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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 577 records · Page 32Linked to original sources
PubMed1991

The 5' insulin gene polymorphism and the genetics of vascular complications in type 1 (insulin-dependent) diabetes mellitus.

Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5' to the insulin gene on chromosome 11 and diabetic nephropathy. This was done by comparison of those diabetic patients homozygous for class 1 alleles at the 5' insulin gene polymorphism locus to 1/3 heterozygotes in a well-characterized series of 324 insulin-requiring diabetic patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Proteinuria (defined as greater than or equal to 0.3 g protein/l urine), was used as suggestive evidence for diabetic nephropathy. Hypertension, a frequent associated finding in diabetic patients with nephropathy, was defined as a blood pressure greater than 140/90 or a history of previous treatment of hypertension. The two genotypically defined groups did not differ from each other in regard to sex ratio, age at diagnosis, age at examination, duration of diabetes, body mass, HbAlc or C-peptide. The 1+1 group had a higher prevalence of proteinuria, 29% as compared to 16.2% in other genotypes (p less than 0.05). There was no significant difference in the frequency of hypertension between the two genotypic groups. This finding suggests that the 5' insulin gene polymorphism may be associated with risk for nephropathy, but the pathophysiologic mechanism remains unclear.

Blood Pressure↗
PubMed1991

Expression of the X protein of hepatitis B virus in insect cells using recombinant baculoviruses.

The baculovirus system was used to express the X protein of human hepatitis B virus (HBV). The X open reading frames (X ORFs) from cloned viral DNA of the HBV subtypes ayw and adr were introduced into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV). The HBV-DNA of subtype adr derived from a hepatocellular carcinoma contains an X ORF and a 5' extended preX/X ORF, which were both used to construct X recombinant baculoviruses. Infection of Sf9 insect cells with these recombinant viruses yielded large amounts of the respective X proteins. They were identified by a set of mouse monoclonal antibodies directed against different epitopes of the ayw X protein using immunoblotting techniques. A subpopulation of the X protein expressed is modified, thus raising the molecular weight from the expected size of 17 kD to 21 kD. Indirect immunofluorescence and immunoelectron microscopy was performed to characterize the subcellular distribution of the X protein expressed in Sf9 cells. Data are presented that it accumulates as large globular structures within the cytoplasm and the nucleus of the infected cells.

Animals↗
PubMed1991

HLA-DR and the 5' insulin gene polymorphism in insulin-dependent diabetes.

While the human leukocyte antigen (HLA) region provides the major susceptibility for insulin-dependent (type I) diabetes mellitus (IDDM), other (non-HLA) genes must also play a role. Population studies have shown an increased frequency of small insertions (class I alleles) 5' to the insulin gene in individuals with IDDM, suggesting that this region may account for part, if not all, of the non-HLA genetic predisposition. However, no data are available as to whether the relation of the insulin gene polymorphism is to a DR-defined subset of IDDM or with all of IDDM. To test the hypothesis that specific combinations of HLA and insulin gene polymorphism alleles may interact in providing susceptibility for IDDM, HLA-DR and 5' insulin gene insertion size have been determined in 300 individuals with IDDM. The frequency of class 1 insulin gene alleles in the entire sample is 0.79 and the frequency of class 3 alleles (large inserts) is 0.20. The frequencies of class 1 alleles were equal across all DR classes: 0.79 in the DR3/X IDDM subjects, 0.80 in the DR4/X, 0.79 in the DR3/4, and 0.78 in those with DRX/X. Additionally, the frequencies of class 1/1 homozygotes and 1/3 heterozygotes were similar between HLA-DR types. These results suggest that the HLA region and the region 5' to the insulin gene provide independent and nonsynergistic genetic risks for IDDM.

Diabetes Mellitus, Type 1↗
PubMed1991

Antimitochondrial antibody profiles determined at early stages of primary biliary cirrhosis differentiate between a benign and a progressive course of the disease. A retrospective analysis of 76 patients over 6-18 years.

