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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 631 records · Page 35Linked to original sources
PubMed1990

Anti-mitochondrial antibodies (anti-M7) in heart diseases recognize epitopes on bacterial and mammalian sarcosine dehydrogenase.

The anti-mitochondrial antibody (AMA) anti-M7 has been shown to occur exclusively in sera from patients with acute and chronic myocarditis. Applying different enzymes of the inner mitochondrial membrane to ELISA, anti-M7-positive sera reacted only with sarcosine dehydrogenase (SD) from Pseudomonas aeruginosa. Testing these sera in the Western blot against a commercially available SD as well as against SD prepared from rat liver mitochondria, a determinant at 42 kD and 90 kD, respectively, was visualized. Using submitochondrial particles (SMP) from bovine heart and rat liver another major determinant at 64 kD could be observed with both antigen fractions. Liver SMP also expressed the SD-related, 90-kD epitope. Sera from patients with other AMA-positive and AMA-negative autoimmune diseases were negative with these different determinants. The identity of the 64-kD epitope on heart and liver SMP as well as the 42-kD polypeptide of bacterial SD and the 90-kD epitope on mammalian SD was proven by absorption studies and by elution of antibodies from the antigen bound to the immobilon sheets after immunoblotting. The SD enzyme activity was not affected by anti-64-kD and anti-42-kD antibodies in vitro. It is concluded that anti-M7 antibodies may be stimulated by an antigen expressed on cardiocytes during an infection which shares epitopes with SD, an evolutionary highly conserved protein. SD-sensitized B cell clones could therefore be triggered by the M7-antigen which shows homology to SD.

Animals↗
PubMed1990

The Wisconsin epidemiologic study of diabetic retinopathy: an update.

Population-based epidemiologic data on the incidence and progression of diabetic retinopathy are important in developing approaches to preventing diabetic retinopathy, in medical counselling and rehabilitative services. The objectives of the Wisconsin Epidemiological Study of Diabetic Retinopathy were as follows: (1) to describe the prevalence, incidence, and progression of diabetic retinopathy and its component lesions, and to determine the incidence of visual impairment in a large population-based cohort; and (2) to determine the relationships between incidence and progression of diabetic retinopathy and risk factors in this cohort. Grading of stereoscopic fundus photographs was performed at the University of Wisconsin Fundus Photograph Reading Centre for photographs from both the baseline examination in 1980-1982 and follow-up examination four years later. Insulin-taking persons diagnosed to have diabetes before 30 years of age had the highest prevalence (71%), four-year incidence (59%) and progression to proliferative diabetic retinopathy (11%) while older-onset persons diagnosed to have diabetes at or after 30 years of age and not using insulin had the lowest prevalence (39%), incidence (34%) and progression to proliferative diabetic retinopathy (3%). These incidence data indicate that a substantial proportion of older onset diabetic people, a group previously thought to be protected from retinopathy, developed it during the four-year interval and underscores the need for careful ophthalmologic examination.

Adult↗
PubMed1990

Human trk oncogenes activated by point mutation, in-frame deletion, and duplication of the tyrosine kinase domain.

Malignant activation of the human trk proto-oncogene, a member of the tyrosine protein kinase receptor family, has been implicated in the development of certain human cancers, including colon and thyroid papillary carcinomas. trk oncogenes have also been identified in cultured cells transfected with various DNAs. In this study, we report the characterization of three in vitro-generated trk oncogenes, trk2, trk4, and trk5 (R. Oskam, F. Coulier, M. Ernst, D. Martin-Zanca, and M. Barbacid, Proc. Natl. Acad. Sci. USA 85:2964-2968, 1988), in an effort to understand the spectrum of mutational events that can activate the human trk gene. Nucleotide sequence analysis of cDNA clones of trk2 and trk4 revealed that these oncogenes were generated by a head-to-tail arrangement of two trk tyrosine protein kinase domains connected by a purine-rich region. These oncogenes code for cytoplasmic molecules of 67,000 (p67trk2) and 69,000 (p69trk4) daltons. In contrast, the product of the trk5 oncogene, gp95trk5, is a cell surface glycoprotein of 95,000 daltons. This oncogene was generated by a 153-base-pair in-frame deletion within sequences coding for the extracellular domain of the trk receptor. This activating deletion encompasses a triplet coding for one of the nine cysteine residues that the trk receptor shares with the product of the highly related trkB tyrosine protein kinase gene. Introduction of a single point mutation (TGT----AGT) in this codon resulted in a novel trk oncogene whose product, gp140S345, differs from the nontransforming trk proto-oncogene receptor in a single amino acid residue, Ser-345 instead of Cys-345. These results illustrate that multiple molecular mechanisms, including point mutation, internal deletion, and kinase domain duplication, can result in the malignant activation of the human trk proto-oncogene.

