Insulin-like growth factors (IGFs) and IGF-binding proteins in diabetic kidney disease.
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Biomedical subjects
Publications and source records attributed to O Weiss.
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Deletion of the amino-terminal 17 residues from human ADP-ribosylation factor (ARF) resulted in a protein ([delta 1-17]mARF1p) devoid of ARF activity but which retained the ability to bind guanine nucleotides with high affinity. Unlike the wild type, the binding of guanine nucleotides to this deletion mutant was found to be independent of added phospholipids. A chimeric protein was produced, consisting of 10% (the amino-terminal 17 amino acids) human ARF1p and 90% ARL1p, an ARF-like protein (55% identical protein sequence) from Drosophila. This chimera was found to have ARF activity, lacking in the parental ARL1 protein. Thus, the amino terminus of ARF1p was shown to be a critical component of ARF activity. A synthetic peptide, derived from the amino terminus of ARF1p, has no ARF activity. Rather, the peptide was found to be a specific inhibitor of ARF activities. This peptide was also found to be a potent and specific inhibitor of both an in vitro intra-Golgi transport assay and the guanosine 5'-3-O-(thio)triphosphate-stimulated accumulation of coated vesicles and buds from Golgi preparations. We conclude that ARF is required for the budding of coated vesicles from the Golgi stacks and serves a regulatory role in protein secretion through the Golgi in eukaryotic cells.
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Outpatient medical care was well organised in the former GDR. Contrary to the FRG in the GDR a governmental Public Health system had been developed with only few privately established physicians. The care was mainly carried by outpatient departments in the city and in the country as well as by governmental doctors' practices. The personnel development and the results of the work are described and the advantages and disadvantages of this form of organisation of outpatient care are characterised.
In the former GDR, in-patient treatment had been performed mainly by governmental hospitals. Between 1950 and 1989 the number of hospitals was reduced from 1060 to 539 by closing uneconomic small hospitals or by combining them with bigger ones. During the same period the number of beds decreased from 197,219 to 163,305. Finally, 98.2 bed accommodations existed per 10,000 inhabitants. Information is given on personnel, financing and on the structural status of the hospitals. In-patients discharges of the hospitals were recorded by uniform documentation over about 20 years. It was therefore possible to evaluate in-patient morbidity.
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The ADP-ribosylation factor (ARF) is a member of the small molecular weight GTP-binding protein family and serves as the cofactor in the cholera toxin-catalyzed activation of the stimulatory regulatory subunit (Gs) of adenylate cyclase. Bovine Arf1 has been expressed at high levels and purified from bacteria. The recombinant Arf1 was compared with purified bovine brain Arf and shown to be nearly identical with respect to immunoblotting, guanine nucleotide binding, GTP hydrolysis, and cholera toxin cofactor activities. The only known chemical difference between the recombinant and brain proteins is the lack of myristic acid at the amino terminus of the expressed protein. The preparation of nucleotide-free Arf1 has allowed a more accurate determination of the binding constants for guanine nucleotides and revealed a significantly higher affinity for GDP than was previously determined. The effect of magnesium ions on nucleotide affinities was also determined and found to be quite different for the different guanine nucleotides. We have shown that GDP binds to the protein in the absence of magnesium, while GTP or guanosine 5'-O-(thiotriphosphate) can only bind to Arf1 in the presence of nanomolar (or higher) levels of the free metal. This characterization of the nucleotide binding and the ability to produce large amounts of a single species of ARF with full retention of a range of activities should greatly facilitate subsequent studies on the structure and function of ARF.
