Radiotherapy for severe, progressive thyroid-associated ophthalmopathy: long-term results with comparison of scoring systems.
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Adolescent↗
Biomedical subjects
W Becker
Publications and source records attributed to W Becker.
Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse.
New Zealand Obese (NZO) mice exhibit a polygenic syndrome of hyperphagia, obesity, hyperinsulinemia, and hyperglycemia similar to that observed in young diabetes mutant mice on the C57BLKS/J background (C57BLKS/J-Lepr(db)/Lepr(db)). Here we show that in NZO this syndrome is accompanied by a marked elevation of the leptin protein in adipose tissue and serum. The promoter region and the complementary DNA of the ob gene of NZO mice, including its 5'-untranslated region, are identical with the wild-type sequence (C57BL, BALB/c), except that the transcription start is located 5 bp upstream of the reported site. In contrast to C57BLKS/J+/+ and C57BL/6J-Lep(ob)/Lep(ob) mice, NZO mice failed to respond to recombinant leptin (7.2 microg/g) with a reduction of food intake. Leptin receptor messenger RNA as detected by PCR appears as abundant in hypothalamic tissue of NZO mice as in tissue from lean mice. Ten nucleotide polymorphisms are found in the complementary DNA of the leptin receptor, resulting in two conservative substitutions (V541I and V651I) in the extracellular part of the receptor and one nonconservative substitution (T1044I) in the intracellular domain between the presumed Jak and STAT binding boxes. However, these mutations are also present in the related lean New Zealand Black strain (body fat at 9 weeks: New Zealand Black, 6.2 +/- 1.3%; NZO, 17.0 +/- 1.7%). Thus, the polymorphic leptin receptor seems to play only a minor, if any, role in the obesity and hyperleptinemia of the NZO mouse. It is suggested that the main defect in NZO is located distal from the leptin receptor or at the level of leptin transport into the central nervous system.
Adipose Tissue↗
Photopenia in chronic vertebral osteomyelitis with technetium-99m-antigranulocyte antibody (BW 250/183).
UNLABELLED: Photon-deficient areas in 99mTc/111 in white blood cell (WBC) images for diagnosing vertebral osteomyelitis have been published often. This study retrospectively evaluated whether the use of 99mTc-labeled monoclonal antigranulocyte antibodies (BW 250/183) is superior to WBC and whether it offers higher specificity. METHODS: The study included 81 patients (46 men, 35 women; mean age 55 +/- 2 yr; from 1989 to 1995) with clinically suspected vertebral osteomyelitis who underwent scintigraphic imaging after intravenous injection of 555 MBq 99mTc-labeled monoclonal antigranulocyte antibodies. Forty patients suffered from osteomyelitis (20 men, 20 women; mean age 56 +/- 6 yr), 6 patients had metastases, 28 patients had spondylosis and disk herniation and 5 patients vertebral compression fractures. Diagnosis was not histologically verified in 2 patients. Planar imaging was performed at 4 and 24 hr postinjection. Histology of osteomyelitis was available in 30 patients, clinical follow-up in 10 patients. Visual uptake scores and quantitative uptake scores of the suspected areas were calculated. The results were compared to a semiquantitative histological score (high, medium, low grade) as well as to the scintigraphic scores. RESULTS: Scintigraphy showed photopenia in all patients with histologically proven vertebral osteomyelitis, independent of the grade of infection. A quantitative evaluation of 4 and 24 hr postinjection demonstrated a 58% increase of the uptake score in cases of histologically proven high-grade infections. This increase was seen predominantly in the thoracic spine but not in lumbar spine. All nonosseous paravertebral abscesses (n = 2) showed positive images and an increasing uptake over 24 hr. CONCLUSION: Paravertebral soft tissue infections can be differentiated excellently, whereas vertebral osteomyelitis, vertebral tumors or fractures can be localized, but no differentiation is possible.
Aged↗
[Importance of iterative reconstruction ISA in the diagnosis of liver hemangioma].
