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Biomedical subjects

J Zimmermann

Publications and source records attributed to J Zimmermann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Schizophrenia, schizotypal and delusional disorders (F2). Results from the ICD-10 field trial of the Diagnostic Criteria for Research in German-speaking countries.

The results of the ICD-10 field trial of the Diagnostic Criteria for Research in German-speaking countries concerning section F2, "Schizophrenia, schizotypal and delusional disorders', are presented. From a total of 39 cases (written case reports and video tapes) 5 met the criteria for schizophrenia (F20) with 201 ratings. The majority of clinicians rated the ease of diagnosis, confidence of diagnosis, and goodness of fit positive. The reliability of the 2-character diagnoses was excellent (F2; kappa = 0.88), as was the case for the category schizophrenia (F20; kappa = 0.89) and was higher than in the comparable study concerning the Clinical Diagnostic Guidelines.

Adolescent↗
PubMed1996

Clinical course of hypophosphatemic rickets in 23 adults.

Twenty-three adult patients (19 females, 4 males) with x-linked hypophosphatemic rickets (HPR) underwent a retrospective evaluation of the clinical course and a clinical examination by a nephrologist, orthopedic surgeon and dentist. Blood and urine analysis, bone density measurements with QCT and DEXA, ultrasonic examination of the kidneys were performed and the patients were asked to fill in a standardized questionnaire on pain and psychosocial rehabilitation. Mean final height was 152.4 cm +/- 8.5 SD in females and 157.3 cm +/- 8.9 SD in males. Decreased joint mobility was seen in all patients, deviations of the normal leg axis in 18/23 patients in spite of 69 correcting osteotomies in the past. Dental (n = 14) and psychosocial problems were associated with inability to work (n = 8). There was a trend that patients with a very low Tp/GFR had a more severe course of the disease. Early therapy with vitamin D metabolites and phosphate had a beneficial effect on growth, bone density and deformations. Eight patients had nephrocalcinosis due to vitamin D and phosphate therapy and had normal kidney function. Four patients had urinary tract abnormalities. We conclude that patients with HPR should receive continuous interdisciplinary care given by nephrologists, orthopedic surgeons, physiotherapists and dentists not only during childhood but also as adults.

Adult↗
PubMed1996

Influence of nitric oxide on renal function in toxic acute renal failure in the rat.

Besides other mechanisms, nitric oxide (NO) plays a major role in maintaining the high renal blood flow (RBF) and is also involved in the regulation of glomerular hemodynamics and contractility of mesangial cells. We examined the hypothesis that L-arginine-derived NO exerts beneficial effects in toxic acute renal failure (ARF) in the rat. To induce ARF uranyl nitrate (UN) was given intravenously as a bolus injection (25 mg/kg over 5 min) following a basal period. After the initiation phase of ARF (3 h) saline in the control group (C) and drugs in the experimental groups (I-III, each n = 8) were administered for 60 min. Group I: Arg (= L-arginine, 300 mg/kg), group II: MeArg (= N-methyl-L-arginine, 30 mg/kg), group III: Arg + MeArg (300 mg/kg, 30 mg/kg respectively). The experiments were continued for additional 60 min following the infusion period. Glomerular filtration rate (GFR, inulin clearance) was reduced 3 h after UN to about 50% of normal values in group I-III and control group. After infusion of Arg GFR had significantly improved, but remained unchanged after MeArg in relation to control. One hour after the infusion period these effects were even more pronounced. We conclude that NO exerts beneficial effects on renal function in this animal model of ARF. These results underline the regulatory role of the L-arginine/NO pathway for renal function not only under basal conditions but also in ARF.

Acute Kidney Injury↗
PubMed1996

Endotoxin-induced acute renal failure in the rat: effects of urodilatin and diltiazem on renal function.