The physiology of mechanoreceptive lateral line areas was investigated in the thornback guitarfish, Platyrhinoidis triseriata, from medulla to telecephalon, using averaged evoked potentials (AEPs) and unit responses as windows to brain functions. Responses were analysed with respect to frequency sensitivity, intensity functions, influence of stimulus repetition rate, response latency, receptive field (RF) organization and multimodal interaction. 1. Following a quasi-natural vibrating sphere stimulus, neural responses were recorded in the medullary medial octavolateralis nucleus (MON), the dorsal (DMN) and anterior (AN) nucleus of the mesencephalic nuclear complex, the diencephalic lateral tuberal nucleus (LTN), and a telencephalic area which may correspond to the medial pallium (Figs. 2, 3, 13, 14, 15, 16). 2. Within the test range of 6.5-200 Hz all lateral line areas investigated responded to minute water vibrations. Best frequencies (in terms of displacement) were between 75 and 200 Hz with threshold values for AEPs as low as 0.005 microns peak-to-peak (p-p) water displacement calculated at the skin surface (Fig. 6). 3. AEP-responses to a vibrating sphere stimulus recorded in the MON are tonic or phasic-tonic, i.e., responses are strongest at stimulus onset but last for the whole stimulus duration in form of a frequency following response (Fig. 3). DMN and AN responses are phasic or phasic-tonic. Units recorded in the MON are phase coupled to the stimulus, those recorded in the DMN, AN or LTN are usually not (Figs. 5, 8, 9). Diencephalic LTN and telencephalic lateral line responses (AEPs) often are purely phasic. However, in the diencephalic LTN tonic and/or off-responses can be recorded (Fig. 11). 4. For the frequencies 25, 50, and 100 Hz, the dynamic intensity range of lateral line areas varies from 12.8 to at least 91.6 dB (AEP) respectively 8.9 and 92 dB (few unit and single unit recordings) (Fig. 7). 5. Mesencephalic, diencephalic, and telecephalic RFs, based on the evaluation of AEPs or multiunit activity (MUA), are usually contralateral (AN and LTN) or ipsi- and contralateral (telencephalon) and often complex (Figs. 10, 12, 16). 6. In many cases no obvious interactions between different modalities (vibrating sphere, electric field stimulus, and/or a light flash) were seen. However, some recording sites in the mesencephalic AN and the diencephalic LTN showed bimodal interactions in that an electric field stimulus decreased or increased the amplitude of a lateral line response and vice versa (Fig. 13 B).
Recording electroretinograms (ERGs) of fish prior to olfactory stimulation and after application of odor substances to the nostrils revealed a modulatory effect by chemoreceptive afferents on retinal responsiveness. The b-wave amplitude was increased in animals previously stimulated with dissolved food extracts. It is suggested that this phenomenon is related to well known behavioral effects of chemoreceptive stimulation on visually guided postural control mechanisms. The result for the first time suggests a behaviorally significant function of efferent optic nerve fibers.
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The mixed haemadsorption (MHA) method was employed for detection of several normal antigenic components on the surface of human colon carcinoma cells (HT-29). The antigens were expressed by cells in monolayer cultures and in suspensions prepared by monolayer trypsinization, and by cells of tumours growing progressively in athymic mice. The plasma of such animals bearing medium sized and large, non-necrotic tumours contained all the antigens, as determined by the radial diffusion immune haemolysis method (RDIH); the plasma of animals with small or large heavily necrotic tumours did not contain detectable amounts of any of the determinants. The half-life of the determinants in the circulation as extracellular entities was ca. 20 h. The same antigens, and fibronectin, were found to be ubiquitously represented in normal human plasma. It is proposed that the presence of membrane antigens in plasma is the result of physiological shedding of cell surface constituents by living cells.
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The values of the per cent 24 h radioiodine uptake in the GDR are above 60--70% and speak for a low alimentary intake of iodine or renal excretion of iodine below 40 micrograms J/d. Like the struma prevalences they show a tendency increasing from north to south and characterize the whole European situation of iodine deficiency including its decrease from west to east. The mean values of radioiodine uptake of 71.7 +/- 13.2% (n = 110) in euthyroids of the district of Karl-Marx-Stadt correspond to the iodine deficiency as it occurs approximately in the districts of Erfurt, Dresden, Munich or Freiburg/B. The alimentary iodine intake of 38.4 +/- 17.2 micrograms J/d and the renal iodine excretion of 29.9 +/- 16.1 micrograms J/d, calculated from the 24 h radioiodine accumulation values of 40 euthyroid persons by means of a mathematical model developed by Oddie and co-workers were low. The latter only slightly differed (P less than 0.05) from its chemically estimated excretion of iodine in the urine: 23.1 +/- 16.9 micrograms J/g creatinine (n = 73). Between the calculated and chemically estimated excretion of iodine there was a relatively strict correlation of r = 0.68 (n = 26; P less than 0.001). The introduction of an iodine prophylaxis is regarded as an urgent necessity. Later on a new estimation of the regional "normal values" is necessary for the per cent radioiodine uptake.
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