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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 487 records · Page 27Linked to original sources
PubMed1993

The V kappa genes of the L regions and the repertoire of V kappa gene sequences in the human germ line.

Only 14 of the 25 V kappa genes and pseudogenes had been found before as parts of the L regions. The cloning and linking described in the accompanying report allowed us now to assign to Lp or Ld some V kappa genes which had been found before on scattered clones. In addition the sequences of several still unknown genes are reported here, thus completing the publication of the V kappa genes of the kappa locus as far as they are potentially functional or have only one or two 1-bp defects. Of the V kappa genes of the kappa locus, 32 are potentially functional, 16 have minor defects, 3 have both potentially functional and slightly defective alleles and 25 are pseudogenes which amounts to a repertoire of 76 V kappa-related gene sequences. The V kappa genes of the L regions are, within the subgroups, particularly similar to each other, which is in part due to common evolutionary origins and in part caused by gene conversion-like events. One donor-acceptor pair could be clearly identified, since converted and not-converted alleles of the acceptor gene were found. In other cases the duplicates of the converted genes served as non-converted controls.

Alleles↗
PubMed1993

Expressed human immunoglobulin kappa genes and their hypermutation.

The question of which germ-line V kappa genes are expressed was studied by sequencing 70 different cDNA clones from a human spleen library and one clone from a fetal liver library. The sequences were compared to a data base containing all germ-line V kappa gene and pseudogene sequences. In addition, 51 rearranged genomic V kappa genes, 170 cDNA and 74 kappa proteins from the literature were assigned to specific germ-line V kappa genes and included in the comparisons. Not all the known, potentially functional V kappa genes were found to be expressed, while some genes with minor defects are. The total number of expressed genes is smaller than expected: so far 21 germ-line genes and 5 pairs of duplicated identical genes are known to be transcribed. The corresponding numbers for rearranged genomic V kappa genes and kappa proteins are 17 plus 4 and 7 plus 7, respectively. A second aim of the study was to find out whether the expressed repertoire contains derivatives of germ-line V kappa genes still missing in our data base; no evidence for the existence of such genes was found. Several cDNA clones contained additional nucleotides between the V kappa and J kappa gene segments, which may be germ-line derived, inserted by terminal deoxynucleotidyl transferase or introduced by other mechanisms. Somatic gene conversion seems not to play a major role in creating the human kappa gene diversity. Various aspects of the hypermutation of kappa genes are discussed and the formation of block mutations, i.e. the alterations of two or more adjacent nucleotides is stressed as a remarkable feature of the process.

Amino Acid Sequence↗
PubMed1993

Glycated haemoglobin, plasma glucose and diabetic retinopathy: cross-sectional and prospective analyses.

Among Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus the relationships between glycated haemoglobin (HbA1), fasting or 2-h post-load plasma glucose and diabetic retinopathy were examined by cross-sectional and prospective analyses, and the strengths of the associations were directly compared by receiver operating characteristic analysis. In the cross-sectional analysis, HbA1, fasting and 2-h plasma glucose were each significantly related to retinopathy among 789 diabetic subjects by separate logistic models. In a stepwise multiple logistic model in which HbA1, fasting and 2-h plasma glucose were included, HbA1 was selected as having the strongest association with retinopathy and neither fasting nor 2-h plasma glucose contributed significantly to the model once HbA1 was entered. Similarly, in the prospective analysis, HbA1, fasting and 2-h plasma glucose all predicted retinopathy in 227 diabetic subjects by separate proportional-hazards models. In a stepwise proportional-hazards model with HbA1, fasting and 2-h plasma glucose available to the model, HbA1 was again selected as having the strongest association with the incidence of retinopathy, and neither fasting nor 2-h plasma glucose significantly added to the prediction of retinopathy. A receiver operating characteristic analysis was used to determine if HbA1 was statistically significantly better than fasting or 2-h plasma glucose in assessing the risk for retinopathy. In neither the cross-sectional nor the prospective data did the area under the receiver operating characteristic curve for HbA1 differ significantly from that for fasting or 2-h plasma glucose (p > 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Assessment of genotoxic effects by lindane.