AIM: To evaluate whether the iterative reconstruction methodology ISA is superior to the standard technique of filtered back-projection. METHODS: In a retrospective study, we evaluated images of 39 patients with solitary or multiple liver tumors who underwent blood pool imaging in SPECT technique in order to prove or exclude the presence of hemangioma. RESULTS: Activity accumulations in accordance with the diagnosis of liver hemangioma could be visualized in 34 cases by the iterative, in 31 cases by the filtered back-projection methodology. As compared to filtered back-projection, the iteratively reconstructed lesions showed higher tumor-to-background ratios and were more easily distinguished from structures in their neighborhood. Furthermore, the iterative methodology resulted in a more homogeneous activity distribution in the liver, whereas the inhomogeneous "patchy" structure of the liver parenchyma in filtered back-projection provokes difficulties in the distinction from reconstruction artifacts. A clearer visualization of vessels and a better distinction between the right kidney and the liver was possible by the iterative algorithm, leading to advantages in the recognition of centrally or dorsally located lesions in the right hepatic lobe. CONCLUSION: These data indicate that the use of our iterative algorithm in performing liver blood pool imaging yields a higher sensitivity and a better diagnostic accuracy in diagnosing liver hemangioma.
Adult↗
The serine proteinase inhibitor antileukoproteinase specifically accumulates in normal but not in arthritic cartilage.
OBJECTIVE: To investigate whether the serine proteinase inhibitor antileukoproteinase (aLP) specifically accumulates in articular and extraarticular cartilage in normal and arthritic rats after intravenous (i.v.) injection. METHODS: [123I] or [125I] radiolabeled aLP and a control protein of comparable size were injected iv into normal rats or rats with chronic, antigen induced arthritis (AIA). Joint accumulation of the 2 proteins was followed by scintigraphy and organ tissue radioactivity was assessed by autoradiography and well counter measurements. Immunoprecipitation of aLP from articular cartilage was also performed and the content of charged molecules in normal and arthritic cartilage determined using toluidine blue staining. RESULTS: The accumulation of both radiolabeled aLP and control protein in the normal joint was clearly detectable by scintigraphy, with significant differences between the 2 proteins. In accordance with the scintigraphic data, direct tissue radioactivity measurements, immunoprecipitation, and autoradiography showed highly specific accumulation of radiolabeled aLP in articular and extraarticular cartilage of normal rats. The specific accumulation of aLP in articular cartilage was lost in rats with AIA in parallel with a loss of charged matrix molecules. CONCLUSION: I.v. injected serine protease inhibitor aLP specifically accumulates in articular and extraarticular cartilage of normal rats. This physiological pathway of cartilage accumulation, lost in proteoglycan depleted arthritic cartilage, may serve to maintain the local balance between proteinase function and inhibition.
Animals↗
Influences on food choice perceived to be important by nationally-representative samples of adults in the European Union.
OBJECTIVE: The purpose of this baseline survey was to obtain comparable data on perceived influences on food choice from EU member countries as the starting point for EU healthy eating promotion campaigns and programmes. DESIGN: A cross-sectional study in which quota-controlled, nationally-representative samples of approximately 1000 adults from each country completed a face-to-face interview-assisted questionnaire. SETTING: The survey was conducted between October 1995 and February 1996 in the 15 member states of the European Union. SUBJECTS: 14331 subjects (aged 15 y upwards) completed the questionnaire. Data were weighted by population size for each country and by sex, age and regional distribution within each member state. RESULTS: The five most important factors influencing consumers food choice were 'quality or freshness' (74%), 'price' (43%), 'taste' (38%), 'trying to eat healthy' (32%) and 'family preferences' (29%). Subjects in different categories (age, sex, education and employment status) selected different factors as having major influence on their food choice. Demographic factors seemed to have greater effects on perceived influences than culture (country): 'quality/freshness', 'price', 'trying to eat healthy', 'family preferences' seemed to be most important in women, 'taste' and 'habit' in males. Females and older and more educated subjects were more likely than other subjects to select 'trying to eat healthy' as having a major influence. 'Price' seemed most important in unemployed and retired subjects.
Adolescent↗
[Monoclonal antibodies show the way. Infections can now be traced faster and yet more certainly. Interview by Gabriele Henning].
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Antibodies, Monoclonal↗
[Oddi's sphincter dysfunction in "idiopathic" recurrent pancreatitis].
