SETTING: Participants were adults aged 43 to 86 years living in Beaver Dam, Wis, when first examined in 1988-1990 (n = 4926); they were reexamined in 1993-1995 (n = 3684). METHODS: All participants were examined and interviewed and stereoscopic color fundus photographs were taken. All procedures were done by standard protocol at both examinations. Incidence of ARM was based on grading using the Wisconsin ARM Grading System. All prescribed and over-the-counter medications in current use 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. No relations were found between most antihypertensive drugs, most central nervous system medications, aspirin and other nonsteroidal anti-inflammatory agents, estrogens, lipid-lowering agents, and incident early ARM over the 5-year period. Age- and sex-adjusted logistic regression analyses suggested possible associations (P<.10) between the use of phenothiazine antidopaminergics (odds ratio [OR], 2.83; 95% confidence interval [CI], 0.97-8.23; P =.06), desiccated thyroid hormones (OR, 2.32; 95% CI, 0.89-6.07; P =.09), and calcium channel blockers (OR, 1.70; 95% CI, 0.93-3.12; P =.08) with incident ARM. When additional information on past use was included in the regression model, the association remained for calcium channel blockers, but not for phenothiazines and desiccated thyroid hormones. A lower incidence of early ARM occurred in those who took antidepressants (OR, 0.34; 95% CI, 0.12-0.94; P =.04) at the baseline examination. CONCLUSION: Although many different medications were being used at the baseline examination in the Beaver Dam Eye Study cohort, there were no striking associations with the 5-year incidence of early ARM.

Adult↗
PubMed2001

Strong acceleration of murine lupus by injection of the SmD1(83-119) peptide.

OBJECTIVE: The mechanisms of IgG anti-double-stranded DNA (anti-dsDNA) antibody induction are incompletely understood. We recently demonstrated a high prevalence of autoantibodies to the C-terminus of SmD1 in patients with systemic lupus erythematosus (SLE) that was closely associated with anti-dsDNA reactivity. The aim of the present study was to analyze the influence of the SmD1 C-terminus on the generation of pathogenic anti-dsDNA antibodies in a murine model of SLE. METHODS: Female lupus-prone prenephritic (NZB x NZW)F1 mice (NZB/NZW mice) as well as female control BALB/c, NZW, and (BALB/c x NZW)F, mice (CWF1 mice) were subcutaneously injected with keyhole limpet hemocyanin (KLH)-coupled SmD1(83-119). Controls received injections of recombinant SmD1 (rSmD1), KLH-rSmD1, KLH-coupled randomized peptide of SmD1(83-119), ovalbumin, or saline. Animals were monitored for survival and proteinuria and for levels of plasma creatinine, urea, and autoantibodies. In addition, histologic examinations were performed and T cell responses against SmD1(83-119) peptide and rSmD1 protein were determined in SmD1(83-119)-treated and -untreated NZB/NZW mice. RESULTS: Immunization with KLH-SmD1(83-119), but not with control peptide, significantly accelerated the natural course of lupus in NZB/NZW mice, with premature renal failure and increased development of anti-dsDNA antibodies. Control strains of mice remained healthy, with no relevant anti-SmD1(83-119) antibodies detectable even after immunization. In contrast to findings in control mice, a T cell response against SmD1(83-119) was already present in unmanipulated NZB/NZW mice, and this response was further amplified after immunization. CONCLUSION: The SmD1(83-119) peptide can influence the pathogenic anti-dsDNA response in the NZB/NZW murine lupus model. The data suggest that an SmD1(83-119)-specific T cell response is critical. Therefore, modulation of these autoantigen-specific T cells by tolerance induction may provide a therapeutic approach to specific immunosuppression in lupus.

Animals↗
PubMed2001

Cytogenetic and histopathologic studies of congenital supratentorial primitive neuroectodermal tumors: a case report.

Primitive neuroectodermal tumors (PNET) represent about 25% of primary central nervous system tumors in childhood, but congenital PNETs are rare. Cytogenetic studies and studies on molecular pathology have identified several genetic alterations in medulloblastoma, but molecular investigations on supratentorial PNETs are infrequent. We present a male newborn with a large congenital PNET of the right cerebral hemisphere and the molecular analysis of the tumor. Tumor tissue was investigated by routine histology and immunohistochemistry. Fluorescence in-situ hybridization was carried out on native tumor tissue to investigate deletions on chromosome 17p and to analyze c-Myc or N-Myc amplifications. Histologic examination revealed a primitive neuroectodermal tumor with massive extension covering almost the entire right hemisphere. Genetic analysis of the native tumor tissue of our patient excluded a deletion of chromosome 17p. An amplification of the c-Myc or N-Myc oncogene was absent using fluorescence in-situ hybridization. Despite unremarkable genetic analysis in our case prognosis was poor, suggesting that there are additional, yet unknown constitutional genetic aberrations in the pathogenesis of congenital supratentorial PNET.

Biomarkers, Tumor↗
PubMed2001

Diagnosing dural metastases: the value of 1H magnetic resonance spectroscopy.

The purpose of this study was to assess the value of MRI, MR spectroscopy (MRS) and intra-arterial angiography in the preoperative diagnosis of extra-axial dural-based masses. We prospectively studied 54 patients who underwent preoperative MRI, MRS and angiography. Histologically there were 50 meningiomas and four dural metastases. MRI and angiography did not allow reliable differentiation between meningiomas and metastases. MRS showed elevated choline/creatine ratios in both meningiomas and metastases, but there were prominent lipid signals in all metastases and a lactate peak in two. This spectroscopic pattern was not found in meningiomas. However, following embolisation, they showed similar spectra, due to ischaemia and necrosis. We therefore believe MRS to be valuable in differential diagnosis of dural metastases and meningiomas prior to embolisation.

