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R Klein

Publications and source records attributed to R Klein.

At least 109 records · Page 6Linked to original sources
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↗
PubMed2001

[Frequency of the common cold in healthy subjects during exposure to a lectin-rich and a lectin-poor mistletoe preparation in a randomized, double-blind, placebo-controlled study].

BACKGROUND/OBJECTIVE: Mistletoe preparations have immunomodulatory properties in vitro and in vivo. We wanted to investigate whether or not these properties have an effect on the frequency of the common cold in healthy subjects. PROBANDS AND METHODS: During a randomized, placebo-controlled, double-blind study 16 volunteers received the mistletoe lectin(ML)-poor preparation Iscador Pini(R) (IP), 16 the ML-rich preparation Iscador Quercus spezial(R) (IQ), and 16 placebo (physiological saline solution) twice a week subcutaneously for 12 weeks. Weekly during weeks 1-12 and finally at week 26, a careful history of common cold symptoms was taken. Because the frequency of the common cold was not the main outcome criterion in this study, the number of cases needed to treat was not adjusted to this criterion. RESULTS: The mean frequency of the common cold during the 12 weeks of injection was 1.5 in the placebo, 1.4 in the IP and 1.1 in the IQ group. During this period in 2.3 (placebo), 1.9 (IP) and 1.4 (IQ) weeks symptoms of common cold were present. The difference in favor to IQ lasted until the end of the observation period in week 26. It was, however, not significant. Leukocyte and granulocyte count as well as C-reactive protein were not different between the groups. CONCLUSIONS: The study showed a trend (p = 0.4, exact Kruskal- Wallis test) to reduced frequency and duration of the common cold in subjects who were exposed to IQ.

Adult↗
PubMed2001

Effect of contact stress on friction and wear of ultra-high molecular weight polyethylene in total hip replacement.

This paper studies the effect of contact stress on friction and wear of ultra-high molecular weight polyethylene (UHMWPE) acetabular cups by means of friction and wear joint simulator testing under serum lubrication. For a given applied load, increasing the contact stress by increasing the ball/socket radial clearance decreased both the coefficient of friction and the wear rate. Friction and wear were highly correlated. The dependence of friction on contact stress for the UHMWPE socket under serum lubrication was similar to that of semi-crystalline polymers under dry sliding. This finding indicates the occurrence of partial dry contact at asperity levels for the metal-polyethylene ball-in-socket joint under serum lubrication.

Arthroplasty, Replacement, Hip↗
PubMed2001

Peak expiratory flow rate: relationship to risk variables and mortality: the Wisconsin Epidemiologic Study of diabetic retinopathy.

OBJECTIVE: To examine correlates of peak expiratory flow rate in people with type 1 diabetes and to evaluate the relationship of peak expiratory flow rate to mortality. RESEARCH DESIGN AND METHODS: A cohort study that was originally designed to determine the prevalence, incidence, and severity of diabetic retinopathy also provided the opportunity to measure peak expiratory flow rate. This was first measured at a 10-year follow-up and was evaluated in regard to risk factors for microvascular complications of diabetes. Mortality during 6 years of follow-up after the measurement was also ascertained. RESULTS: In multivariable analysis, peak expiratory flow rate was associated with sex, age, height, BMI, history of cardiovascular disease, pulse rate, duration of diabetes, glycosylated hemoglobin, and end-stage renal disease. Peak expiratory flow rate was significantly associated with survival in categorical analyses. Even after considering age, sex, renal disease, history of cardiovascular disease, respiratory symptoms, duration of diabetes, cigarette smoking, and hypertension, peak expiratory flow rate was still significantly related to survival (hazard ratio 0.61 [95% CI 0.46-0.82]). CONCLUSIONS: These data indicate that peak expiratory flow rate is associated with risk factors for other complications of diabetes. In addition, peak expiratory flow rate is a significant predictor of survival over even a relatively short period of time (6 years) in patients with younger-onset diabetes.

Adolescent↗
PubMed2001

Diabetes and diabetic retinopathy in a Mexican-American population: Proyecto VER.