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Common Bile Duct Diseases↗
The rabbit ileal lipid-binding protein. Gene cloning and functional expression of the recombinant protein.
A bile-acid-binding protein of Mr 14000 has been previously identified by photoaffinity labeling in rabbit ileal brush border membrane vesicles [Kramer et al. (1993) J. Biol. Chem. 268, 18035-18046]. This peripheral membrane-associated protein was purified and identified as an ileal lipid-binding protein. It was further shown to be identical to the cytosolic 14-kDa bile-acid-binding protein from the same tissue. Starting with sequence information from tryptic fragments, we cloned and sequenced the gene and its transcript. It has four exons (123, 176, 90, 115 bp) and three introns (1372, 2291, 3137 bp) and a similar structure as the genes from other members of the fatty-acid-binding protein family. The deduced protein has 128 amino acid residues and a calculated molecular mass of 14404 Da. It exhibits high similarity to its human (83%), mouse (77%), rat (76%) and porcine (72%) counterparts. Furthermore, the recombinant protein was produced in Escherichia coli and shown to be identical to native protein from ileal tissue. Functionality of the recombinant protein was demonstrated by labeling with various photoaffinity derivatives of bile acids. Ranking of the photolabeling efficiency of these probes towards the recombinant protein was comparable to the respective ranking towards the native protein. Polyclonal antibodies that were raised in hens against the recombinant protein, specifically recognized the ileal lipid-binding protein in the brush border membrane and cytosol from rabbit ileum. In contrast, no labeling was observed with jejunal tissue. Our results suggest a specific role of the membrane-associated ileal lipid-binding protein for the process of ileal bile acid uptake.
Affinity Labels↗
Cloning of a novel member (ARL5) of the ARF-family of Ras-related GTPases.
A novel ras-related GTPase with a unique structure was cloned by PCR-amplification with degenerate primers and screening of a rat fat cell cDNA library. The deduced amino acid sequence of the cDNA comprises all 6 GTP binding motifs which are conserved in Ras-related GTPases. The sequence is similar to that of ADP-ribosylation factors (ARF), and shows several structural features typical for the ARF-family. Because its closest relative is the GTPase ARL1 (49% identical amino acids, 54% identical nucleotides within the coding region), the protein was designated ARL5 (ARF-like protein 5). Low amounts of mRNA were found in most rat tissues examined (heart, skeletal muscle, fat, liver, kidney, lung, spleen, intestine, testis, and thymus) with highest levels in brain, intestine, and thymus.
3T3 Cells↗
cDNA cloning and characterization of rat Clk3, a LAMMER kinase predominately expressed in testis.
A cDNA clone of a protein kinase with high similarity to the Clk (Cdc2-like kinases) subfamily was isolated from a rat brain library and characterized. Its deduced amino acid sequence exhibited a 99% identity with human Clk3 and was therefore designated rat Clk3. In addition to the protein kinase domain, the sequence (490 amino acids) comprises an N-terminal domain with a strikingly high portion of basic amino acids. A glutathione S-transferase fusion protein of Clk3 catalyzed autophosphorylation of the kinase but not phosphorylation of the exogenous substrates histone or casein. By Northern blot analysis of different rat tissues, mRNA of Clk3 was detected predominately in testis, suggesting that this kinase regulates a predominately testicular function.
Amino Acid Sequence↗
Alternative mRNA splicing of the novel GTPase Rab28 generates isoforms with different C-termini.
A novel ras-related gene (rab28) was identified by a PCR-based cloning approach and subsequent screening of rat fat cell and brain cDNA libraries. The deduced amino acid sequence of the cDNA is distantly related with members of the Rab family (31-33% sequence identity, mainly restricted to the six GTP-binding motifs). Cloning of the human homologue of Rab28 by a PCR-based approach revealed the existence of two isoforms (hRab28S, hRab28L) which differ only by a 95-bp insertion within the coding region. This insertion generates an alternative sequence of the 30 C-terminal amino acids of the protein. Both C-termini of the human homologues comprise farnesylation motifs, but differ strikingly in a stretch of 13 amino acids. By PCR, mRNA of hRab28S was detected in most tissues investigated (cortex, liver, kidney, skeletal muscle, adipose tissue, testis and urothelium), whereas hRab28L was predominant in testis. Recombinant Rab28 proteins showed specific binding of radiolabeled guanosine 5'-O-[gamma-thio]triphosphate and rapidly hydrolysed [alpha-32P]GTP; there was no difference in the GTP binding characteristics of the two isoforms hRab28S and hRab28L. It is suggested that the isoforms are derived from the same gene by alternative mRNA splicing, and that their functions differ in a parameter unrelated to its basic role as a GTPase.