Amino Acid Sequence↗
PubMed1990

Mouse monoclonal antibody directed against hepatitis B virus X protein synthesized in Escherichia coli: detection of reactive antigen in liver cell carcinoma and chronic hepatitis.

A mouse monoclonal antibody directed against the protein product of the hepatitis B virus X open reading frame was prepared. This antibody was used to screen liver tissue sections from patients with chronic hepatitis (CH) and patients with liver cell carcinoma (LCC). Reactive antigen was detected by immunohistochemistry in about 30% auf the samples from CH patients and in about 80% of the samples from LCC patients regardless of whether tumor or surrounding nontumor tissue was analyzed. A predominant localization of the antigen in the cytoplasm was observed. In liver sections of CH patients the presence of HBx or HBx-related protein appeared to correlate with the presence of the classical viral antigens HBs- and/or HBcAg. A similar correlation was not found in liver or tumor tissue samples from LCC patients. The occurrence of X-monoclonal-antibody-reactive protein (Xarp) at a low frequency in liver tissue from patients without hepatitis B virus related disease suggests that Xarp in some cases may not be identical with the putative viral X antigen.

Animals↗
PubMed1990

Research, policy, and the National Health Service.

The National Health Service is a system designed to bring about a rational use and distribution of resources yet which largely ignores the contribution of the research community. With a relatively closed health policy arena, there are few customers for policy-oriented research. With responsibility for funding research concentrated at the center and responsibility for delivering services at the periphery, the research community finds itself in limbo. In comparison to both the U.S. and Canada, Britain therefore offers an example of research both underfinanced and undervalued. However, research has made some significant contributions in areas where there has been a perceived use for its findings to support service developments. And the changes now being introduced in Britain's NHS are likely to create a new market for research as the system adopts some North American ideas and becomes less consensual and more pluralistic.

Health Policy↗
PubMed1990

Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system.

We have examined the expression of the trkB gene, which encodes a member of the family of protein tyrosine kinase (TK) transmembrane receptors, during mouse embryogenesis using in situ hybridization and Northern analysis. Transcripts were first detected in the neuroepithelium and in the neural crest of 9.5 day embryos with regions of high expression in the neural folds and at the lateral neuroepithelium. However, during the process of cephalization and development of the peripheral nervous system, transcripts were detected in most neural tissues, including the brain, spinal cord, cranial and spinal ganglia, and along the pathways of axonal tracts extending peripherally. In the adult brain, expression continues in a complex pattern that is confined to specific regions or neuron types. The expression of trkB, a TK receptor, in early embryogenesis, and specifically in neural tissues, is consistent with the notion that this gene plays a role in the events that regulate the development of the nervous system.

Animals↗
PubMed1990

Wisconsin Epidemiologic Study of Diabetic Retinopathy. XII. Relationship of C-peptide and diabetic retinopathy.

The relationship between plasma C-peptide and the frequency and severity of diabetic retinopathy was examined in a population-based study in Wisconsin in 1984-1986. Individuals with younger- (n = 835) and older- (n = 940) onset diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. The highest frequencies and most severe retinopathy were found in insulin-using individuals with undetectable or low plasma C-peptide (less than 0.3 nM), whereas the lowest frequencies of retinopathy were found in older-onset overweight individuals not using insulin. In older-onset individuals using insulin, having no detectable C-peptide was significantly associated with the presence of proliferative retinopathy. Otherwise, within each group (younger onset using insulin, older onset using insulin, and older onset not using insulin), after controlling for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide and lower frequency of or less severe retinopathy.

C-Peptide↗
PubMed1990

Is insulinlike growth factor I associated with diabetic retinopathy?

Insulinlike growth factor I (IGF-I) is the mediator of the growth-promoting effects of growth hormone and has been suspected of playing a role in the pathogenesis of proliferative diabetic retinopathy (PDR). However, previous attempts to correlate IGF-I levels with PDR have yielded conflicting results. We determined IGF-I levels in a large population-based study of 682 early-onset (diagnosed before 30 yr of age) adult (greater than or equal to 18 yr old) insulin-taking diabetic subjects. PDR was found in 25% of the population. IGF-I levels were measured by radioimmunoassay. The mean serum level of IGF-I was 277 +/- 108 micrograms/L (mean +/- SD). Spearman rank correlations showed statistically significant negative correlations between IGF-I levels and age (r = -0.51, P less than 0.0001), duration of disease (r = -0.36, P less than 0.0001), and glycosylated hemoglobin (r = -0.09, P less than 0.05). There was a significant trend (P less than 0.001) toward decreasing risk of PDR with increasing IGF-I. However, after controlling for duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, and the presence of proteinuria and/or creatinine greater than or equal to 265 microM in a multiple logistic regression model, IGF-I was not significantly associated with PDR. These data suggest that IGF-I may not be a risk factor for the development of PDR.