Acute renal failure (ARF) due to endotoxins is a common problem in clinical medicine. Endotoxins are released from the outer membrane of the gram-negative bacterial envelope and are composed of lipopolysaccharides (LPS). Although systemic hypotension often is present, LPS-induced ARF is characterized by marked intrarenal vasoconstriction. Both calcium channel blockers and natriuretic peptides are able to antagonize vasoconstricting signals and have been reported to exert beneficial effects in toxic and ischemic ARF: We investigated the effects of diltiazem (Dil, 300 micrograms/kg) or urodilatin (Uro, 40 micrograms/kg) or a combination of both (same doses) on renal function in early LPS-induced ARF: One hour after induction of ARF by i.v. injection of LPS glomerular filtration rate (GFR, clearance of fluorescence-marked inulin) was distinctly reduced to about 54% of basal values. In the following infusion period (60 min) a significant increase of GFR was observed with diltiazem (1.54 +/- 0.11 ml/min), urodilatin (1.60 +/- 0.10 ml/min) and the combination of both drugs (1.66 +/- 0.04 ml/min) compared to controls (1.17 +/- 0.08 ml/min). Combined administration did not cause additive effects. Also 60 and 120 minutes after stopping of drug infusion elevated GFR could be maintained in all experimental groups. Due to their vasorelaxing activity both Uro and Dil induced a decrease of mean arterial blood pressure in comparison with controls and revealed remarkable diuretic and natriuretic activity. In conclusion our results underline that marked intrarenal vasoconstriction in LPS-induced ARF can be antagonized by the well known relaxing potency of Uro and Dil towards vascular smooth muscle and mesangial cells. Both Uro and Dil were capable of improving suppressed renal function in the early phase of LPS-induced ARF in the rat as long as severe systemic hypotension is absent.

Acute Kidney Injury↗
PubMed1996

Hemorheology, plasma protein composition and von Willebrand factor in type I diabetic nephropathy.

Patients with IDDM, especially those with albuminuria are at high risk for macrovascular and microvascular complications. Besides the major classic risk factors altered hemorheology may also play a role. Plasma viscosity, erythrocyte aggregation and erythrocyte deformability are the major determinants of blood flow in the microcirculation. Therefore, these hemorheological parameters and plasma protein composition were evaluated in 58 IDDM-patients with none (N0), incipient (N1: albuminuria 30-300 mg/day) and overt clinical nephropathy (N2: albuminuria > 300 mg/day). As an estimate of endothelial injury plasma levels of von Willebrand Factor (vWF) were investigated. Patients with incipient and clinical nephropathy exhibited increasing blood levels of fibrinogen (N0 = 2.47 +/- 0.09, N1 = 2.71 +/- 0.15, N2 = 3.49 +/- 0.24 g/l, p < 0.001), alpha 2-macroglobulin (N0 = 257 +/- 11, N1 = 251 +/- 21, N2 = 382 +/- 43 mg/100 ml, p < 0.01) and haptoglobin (N0 = 174 +/- 16, N1 = 216 +/- 39, N2 = 278 +/- 36 mg/100 ml, p < 0.05), whereas serum albumin concentration decreased (N0 = 5.1 +/- 0.1, N1 = 4.7 +/- 0.1, N2 = 4.1 +/- 0.2 g/100 ml, p < 0.001). In the same patients erythrocyte aggregation (N0 = 10.0 +/- 0.4, N1 = 12.1 +/- 0.5, N2 = 12.9 +/- 0.6, p < 0.001), plasma viscosity (N0 = 1.34 +/- 0.01, N1 = 1.38 +/- 0.02, N2 = 1.40 +/- 0.02 mPas, p < 0.05) and erythrocyte rigidity (N0 = 0.05 +/- 0.01, N1 = 0.15 +/- 0.05, N2 = 0.09 +/- 0.02, p < 0.05) were increased, predominantly in those with overt clinical nephropathy. Erythrocyte aggregation was positively correlated with plasma concentrations of fibrinogen (r = 0.65, p < 0.001) and alpha 2-macroglobulin (r = 0.35, p < 0.05), but negatively with plasma albumin concentration (r = -0.49, p < 0.001). Plasma viscosity was positively correlated with plasma concentrations of fibrinogen (r = 0.46, p < 0.001) and haptoglobin (r = 0.46, p < 0.001). Von Willebrand Factor levels were higher in patients with overt clinical nephropathy (N0 = 126 +/- 8, N1 = 136 +/- 12, N2 = 163 +/- 14%, p < 0.09, PN0-N2 < 0.05). A significant correlation between vWF and the rheological determinants could not be detected. These data demonstrate that blood rheology is profoundly altered in patients with IDDM and nephropathy. Elevated levels of vWF may indicate endothelial damage, and changes in plasma viscosity as well as erythrocyte aggregability seem to be the result of altered plasma protein composition due to proteinuria. These abnormalities in hemorheology may be an aggravating factor promoting microvascular and macrovascular damage in patients with type I diabetes mellitus and nephropathy.

