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Biomedical subjects

O Weiss

Publications and source records attributed to O Weiss.

At least 19 recordsLinked to original sources
PubMed1998

Correlations in protein sequences and property codes.

Correlation functions in large sets of non-homologous protein sequences are analysed. Finite size corrections are applied and fluctuations are estimated. As symbol sequences have to be mapped to sequences of numbers to calculate correlation functions, several property codes are tested as such mappings. We found hydrophobicity autocorrelation functions to be strongly oscillating. Another strong signal is the monotonously decaying alpha-helix propensity autocorrelation function. Furthermore, we detected signals corresponding to an alteration of positively and negatively charged residues at a distance of 3-4 amino acids. To look beyond the property codes gained by the methods of physical chemistry, mappings yielding a strong correlation signal are sought for using a Monte Carlo simulation. The mappings leading to strong signals are found to be related to hydrophobicity of alpha-helix propensity. A cluster analysis of the top scoring mappings leads to two novel property codes. These two property codes are gained from sequence data only. They turn out to be similar to known property codes for hydrophobicity or polarity.

Amino Acids↗
PubMed1998

Gene expression of insulin-like growth factor-I, its receptor and binding proteins in retina under hypoxic conditions.

Hypoxia is the main stimulus for neovascularization in the retina. Insulin-like growth factor-I (IGF-I) is thought to be one of the mediators of this process. Severe persistent hypoxia, as occurs in central retinal artery occlusion, is associated with less retinal neovascularization than relative hypoxia. To study the influence of different types of hypoxia on the IGF system, we used a model of neonatal rat retina that responds with neovascularization to a relative hypoxic stimulus produced by alternating oxygen concentrations in the respired air. We studied the influence of 24-hour hypoxia (10% oxygen), 48-hour hyperoxia (75% oxygen), and relative hypoxia (shifting from 48 hours in 75% oxygen to 24 hours in room air) on the gene expression of IGF-I, IGF-I receptor (IGF-IR), and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in retina using a solution hybridization RNase protection assay. Hypoxia induced a significant increase in retinal IGF-IR (178%), IGFBP-2 (227%), and IGFBP-3 (317%) mRNA; however, retinal IGF-I mRNA was reduced, as well as serum growth hormone (GH). Relative hypoxia caused a similar but less pronounced trend in the gene expression of IGF-IR and the binding proteins, whereas retinal IGF-I mRNA was unchanged and serum GH was elevated. Both hypoxia and relative hypoxia may cause IGF system stimulation in the retina through upregulation of IGF-IR and IGFBPs. This stimulation may result in neovascularization. However, during hypoxia, low levels of tissue oxygenation and reduced local production of IGF-I may impede the neovascularization process.

Animals↗
PubMed1998

Sequence periodicity in complete genomes of archaea suggests positive supercoiling.

The topological state of genomic DNA is of importance for its replication, recombination and transcription. The wrapping of the DNA around nucleosomes is associated with sequence periodicities (Trifonov and Sussman, Proc. Natl. Acad. Sci. USA, 77, pp. 3816-20). Recently, also the negative supercoiling of eubacterial DNA was related to 11 base pair (bp) periodicity (Herzel et al. Physica A, 249, pp. 449-59). Archaeal plasmids and a virus-like particle from Sulfolobus are positively supercoiled, but the superhelical conformation of archaeal genomic DNA is still uncertain. The problem of superhelicity can now be addressed via a comparative statistical analysis of the available complete genomes. For this purpose one has to look for periodicities which are in phase with the helical repeat of 10-11 bp. Similar periodicities are induced, however, by the amphipatic character of alpha-helices of encoded proteins (Zhurkin, Nucl. Acids Res., 9, pp. 1963-71). We show that these protein-induced periodicities are extended over a few periods only. The periods of additional long-ranging oscillations deviate significantly from the value for free DNA. A period of 11 bp in Eubacteria reflects negative supercoiling, whereas the significantly different period of thermophilic Archaea close to 10 bp suggests positive supercoiling of archaeal genomes.

DNA, Archaeal↗
PubMed1998

The endogenous insulin-like growth factor system in radiocontrast nephropathy.

The response of insulin-like growth factor (IGF) I in acute renal failure was evaluated in a model of radiocontrast nephropathy associated with selective necrosis of medullary thick ascending limbs. In brief, rats were administered radiocontrast medium or vehicle injections for controls after combined inhibition of prostanoids and nitric oxide. Twenty-four hours after the insult, tissue mRNAs for IGF-I, the IGF-I receptor, and IGF-binding proteins (IGFBP) 1 and 3 were assayed in cortex, medulla, and liver by solution hybridization-RNase protection assay, and IGFBPs were measured in serum and tissue by Western ligand blotting. Cortical IGF-1 increased, whereas medullary IGF-I mRNA decreased. Renal IGFBPs decreased, whereas IGFBP-1 mRNA increased. The IGF system in the liver was unchanged. We conclude that general changes in renal IGFBPs in this experimental model of acute renal failure might increase the level of cortical IGF-I in a way that could modulate medullary recovery.

