PubMed HealthSearch

Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 19 recordsLinked to original sources

The single-copy gene psbS codes for a phylogenetically intriguing 22 kDa polypeptide of photosystem II.

Recombinant phages that encode the complete precursor polypeptide for the 22 kDa polypeptide associated with photosystem II have been serologically selected from two lambda gt11 expression libraries made from polyadenylated RNA of spinach seedlings. The cDNAs hybridize to a 1.3 kb RNA species. The precursor protein is comprised of 274 amino acid residues and carries an N-terminal transit peptide of probably 69 amino acid residues. The mature protein exhibits four predicted transmembrane segments and is shown to be an integral component of photosystem II originating in a single-copy gene. The unique characteristics of this protein are: (i) it is the result of a gene-internal duplication of an ancestor with two membrane spans, (ii) a striking resemblance to LHC I/II, CP24/CP29 apoproteins, and ELIPs, although it does not bind chlorophyll and is present in cyanobacteria, and, as these proteins, (iii) it integrates into the membrane with uncleaved routing signals that display remarkable resemblance to patterns found in bipartite transit peptides.

Amino Acid Sequence

[The analysis of a severe side effect of a cartilage-protective agent by immunological studies].

After 18 intramuscular injections of Arumalon, a 62-year-old woman with degenerative hip-joint changes developed a severe illness with fever up to 39 degrees C, swellings of the finger, hand and knee joints, as well as a local skin rash and changes in the blood (WBC 1900/microliters, platelets 113,000/microliters), and increase in liver enzymes (GOT 83 U/l, GPT 93 U/l, lactate dehydrogenase 693 U/l). Arumalon, a glucosaminoglycan-peptide complex containing a watery extract of bovine cartilage and bone marrow, is used as a cartilage-protecting medication. The close temporal relationship between the injections and the symptoms suggested that the illness was drug-induced. This view was supported by a positive lymphocyte transformation test with Arumalon and its constituents, as well as by the demonstration of Arumalon-specific antibodies in the cultured lymphocyte fluid while the serum was negative for the antibodies. The illness took a protracted course. The patient became completely free of symptoms only after a year on a maintenance dose of prednisone, 15 mg daily. As a local inflammatory reaction was noted at the very start of the Arumalon injections, presensitization against the foreign proteins in Arumalon cannot be excluded. This is also supported by the fact that the specific lymphocyte proliferation was essentially unchanged even after nine months. This case illustrates the importance of careful assessment of increased and repeated manifestations of local reaction during Arumalon treatment, in particular in view of the risk of systemic side effects.

Acute Disease

[Immunological diagnosis in non-viral liver diseases].

The demonstration of defined autoantibody specificities in autoimmune liver diseases allows the differentiation between chronic inflammatory processes affecting mainly the parenchyma (autoimmune chronic active hepatitis) or the bile ducts (primary biliary cirrhosis, primary sclerosing cholangitis). Furthermore, overlap syndromes between the different autoimmune liver diseases as well as with other disorders including collagen disorders can be observed. The determination of antibody-profiles--especially in PBC--is helpful to evaluate the prognosis of the disease even in early stages.

Autoantibodies

Determination of the stereoconfiguration of natural pterins by chiral high-performance liquid chromatography.

The separation of D- and L-enantiomers of 6-(polyhydroxypropyl)pterins was obtained by ligand-exchange chromatography using a reversed-phase column at 12 degrees C with a mobile phase containing D-phenylalanine as the chiral modifier and Cu(II) as the metal ion. This allowed the determination of the stereoconfiguration of natural pterins from very small amounts of biological sample containing pterins in the picomole range (nanogram range). Fluorescence detection was used both to increase the sensitivity and to confirm the identification by on-line fluorescence spectroscopy and comparison with reference compounds. The stereoconfiguration of optically active pterins present in a bacterium (Escherichia coli), in a ciliate protozoan (Tetrahymena pyriformis), in an amoeba (Dictyostelium discoideum), and in mammals (human urine) was obtained and compared to earlier determinations. Incidental findings resulting from the application of this method were that human urinary monapterin and the major pterin of T. pyriformis were identified as a D-monapterin, which, until now, was not known as a natural pterin.

Adult

Secondary metabolites by chemical screening. 17. Nigericinol derivatives: synthesis, biological activities, and modeling studies.

The synthesis and the biological activity of C-1-reduced nigericin derivatives (nigericinols) are described and discussed. The dichloronigericinol 7 impressively demonstrated that the C-1 carboxylic acid moiety was not required for a distinct activity against bacteria and viruses. Based on the correlation between K+/H+ antiport activities and antibacterial activities it was deduced that the mode of action of the described nigericinols are related to their ionophoric properties. Molecular modeling studies showed that the efficiency of the nigericinols as ionophores correlates, qualitatively, with the probability of forming a cyclic structure, with the exception of 7.