OBJECTIVES: The prevalence rate of diabetes is probably higher in Hispanics than in Caucasians, although there is controversy about differences in the risk of diabetic retinopathy. The purpose of the study is to determine the prevalence rates of diabetes and diabetic retinopathy in a population-based study of Hispanics aged > or = 40 years. RESEARCH DESIGN AND METHODS: Proyecto VER is a random sample of Hispanic populations aged > or = 40 years in Arizona. A total of 4,774 individuals (71.6% of the eligible sample) completed the examinations. Diabetes was defined as self-report of a physician diagnosis or HbA(1c) value of > or = 7.0%. Diabetic retinopathy was assessed on stereo fundus photographs of fields 1, 2, and 4. RESULTS: The prevalence rate of diabetes in the Hispanic community (individuals > or = 40 years of age) was 22%. The prevalence rate of diabetic retinopathy (DR) was 48%; 32% had moderate to severe nonproliferative and proliferative retinopathy. DR increased with increasing duration of diabetes and increasing level of HbA(1c). The prevalence rate of DR-like changes in the sample of individuals without diabetic retinopathy was 15% and was not associated with hypertension, systolic blood pressure, or diastolic blood pressure. CONCLUSIONS: The prevalence rate of diabetes in this population of Hispanics is high, almost twice that of Caucasians. The prevalence rate of DR is high but similar to reports in a Caucasian population. The prevalence rate of 9% moderate to severe retinopathy in the newly diagnosed group suggests that efforts to improve detection and treatment of diabetes in Hispanics may be warranted.

Adult↗
PubMed2001

Sunlight and the 5-year incidence of early age-related maculopathy: the beaver dam eye study.

OBJECTIVE: To investigate the relation of sunlight exposure and indicators of sun sensitivity with the 5-year incidence of early age-related maculopathy (ARM). DESIGN: Longitudinal, population-based study. Participants (aged 43-86 years at baseline) in the Beaver Dam Eye Study were reexamined from 1993 to 1995, 5 years after the baseline examination. Questionnaire data about sunlight exposure and sun sensitivity were obtained at baseline. Additional information about earlier life patterns of exposure was ascertained at follow-up. Stereoscopic color fundus photographs were graded to determine the presence of ARM at the 5-year follow-up in eyes free from signs of early ARM at the baseline examination. RESULTS: Leisure time spent outdoors while persons were teenagers (aged 13-19 years) and in their 30s (aged 30-39 years) was significantly associated with the risk of early ARM (odds ratio, 2.09; 95% confidence interval, 1.19-3.65). There was a slight, but nonsignificant, protective effect associated with use of hats and sunglasses while persons were teenagers and in their 30s (odds ratio, 0.72; 95% confidence interval, 0.50-1.03). People with red or blond hair were slightly more likely to develop early ARM than people with darker hair (odds ratio, 1.33; 95% confidence interval, 0.97-1.83). There were no associations between estimated ambient UV-B exposure or markers of sun sensitivity and the incidence of early ARM. CONCLUSION: Exposure to sunlight may be associated with the development of early ARM.

Adult↗
PubMed2001

Macular edema and retinal hard exudates in African Americans with type 1 diabetes: the New Jersey 725.

OBJECTIVE: To determine frequency and associated risk factors for macular edema and retinal hard exudates in hospitalized African Americans with type 1 diabetes. SUBJECTS AND METHODS: Included were 725 African Americans with type 1 diabetes who participated in the New Jersey 725. Clinical evaluations consisted of a structured clinical interview, ocular examination, stereoscopic fundus photographs, and blood pressure measurements. Presence of macular edema and hard exudates was determined via masked grading of fundus photographs. Biological evaluations included blood and urine assays. RESULTS: Of the 725 patients, 89 (12.3%) had macular edema and 149 (20.6%) had retinal hard exudates in at least 1 eye. The presence of macular edema and hard exudates was significantly associated with older age at examination, longer duration of diabetes, and severity of diabetic retinopathy. Presence of proteinuria, missing insulin injections at least once a week, and longer duration of diabetes were significantly and independently associated with macular edema. Presence of proteinuria, male sex, higher low-density lipoprotein cholesterol levels, and longer duration of diabetes were significantly and independently associated with severity of retinal hard exudates. CONCLUSION: Macular edema and hard exudates are common in African Americans with type 1 diabetes, particularly in patients with evidence of renal disease.