Adult↗
PubMed1995

Purification, characterization and specificity of chondroitin lyases and glycuronidase from Flavobacterium heparinum.

The chondroitin lyases from Flavobacterium heparinum (Cytophaga heparinia) have been widely used in depolymerization of glycosaminoglycan and proteoglycan chondroitin sulphates. Oligosaccharide products derived from chondroitin sulphate can be further degraded by glycuronidases and sulphatases obtained from the same organism. There has been no reported purification of these enzymes to homogeneity nor is there any information on their physical and kinetic characteristics. The absence of pure enzymes has resulted in a lack of understanding of the optimal conditions for their catalytic activity and their substrate specificity. This has limited the use of these enzymes as reagents for preparation of oligosaccharides for structure and activity studies. Reproducible schemes to purify a chondroitin AC lyase, a glycuronidase and chondroitin B lyase from Flavobacterium heparinum to apparent homogeneity are described. Chondroitin AC lyase (chondroitinase AC, EC 4.2.2.5), glycuronidase [chondro-(1-->3)-glycuronidase, no EC number] and chondroitin B lyase (chondroitinase B, no EC number) have M(r) values (assessed by SDS/PAGE) of 74,000, 41,800 and 55,200 respectively, and isoelectric points (determined by isoelectric focusing) of 8.85, 9.28 and 9.05 respectively. Chondroitin lyase AC and B contain pyroglutamic acid at their N-termini precluding their analysis by Edman degradation. Deblocking with pyroglutamate aminopeptidase facilitated the determination of their N-terminal sequences. The kinetic properties of these enzymes have been determined as well as the optimum conditions for their catalytic activity. The specificity of the glycouronidase, determined using 17 different disaccharide substrates, shows that it only acts on unsulphated or 6-O-sulphated 1-->3 linkages. The chondroitin lyases are both endolytic enzymes, and oligosaccharide mapping shows their expected specificity towards the chondroitin and dermatan sulphate polymers.

Amino Acids↗
PubMed1995

Efficient low redundancy large-scale DNA sequencing at EMBL.

An efficient low redundancy DNA sequencing strategy should allow high accuracy determination of the consensus sequence on both strands of a DNA fragment from a minimal number of sequencing reactions with minimal overlap. At EMBL we developed a directed strategy for cosmid-scale sequencing based on primer walking, whereas most other sequencing projects of this scale rely on the random 'shotgun' strategy. In our strategy, highly accurate raw data are obtained from automated double-stranded Sanger dideoxy sequencing with inexpensive walking primers (8 to 10 $ per primer), T7 DNA polymerase and internal labelling by fluorescein-15- dATP on A.L.F. DNA sequencers (Pharmacia Biotech). The use of 60-cm long glass plates enables reading length of up to 1000 bases. Comparing various random and directed sequencing strategies in the course of the European Community yeast genome sequencing project on cosmids from chromosomes IX, XI and XV, primer walking was found to be the strategy resulting in the lowest possible redundancy of 2.6 to 2.8. Future development of the sequencing strategy is based on the new EMBL 2-dye sequencing device for simultaneous sequencing on both strands, and implementation of an initial limited random sequencing phase to reduce the number of walking primers required by a factor of 3, while still maintaining a low redundancy of approx. 3.

