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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 127 records · Page 7Linked to original sources
PubMed2000

The structural protein E of the archaeal virus phiCh1: evidence for processing in Natrialba magadii during virus maturation.

phiCh1 is a lysogenic virus for the haloalkalophilic archaeon Natrialba magadii. The virus morphology resembles other members of Myoviridae infecting Halobacterium species. The gene of the major capsid protein E of virus phiCh1 was cloned and the DNA sequence was determined. Gene E was mapped to a 3.2-kbp ClaI fragment, localized to the 5'-end of the phiCh1 genome. The complete nucleotide sequence of this region was determined and the identity of gene E was confirmed by comparing the experimentally determined N-terminal amino acid sequence of the purified protein to the translated DNA sequence of its open reading frame. We present evidence that the gene E product is proteolytically cleaved between Lys(16) and Asn(17) to yield the 305 residue polypeptides found in the mature viral capsid. Processing of the protein itself during virus development was determined by 2D gel electrophoresis using protein E-specific antibodies. Sequence similarity studies revealed an 80% identity to capsid protein Hp32 of phiH, infecting Halobacterium salinarum. RT-PCR analysis as well as Western blot studies revealed gene E as a late gene. Transcripts and proteins could be detected shortly before onset of lysis of the lysogenic strain N. magadii L11.

Amino Acid Sequence↗
PubMed2000

Role of brain insulin receptor in control of body weight and reproduction.

Insulin receptors (IRs) and insulin signaling proteins are widely distributed throughout the central nervous system (CNS). To study the physiological role of insulin signaling in the brain, we created mice with a neuron-specific disruption of the IR gene (NIRKO mice). Inactivation of the IR had no impact on brain development or neuronal survival. However, female NIRKO mice showed increased food intake, and both male and female mice developed diet-sensitive obesity with increases in body fat and plasma leptin levels, mild insulin resistance, elevated plasma insulin levels, and hypertriglyceridemia. NIRKO mice also exhibited impaired spermatogenesis and ovarian follicle maturation because of hypothalamic dysregulation of luteinizing hormone. Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction.

Adipose Tissue↗
PubMed2000

The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.

BACKGROUND: Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations. OBJECTIVE: To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus. METHODS: We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates. RESULTS: Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively). CONCLUSIONS: Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.

Aged↗
PubMed2000

Shc-binding site in the TrkB receptor is not required for hippocampal long-term potentiation.

Recent evidence shows that neurotrophins are not only involved in neuronal survival and differentiation but also in modulating synaptic strength in the developing and adult nervous system. To understand how neurotrophins induce changes in synaptic strength, we have investigated signaling pathways downstream of the TrkB receptor, which binds brain-derived neurotrophic factor (BDNF) or NT-4/5. To test whether the Shc-site activated signaling pathway, which has been shown to be important for neuronal survival in vivo, also plays a role in processes like long-term potentiation (LTP), we have generated a mouse strain carrying a mutation in the Shc-binding site of the TrkB receptor. In hippocampal slices from these mice we investigated whether basal synaptic transmission, early-LTP (E-LTP) or late-LTP (L-LTP) were affected by this mutation. We found that homo- and heterozygous mutant mice show no difference in the induction-rate or magnitude of E-LTP and L-LTP induced by theta-burst or tetanus stimulation, suggesting that the Shc-binding site in the TrkB receptor and its downstream activated signaling cascade is not involved in hippocampal synaptic plasticity.

Animals↗
PubMed2000

Recreational firearm use and hearing loss.