Aged↗
PubMed2001

Increased microglia proliferation separates pilocytic astrocytomas from diffuse astrocytomas: a double labeling study.

It is not known how many non-tumorous cells in gliomas contribute to the proliferation rate. We investigated the proliferative activity of microglia in an immunohistochemical double-labeling study of pilocytic astrocytomas and astrocytomas WHO grade II-IV using the antibodies MIB-1 (Ki67) as proliferation-marker and Ki-M1P (CD68) as microglia marker. We found the highest indices of proliferating microglia in pilocytic astrocytomas with an average rate of 32% (+/- 6.8) of all proliferating cells. In contrast, the proliferation indices of microglia were lowest in fibrillary astrocytomas with 8.6% (+/- 2.5) of all proliferating cells. In anaplastic astrocytomas and glioblastomas the percentage of proliferating microglia showed a slight increase to 8.8% (+/- 3.6) and 13.4% (+/- 8.7), respectively. We conclude that microglial cells in astrocytic brain tumors proliferate and show different proliferative activities at different grades of malignancy with the highest rates of proliferating microglia especially in pilocytic astrocytomas. Thus, the proliferation rate does not solely reflect the proliferation of tumor cells, but also of non-tumorous cells. This should be considered in particular when proliferation rates are used as a criterion for prognosis and grading of pilocytic astrocytomas.

Antigens, CD↗
PubMed2001

The relation of socioeconomic factors to the incidence of early age-related maculopathy: the Beaver Dam eye study.

PURPOSE: To investigate the relationship between socioeconomic factors and the 5-year incidence of age-related maculopathy. METHODS: The Beaver Dam Eye Study, a population-based cohort study, examined 3681 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, at baseline and 5 years later. Standardized protocols for physical examination, including administration of a questionnaire that included questions regarding income, education level, and status and type of employment, and fundus photography to determine age-related maculopathy, were performed. RESULTS: While controlling for age and sex, less education, and being in a service-related occupation compared with a white collar professional occupation, was associated (P <.05) with the incidence of early age-related maculopathy. CONCLUSION: These data show an association of education and occupation but not income with the incidence of early age-related maculopathy that appears independent of smoking or vitamin supplement use status.

Adult↗
PubMed2001

The relation of coffee and caffeine to the 5-year incidence of early age-related maculopathy: the Beaver Dam Eye Study.

PURPOSE: To examine the relationship between coffee and caffeine consumption and the 5-year incidence of early age-related maculopathy and its component lesions, soft indistinct drusen or pigmentary abnormalities. DESIGN: A prospective cohort study conducted from 1988 to 1995 with an average follow-up of 4.8 years. METHODS: Data from baseline and 5-year follow-up examinations were analyzed for Beaver Dam Eye Study participants (n = 3435). The Wisconsin Age-Related Maculopathy Grading System was used to assess the presence and severity of early age-related maculopathy. RESULTS: Men were more likely to be coffee and caffeine drinkers than were women. For both men and women, coffee and caffeine intake decreased with age. Coffee and caffeine consumption were not associated with the 5-year incidence of early age-related maculopathy, soft indistinct drusen, or pigmentary abnormalities. CONCLUSION: Neither a history of coffee nor caffeine consumption is associated with incident early age-related maculopathy.

Adult↗
PubMed2001

Asteroid hyalosis in a population: the Beaver Dam eye study.

PURPOSE: To estimate the prevalence of asteroid hyalosis and to examine correlates of asteroid hyalosis in a population-based cohort. METHODS: The population of Beaver Dam, Wisconsin, that was 43 to 86 years of age was examined from 1988 to 1990 (n = 4926). The population is predominantly white (99.4%) northern European. Asteroid hyalosis was determined from stereoscopic fundus photographs of three standard fields. RESULTS: Fundus photographs were gradable in 4747 subjects. Asteroid hyalosis was present in 1.2% (95% confidence interval, 0.9,1.5%). In subjects in which it was present, asteroid hyalosis was bilateral in 9%. Prevalence increased significantly (P <.001) with age from 0.2% in subjects 43 to 54 years to 2.9% in subjects 75 to 86 years. After adjusting for age, men were more likely (1.8%) to have asteroid hyalosis than women (0.8%). After adjusting for age and sex, asteroid hyalosis was significantly more likely to be found in subjects with greater body mass (P =.02) and higher alcohol consumption (P =.03). There were nonsignificant trends with systolic blood pressure (P =.07), serum cholesterol (P =.09), and serum albumin (P =.09). It was not significantly associated (P >.05) with diastolic blood pressure, hypertension, diabetes, cardiovascular disease history, high-density-lipoprotein cholesterol, serum calcium, cigarette smoking, physical activity, intraocular pressure, or refractive error. These relationships were confirmed in a multivariable logistic model. CONCLUSIONS: The current study documents the infrequency of asteroid hyalosis in the population as graded from three photographic fields of the fundus. It does not support previous observations of an association of asteroid hyalosis with diabetes or refractive error. The relevance of the new associations reported (body mass, alcohol) remains to be determined.

Adult↗
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↗