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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 397 records · Page 22Linked to original sources

Hypertension and lens opacities from the Beaver Dam Eye Study.

PURPOSE: To examine the relationship between hypertension and lens opacities, and the use of antihypertensive agents. METHODS: A total of 4,926 adults, 43 to 84 years of age, living in Beaver Dam, Wisconsin, at the time of a private census, were invited to participate in a study that included a medical interview and an examination that included ocular photography. All study procedures and photographic grading were done according to standard protocols. RESULTS: According to analysis with the Liang-Zeger multiple logistic regression model, people with hypertension were more likely to have posterior subcapsular opacities than people without hypertension (odds ratio, 1.39; 95% confidence interval, 1.05, 1.84). Specific medications for hypertension did not meaningfully affect the risk. Hypertension was associated with increased risk in both those with and without diabetes. CONCLUSIONS: Hypertension is associated with increased risk of posterior subcapsular opacities. The pathophysiologic mechanisms that may explain the relationship are unknown. Incidence data will give a better indication of temporal relationship between hypertension, medications to lower blood pressure, and lens opacities.

Adult↗

Incidence of cataract surgery in the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

PURPOSE: We studied the incidence of cataract extraction in people with diabetes of long duration to determine which factors are associated with higher risk of surgery. METHODS: We recruited a probability sample of all persons receiving care for diabetes in an 11-county area of southern Wisconsin for a prevalence study of diabetic retinopathy. All 2,366 subjects were examined between September 1980 and June 1982. During the slit-lamp examinations, presence of the lens, whether natural or prosthetic, was noted. The subjects were reexamined four and ten years after the initial prevalence study. Occurrence of cataract extraction in the interim between examinations was recorded. RESULTS: In the younger-onset group there was an 8.3% (95% confidence interval, 6.2%, 10.8%) cumulative incidence, and in the older-onset group there was a 24.9% (95% confidence interval, 21.3%, 28.5%) cumulative incidence of cataract surgery in the ten-year interval. Characteristics statistically significantly related to cataract surgery in the younger-onset group in multivariate analysis were age, severity of diabetic retinopathy, and proteinuria. In the older-onset group, age and use of insulin were associated with increased risk. CONCLUSIONS: These data indicate that cataract surgery is a relatively frequent occurrence in people with diabetes. This finding needs to be considered to plan for health care for people with diabetes.

Adolescent↗

Alcohol use and age-related maculopathy in the Beaver Dam Eye Study.

PURPOSE: Because there are few epidemiologic data examining the relationship between alcohol use and age-related maculopathy, we investigated this relationship via the population-based Beaver Dam Eye Study. METHODS: Alcohol consumption in the year before examination was determined by a standardized questionnaire. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs. RESULTS: While controlling for other factors, consumption of beer in the past year was related to greater odds of increased retinal pigment degeneration (odds ratio, 1.13; 95% confidence interval, 1.02, 1.25) and exudative macular degeneration (odds ratio, 1.41; 95% confidence interval, 1.05, 1.88). Current consumption of neither wine nor liquor was related to early or late age-related maculopathy. CONCLUSIONS: These data suggest a relationship between beer consumption and greater odds of having exudative macular degeneration. Whether this is from a toxic effect specific to beer or from other unknown confounders cannot be determined.

Adult↗

Physical activity and the risk of progression of retinopathy or the development of proliferative retinopathy.

OBJECTIVE: To determine if physical activity is associated with the 6-year risk of progression of retinopathy or incidence of proliferative retinopathy. RESEARCH DESIGN AND METHODS: Participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy who were free of proliferative retinopathy at the 1984 to 1986 examination and in whom diabetes had developed when younger than 30 years of age (n = 606) were evaluated after a 6-year follow-up period. Stereoscopic fundus photographs were graded for the presence and severity of retinopathy. Physical activity was assessed by a questionnaire. RESULTS: There were no associations between any of the measures of physical activity and two-step progression of retinopathy or the development of proliferative retinopathy during the follow-up period. No associations were seen even for those with more severe preproliferative retinopathy at the 1984 to 1986 examination or for the subset engaging in strenuous activity such as weight lifting. CONCLUSIONS: Physical activity does not appear to be associated with either an increased or decreased risk of progression of retinopathy or the development of proliferative retinopathy in people with insulin-dependent diabetes mellitus.