Adipose Tissue↗
Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII.
The cDNA of a novel, ubiquitously expressed protein kinase (Dyrk) was cloned from a rat brain cDNA library. The deduced amino acid sequence (763 amino acids) contains a catalytic domain that is only distantly related to that of other mammalian protein kinases. Its closest relative is the protein kinase Mnb of Drosophila, which is presumably involved in postembryonic neurogenesis (85% identical amino acids within the catalytic domain). Outside the catalytic domain, the sequence comprises several striking structural features: a bipartite nuclear translocation signal, a tyrosine-rich hydrophilic motif flanking the nuclear localization signal, a PEST region, a repeat of 13 histidines, a repeat of 17 serine/threonine residues, and an alternatively spliced insertion of nine codons. A recombinant glutathione S-transferase-Dyrk fusion protein catalyzed autophosphorylation and histone phosphorylation on tyrosine and serine/threonine residues with an apparent Km of approximately 3.4 microM. Exchange of two tyrosine residues in the "activation loop" between subdomains VII and VIII for phenylalanine almost completely suppressed the activity and tyrosine autophosphorylation of Dyrk. Tyrosine autophosphorylation was also reduced by exchange of the tyrosine (Tyr-219) in a tyrosine phosphorylation consensus motif. The data suggest that Dyrk is a dual specificity protein kinase that is regulated by tyrosine phosphorylation in the activation loop and might be a component of a signaling pathway regulating nuclear functions.
Amino Acid Sequence↗
Molecular cloning and characterization of a novel mammalian protein kinase harboring a homology domain that defines a subfamily of serine/threonine kinases.
The cDNA of a novel protein kinase (referred to as SNRK) was isolated from a rat fat cell cDNA library with a probe generated by a cloning approach based on the polymerase chain reaction. The encoded polypeptide (746 amino acids, Mr=81627) contains all conserved subdomains characteristic of the protein serine/threonine kinase family. A recombinant fusion protein with glutathione S-transferase catalysed autophosphorylation as well as phosphorylation of histone, confirming that SNRK has indeed protein kinase activity. By Northern blot hybridization, a 5-kb mRNA was detected in brain, heart, fat cells, intestine, testis, ovary, adrenal gland and thymus. In 3T3-L1 cells. SNRK was specifically expressed in the differentiated, adipocyte-like phenotype, whereas its mRNA was not detected in fibroblasts. Sequence comparisons of its catalytic domain relate SNRK to the SNF1 family of protein kinases. The noncatalytic domain comprises several intriguing structural features, including a glycine-rich region, two PEST sequences, and a bipartite nuclear localization signal which is preceded by a stretch of ten consecutive acidic residues. This part of the sequence exhibits no extended similarity with other proteins. In addition, we detected a high degree of sequence similarity with other SNF1-related proteinases in a small region (30-35 amino acids) flanking the C-terminus of the catalytic domain. This domain (designated the SNH domain) appears to define the subfamily of SNF1-related protein kinases and might represent a new type of regulatory domain of protein kinases.
3T3 Cells↗
[High level of protein in Swedish food. A health risk?].
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Adolescent↗
Long-term and rapid regulation of ob mRNA levels in adipose tissue from normal (Sprague Dawley rats) and obese (db/db mice, fa/fa rats) rodents.