Animals↗
PubMed1995

Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class.

The platelet-derived growth factor (PDGF) receptor is a member of the transmembrane growth factor receptor protein family with intrinsic protein-tyrosine kinase activity. We describe a potent protein-tyrosine kinase inhibitor (CGP 53716) that shows selectivity for the PDGF receptor in vitro and in the cell. The compound shows selectivity for inhibition of PDGF-mediated events such as PDGF receptor autophosphorylation, cellular tyrosine phosphorylation, and c-fos mRNA induction in response to PDGF stimulation of intact cells. In contrast, ligand-induced autophosphorylation of the epidermal growth factor (EGF) receptor, insulin receptor, and the insulin-like growth factor I receptor, as well as c-fos mRNA expression induced by EGF, fibroblast growth factor, and phorbol ester, was insensitive to inhibition by CGP 53716. In antiproliferative assays, the compound was approximately 30-fold more potent in inhibiting PDGF-mediated growth of v-sis-transformed BALB/c 3T3 cells relative to inhibition of EGF-dependent BALB/Mk cells, interleukin-3-dependent FDC-P1 cells, and the T24 bladder carcinoma line. When tested in vivo using highly tumorigenic v-sis- and human c-sis-transformed BALB/c 3T3 cells, CGP 53716 showed antitumor activity at well-tolerated doses. In contrast, CGP 53716 did not show antitumor activity against xenografts of the A431 tumor, which overexpresses the EGF receptor. These findings suggest that CGP 53716 may have therapeutic potential for the treatment of diseases involving abnormal cellular proliferation induced by PDGF receptor activation.

3T3 Cells↗
PubMed1995

Simultaneous on-line DNA sequencing on both strands with two fluorescent dyes.

We describe an automated DNA-sequencing technique which allows both the simultaneous sequencing from the two strands of double-stranded templates and the subsequent detection of the sequencing products online and in parallel. The technique is based on hardware technology also used in the ALF DNA sequencer (Pharmacia, Uppsala). A helium-neon laser was mounted into the sequencing device additionally to the standard argon laser. Two different primers, labeled with either fluorescein or Texas red, are used in a single sequencing reaction resulting in an output of two sequences. Both sequencing products are then analyzed on-line in the same lanes of a gel. This technique is especially useful for the complete sequencing of DNA fragments up to 1 kb. High accuracy sequencing of PCR products in double-stranded form can now be accomplished in only one sequencing reaction.

Fluorescent Dyes↗
PubMed1995

Heparan sulfate primed on beta-D-xylosides restores binding of basic fibroblast growth factor.

Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). Mutant Chinese hamster ovary cells (pgsA-745) deficient in xylosyltransferase are unable to initiate glycosaminoglycan synthesis and hence can not bind bFGF to low- and high-affinity cell surface receptors. Exposure of pgsA-745 cells to beta-D-xylopyranosides containing hydrophobic aglycones resulted in restoration of bFGF binding in a manner similar to that induced by soluble heparin or by heparan sulfate (HS) normally associated with cell surfaces. Restoration of bF-GF binding correlated with the ability of the beta-D-xylosides to prime the synthesis of heparan sulfate. Thus, both heparan sulfate synthesis and bFGF receptor binding were induced by low concentrations (10-30 microM) of estradiol-beta-D-xyloside and naphthyl-beta-D-xyloside, but not by cis/trans-decahydro-2-naphthyl-beta-D-xyloside, which at low concentration primes mainly chondroitin sulfate. The obligatory involvement of xyloside-primed heparan sulfate in restoration of bFGF-receptor binding was also demonstrated by its sensitivity to heparinase treatment and by the lack of restoration activity in CHO cell mutants that lack enzymatic activities required to form the repeating disaccharide unit characteristic of heparan sulfate. Xyloside-primed heparan sulfate binds to the cell surface. Restoration of bFGF receptor binding was induced by both soluble and cell bound xyloside-primed heparan sulfate and was abolished in cells that were exposed to 0.5-1.0 M NaCl prior to the bFGF binding reaction. These results indicate that heparan sulfate chains produced on xyloside primers behave like heparan sulfate chains attached to cellular core proteins in terms of affinity for bFGF and ability to function as low-affinity sites in a dual receptor mechanism characteristic of bFGF and other heparin-binding growth promoting factors.