OBJECTIVE: To assess the relation between recreational firearm use and high-frequency hearing loss in a population of older adults. DESIGN: Cross-sectional, population-based cohort study. SETTING: The midwestern community of Beaver Dam, Wis. PARTICIPANTS: A population-based sample of 3753 participants (83% of those eligible), aged 48 to 92 years, participated in the baseline phase of the Epidemiology of Hearing Loss Study. INTERVENTION: None. MAIN OUTCOME MEASURES: Lifetime and past year self-reported firearm use during target shooting and hunting were assessed by interview. Hearing thresholds were measured by pure-tone audiometry. RESULTS: After age and other factors were adjusted for, men (n = 1538) who had ever regularly engaged in target shooting (odds ratio, 1.57; 95% confidence interval, 1.12-2.19) or who had done so in the past year (odds ratio, 2.00; 95% confidence interval, 1.15-3.46) were more likely to have a marked high-frequency hearing loss than those who had not. Risk of having a marked high-frequency hearing loss increased 7% for every 5 years the men had hunted (odds ratio, 1.07; 95% confidence interval, 1.03-1.12). Thirty-eight percent of the target shooters and 95% of the hunters reported never wearing hearing protection while shooting in the past year. CONCLUSIONS: These results indicate that use of recreational firearms is associated with marked high-frequency hearing loss in men. There is a need for further education of users of recreational firearms regarding the risk of hearing impairment associated with firearm use and the availability and importance of appropriate hearing protection.

Aged↗
PubMed2000

Vitamin supplement use and incident cataracts in a population-based study.

OBJECTIVE: To determine the relationship between vitamin supplement use and the 5-year incidence of nuclear, cortical, and posterior subcapsular cataract in the Beaver Dam Eye Study cohort. DESIGN: The 5-year incidence of cataract, determined from slitlamp (nuclear cataract) and retroillumination (cortical and posterior subcapsular cataract) photographs, was assessed in a population-based cohort of persons participating in baseline (1988-1990) and follow-up (1993-1995) examinations. Detailed data regarding the type, dosage, and duration of supplement use were obtained by in-person interviews at follow-up. PARTICIPANTS: Residents of Beaver Dam, Wis, aged 43 to 86 years, were identified by private census. Of the 3684 participants in both baseline and follow-up examinations, 3089 were eligible for incident cataract analysis in the present study. RESULTS: Compared with nonusers, the 5-year risk for any cataract was 60% lower among persons who, at follow-up, reported the use of multivitamins or any supplement containing vitamin C or E for more than 10 years. Taking multivitamins for this duration lowered the risk for nuclear and cortical cataracts but not for posterior subcapsular cataracts (odds ratios [95% confidence intervals] = 0.6 [0.4-0.9], 0.4 [0.2-0.8], and 0.9 [0.5-1.9], respectively). Use of supplements for shorter periods was not associated with reduced risk for cataract. Measured differences in lifestyle between supplement users and nonusers did not influence these associations, nor did variations in diet as measured in a random subsample. CONCLUSIONS: These data add to a body of evidence suggesting lower risk for cataract among users of vitamin supplements and stronger associations with long-term use. However, the specific nutrients that are responsible cannot be ascertained at this time, and unmeasured lifestyle differences between supplement users and nonusers may explain these results. Arch Ophthalmol. 2000;118:1556-1563

Adult↗
PubMed2000

Prevalence of and risk factors for dry eye syndrome.

OBJECTIVE: To examine risk factors for the prevalence of dry eye syndrome in a population-based cohort. METHODS: The prevalence of dry eye was determined by history at the second examination (1993-1995) of the Beaver Dam Eye Study cohort (N = 3722). RESULTS: The cohort was aged 48 to 91 years (mean +/- SD, 65 +/- 10 years) and 43% male. The overall prevalence of dry eye was 14.4%. Prevalence varied from 8.4% in subjects younger than 60 years to 19. 0% in those older than 80 years (P<.001 for test of trend). Age-adjusted prevalence in men was 11.4% compared with 16.7% in women (P<.001). After controlling for age and sex, the following factors were independently and significantly associated with dry eye in a logistic model: history of arthritis (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.56-2.33), smoking status (past, OR, 1.22; 95% CI, 0.97-1.52; current, OR, 1.82; 95% CI, 1.36-2.46), caffeine use (OR, 0.75; 95% CI, 0.61-0.91), history of thyroid disease (OR, 1.41; 95% CI, 1.09-1.84), history of gout (OR, 1.42; 95% CI, 1.02-1.96), total to high-density lipoprotein cholesterol ratio (OR, for 1 unit, 0.93; 95% CI, 0.88-0.99), diabetes (OR, 1.38; 95% CI, 1.03-1.86), and multivitamin use (past, OR, 1.35; 95% CI, 1. 01-1.81; current, OR, 1.41; 95% CI, 1.09-1.82). Nonsignificant variables included body mass; blood pressure; white blood cell count; hematocrit; history of osteoporosis, stroke, or cardiovascular disease; history of allergies; use of antihistamines, parasympathetics, antidepressants, diuretics, antiemetics, or other drying drugs; alcohol consumption; time spent outdoors; maculopathy; central cataract; and lens surgery. CONCLUSION: The results suggest several factors, such as smoking, caffeine use, and multivitamin use, could be studied for preventive or therapeutic efficacy. Arch Ophthalmol. 2000;118:1264-1268