Acute Kidney Injury↗
PubMed1998

The effect of low dose octreotide administration on renal function and on gene expression of IGF-I axis components in experimental diabetes mellitus.

The present study was undertaken to assess the chronic effects of low dose octreotide (Oc) administration in rats with experimental diabetes mellitus (DM). Metabolic and clearance studies were performed in control normal rats, in rats with streptozotocin-induced DM of 1 week duration and in similar DM rats treated with Oc, 10-20 microg/day. Gene expression of IGF-I, IGF-I receptor (IGF-I R) and IGF-binding protein-1 (IGFBP-1) was examined in renal tissue from normal DM animals and DM animals treated with Oc 10, 20 and 100 microg/day. Seven days of Oc administration, 10 microg/day, in rats with experimental DM, was associated with enhanced hyperglycemia, increased glomerular filtration rate and urinary sodium excretion as compared with untreated DM animals. After a higher Oc dose, 20 microg/day, however, there were no significant changes in renal function and in glycemic control. Significant increases in kidney weight and kidney weight/body weight ratio were seen in DM rats as compared with control intact animals. These changes were not affected by Oc therapy in various doses. Induction of DM was associated with a marked increase in renal IGFBP-1 mRNA expression. There were no significant changes in the expression of IGF-I or IGF-I R mRNA. Oc therapy in a low or high dose did not affect gene expression of IGF-I, IGF-I R or IGFBP-1. Thus, the response to chronic low dose Oc administration of DM rats may vary from enhanced hyperglycemia and hyperfiltration to a lack of change in renal function or in glycemic control. Low dose Oc therapy was not associated with significant variations in renal mass or in the gene expression of IGF-I axis components. These findings are at variance with previously published studies which show a suppressive effect of Oc on renal function and growth in experimental diabetes. This apparent discrepancy may be related to the duration of treatment or to a biphasic physiological effect of Oc when used in different doses.

Animals↗
PubMed1998

Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.

The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration. Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control. We studied the effects of octreotide treatment on the intrarenal IGF axis at 2 and at 7 days after the induction of STZ diabetes. Two days after induction of diabetes, kidney IGF-I was increased from 850 +/- 43 ng/g tissue in controls to 1,648 +/- 165 ng/g tissue (P < 0.001) in diabetic animals. The diabetes-associated increase in renal IGF-I 48 h after STZ injection was totally prevented by octreotide (IGF = 780 +/- 57 ng/g tissue). However, 7 days after the induction of diabetes, kidney IGF-I was similar to that of control and was not affected by octreotide. No difference in serum IGF-I was observed between controls and diabetic rats after 2 days of diabetes; however, octreotide treatment resulted in a significant decrease of serum IGF-I after 2 days when compared with control rats (P < 0.05). Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged in rats from either group. Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls. Octreotide treatment prevented the diabetes-associated rise in renal IGFBP-1 mRNA and protein. However, 7 days after the induction of diabetes, renal IGFBP-1 mRNA and protein were similarly increased in both octreotide-treated or untreated diabetic rats. Renal IGFBP-3 gene expression and protein and IGFPB-5 mRNA remained unchanged after 2 and 7 days of diabetes when treated or untreated with octreotide. We conclude that the well-known inhibitory effect of octreotide on the early increase in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels.

Animals↗
PubMed1997

Optimization of road networks using evolutionary strategies

A road network usually has to fulfill two requirements: (i) it should as far as possible provide direct connections between nodes to avoid large detours; and (ii) the costs for road construction and maintenance, which are assumed proportional to the total length of the roads, should be low. The optimal solution is a compromise between these contradictory demands, which in our model can be weighted by a parameter. The road optimization problem belongs to the class of frustrated optimization problems. In this paper, a special class of evolutionary strategies, such as the Boltzmann and Darwin and mixed strategies, are applied to find differently optimized solutions (graphs of varying density) for the road network, depending on the degree of frustration. We show that the optimization process occurs on two different time scales. In the asymptotic limit, a fixed relation between the mean connection distance (detour) and the total length (costs) of the network exists that defines a range of possible compromises. Furthermore, we investigate the density of states, which describes the number of solutions with a certain fitness value in the stationary regime. We find that the network problem belongs to a class of optimization problems in which more effort in optimization certainly yields better solutions. An analytical approximation for the relation between effort and improvement is derived.