The well known and previously widespread insecticide lindane has been re-assessed for DNA-damaging activity. A first group of investigations using standard in vitro and in vivo mutagenicity assays did not indicate any genotoxic effects of lindane at all. The assay systems used were for the induction of HPRT mutations and sister chromatid exchanges in CHO cells cultured in vitro, and for micronuclei induction in vivo in bone marrow cells of rats, hamsters and mice. Also, lindane was assessed for its potential to induce sister chromatid exchanges in vivo in the bone marrow of Chinese hamsters. These specific assay systems had not been used previously for elucidating the genotoxic effects of this compound, but they are basically similar to other standard mutagenicity assays in which lindane has been shown to be devoid of genotoxic activity. The second part of the investigations was directed at re-evaluating a previously reported positive effect of the compound in primary rat hepatocytes in vitro. We performed in vitro and in vivo studies with hepatocytes from the rat liver and used alkaline elution to detect DNA damage. However, we could not demonstrate that lindane induced genotoxicity, unless considerable concomitant cytotoxicity was apparent as well. Finally, since lindane can be ingested and inhaled by humans, we also measured the induction of DNA damage in local target organs of absorption using single cell micro-gel-electrophoresis (the comet assay). In these cases lindane was genotoxic in cells of the gastric and nasal mucosa in vitro and also in vivo following appropriate routes of application (oral and inhalational exposure).

Administration, Inhalation↗
PubMed1993

Is there an ethnic difference in the effect of risk factors for diabetic retinopathy?

Mexican Americans have an increased prevalence and incidence of non-insulin-dependent diabetes mellitus (NIDDM). In addition, Mexican American diabetic subjects have an increased prevalence of retinopathy relative to Caucasian diabetic subjects. In Mexican American diabetic subjects, established risk factors may have a stronger effect on diabetic retinopathy, compared to Caucasian diabetic subjects. In this report, we compare the effect of established risk factors (age at examination, gender, age at diagnosis of diabetes, duration of diabetes, glycemia, type of therapy, systolic and diastolic blood pressure, and hypertension prevalence) between Caucasian diabetic subjects (n = 478), a low-risk population for NIDDM (Wisconsin Epidemiologic Study of Diabetic Retinopathy), and Mexican American diabetic subjects (n = 231), a high-risk population for NIDDM (San Antonio Heart Study). Retinopathy was classified into two categories (any or none) as assessed by seven standard stereoscopic retinal photographs read at the University of Wisconsin Reading Center. Mexican American diabetic subjects in Texas had an increased prevalence of any retinopathy (odds ratio = 1.71, 95% confidence interval: 1.25, 2.34), compared to Caucasian diabetic subjects in Wisconsin. Longer duration of diabetes, more severe glycemia, earlier age at diagnosis, and insulin therapy were associated with diabetic retinopathy in both Mexican Americans and Caucasians. Socioeconomic status was not associated with prevalence of retinopathy. Moreover, the effect of risk factors for retinopathy was similar in both ethnic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Sex hormones and the incidence of severe retinopathy in male subjects with type I diabetes.

BACKGROUND: Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. METHODS: The authors measured total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and dehydroepiandrosterone-sulfate levels in 44 men with type I diabetes participating in the 1984 to 1986 re-examination phase of the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based study of diabetic complications. The mean age was 32.7 years, and the mean duration of diabetes was 15.4 years. Subjects who progressed to proliferative or preproliferative retinopathy 6 years later (cases, n = 22) were compared with subjects who had little or no progression (controls, n = 22). Both groups were matched on initial level of retinopathy. Seven stereoscopic retinal photographs of each eye were obtained at both examinations, and the photographs were read by the University of Wisconsin Reading Center. RESULTS: Sex hormone-binding globulin concentrations (nmol/l) were significantly lower (reflecting increased androgenicity) in cases than in controls (22.4 +/- 11.4 versus 32.5 +/- 19.8; P = 0.04). No other statistically significant differences in hormone levels were observed. CONCLUSION: Neither serum testosterone nor other sex hormones were related to the incidence of severe retinopathy. The relationship to low-serum sex hormone-binding globulin suggests that increased androgenicity may be associated with the progression of retinopathy in male subjects with type I diabetes.

Adult↗
PubMed1993

Relationship of drinking alcohol and smoking to prevalence of open-angle glaucoma. The Beaver Dam Eye Study.

PURPOSE: To evaluate a possible association of glaucoma with alcohol ingestion and cigarette-smoking behavior. METHODS: A population-based survey was performed of persons 43 to 84 years of age in Beaver Dam, Wisconsin (n = 4926). The diagnosis of glaucoma was based on visual field testing, measurement of intraocular pressure, and cup-to-disc ratios based on detailed protocols for examination, measurement, and gradings of photographs. Alcohol intake and smoking history were based on questionnaire responses. The prevalence of glaucoma in "heavy drinkers," whether current or past, was contrasted with the prevalence in those not reporting heavy drinking. Prevalences in never, past, and current smokers were compared. RESULTS: There was no difference in frequency of glaucoma by drinking status. Similarly, there was no difference in the frequency of glaucoma by cigarette-smoking status. CONCLUSION: In these prevalence data, neither heavy drinking nor cigarette-smoking behavior was related to the prevalence of open-angle glaucoma. This finding may reflect a real absence of a pathologic effect.