Adult↗
PubMed2000

A longitudinal study of autoantibodies against central nervous system tissue and gangliosides in connective tissue diseases.

Our objective was to investigate longitudinally, antibodies against central nervous tissue (anti-CNS) derived from bovine brain and gangliosides GM 1, GD1a, GD1b, and GT1b in 91 patients with connective tissue diseases (systemic lupus erythematosus, n = 38; mixed connective tissue disease, n = 16; primary Sjogren's syndrome, n = 7; progressive systemic sclerosis, n= 13; polymyositis/dermatomyositis, n=4; overlap syndrome, n = 5; undifferentiated connective tissue disease, n = 8). Anti-CNS and anti-ganglioside antibodies, measured by enzyme-linked immunosorbent assay, were found in 73% and 63% of patients, respectively. Anti-CNS positive sera were also reactive in Western blotting in 74% of cases and recognized up to 14 different polypeptides from 29 to 130 kDa. Anti-CNS and anti-ganglioside antibodies reflected only in a limited extent the disease activity. In 27 of 58 patients, anti-CNS antibodies remained positive independently of disease activity and antibody levels did not correlate with the phases of exacerbations. A total of 36 of 60 anti-CNS-positive patients, in contrast to two of 22 anti-CNS-negative patients, had major neuropsychiatric manifestations (P < 0.001). Anti-ganglioside antibodies were not significantly associated with neuropsychiatric manifestations. In conclusion, our longitudinal data suggest that anti-CNS antibodies may be an important marker for the diagnosis of cerebral involvement in connective tissue diseases, but the pathogenic role of these autoantibodies remains to be determined.

Adolescent↗
PubMed2000

Detection of elastase from Pseudomonas aeruginosa in sputum and its potential role in epithelial cell permeability.

Most clinical strains of Pseudomonas aeruginosa produce elastase, a zinc metalloprotease that is implicated in the pathogenesis of infections related to these organisms. To better understand the physiologic role of this protease in the regulation of airway permeability, we developed a panel of specific monoclonal antibodies (mAb) against purified Pseudomonas elastase (PE) that do not react with either neutrophil elastase or porcine pancreatic elastase. These mAbs were used in a competitive enzyme-linked immunosorbent assay to determine the concentrations of PE in sputum samples from patients with pulmonary infections. Sputum from patients infected with P. aeruginosa showed a varying amount of PE, whereas others indicated no signals. We also found that the mAbs blocked the effect of PE on epithelial barrier function in vitro on the basis of measurement of transmonolayer electrical resistance of polarized epithelial cells as an index of paracellular permeability.

Adolescent↗
PubMed2000

Arcus senilis and mortality in a population with diabetes.

PURPOSE: To estimate the prevalence of arcus senilis and its association with mortality in a diabetic population. METHODS: A cohort of persons with younger (n = 996) and older onset (n = 1,370) diabetes was examined. Mortality information was obtained from death certificates. RESULTS: Prevalence of arcus senilis increased with age and was higher in men than in women. In the younger onset group, it was also associated with a history of cardiovascular disease. As a risk factor for mortality after controlling for age and sex, arcus senilis was not associated with death from all causes, ischemic heart disease, or stroke. CONCLUSION: Arcus senilis provides no more information about mortality risk than age of the person.