Animals↗
PubMed1995

Nucleotide sequence and analysis of the centromeric region of yeast chromosome IX.

We have determined the nucleotide sequence of a cosmid (pIX338) containing the centromere region of yeast (Saccharomyces cerevisiae) chromosome IX. The complete nucleotide sequence of 33.8 kb was obtained by using an efficient directed sequencing strategy in combination with automated DNA sequencing on the A.L.F. DNA sequencer. Sequence analysis revealed the presence of 17 open reading frames (ORFs), four of them previously known yeast genes (sly12, pan1, sts1 and prl1), a tRNA gene and the centromere motif. Exhaustive database searches detected sequence homologues of known function for as many as 14 of the 17 ORFs. These include a mammalian tyrosine kinase substrate; the Escherichia coli cell cycle protein MinD; the human inositol polyphosphate-5-phosphatase (gene OCRL) involved in Lowe's syndrome, a developmental disorder; and helicases, for which the new yeast member defines a distinct DEAD/H-box subfamily. A surprisingly large fraction of the ORFs (at least six out of 17) in the centromeric region are apparently involved in RNA or DNA binding.

Adenosine Triphosphatases↗
PubMed1995

Structure and role of the terminal repeats of Epstein-Barr virus in processing and packaging of virion DNA.

The linear virion Epstein-Barr virus (EBV) DNA is terminated at both ends by a variable number of direct, tandemly arranged terminal repeats (TRs) which are approximately 500 bp in size The number of TRs at each terminus can vary. After infection of host cells, the EBV DNA circularizes via the TRs by an unknown mechanism, and replication of the viral DNA during the lytic phase of the EBV life cycle leads to large DNA concatemers which need to be cleaved into virion DNA units, eventually. This cleavage event occurs at an unknown locus within the TRs of EBV, which are the cis-acting elements essential for cleavage of the concatemers and encapsidation of the virion DNA. To investigate the mechanism of DNA processing during genome circularization and cleavage of concatemeric DNA, the genomic termini of EBV were cloned, sequenced, and analyzed by direct labeling of the virion DNA. Both termini ended with identical 11-bp elements; the right end has acquired an additional 9-bp stretch that seemed to originate from the leftmost unique sequences. The left terminus is blunt, whereas the right terminus appears to have a 3' single-base extension. In a transient packaging assay, a single terminal repeat was found to be sufficient for encapsidation of plasmid DNA, and mutagenesis of the TR element defined a region of 159 bp, including the 11-bp element, which is essential for packaging. These results indicate that the genomic termini of EBV are not generated by a simple cut of a hypothetical terminase. The mechanism for cleavage of concatemers seems to involve recombination events.

Base Sequence↗
PubMed1995

Effects of urodilatin and diltiazem on renal function in ischemic acute renal failure in the rat.

In humans as well as in experimental models the hallmark of ischemic acute renal failure (ARF) is a profound diminution in glomerular filtration rate (GFR) and renal blood flow. Both calcium antagonists and a-ANP have been reported to exert beneficial effects in ischemic ARF. No data, however, exist about combined administration of the natriuretic peptide urodilatin and calcium channel blockers. We therefore investigated the effects of urodilatin (URO, 40 micrograms/kg/h, i.v.) and diltiazem (DIL, 300 micrograms/kg/h, i.v.) in the rat given immediately after clamping of both renal arteries for 40 min. Compared to controls (0.07 +/- 0.01) depressed GFR (ml/min/100 g) was clearly elevated with URO (0.16 +/- 0.03), DIL (0.13 +/- 0.03) and URO + DIL (0.14 +/- 0.02) after the ischemic lesion. After cessation of drug delivery the beneficial effects were blunted in the URO group, in contrast to the DIL and URO + DIL group, where GFR was significantly elevated compared to controls even 3 h after starting reperfusion. Besides that also urine flow, sodium excretion and blood pressure were examined. In conclusion both URO and DIL exert beneficial effects in ischemic ARF in the rat while infused. In contrast to URO DIL showed prolonged beneficial effects even after cessation of drug delivery. An additional effect of both drugs could not be observed.