Adult↗

Racial/ethnic differences in age-related maculopathy. Third National Health and Nutrition Examination Survey.

PURPOSE: To investigate the prevalence of age-related maculopathy in three racial/ethnic groups, non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. METHODS: People 40 years of age or older who participated in a nationally representative population-based sample of the Third National Health and Nutrition Examination Survey were examined from 1988 to 1991. Age-related maculopathy was determined by grading of fundus photographs using a standardized protocol for a sample of 4007 persons. RESULTS: The prevalence of any age-related maculopathy in the civilian noninstitutionalized United States population including those 40 years of age or older was 9.2% as estimated from the sample. Prevalence was higher in non-Hispanic whites (9.3%) compared with non-Hispanic blacks (7.4%) and Mexican Americans (7.1%). Before 60 years of age, Mexican Americans (odds ratio [OR], 1.53; 95% confidence interval [CI] 1.0-2.35) and non-Hispanic blacks (OR, 1.59; 95% CI, 0.86-2.95) had a greater chance of having any maculopathy than non-Hispanic whites; thereafter, Mexican Americans (OR, 0.63; 95% CI, 0.44-0.90) and non-Hispanic blacks (OR, 0.50; 95% CI, 0.37-0.68) had a lesser chance than non-Hispanic whites. CONCLUSION: These survey data indicate that age-related maculopathy is prevalent in all groups studied. Differences among the racial/ethnic groups vary by age and sex.

Adult↗

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema.

BACKGROUND: As part of a population-based study of diabetes mellitus, the incidence of macular edema over a 10-year period and its relation to various risk factors are examined. METHODS: There were 891 younger-onset people with a diagnosis of having had diabetes before 30 years of age who were taking insulin at baseline examination and 987 older-onset people with a diagnosis of having had diabetes at 30 years of age or older who participated in baseline and 4-year examinations. Of these, 765 younger-onset and 533 older-onset people also participated in a 10-year examination. The presence of macular edema at baseline and follow-up examinations was determined from gradings of stereoscopic fundus photographs. RESULTS: The incidence of macular edema over the 10-year period was 20.1% in the younger-onset group, 25.4% in the older-onset group taking insulin, and 13.9% in the older-onset group not taking insulin. The incidence of macular edema over the 10-year period was associated with higher levels of glycosylated hemoglobin and more severe retinopathy in both younger- and older-onset groups, and with being female and increased diastolic blood pressure in the older-onset group. CONCLUSIONS: These data suggest a relatively high incidence of macular edema. The authors' data also suggest that a reduction in hyperglycemia may result in a beneficial decrease in the incidence of macular edema.

Adult↗

Activation of a murine autoreactive B cell by immunization with human recombinant autoantigen La/SS-B: characterization of the autoepitope.

Immunization of Balb/c mice with a homogeneously purified recombinant human La/SS-B protein resulted in activation of an autoreactive B cell secreting a novel monoclonal anti-La antibody termed La4B6. La4B6 reacted with La protein from a variety of sources including human, bovine, rat and mouse. ATP blocked the binding of La4B6 to recombinant La protein. The human epitope was identified as consisting of the amino acid sequence SKGRRFKGKGKGN, which includes the proposed ATP-binding site of the La protein. In the human and bovine La protein, the epitope exists as a continuous amino acid sequence. In rat and mouse the epitope was found to consist of the amino acid sequence SKG interrupted by a species-specific insert of 16 amino acids, and followed by the second half of the epitope, the amino acid sequence RRFKGKGKGN. Our data suggest that in the case of the rat and mouse La proteins the two separated parts of the epitope are able to form a conformational epitope which looks similar to the continuous human epitope.

3T3 Cells↗

Species identification and antibiotic susceptibility of enterococci isolated from clinical specimens of hospitalized patients.