Adult↗
PubMed1993

Is gross proteinuria a risk factor for the incidence of proliferative diabetic retinopathy?

PURPOSE: To examine the relationship between gross proteinuria, measured at the initial examination, and the 4-year incidence of proliferative diabetic retinopathy (PDR) in a population-based study in Wisconsin. METHODS: Gross proteinuria was measured by reagent strip. Diabetic retinopathy was determined from stereoscopic fundus photographs in a masked fashion using the modified Airlie House classification scheme. RESULTS: In the younger-onset group taking insulin (n = 693), the relative risk of proliferative retinopathy developing in those with gross proteinuria at baseline was 2.32 (95% confidence interval [CI]: 1.40,3.83) compared with those without gross proteinuria. For the older-onset group taking insulin, the relative risk was 2.02 (95% CI: 0.91,4.44), and for those not taking insulin it was 1.13 (95% CI: 0.15,8.50). After controlling for other risk variables, the relationship was of borderline statistical significance (P = 0.052) in the younger-onset group with no or early nonproliferative retinopathy at baseline. CONCLUSION: These data suggest that gross proteinuria is a risk indicator for proliferative retinopathy in younger-onset patients with diabetes. These patients might benefit from having regular ophthalmologic evaluation.

Adult↗
PubMed1993

The association of microalbuminuria with diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

PURPOSE: To investigate the relationship between microalbuminuria and the presence and severity of diabetic retinopathy in a large population-based cohort of individuals with diabetes. METHODS: Microalbuminuria was measured by an agglutination inhibition assay in random urine samples obtained from participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (n = 1139) who did not have hematuria, gross proteinuria, or a history of renal disease. Retinopathy was determined from stereoscopic color fundus photographs graded according to a modification of the Airlie House Classification System. RESULTS: Younger-onset (diagnosed with diabetes before 30 years of age) and older-onset (diagnosed with diabetes when 30 years of age or older) individuals with microalbuminuria were more likely to have retinopathy than those without microalbuminuria. Younger-onset individuals who had microalbuminuria at the time of examination were more likely to have proliferative retinopathy than younger-onset subjects with normoalbuminuria. These relationships remained after controlling for glycemia, hypertension, duration of diabetes, and other potential confounders. CONCLUSIONS: Microalbuminuria is associated cross-sectionally with the presence of retinopathy in persons with diabetes and with the presence of proliferative disease in younger-onset individuals. These data suggest that microalbuminuria may be a marker for the risk of proliferative retinopathy developing. If longitudinal studies confirm these findings, individuals with insulin-dependent diabetes mellitus (IDDM) who have microalbuminuria may benefit from ophthalmologic follow-up.

Adult↗
PubMed1993

The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study.

PURPOSE: To examine the association between cardiovascular disease and its risk factors to age-related maculopathy in a population-based study of people between the ages of 43 and 86 years (n = 4926) between 1988 and 1990. METHODS: Population-based prevalence study using standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy. Standard univariate and multivariate analyses were performed. RESULTS: After controlling for age, early age-related maculopathy was related to low total serum cholesterol levels in women and a high high-density lipoprotein (HDL) cholesterol level and a low total cholesterol/HDL-cholesterol ratio in men. After controlling for age and sex, age-related exudative macular degeneration was associated with higher hematocrit values (odds ratio, 1.09; 95% confidence interval, 1.00, 1.19) and higher leukocyte count (odds ratio, 1.10; 95% confidence interval, 1.00, 1.19). There was no statistically significant relationship between blood pressure, hypertension, or history of cardiovascular disease and exudative macular degeneration or geographic atrophy. CONCLUSION: With the exception of relationships between serum lipids and early age-related maculopathy, and hematocrit values, leukocyte counts, and exudative macular degeneration, these data suggest that most cardiovascular disease risk factors are not related to age-related maculopathy. Further longitudinal study is needed.

Adult↗
PubMed1993

Excimer laser photorefractive keratectomy with tapered transition zone for high myopia. A preliminary report of six cases.

To improve the stability of refraction after photorefractive keratectomy (PRK) to correct myopia, we developed a new ablation profile with a 1.5 mm wide tapered transition zone bordering the refractive zone. The treated area's total diameter was 7 mm, the diameter of the refractive zone, 4 mm. The effect of the tapered transition zone on refraction stability was investigated in a 12-month follow-up study of six eyes of six patients. All eyes were partially sighted, with corresponding fundus changes and myopia of between -12.0 diopters (D) and -24.0 D. The therapeutic goal was to reduce myopia by 10.0 D to 13.0 D. All patients were treated unilaterally. The change in refraction in five eyes 12 months after surgery was < or = 1.0 D as compared with the first month postoperatively. In one case the change after 12 months was 2.75 D. There was less regression after PRK with the transition zone than with a conventional ablation profile (i.e., stability was improved). However, epithelial healing took longer.