Acute Kidney Injury↗
PubMed1995

Generation and activity of the ternary gelatinase B/TIMP-1/LMW-stromelysin-1 complex.

Incubation of progelatinase B, isolated from human polymorphonuclear leukocytes, with TIMP-1 leads to the formation of the progelatinase B/TIMP-1 complex. This complex behaves like a Janus in a similar manner as we previously described for the progelatinase A/TIMP-2 complex. It shows the properties of TIMP-1 and is a better inhibitor for gelatinase A than for gelatinase B. Treatment with trypsin leads to activation of the binary complex. The activity, however, amounts only to slightly more than 10% of the activity of free gelatinase B, not complexed with TIMP-1. When the progelatinase B/TIMP-1 complex inhibits an active matrix metalloproteinase, a ternary complex is generated that after activation displays a distinct higher proteolytic activity than the active binary complex. The active binary complex cannot be transformed into the active ternary complex.

Amino Acid Sequence↗
PubMed1995

Primer design for automated DNA sequencing utilizing T7 DNA polymerase and internal labeling with fluorescein-15-dATP.

We have identified additional criteria for the walking primer design that improve the success rate of automated fluorescent DNA sequencing using the internal labeling technique and T7 DNA polymerase. These criteria resulted from the evaluation of over 220 sequences generated with walking primers and fluorescein-15-dATP as internal label in the course of the European Community (EC) yeast genome sequencing project. In this project primers were designed using standard commercial software. Intensities of sequencing signals varied over a broad range from very strong to very weak, depending on the primers used. This led us to evaluate primer performance relative to (i) the template sequence immediately downstream of the primer binding site and (ii) the primer sequence itself. Our experiments show that the position of the first labeled dATP to be incorporated downstream of the primer into the growing strand is substantial for the signal intensity of the sequence. The closer to the primer that the first 'A' is incorporated, the stronger the peak intensities are. An additional feature of sequencing with native T7 DNA polymerase is its ability to remove a 3'-terminal 'A' of the primer by the 3'-->5' exonuclease activity and to exchange the nucleotide with a labeled dATP by the polymerase activity.

Binding Sites↗
PubMed1995

[The use of contrast media for quality assurance in radiotherapy planning].

PURPOSE: The target volume definition in radiation therapy was evidently improved by CT and MRI. Basis of treatment planning, however, remains the therapy simulator. Important instruments for adequate fluoroscopic treatment planning are contrast media that recently have been applied less out of legal and professional reasons. Aim of this work is to evaluate the possible benefit of contrast media applications. PATIENTS AND METHODS: In 1303 simulations between 1.1.1993 and 30.9.1993 105 times intravenous contrast media were applied, supplied by oral or endolymphatic contrast agents. It was studied if the previously intended plan had to be altered due to contrast media application. RESULTS: In 17 out of 105 cases (16.2%) the target volume or the preplanned technique had to be altered after contrast media application. Main reason was the existence of anatomical variations especially in kidney and small bowel detected by use of contrast agents. So standard indications for contrast media applications were defined. CONCLUSIONS: Contrast media are an important tool in treatment planning that should be orientated on diagnostical standards. Applications of contrast agents facilitate the detection of anatomical variations and the selection of the appropriate technique in order to shield sensitive tissues. The therapeutical and legal benefit outweigh potential hazards due to intolerances or professional obstacles.

Contrast Media↗