Seventy-six patients with clinically and histologically defined primary biliary cirrhosis, who were in stage I/II at the time of first diagnosis and could be followed for 6-18 years (mean 10 years), were analysed with respect to their clinical course. Forty-four of the 76 patients remained in stage I/II during the observation period (group 1), while 32 progressed to late stages (group 2). Sera of these patients were retested for anti-M2, anti-M4, anti-M8 and anti-M9 antibodies by ELISA and the complement fixation test (CFT). Four different AMA-profiles A-D could be differentiated in these patients: profile A, only anti-M9 positive by ELISA; B, anti-M9 and/or anti-M2 positive by ELISA; C, anti-M2, anti-M4 and/or anti-M8 positive by ELISA; and D, anti-M2, anti-M4 and/or anti-M8 positive by ELISA and CFT. When the natural courses of patients and the four different AMA-profiles were compared retrospectively it became evident that 97% of group 2 patients already had the AMA-profile C/D at entry into the study. Of the patients in group 1 70% had the AMA-profile A/B. Increases in bilirubin levels during the course of the disease were observed preferentially in patients of group 2 (profile C/D). We conclude that the determination of AMA-profiles in PBC patients is a sensitive approach for the early prediction of the outcome of the disease.

Adult↗
PubMed1991

The major pterin in Tetrahymena pyriformis is 6-(D-threo-1,2,3-trihydroxypropyl)-pterin (D-monapterin) and not 6-(L-threo-1,2-dihydroxypropyl)-pterin (ciliapterin).

The major pterin in Tetrahymena pyriformis, strain W, earlier suggested to be L-threo-biopterin and named ciliapterin [1] is now identified as D-threo-neopterin (D-monapterin). This is the first example of a natural D-monapterin. This compound was characterized by its chromatographic behavior, its fluorescence properties and by its oxidation product with alkaline permanganate. The final identification was obtained by comparison with an authentic material using an exchange ligand chromatography method with D-phenylalanine as chiral modifier and Cu (II) as metal ion. D-monapterin is also present as the major pterin in Tetrahymena pyriformis strains GL and ST, and in Tetrahymena thermophila.

Animals↗
PubMed1991

The role of socioeconomic factors in the survival of patients with colorectal cancer in Saarland/Germany.

The role of socioeconomic factors in the survival of patients with colorectal cancer was assessed using data from the cancer registry of Saarland/Germany, and census information. Among 2627 patients with colorectal cancer diagnosed from 1974 to 1983, patients from communities in the lowest of three categories defined by socioeconomic factors showed significantly lower survival rates than patients from other communities. After adjustment for potential biological and other sociogeographic risk factors in multivariate analyses, relative hazard of death associated with low socioeconomic status (SES) compared with high SES was estimated to be 1.22 (95% CI: 1.01-1.47) for colon cancer and 1.32 (95% CI: 1.09-1.60) for rectum cancer. The results are in agreement with earlier studies from North America, Hawaii and Sweden and indicate that an attempt to improve health care services and acceptance and possibly other relevant general living conditions in socioeconomically less privileged communities may be a rewarding approach towards increasing survival of patients with colorectal cancer.

Aged↗
PubMed1991

The Beaver Dam Eye Study: visual acuity.

Few current population-based data on visual impairment are available. Visual acuity and impairment were measured in 4926 people between the ages of 43 and 86 years in the defined population participating in the Beaver Dam Eye Study. Visual acuity was measured after refraction, using standardized protocols. Of a possible maximum score of 70 (20/10), the mean number of letters correctly identified (right eye) varied from 55.7 (20/20, n = 1515) in people between the ages of 43 and 54 years to 41.2 (20/40, n = 795) in people 75 years of age or older. Age-specific mean visual acuity scores were consistently and significantly lower in women, who identified three fewer letters on the average than men. Rates of any visual impairment (20/40 or worse in the better eye) or legal blindness (20/200 or worse in the better eye), increased from 0.8% and 0.1%, respectively, in people between the ages of 43 and 54 years to 21.1% and 2.0%, respectively, in people 75 years of age or older. Multivariate analyses showed both sex (women) and age (older) to be significant and independent predictors of poorer visual acuity.

Adult↗
PubMed1991

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate.