Adult↗
PubMed1993

Does motion-induced grouping modulate the flanker compatibility effect?: A failure to replicate Driver & Baylis.

Several experiments explored the possibility that motion-induced grouping would modulate the spatial distribution of the flanker compatibility effect (FCE). Subjects were required to make a speeded decision about a central target letter embedded in a five letter string. On each trial the identity of the near or far letters was either compatible or incompatible with the correct response while the remaining letters were neutral. In contrast to the findings of Driver & Baylis (1989), when the far distractors and the target moved together while the near distractors remained stationary, we did not find that the FCE for the far distractors was greater than the FCE for the stationary near distractors. Moreover, the pattern of response latencies in this moving condition were not different from what we observed when all letters remained stationary. Accuracy was affected, but not in the direction predicted by the view that attention is directed to perceptual groups. Modulation of the distribution of attention in response to motion-induced grouping is not a robust phenomenon. Nevertheless, a simple spotlight model of attention is challenged by demonstrations in the literature that perceptual grouping mediated by static properties such as closure, colour and good continuation strongly influence the spatial distribution of the FCE and that the allocation of attention in search is strongly influenced by stimulus motion.

Adult↗
PubMed1993

Glycosylated hemoglobin concentrations and vitamin E, vitamin C, and beta-carotene intake in diabetic and nondiabetic older adults.

Studies indicate that large doses of all-rac-alpha-tocopherol in people with diabetes or ascorbic acid in nondiabetic subjects reduces protein glycosylation. The mechanisms by which these nutrients influence glycosylation are poorly understood but may be related to their ability to function as antioxidants. We examined the relationship between glycosylated hemoglobin (GHb) and intake of vitamins E and C and beta-carotene in a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study. In people with diabetes, no significant associations were observed between GHb and intake of vitamins E and C and beta-carotene. In people without diabetes, energy-adjusted vitamin C intake was negatively associated with GHb after age and sex were controlled for (dietary, P = 0.02; total, P = 0.04). No significant relationships between GHb and intake of vitamin E and beta-carotene were observed.

Adult↗
PubMed1993

Nutrient supplements contribute to the dietary intake of middle- and older-aged adult residents of Beaver Dam, Wisconsin.

Intake of macronutrients and micronutrients was estimated from a diet history questionnaire in a population-based sample of persons (n = 2152), 43-86 y of age. Men and women 65 y of age or older consumed less protein, fat, cholesterol, niacin, riboflavin, calcium, iron, zinc and lycopene than their middle-aged counterparts. After including nutrient intake from supplements, age differences in intake were no longer significant for zinc in women or for niacin and iron in men. After further adjusting for energy intake, only protein, cholesterol, and lycopene mean intakes were lower in older compared with middle-aged men and women. Regular use of supplements was most prevalent among older men and women (40 and 48%, respectively). Supplement use was greater in the current time period compared with retrospective reports of supplement use 10 y before interview. The impact of supplement intake on median values of intake was greatest in women, particularly for vitamins A, C and E, riboflavin and calcium. The high prevalence of supplement use emphasizes the importance of considering this source of nutrients in future investigations in which dietary intake is measured.

Adult↗
PubMed1993

A diet history questionnaire ranks nutrient intakes in middle-aged and older men and women similarly to multiple food records.

We evaluated the reproducibility of a modified version of the National Cancer Institute diet history questionnaire and also studied comparability of nutrient estimates from this questionnaire to those from four 2-d food records. Subjects (n = 211) were from a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study in south-central Wisconsin. Median age-specific correlation coefficients between the questionnaire, administered twice at a 3-mo interval, were 0.8 in men and 0.7 in women (range = 0.5 to 0.9). Questionnaire estimates of protein, cholesterol, thiamin, niacin, iron and zinc were consistently lower than food record estimates whereas estimates of fat were higher. Correlation coefficients between estimates from the questionnaire and records were generally > 0.5, indicating overall good agreement in ranking. However, the range in correlation coefficients was wide [ranging from 0.06 for iron (without supplements) in middle-aged women to 0.8 for alcohol in middle-aged men and women]. Questionnaire estimates similarly classified persons into the lowest two food record quintiles of intake 50 to 93% of the time depending on nutrient. These results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records.

Adult↗