Increased levels of mRNA transcribed from the ob gene in adipose tissue of obese/hyperinsulinaemic Zucker (fa/fa) rats were detectable as early as 3 weeks after birth and continued to rise there after in parallel with body weight and serum insulin. mRNA levels of two other fat-specific genes (ARL4, FST44) were unaltered. In C57BL/KsJ db/db mice, ob mRNA levels also increased in parallel with body weight and serum insulin, and remained elevated in older animals when insulin levels decreased. In heterozygous control animals (db/+; fa/Fa), mRNA levels were comparable with those in the homozygous controls. In normal Sprague Dawley rats, the ob mRNA increased continuously, but more slowly than in Zucker rats, in parallel with body weight and insulin levels, and reached 15 times higher levels in the heaviest rats (400 g) studied. In Sprague Dawley rats made diabetic by an injection of streptozotocin, ob mRNA levels were reduced by approximately 50% after 24 h. A 24-h fasting period reduced the ob mRNA by 50% in lean Sprague Dawley and Fa/Fa, but not in obese Zucker fa/fa rats, although insulin levels were reduced in both groups. These data indicate that ob mRNA levels increase in both normal and obese rodents in parallel with age, body weight and serum insulin, reflecting an early (Zucker rats, db-mice) or slowly developing (Sprague Dawley rats) resistance to leptin and insulin. This increase does not appear to be mediated by the recently described rapid regulation of ob mRNA by insulin, but seems to be due to a different, long-term control mechanism which signals the size of the fat depots.
Adipose Tissue↗
Comparison of the effects of insulin, PDGF, interleukin-6, and interferon-gamma on glucose transport in 3T3-L1 cells: lack of cross-talk between tyrosine kinase receptors and JAK/STAT pathways.
The effects of insulin, insulin-like growth factor (IGF)-I, platelet-derived growth factor (PDGF), interleukin (IL)-6 and interferon-gamma on 2-deoxyglucose uptake and insulin receptor substrate (IRS)-1 phosphorylation were compared in 3T3-L1 cells at confluence and after differentiation to the adipocyte-like phenotype. Insulin and IGF-I produced the expected stimulation of glucose transport and tyrosine phosphorylation of IRS-1 in both confluent and differentiated cells. In contrast, IL-6 and interferon-gamma failed to stimulate glucose transport or IRS-1 phosphorylation, although a marked stimulation of the JAK/STAT pathways as shown by acute-phase response factor (APRF)/Stat3 or Stat1 activation was observed in fibroblasts (IL-6, interferon-gamma) and adipocytes (IL-6). PDGF-AA and PDGF-BB stimulated glucose transport in confluent, undifferentiated cells to the same extent as insulin (approximately six-fold stimulation), but produced only a small portion of the effect of insulin in differentiated cells. Similarly, mRNA levels and autophosphorylation of PDGF receptors were much lower in differentiated cells than in confluent fibroblasts. In contrast to insulin and IGF-I, PDGF failed to stimulate tyrosine phosphorylation of IRS-1. All effects of insulin, IGF-I, and PDGF on glucose transport were inhibited by Wortmannin; the half-maximally inhibiting concentration (IC50) of Wortmannin was increased by insulin. These data demonstrate distinct signalling potentials of the investigated receptors, and indicate that the IL-6 and interferon-gamma controlled JAK/STAT pathways lack the potential to stimulate glucose transport. IRS-1 does not appear to be involved in the PDGF receptor-mediated effects, whereas activation of phosphatidylinositol (PI) 3-kinase is a crucial event in all pathways leading to stimulation of glucose transport.
3T3 Cells↗
Distribution of the mRNA for protein phosphatase T in rat brain.
We have recently cloned a novel protein serine/threonine phosphatase (PPT) from rat mRNA which is predominantly expressed in the brain (Becker et al., J. Biol. Chem., 269 (1994) 22586-22592). In the present study, the regional distribution of PPT mRNA in the brain of adult rats was characterized by in situ hybridization histochemistry. PPT mRNA was found to be differentially expressed throughout the rat brain. Highest transcript levels were found in specific neuronal populations (hippocampus, piriform cortex, taenia tecta, medial habenula, granular cell layer of the cerebellum) as well as in the choroid plexus of the third and lateral ventricles. In contrast, expression levels in some brain areas, e.g., caudate putamen and white matter, were beyond the detection limit of in situ hybridization. The pattern of expression of PPT in rat brain differs from that of other protein serine/threonine phosphatases and may reflect specific functions of this phosphatase.
Animals↗