Over a 4-month period, a total of 315 enterococci were isolated from various clinical specimens of hospitalized patients. By applying an array of biochemical tests, all strains were accurately identified to the species level, and their susceptibilities to clinically relevant antibiotics were determined by a standardized agar dilution technique. E. faecalis and E. faecium accounted for 87.3% and 9.2% of isolates, respectively. E. avium (1%), E. gallinarum (1%), E. durans (0.6%), E. hirae (0.6%), and E. casseliflavus (0.3%) isolates were also identified. Eleven strains of E. faecium and 1 E. hirae isolate were resistant to ampicillin, but none of the isolates produced beta-lactamase. Twenty-three E. faecium and 3 E. faecalis strains as well as 1 E. hirae isolate revealed imipenem resistance. A total of 25.4% enterococci (60 E. faecalis and 19 E. faecium isolates, 1 E. hirae strain) were erythromycin-resistant. Twelve strains (11 E. faecium and 1 E. avium) exhibited ciprofloxacin resistance. High-level resistance to streptomycin was found in 58 (21.1%) E. faecalis, 9 (31%) E. faecium, and both E. hirae strains, whereas high-level gentamicin resistance (HLGR) was exclusively seen in the species E. faecalis (11.6% of isolates belonging to this species). A simple agar screening test containing 500 micrograms of gentamicin per ml proved to be highly reliable for detection of HLGR. The structural gene coding for HLGR was specifically amplified by the polymerase chain reaction in all isolates showing this resistance trait. Moreover, the gene was specifically detected by a nonradioactively labelled oligonucleotide probe in colony blot hybridization assays, indicating the potential application of these molecular approaches as a diagnostic tool.

Ampicillin↗

Countertransference issues in group psychotherapy with HIV-positive and AIDS patients.

Mental health professionals are increasingly aware of the special difficulties encountered by therapists working with HIV-positive and AIDS patients. In this report, countertransference issues experienced by therapists leading a psychotherapy group for heterosexual, drug-using HIV-positive and AIDS patients in an inner city hospital are explored. Countertransference is discussed under the headings of helplessness, death anxiety, and anger.

Acquired Immunodeficiency Syndrome↗

Rationing in the NHS: the dance of the seven veils-in reverse.

The 1991 reforms of the National Health Service set up the expectation that rationing would in future be explicit instead of, as in the past, implicit. This has not happened. Research carried out at the University of Bath shows that very few health authorities are rationing by exclusion on the Oregon model. Instead, both central Government and health authorities are continuing to diffuse responsibility among the medical profession. This paper analyses the reasons why. Rationing by delay and dilution are more significant-as well as less visible-than rationing by exclusion. And it is the medical profession which controls the flow of patients through waiting lists and the way in which resources are used during treatment. Similarly, it is in the self-interest of both central Government and health authorities that their resource decisions should continue to be disguised behind the veils of clinical discretion. Despite pressures for greater transparency, Britain's opaque form of rationing may therefore survive.

Forecasting↗

Association of dietary and life-style factors with sex hormones in postmenopausal women.

We examined the relations between endogenous sex hormones and alcohol intake, dietary constituents, and life-style factors in a population-based sample of 253 postmenopausal women not using replacement hormones. Estrone, dihydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), and free and total testosterone were measured in serum. Age and years since menopause were negatively associated with dihydroepiandrosterone sulfate and positively associated with sex hormone-binding globulin levels. Higher relative weight was strongly and negatively associated with sex hormone-binding globulin. Other factors were only very weakly associated with sex hormones. Since, except for weight, few potentially modifiable factors appear to influence these hormone profiles, it may be that behaviors earlier in life mediate hormone levels and subsequent disease risk.

Adult↗

Mitochondrial antigen/antibody systems in primary biliary cirrhosis: revisited.