Anti-Bacterial Agents

Lack of association between lipoprotein (a) concentrations and coronary heart disease mortality in diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Recently, considerable data have suggested that lipoprotein (a) [Lp(a)] is a strong independent risk factor for coronary heart disease. Since Lp(a) is increased in both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), this study examined the relationship of Lp(a) concentrations to coronary heart disease (CHD) mortality in the 4-year follow-up of the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Twenty-four older-onset subjects and 11 younger-onset subjects who died of CHD (cases) before the age of 70 were matched by age, gender, and type of diabetes to subjects who remained alive (controls). The distribution and mean levels of Lp(a) in the cases and controls were very similar, suggesting a lack of association between Lp(a) concentrations and CHD mortality. Although the number of subjects was small, caution should be used in extrapolating results on Lp(a) relationships in nondiabetic subjects to diabetic subjects.

Biomarkers

Clinical relevance of antibodies against serotonin and gangliosides in patients with primary fibromyalgia syndrome.

The fibromyalgia syndrome (FMS) is a non-articular rheumatic disorder associated with disturbances in serotonin metabolism. In order to evaluate whether patients with FMS suffer from an autoimmune disorder, we tested sera from 50 clinically well-defined FMS patients for non-organ-specific and organ-specific antibodies by enzyme-linked immunosorbent assay and immunofluorescence test. Common antibodies against nuclei, mitochondria, and microsomes were not increased in these patients compared to healthy controls. However, 74% had antibodies against serotonin and gangliosides. The clinical and diagnostic relevance of these antibodies is supported by the absence of anti-serotonin antibodies in other rheumatic disorders such as rheumatoid arthritis, polymyalgia rheumatica, and collagen diseases. These antibodies may belong to the group of antireceptor antibodies, considering the fact that gangliosides are an important component of the serotonin receptor. It remains to be determined whether these antibodies are of pathogenetic relevance, interfering with serotonin binding and thereby inducing symptoms associated with FMS.

Adult

The trkB tyrosine protein kinase is a receptor for neurotrophin-4.

Neurotrophin-4 is a novel member of the nerve growth factor family of neurotrophins recently isolated from Xenopus and viper DNA. We now report that the Xenopus NT-4 protein (XNT-4) can mediate some of its biological properties through gp145trkB, a murine tyrosine protein kinase previously identified as a primary receptor for the related brain-derived neurotrophic factor (BDNF). XNT-4 displaces 125I-labeled BDNF from binding to cells expressing gp145trkB receptors, induces their rapid phosphorylation on tyrosine residues, and causes the morphologic transformation of NIH 3T3 cells when coexpressed with gp145trkB. Moreover, XNT-4 induces the differentiation of PC12 cells into sympathetic-like neurons only if they ectopically express gp145trkB receptors. None of these biochemical or biological effects could be observed when XNT-4 was added to cells expressing the related receptors. Replacement of one of the extracellular cysteines (Cys-345) of gp145trkB by a serine residue prevents its activation by XNT-4 but not by BDNF. Therefore, XNT-4 and BDNF may interact with at least partially distinct domains within the gp145trkB receptor.

Adrenal Gland Neoplasms

Change in glycemia in a four-year interval in younger-onset insulin-dependent diabetes.

Hyperglycemia is an important risk factor for the development of retinopathy and nephropathy in people with diabetes mellitus. There are few population-based data on changes in glycemia over time. The purpose of this study was to examine changes in glycemia, as measured by glycosylated hemoglobin in 1980 to 1982 and in 1984 to 1986, in a large population-based study of people who were diagnosed to have diabetes before the age of 30 years and who used insulin (n = 697). Glycosylated hemoglobin was measured by a microcolumn technique at both examinations. There was a significant (P < .001) fall in the mean glycosylated hemoglobin from 10.8 to 10.1% over the 4-year interval of the study. In contrast, there was no change in the glycosylated hemoglobin (6.2%) in a similarly aged nondiabetic comparison group over the same period. The decrease in mean glycosylated hemoglobin over the 4-year period in the diabetic group was associated with several characteristics of diabetes management. These include changes in the insulin regimen (going from intermediate- or long-acting insulin only to combinations with short-acting insulin), an increase in the number of doses of insulin per day, and a higher frequency of self-monitoring of blood glucose level. It was also associated with an increased number of reported insulin reactions. These data suggest that recent changes in treatment and management of diabetes may be related to a significant decrease in glycemia.

Adult

Detection of drusen and early signs of age-related maculopathy using a nonmydriatic camera and a standard fundus camera.