Serum total and high-density lipoprotein (HDL) cholesterol were measured in a sample of individuals examined between 1984 and 1986 for the Wisconsin Epidemiologic Study of Diabetic Retinopathy. There was a significant trend for increasing severity of diabetic retinopathy and of retinal hard exudate with increasing cholesterol in insulin-using persons. Cholesterol levels were not related to the severity of either ocular condition in older-onset patients. High-density lipoprotein-cholesterol was unrelated to the severity of either lesion. In multiple logistic regression analyses, cholesterol was not a significant factor in describing the severity of retinopathy in any group but was a significant factor in describing the severity of retinal hard exudate. Glycosylated hemoglobin and diastolic blood pressure were significant descriptors of the severity of retinopathy in younger-onset patients in these multivariate analyses. Diastolic blood pressure added significantly to explaining the severity of hard exudate in older-onset insulin users. These data support the current management strategies for diabetes, which include control of level of glycemia, blood pressure, and blood lipids.

Adult↗
PubMed1991

The Wisconsin age-related maculopathy grading system.

A new system for grading age-related maculopathy is described and measures of reliability are reported. A number of characteristics of age-related maculopathy are graded in a semiquantitative fashion from stereoscopic 30 degrees color fundus photographs, using a grid to define subfields, standard circles printed on plastic to assess size and area, and a specially designed lightbox to allow better discrimination of subtle drusen. The degree of exact agreement achieved between two trained graders across a variety of lesions ranged from 67.1% for drusen size to 99.6% for geographic atrophy. Kappa scores ranged from 0.55 (for drusen confluence) to 0.95 for geographic atrophy. This system will be useful in epidemiologic studies and clinical trials.

Aging↗
PubMed1991

Combining shape and position expectancies: hierarchical processing and selective inhibition.

Two experiments report the effects of generating a concurrent position expectancy and form expectancy. Ss were precued to a stimulus position where 1 target shape was most probable, and they made a speeded 2-choice response to the orientation of the displayed shape. Response time (RT) was faster for an expected position than an unexpected position and faster for a likely shape than for an unlikely shape. This replicates the work of Lambert and Hockey (1986). It was also observed, however, that when a stimulus appeared at an unexpected position where 2 shapes were equally improbable, RT was slower for the shape that had been likely rather than unlikely at the cued position. This finding is incompatible with the probability-matching hypothesis of Lambert and Hockey. The data support a hierarchical-expectancy model of attentional selectivity.

Adolescent↗
PubMed1991

[Significance of autoimmunity in various forms of uveitis].

Autoimmune diseases are the result of a false recognition by the immune system of the own tissue as foreign. Suppressor cells serve to inhibit these mechanisms, however, their influence can be bypassed by other cells. Many antigen structures have been isolated in the uvea. With them it is possible to induce a model of autoimmune uveitis. The diagnostic value of eye specific and non-specific autoantibodies in uveitis patients was studied. In this report are show indications of autoimmune phenomena in the following diseases: sympathetic uveitis, Behçet's disease, Vogt-Koyanagi-Harada syndrome and birdshot retinopathy.

Animals↗
PubMed1991

Cost-effectiveness of strategies for detecting diabetic retinopathy.

A computer model has been developed to determine cost-effectiveness of screening and treatment for diabetic retinopathy from a societal viewpoint. This model was used to evaluate biannual and annual screening programs using ophthalmoscopy, fundus photography with a "nonmydriatic camera," and photography with a "mydriatic camera." Computations were performed for three subpopulations formed by patients with younger onset diabetes (age at diagnosis less than 30 years) of 5 years or more duration, with older onset diabetes (age at diagnosis greater than or equal to 30 years) who are taking insulin, and with older onset diabetes not taking insulin. Population characteristics are from a well-described southern Wisconsin population where data are available, but the computer model may be specialized to other population. Generally costs of screening programs appear to be recovered by avoided costs of blindness in the population subgroups taking insulin; however, the cost of screening programs generally are not recovered by avoiding costs of blindness in the older onset population subgroup not taking insulin. It was estimated that supplying annual examination with mydriatic fundus photography as a screening program to a cohort of 1,000 diabetics from the younger onset population who have been diagnosed at least 5 years and who are currently not receiving care might save 319 sight years over the lifetime of the cohort. This program will save 62 sight years in an older onset cohort who are taking insulin, and 21 sight years in the older onset population not taking insulin (all benefits are presented as present values computed with an annual discount rate of 5%). Other programs achieve slightly lower savings in each subpopulation.

Adult↗
PubMed1991

Sporotrichal arthritis.

Sporotrichal arthritis is a rare disease entity. Diagnosis is often difficult and delayed. Presentation may be either monoarticular or polyarticular. A case of polyarticular sporotrichal arthritis which exemplifies these problems is reported.