Methods for the evaluation of the four antimitochondrial antibody subtypes in primary biliary cirrhosis - anti-M2, -M4, -M8, -M9 - are described. The importance of the application of different preparations for the demonstration of complement fixing antibodies and the detection of antibodies by ELISA or Western blotting is emphasized. Complement fixing antigens can be prepared by discontinuous isopynic sucrose density gradient centrifugation using mitochondrial subfractions derived with from beef heart (M2), rat liver (M4), or pig kidney (M8). Anti-M9 antibodies do not fix complement. For ELISA, the pyruvate dehydrogenase or the ATPase-associated antigen fraction (M2), the sulfite oxidase fraction (M4), and the chromatographically purified M8-fraction should be used. The same antigen fractions are suitable for Western blotting, but anti-M4 and anti-M8 by ELISA and Western blotting a purified fraction prepared from rat liver has to be applied. Correlating antimitochondrial antibody-subtypes with clinical condition and the natural course, there is convincing evidence that especially the presence of complement fixing antibodies against the subtypes M2, M4, and M8 is a reliable indicator for a more active course. Patients expressing only anti-M9 (without anti-M2) have biochemically all the typical features also found in classical anti-M2 positive primary biliary cirrhosis patients, but seem not to advance to late stages. Since these antimitochondrial antibody-subtypes are present even in very early stages stages without changing their pattern during the course, antimitochondrial antibody-profiles can also be taken as early prognostic parameters. The evaluation of the immunological activity by antimitochondrial antibody-subtype testing may further facilitate the decision whether therapy with ursodeoxycholic acid should be combined with steroids and/or immunosuppressive agents. The role of mitochondrial autoantigens in the induction of this chronic destructive bile duct process is also discussed. The concept is put forward that not bile ducts but naive(?) B-cells expose the different mitochondrial antigens, thereby stimulating autoreactive T-cells to provide a second signal for antibody production. The degree of breakage of tolerance to the different mitochondrial epitopes may be one crucial factor which determines the diversity of antimitochondrial antibody-subtypes in patients with primary biliary cirrhosis.

Animals↗

ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites.

The Eph receptors are the largest known family of receptor tyrosine kinases and are notable for distinctive expression patterns in the nervous system and in early vertebrate development. However, all were identified as orphan receptors, and only recently have there been descriptions of a corresponding family of ligands. We describe here a new member of the Eph ligand family, designated ELF-2 (Eph ligand family 2). The cDNA sequence for mouse ELF-2 indicates that it is a transmembrane ligand. It shows closest homology to the other known transmembrane ligand in the family, ELK-L/LERK-2/Cek5-L, with 57% identity in the extracellular domain. There is also striking homology in the cytoplasmic domain, including complete identity of the last 33 amino acids, suggesting intracellular interactions. On cell surfaces, and in a cell-free system, ELF-2 binds to three closely related Eph family receptors, Elk, Cek10 (apparent ortholog of Sek-4 and HEK2), and Cek5 (apparent ortholog of Nuk/Sek-3), all with dissociation constants of approximately 1 nM. In situ hybridization of mouse embryos shows ELF-2 RNA expression in a segmental pattern in the hindbrain region and the segmenting mesoderm. Comparable patterns have been described for Eph family receptors, including Sek-4 and Nuk/Sek-3, suggesting roles for ELF-2 in patterning these regions of the embryo.

Amino Acid Sequence↗

Insulin-like growth factor-I is related to glycemic control in children and adolescents with newly diagnosed insulin-dependent diabetes.

To address the relationship of insulin-like growth factor-I (IGF-I) to diabetes control, we determined IGF-I levels in 137 subjects age 17 yr and younger with recently diagnosed insulin-dependent diabetes mellitus in a population-based cohort study between 3 and 11 months after diagnosis (mean 4.9 months). Initial determinations of IGF-I, 24-h urine C-peptide and microalbuminuria, age, sex, height, weight, body mass index, pubertal stage, and glycosylated hemoglobin (GHb) were obtained. IGF-I levels ranged from 11-439 ng/mL, were strongly related to age (r = 0.74, P < 0.001), and were higher in females than males at any given age (P < 0.01). IGF-I was inversely related to GHb (partial r = -0.43, P < 0.001) after adjustment for sex and age. The relationship between IGF-I and GHb did not change between age groups (< 6, 6-9, > or = 10 yr of age; P = 0.50), and it did not change between prepubertal and pubertal subjects (P = 0.95). IGF-I was not related to 24-h urine C-peptide or microalbuminuria. These results suggest that lower IGF-I levels are related to poorer metabolic control of diabetes in the period following insulin-dependent diabetes mellitus diagnosis in all young persons regardless of age or pubertal status.