Journal Article↗
PubMed1997

[Value of training courses in minimally invasive surgery].

The actual situation regarding the education für MIS requires the optimisation and standardisation of the training system. This paper presents the results of an inquiry about the evaluation of the course of operative laparoscopy. 80-90% of those interviewed made the comments "very good" and "good", with regard to the imparting of the theoretic foundation of the technique of endoscopic operations, for sufficient possibility of manual training and for the realistic setting of the animal organ model compared with the clinical operation. Because of our experience, we recommend attending such training courses before starting laparoscopic operations.

Attitude of Health Personnel↗
PubMed1995

Insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the kidney of the chronically hypoinsulinemic rat and hyperinsulinemic rat.

Acute streptozotocin (STZ)-induced diabetes in rats causes a transient increase in insulin-like growth factor-I (IGF-I) in the kidney, followed by a rapid renal hypertrophy and constant renal hyperperfusion. However, renal IGF-I levels return to normal within 4 days. Thus, hyperperfusion, which is independent of renal hypertrophy of the chronically diabetic kidney, is not explained by increased renal IGF-I. We studied IGF-I and IGF-I receptor gene expression in the kidney of rats with long-standing STZ-induced diabetes. IGF-I mRNA level in the chronically diabetic kidney was approximately 50% of that in control rats, whereas IGF-I receptor mRNA was increased approximately threefold. Ten days' treatment with insulin 65 days after induction of diabetes resulted in a glucose-dependent decrease in IGF-I receptor mRNA. Chronic hyperinsulinemia with near normoglycemia did not change gene expression of either IGF-I or IGF-I receptor. The studies suggest that glucose levels per se, independent of insulin levels, play an important role in the regulation of IGF-I receptor gene expression in the chronically diabetic kidney. Furthermore, kidney hyperperfusion in chronic diabetes is coupled with the increase in IGF-I receptor mRNA, despite normal kidney IGF-I levels.

Animals↗
PubMed1995

Insulin-like growth factor-1 (IGF-1) enhances recovery from HgCl2-induced acute renal failure: the effects on renal IGF-1, IGF-1 receptor, and IGF-binding protein-1 mRNA.

Several growth factors have been found to play an important role in the recovery from acute renal failure (ARF). The effect of the continuous subcutaneous infusion of human recombinant insulin-like growth factor (IGF)-1 (125 micrograms daily by osmotic minipumps) in a rat model of mercuric chloride (HgCl2)-induced ARF was examined. HgCl2 (4 mg/kg) induced ARF with a mortality that was unaffected by IGF-1. However, IGF-1 significantly enhanced functional and histologic recovery in the survivors, as measured by serum creatinine and creatinine clearance and by histologic scoring. Solution hybridization RNAase protection assays showed that renal IGF-1 mRNA, IGF-1 receptor (IGF-1R) mRNA, and IGF-binding protein-1 (IGFBP-1) mRNA were unaffected by exogenous IGF-1, but this treatment significantly increased renal IGF-1 in ARF rats compared with normal rats and ARF rats not receiving IGF-1. After ARF renal mRNA for IGF-1 was decreased, IGF-1R was unchanged and IGFBP-1 was increased. Similar changes occurred in IGF-1-infused ARF rats. Thus, (1) IGF-1 enhances recovery from nephrotoxic ARF both functionally and histologically; (2) in nephrotoxic ARF, there is (a) a reduction in IGF-1 mRNA expression that is not prevented by IGF-1 infusion, and (b) an increase in renal IGFBP-1 mRNA. This may allow a significant increase in renal IGF-1 levels in IGF-1-infused ARF rats, despite the decrease in renal IGF-1 mRNA. A local increase in renal IGFBP-1 and IGF-1 may explain the accelerated recovery from ATN in this model. It was concluded that HgCl2-induced ARF is amenable to improvement by IGF-1 infusion and that the increase in renal IGFBP-1 mRNA may be an important modulator in the recovery of the kidney.

Acute Kidney Injury↗
PubMed1992

The amino terminus of ADP-ribosylation factor (ARF) is a critical determinant of ARF activities and is a potent and specific inhibitor of protein transport.

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.

ADP-Ribosylation Factor 1↗
PubMed1991

[Development of ambulatory medical care in former East Germany].

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.

Ambulatory Care↗
PubMed1991

[Development of bed potential and occupancy in hospitals of East Germany].

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.

Bed Occupancy↗
PubMed1989

Nucleotide binding and cofactor activities of purified bovine brain and bacterially expressed ADP-ribosylation factor.

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.

ADP-Ribosylation Factor 1↗