Adolescent↗
PubMed2001

Psychometric properties of the 25-item NEI-VFQ in a Hispanic population: Proyecto VER.

PURPOSE: To assess the psychometric properties of the NEI-VFQ-25 in a population-based study of older Hispanic persons living in the United States, explore other demographic factors that affect participant response, and observe the comparability of the Spanish and English versions of the instrument. METHODS: A sample of randomly selected block groups in Tucson and Nogales, Arizona, were selected for study. Participants were interviewed at home; a majority of the interviews were conducted in Spanish. The home interview included questions from the NEI-VFQ-25 and HHANES: Presenting acuity was done using ETDRS methodology, followed by a standardized eye examination by an ophthalmologist. The authors analyzed the internal consistency of the NEI-VFQ-25 responses using Cronbach's alpha coefficient and the construct validity by assessing the relationship between presenting acuity and scale scores, adjusting for age and gender. A second model was also explored to determine whether other demographic variables affected scale scores; differences in reporting between the Spanish and English versions was observed in this model, used in a subset of the population that minimized interviewer effect. RESULTS: Of the 4774 participants in the study, 99.7% had completed questionnaires, not completed by proxy. The highest nonresponse rate occurred in the Driving scale, with 25% of participants not driving for reasons other than problems with vision. Internal consistency was high, with Cronbach alpha ranging between 0.65 and 0.86 for scales with multiple items. Adjusting for age and gender, those with presenting acuity worse than 20/40 scored significantly lower than those with presenting acuity 20/40 or better, for all scales. The demographic variables with the most consistent association across the NEI-VFQ-25 scales were presenting acuity, income, and gender. No significant differences in reporting were found between the Spanish and English versions of the questionnaire in the subset of the population. CONCLUSIONS: In this study of Hispanic people age 40 years or older, the NEI-VFQ-25 was sensitive to presenting acuity and other demographic variables, such as age, gender, and income. The findings from this psychometric analysis provide evidence of the reliability and validity of some of the scales in the 25-item NEI-VFQ when used among people with a range of visual acuity level, providing other explanatory variables are also considered.

Activities of Daily Living↗
PubMed2001

Refractive errors and incident cataracts: the Beaver Dam Eye Study.

PURPOSE: To describe the relation between refractive errors and incident age-related cataracts in a predominantly white US population. METHODS: All persons aged 43 to 84 years of age in Beaver Dam, Wisconsin, were invited for a baseline examination from 1988 through 1990 and a follow-up examination 5 years later from 1993 through 1995. At both examinations, participants had refraction and photographic assessment of cataract, according to a standardized protocol. Myopia was defined as a spherical equivalent of -1.0 diopters (D) or less, hyperopia as +1.0 D or more. The relations between refractive errors at baseline and cataract at baseline (prevalent cataract), 5-year incident cataract, and incident cataract surgery were analyzed by using generalized estimating equations. RESULTS: When age and gender were controlled for, myopia was related to prevalent nuclear cataract (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.23-2.27), but not to cortical and posterior subcapsular cataracts. Myopia was not related to 5-year incident nuclear, cortical, and posterior subcapsular cataracts, but was related to incident cataract surgery (OR 1.89; CI 1.18-3.04). Hyperopia was related to incident nuclear (OR 1.56; CI 1.25-1.95) and possibly cortical (OR 1.25; CI 0.96-1.63) cataracts, but not to posterior subcapsular cataract or cataract surgery. After further adjustment for diabetes, smoking, and education, the association between myopia and incident cataract surgery was attenuated (OR 1.60; CI 0.96-2.64), but the associations between hyperopia and incident nuclear and cortical cataracts were unchanged. CONCLUSIONS: These data support the cross-sectional association between myopia and nuclear cataract seen in other population-based studies, but provide no evidence of a relationship between myopia and 5-year incident cataract. Hyperopia may be related weakly to incident nuclear and cortical cataract.

Adult↗