Adult↗
PubMed2000

Reproductive exposures, incident age-related cataracts, and age-related maculopathy in women: the beaver dam eye study.

PURPOSE: To evaluate the relationship of reproductive exposures and incident age-related cataract and maculopathy in women. METHODS: This was a population-based cohort study including all adults 43 to 84 years of age living in Beaver Dam, Wisconsin (a representative midwestern community) who were identified during a census in 1987 to 1988. They were evaluated initially in 1988 to 1990 and at follow-up in 1993 to 1995. Evaluations included medical histories and both fundus and lens photography. All procedures were done according to protocols that were the same at both examinations. All photographs were graded by trained observers using defined grading schemes. The severities of age-related cataracts and maculopathy were determined by grading of photographs. Information on hormone exposures was ascertained from structured interviews. RESULTS: After adjusting for age, the only significant finding for lens end points was a trend indicating a possible protective effect of increasing number of live births and incident posterior subcapsular cataract. There were no significant associations of any reproductive exposure with lesions of early or late age-related maculopathy. CONCLUSIONS: In these population-based data, there is little evidence of association of hormone exposures with incident age-related eye disease in women 5 years later. Longer follow-up of this population, whose mean age is approaching that of heightened incidence, may disclose significant relationships.

Adult↗
PubMed2000

A short questionnaire on visual function of older adults to supplement ophthalmic examination.

PURPOSE: To estimate frequency of self-reported visual dysfunction in specific life situations. METHODS: Performance-based measures of visual function were obtained during the 5-year follow-up examination of the Beaver Dam Eye Study cohort. During the subsequent yearly follow-up telephone call, four questions concerning visual abilities in specific situations were administered. RESULTS: Visual difficulties in everyday life situations were commonly reported by adults aged 48 to 91 years, with only 17% to 35% of persons reporting excellent or very good vision in the four specific situations related to visual function. Visual acuity, near vision, and contrast sensitivity measures do not reflect the visual difficulties encountered in common daily activities in our study population (Spearman correlation coefficients all less than 0.35). CONCLUSIONS: A few simple questions about visual function in common daily activities may give a clinician insights into patient complaints. It may be that environmental changes could improve self-reported visual function.

Activities of Daily Living↗
PubMed2000

The preparation of copper-oxidized LDL for the measurement of oxidized LDL antibodies by EIA.

In the present study we try to define the optimal conditions for preparation of copper-oxidized low-density lipoprotein (oxLDL) to be used for the assay of oxLDL antibodies by enzyme immunoassay (EIA). Oxidation of LDL was monitored by measuring the formation of conjugated dienes at 234 nm and the generation of fluorescent products with emission at 430 nm when excitation is performed at 360 nm. The generation of immunogenic epitopes was evaluated by testing the reactivity of aliquots collected at different times during the oxidation process with human sera with high oxLDL antibody levels and with a purified human oxLDL antibody. The values of fluorescence emission at 430 nm correlated best with reactivity with oxLDL antibodies; strong reactivity was usually associated with values greater than 1.1 U. The time needed for fluorescence emission to reach maximum levels varied between 6 and 14 h for most LDL, but it was considerably longer in a few LDL preparations. The maximal reactivity of oxLDL with oxLDL antibodies was observed when the LDL oxidation reaction was stopped 4 or more hours after the fluorescence readings reached their peak. At this stage of the oxidation reaction, apolipoprotein B fragmentation and aggregation were observed as shown by Western blot analysis. The CV for 13 EIA runs of two reference oxLDL antibodies reacting with four different pools of standardized oxLDL prepared according to the stated guidelines was 14.5 and 3.9%, confirming the reproducibility of our oxidation conditions.

Antigen-Antibody Complex↗