PURPOSE: The study was designed to compare the severity of age-related maculopathy as graded from photographs taken using three different techniques. METHODS: Two methods of nonstereoscopic 45 degrees retinal photography of the macula (through a nonpharmacologically dilated pupil and through a pharmacologically dilated pupil) were compared with results from standard 30 degrees stereoscopic photographs in 112 subjects. Corresponding photographic fields were graded by a masked grader for the presence of any drusen, soft drusen, retinal pigment epithelial degeneration, increased retinal pigmentation, and early and late age-related maculopathy. RESULTS: Exact agreement between gradings of the 45 degrees photographs taken through nonpharmacologically dilated pupils and 30 degrees photographs taken through dilated pupils was 75% for any drusen, 72% for soft drusen, 72% for retinal pigment epithelial degeneration, 74% for increased retinal pigment, 85% for pure geographic atrophy, and 89% for exudative macular degeneration. The kappa scores varied from 0.33 for geographic atrophy to 0.60 for exudative macular degeneration. Slightly higher rates of agreement between gradings were found after dilation. CONCLUSION: These data suggest that 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, should be considered for detection of age-related maculopathy in situations where the pupils cannot be pharmacologically dilated and retinal specialists are not available to examine the fundus.

Fundus Oculi

Diabetes, hyperglycemia, and age-related maculopathy. The Beaver Dam Eye Study.

PURPOSE: The purpose of this study is to examine the association among hyperglycemia, diabetes status, and age-related maculopathy in a population-based study of people between the ages of 43 and 86 years who lived in Beaver Dam, Wisconsin between 1988 and 1990. METHODS: Age-related maculopathy was determined from stereoscopic fundus photographs. RESULTS: In the nondiabetic group (n = 4291), no relationship was found between glycosylated hemoglobin and any signs of age-related maculopathy. Diabetes status was not associated with early age-related maculopathy. People 75 years of age or older with diabetes (n = 85) had a higher frequency of exudative macular degeneration (9.4%) than those without (4.7%) but had similar frequencies of pure geographic atrophy (3.8% for those with diabetes and 3.4% for those without diabetes). The relative risk of exudative macular degeneration in men with diabetes who were 75 years of age or older compared with those who did not have diabetes was 10.2 (95% confidence interval [CI]: 2.4, 43.7); for females it was 1.1 (95% CI: 0.4, 3.0). CONCLUSION: These data suggest that diabetes is not related to early age-related maculopathy or geographic atrophy. The relationship of exudative macular degeneration to diabetes in older men, but not women, may be a result of chance. Further longitudinal study of this observation is needed.

Adult

Prevalence of glaucoma. The Beaver Dam Eye Study.

PURPOSE: The purpose of this study is to determine the prevalence of glaucoma in the population participating in the Beaver Dam Eye Study (n = 4926). METHODS: All subjects were examined according to standard protocols, which included applanation tonometry, examination of the anterior chamber, perimetry, grading of fundus photographs of the optic disc, and a medical history interview. Visual field, cup-to-disc ratio, and intraocular pressure (IOP) criteria were used to define the presence of open-angle glaucoma. Definite open-angle glaucoma was defined by the presence of any two or all three of the following: abnormal visual field, large or asymmetric cup-to-disc ratio, high IOP. RESULTS: The overall prevalence of definite open-angle glaucoma was 2.1%. The prevalence increased with age from 0.9% in people 43 to 54 years of age to 4.7% in people 75 years of age or older. There was no significant effect of sex after adjusting for age. Of the 104 cases of definite open-angle glaucoma, 33 had IOPs less than 22 mmHg in the involved eye. Hemorrhage on the optic disc was found in 46 people; 2 of these had glaucoma. Narrow-angle glaucoma was rare, with two definite cases in the population. CONCLUSION: The prevalence of open-angle glaucoma in Beaver Dam is similar to that in other white populations. Findings from this study re-emphasize the notion that estimates of glaucoma prevalence should be based on assessing multiple risk indicators.

Adult

Prevalence of age-related maculopathy. The Beaver Dam Eye Study.

PURPOSE: The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study. METHODS: The presence and severity of various characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: One or more drusen were present in the macular area of at least 1 eye in 95.5% of the population. People 75 years of age or older had significantly higher frequencies (P less than 0.01) of the following characteristics than people 43 to 54 years of age: larger sized drusen (greater than or equal to 125 microns, 24.0% versus 1.9%), soft indistinct drusen (23.0% versus 2.1%), retinal pigment abnormalities (26.6% versus 7.3%), exudative macular degeneration (5.2% versus 0.1%), and geographic atrophy (2.0% versus 0%). CONCLUSION: These data indicate signs of age-related maculopathy are common in people 75 years of age or older and may pose a substantial public health problem.

Adult