Adolescent↗
PubMed1990

Effect of pregnancy on progression of diabetic retinopathy.

A prospective study was undertaken to determine the effect of pregnancy on diabetic retinopathy. Insulin-taking diabetic women were enrolled; one group was comprised of pregnant women, the other group was comprised of women who were not pregnant. Women were evaluated on referral and again in the postpartum period. The severity of diabetic retinopathy was based on grading of fundus photographs of seven standard photographic fields. The glycosylated hemoglobin, duration of diabetes, current age, diastolic blood pressure, number of past pregnancies, and current pregnancy status were evaluated as risk factors for progression of diabetic retinopathy. After adjusting for glycosylated hemoglobin, current pregnancy was significantly associated with progression (P less than 0.005, adjusted odds ratio 2.3). Diastolic blood pressure had a lesser effect on the probability of progression. The findings from this study indicate that pregnancy and level of glycemia are associated with progression of diabetic retinopathy.

Adult↗
PubMed1990

Is menarche associated with diabetic retinopathy?

The goal of this study was to evaluate the association between menarchal status and diabetic retinopathy. Diabetic retinopathy was present in 51 of 129 females; 7 were premenarchal, and 44 were postmenarchal. The range of severity of retinopathy was greater in the postmenarchal group. In multivariate analyses, duration of diabetes, menarchal status, and diastolic blood pressure were associated with the prevalence of diabetic retinopathy. After partitioning the duration of diabetes into years before and years after menarche, both were significant, but the number of years of diabetes after menarche was more strongly associated. At a 4-yr follow-up examination, more postmenarchal than premenarchal females had progression of their retinopathy (P = 0.06). These data suggest that stage of sexual development, as reflected by menarchal status, is associated with the presence and possibly the risk of progression of diabetic retinopathy.

Adolescent↗
PubMed1990

Weight gain associated with improved glycemic control in population-based sample of subjects with type I diabetes.

Previous studies have suggested that weight gain is an identifiable risk of efforts to lower blood glucose with intensive insulin therapy in type I (insulin-dependent) diabetic subjects. This study examined this relationship in a population-based sample of type I diabetic subjects participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Four hundred five adults (aged greater than or equal to 21 yr) with type I diabetes, who were diagnosed before age 30 yr, were studied from 1980 to 1982 and in a follow-up examination from 1984 to 1986. Weight gain over the 4-yr interval averaged 1.8 +/- 5.9 kg. Weight gain was significantly associated (r = -0.26, P less than 0.001) with improvements in glycosylated hemoglobin levels; the quartile of subjects with the greatest improvements in glycemic control gained 3.4 kg, whereas the quartile of subjects with the smallest improvements in glycemic control lost 0.6 kg. Weight gain was also correlated with increases in the number of shots of insulin per day and change in the treatment regimen from one type of insulin to a combination of short- and long-acting insulins. These results suggest that weight gain may be an adverse consequence of improved glycemic control. Efforts to better understand the mechanism explaining weight gain and to prevent weight gain are needed.

Adult↗
PubMed1990

Oral contraceptives in women with diabetes.

We evaluated the association of oral contraceptive use with the presence and severity of diabetic retinopathy, hypertension, and glycosylated hemoglobin in women of childbearing age who have diabetes. Neither current or past use nor number of years of use of oral contraceptives was associated with severity of retinopathy, hypertension, or current glycosylated hemoglobin. In conclusion, further study of various birth control methods in young women of childbearing age should be considered.

Adolescent↗
PubMed1990

Letter identification declines with increasing retinal eccentricity at the same rate for normal and dyslexic readers.

It has recently been claimed (Geiger & Lettvin, 1987; Perry, Dember, Warm, & Sacks, 1989) that the acuity/eccentricity function is flatter in dyslexics than in normal subjects, with dyslexics showing better performance in the periphery and worse performance at fixation. In these studies, all target letters were presented to the right of fixation, a procedural flaw inviting subjects to optimize performance by directing attention and/or gaze to the right of the designated fixation point. It is suggested that dyslexic and normal readers may differ in the degree to which they might adopt the optimal strategy in this situation. To overcome this problem, target letters were briefly presented at 16 randomly intermixed locations derived from the orthogonal combination of four eccentricities and four directions from fixation (above, below, right, left). The accuracy of letter identification declined with increasing eccentricity at the same rate for good and poor adult readers and dyslexic teenagers. This finding provides no support for the view that the acuity/eccentricity function might vary with and possibly cause differences in reading level.