Adult↗
PubMed1991

Age-related eye disease, visual impairment, and driving in the elderly.

As people age, a number of visual functions such as acuity, visual field, and night vision deteriorate. This decline in vision is associated in part with an increase in vehicular accidents per mile driven by the elderly. Four age-related ocular conditions--cataract, macular degeneration, open-angle glaucoma, and diabetic retinopathy--are primarily responsible for the decline in visual acuity and visual field in the elderly. Few epidemiologic data are available about these diseases, and at present they cannot be prevented. There is need for more information about visual decline and how it affects driving performance and for development of pragmatic approaches for detecting and assessing the elderly driver with functional visual deficits.

Accidents, Traffic↗
PubMed1991

The radioimmunoassay of follicle-stimulating hormone (FSH)-suppressing protein (FSP): stimulation of bovine granulosa cell FSP secretion by FSH.

A RIA for bovine (b) FSH-suppressing protein (FSP) was developed using an antiserum raised in a rabbit to purified 39-kDa bFSP, iodinated 35-kDa FSP as tracer, and purified 35-kDa bFSP as standard. Purified 35-kDa FSP was iodinated using the iodogen procedure, and the iodinated FSP was purified by dye affinity chromatography. After a logit log-dose transformation of the dose-response curves, parallel displacement lines were observed between 31-, 35-, and 39-kDa FSP, bovine follicular fluid, bovine granulosa cell culture medium, and medium from bovine granulosa cells stimulated with bFSH. The specificity of the assay was investigated by comparing the immunoassay levels of FSP with in vitro bioassay levels based on the ability of FSP/inhibin to suppress FSH in rat anterior pituitary cell cultures in fractions obtained throughout the purification procedure of FSP from bovine follicular fluid. This demonstrated that 1) the FSP immunoactivity was associated with in vitro bioactivity in all fractions of the purification procedure; 2) a number of inhibin-related and other proteins showed low (less than 0.5%) or nondetectable cross-reactivity in the RIA; and 3) the in vitro biological to immunological ratios for 31-, 35-, and 39-kDa FSP were similar, indicating that the RIA detects all forms of purified bFSP. The secretion of FSP by bovine granulosa cells in culture was investigated in the presence and absence of bFSH and bLH, respectively. FSP production was proportional to granulosa cell number and decreased from highest levels at 24 h to lowest levels at 96 h of culture. The addition of either bFSH or 8-bromo-cAMP to the culture medium stimulated FSP production by a factor of 2-3 at 48 and 72 h of culture, while the addition of bLH had no effect on FSP production. Theca interna tissue cultured under the same conditions did not produce FSP. In contrast to FSP, stimulation of bovine granulosa cells with bFSH or bLH had no effect on inhibin production during the 96 h of culture, while the addition of bFSH and bLH caused a stimulation of progesterone production at 48 and 72 h of culture. It is concluded that 1) the RIA described here is specific for all mol wt forms of bFSP; 2) FSP was secreted by bovine granulosa cells and not thecal cells in vitro; and 3) FSP secretion by bovine granulosa cells in vitro is regulated by bFSH and not bLH.

Animals↗
PubMed1991

Cause-specific mortality in a population-based study of diabetes.

BACKGROUND: Mortality from vascular diseases has been reported to be high in diabetic persons. METHODS: To evaluate mortality from these and other specific causes, we examined cause-specific age-sex standardized mortality ratios in a geographically defined population of younger onset (diagnosed before age 30 and taking insulin, n = 1200) and older onset (diagnosed after age 30, n = 1772) diabetic persons followed for 8.5 years. Cause of death was determined from death certificates. RESULTS: In younger onset persons, age-sex standardized mortality ratios were significantly high (P less than .05) for all causes of death (7.5) as well as for diabetes (191), all heart disease (9.1), ischemic heart disease (10.1), other heart disease (6.3), nephritis and nephrosis (41.2), accidents (2.9), and all other causes (3.2). In older onset persons, age-sex standardized mortality ratios were significantly high for all causes of death (2.0) as well as for diabetes (16.8), all heart disease (2.3), ischemic heart disease (2.3), other heart disease (2.1), stroke (2.0), and pneumonia and influenza (1.7). CONCLUSIONS: Diabetic persons experience very high mortality, especially from vascular diseases, compared to the general population.

Adult↗