Adolescent↗

Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets.

The trkB and trkC genes are expressed during the formation of the vestibular and auditory system. To elucidate the function of trkB and trkC during this process, we have analysed mice carrying a germline mutation in the tyrosine kinase catalytic domain of these genes. Neuroanatomical analysis of homozygous mutant mice revealed neuronal deficiencies in the vestibular and cochlear ganglia. In trkB (-/-) animals vestibular neurons and a subset of cochlear neurons responsible for the innervation of outer hair cells were drastically reduced. The peripheral targets of the respective neurons showed severe innervation defects. A comparative analysis of ganglia from trkC (-/-) mutants revealed a moderate reduction of vestibular neurons and a specific loss of cochlear neurons innervating inner hair cells. No nerve fibres were detected in the sensory epithelium containing inner hair cells. A developmental study of trkB (-/-) and trkC (-/-) mice showed that some vestibular and cochlear fibres initially reached their peripheral targets but failed to maintain innervation and degenerated. TrkB and TrkC receptors are therefore required for the survival of specific neuronal populations and the maintenance of target innervation in the peripheral sensory system of the inner ear.

Animals↗

Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons.

We have generated double mutant mice deficient in pairs of two different Trk receptors and have analysed the effects on survival and differentiation of dorsal root ganglion (DRG), inner ear cochlear and vestibular sensory neurons. In most combinations of mutant trk alleles, the defects observed in double compared to single mutant mice were additive. However, double homozygous trkA-/-;trkB-/- DRG and trkB-/-;trkC-/- vestibular neurons showed the same degree of survival as single trkA-/- and trkB-/- mice, respectively, suggesting that those neurons required both Trk signaling pathways for survival. In situ hybridisation analysis of DRG neurons of double mutant mice revealed differential expression of excitatory neuropeptides. Whereas calcitonin-gene-related peptide expression correlated with the trkA phenotype, substance P expression was detected in all combinations of double mutant mice. In the inner ear, TrkB- and TrkC-dependent neurons were shown to at least partially depend on each other for survival, most likely indirectly due to abnormal development of their common targets. This effect was not observed in DRGs, where neurons depending on different Trk receptors generally innervate different targets.

Animals↗

Does insulin-like growth factor I predict incidence and progression of diabetic retinopathy?

We evaluated the relationship of insulin-like growth factor (IGF)-I to incidence and progression of diabetic retinopathy over a 6-year interval in a large population-based study of diabetes in southern Wisconsin. Participants included people with younger-onset diabetes (n = 66 adolescents, n = 661 adults > or = 18 years of age) and older-onset diabetes (n = 285 for those using insulin, n = 248 for those not using insulin). Fundus photographs were graded in a masked fashion using standardized protocols to determine the severity of retinopathy in each eye. Serum IGF-I levels were measured during 1984-1986 using a double-antibody radioimmunoassay. Mean IGF-I was highest in adolescents (499.1 micrograms/l), lower in younger-onset adult (280.1 micrograms/l), and lowest in the older-onset group (205.7 and 221.2 micrograms/l for older-onset group using insulin and not using insulin, respectively). The incidence of retinopathy was not significantly higher in people with higher IGF-I levels in any group. The odds of developing diabetic retinopathy in 6 years for each 10 micrograms/l increase in IGF-I after controlling for age, glycosylated hemoglobin, and duration of diabetes at baseline was 1.21 (95% confidence interval [CI] 0.95-1.54) for adolescents; 1.00 (95% CI 0.93-1.08) for younger-onset adults; 0.93 (95% CI 0.85-1.02) for the older-onset group using insulin; and 0.99 (95% CI 0.95-1.04) for the older-onset group not using insulin. In summary, IGF-I was not associated with 6-year incidence or progression of diabetic retinopathy in any of the groups.

Adolescent↗