Adult↗
PubMed1990

Ocular problems in older Americans with diabetes.

Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy from persons with diabetes of older onset whose average age was 65.4 years indicate that 9.9% of the men and 13.3% of the women had some degree of visual impairment, and 1.4% of men and 1.7% of women were legally blind (with an visual acuity of 20/200 or worse in the better eye). Poorer visual acuity was strongly associated with increasing duration of diabetes, but age was also an important factor, with rates of legal blindness increasing markedly after the seventh decade of life in groups of any duration. Conditions responsible for legal blindness were diabetic retinopathy or maculopathy, cataracts, glaucoma, and macular degeneration. Incidence of blindness 4 years after the initial evaluation was related to insulin use, younger age at examination, longer duration of diabetes, and more severe retinopathy at baseline. Worsening of vision was related to higher levels of glycosylated hemoglobin and the presence of macular edema on diabetic retinopathy at baseline. These data indicate that there is a high prevalence of ocular problems among people with diabetes of older onset. The practitioner should suggest to these patients that, soon after the diagnosis of diabetes, they have an ophthalmologic evaluation to determine whether asymptomatic problems are present. This action may lead to timely intervention to prevent loss of vision in some patients.

Age Factors↗
PubMed1990

Neuroretinal rim area in diabetes mellitus.

Neuroretinal rim area (NRA) may indicate the amount of viable optic nerve tissue. Changes in the NRA have been found to occur in people with glaucoma. We sought to determine whether there were effects of retinopathy and intraocular pressure (IOP) on NRA in eyes of people with diabetes. Measurements of optic discs and cups were taken from 35-mm stereoscopic slides taken with a Zeiss fundus camera. The photographs were taken during a population-based study. The difference between disc and cup area was taken to be the NRA. Median photographic NRA from 2085 right eyes was 10.5 mm2. In younger- and older-onset persons, NRA showed a tendency to increase with age and, inconsistently, with the severity of diabetic retinopathy; it decreased with increasing IOP in older-onset persons not taking insulin. The cohort was reevaluated 4 yr later. NRA increased in all groups. Measurements from photographs taken of a nondiabetic comparison group showed no change over the same interval. These data suggest that NRA may be affected by diabetes. This could be due to nerve swelling.

Adolescent↗
PubMed1990

Diabetic retinopathy: possible etiological role of hyperglycemia.

Retinopathy in young people with diabetes is uncommon before puberty. It does, however, appear during the adolescent years. Although the specific mechanisms that trigger the development of this complication are poorly understood, recent evidence suggests that hyperglycemia as reflected by elevated glycosylated hemoglobin is associated with the development and progression of diabetic retinopathy. Because the management of these patients relies heavily upon the compliance of the patient, education as to the nature, treatment and sequelae of diabetes and its complications are essential parts of the medical management of these patients.

Adolescent↗
PubMed1989

trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development.

We have isolated a novel member of the tyrosine protein kinase family of cell surface receptors. This gene, designated trkB, is highly related to the human trk proto-oncogene. At the amino acid level, their respective products share a 57% homology in their extracellular regions including 9 of the 11 cysteines present in the trk proto-oncogene. This homology increases to 88% within their respective tyrosine kinase catalytic domains. Both trk and trkB are equally distantly related to the other members of this gene family of receptors. A biologically active cDNA clone of trkB can direct the synthesis of gp145trkB, a glycoprotein of 145 kd of which only 93 kd correspond to its polypeptide backbone. In adult mice, trkB is preferentially expressed in brain tissue, although significant levels of trkB RNA have also been observed in lung, muscle and ovaries. In addition, trkB transcripts can be detected in mid and late gestation embryos. The trkB locus exhibits a complex pattern of transcription. At least seven RNA species ranging in size from approximately 9 kb to 2 kb have been identified in brain. However, only a subset of these transcripts appears to be expressed in the other tissues. In situ hybridization analysis of 14 and 18 day old mouse embryos indicates that trkB transcripts are localized in the central (CNS) and peripheral (PNS) nervous systems, including brain, spinal cord, spinal and cranial ganglia, paravertebral trunk of the sympathetic nervous system and various innervation pathways. These results suggest that trkB may code for a novel cell surface receptor involved in neurogenesis.

Amino Acid Sequence↗