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Biomedical subjects

M Lang

Publications and source records attributed to M Lang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay.

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.

Female↗
PubMed2001

Simulations on the number of entanglements of a polymer network using knot theory.

Polymer networks, created on the computer using the Bond-Fluctuation-Algorithm, offer the possibility to count the number of entanglements. We generated networks consisting of 5000 chains that were cross linked at their end groups via tetra-functional cross linkers. The analysis of the topology was performed by computing the Homfly polynomial of the entanglements offering a much more precise determination of the knot and entanglement type than the Gaussian linking number. It also allows us to determine the influence of Brunnian links. Results concerning the connection between the chain length and the number of entanglements are shown.

Journal Article↗
PubMed2001

A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.

We describe the identification and in vitro characterization of a series of 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the 20S proteasome. Our initial SAR data demonstrate that the 2-aminobenzylstatine core structure can effectively serve as the basis for designing potent, selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.

Amino Acids↗
PubMed2001

Modeling of the binding mode of a non-covalent inhibitor of the 20S proteasome. Application to structure-based analogue design.

The 2-aminobenzvlstatine derivative I is a 20S proteasome inhibitor of a novel chemical type identified by high throughput screening. The compound specifically inhibits the chymotrypsin-like catalytic activity of the human proteasome with an IC50 value in the micromolar range. Using the crystal structure of the yeast proteasome, we modeled the structure of the human proteasome in complex with 1. As one of the first applications of the model in our oncology programme targeting the proteasome, we designed an analogue of the inhibitor having enhanced stacking/hydrophobic interactions with the enzyme. One order of magnitude in inhibitory potency was gained.

Amino Acids↗
PubMed2001

Significance of a T-lymphocytotoxic crossmatch in liver and combined liver-kidney transplantation.

BACKGROUND: In contrast to kidney transplants a positive crossmatch is no contraindication for liver transplantation (OLT). In liver transplantation, antibody mediated rejections are rarely reported and a liver graft is suspected to have protective effects for kidney grafts when transplanted simultaneously. The aim of this study was to evaluate the effect of a positive crossmatch on outcome after OLT and combined liver and kidney transplantation (CLKTx). METHODS: We analyzed retrospectively the impact of a positive crossmatch on graft survival and rejection episodes after OLT (793pats) and CLKTx (18pats, 2.2%). Immunosuppression consisted of either Cyclosporine- or Tacrolimus-based regimens. RESULTS: A total of 50/811 (6%) of patients had a positive crossmatch, 45/793 (5.6%) with liver transplantation alone and 5/18 (28%) of patients with CLKTx. Follow-up ranged from 1 to 122.5 months (median 45.8 months). One- and 5-year graft survival rates of liver transplants alone with a positive crossmatch were 89.6% and 75.3%, respectively and were 88% and 77.5% in crossmatch negative recipients. Additionally, the incidence of acute and steroid-resistant rejection (44% and 15.5%) was not significantly increased in patients with a positive crossmatch when compared with patients with a negative crossmatch (38% and 19%). None of the patients with a positive crossmatch and CLKTx underwent a hyperacute-rejection episode after transplantation, and kidney graft survival 100%. CONCLUSIONS: In conclusion, a positive crossmatch is no contraindication for OLT and CLKTx. Furthermore, not having to wait for results of donor/recipient crossmatching can shorten cold ischemia time and may improve the clinical outcome.

Adult↗
PubMed2001

Staggered field effect on the one-dimensional S = 1/2 antiferromagnet Yb4As3.

Inelastic neutron scattering measurements of magnetic excitations in the charge-ordered state of Yb4As3 have been performed under magnetic field up to about 6 T. By applying a magnetic field, the spectrum at the one-dimensional wave vector q = 1 [ pi/d] changes drastically from a broad one corresponding to the spinon excitation continuum of the one-dimensional S = 1 / 2 spin system to a sharp one at a finite energy, indicating the opening of an energy gap in the system. The magnetic field dependence of the gap is well fitted by the power law H2/3. The experimental result gives strong evidence for the existence of a staggered field alternating along Yb3+ chains induced by the Dzyaloshinsky-Moriya interaction.

Journal Article↗
PubMed2001

[Surgical procedures and risk factors in therapy of benign multinodular goiter. A statistical comparison of the incidence of complications].

BACKGROUND: The best surgical approach for bilateral resections in the therapy of benign multinodular goiter is still controversial. METHODS: The purpose of this study was to compare different modes of resection concerning differences in complication rates and risk factors influencing the outcome. 2235 thyroid resections for multinodular goiter between 1985 and 1999 were analysed. RESULTS: When compared to bilateral subtotal resection (n = 327; 14.6%), those patients who received lobectomy and contralateral subtotal resection (n = 952; 42.6%) showed a statistically significant higher incidence of temporary hypocalcaemia (22.6% versus 15.9%) only. The "nerve at risk"-analysis demonstrated no significant difference of laryngeal nerve paralysis between the side of lobectomy and subtotal resection, respectively. In comparison to the entire patient population operations for recurrent goiters had an equal operative risk, whereas patients with goiter WHO III or an intrathoracic location had significant higher rates of temporary laryngeal nerve paralysis and hypocalcaemia. CONCLUSIONS: Lobectomy and contralateral subtotal resection offers numerous advantages concerning intraoperative variability and definitive resection of suspicious nodules. With an adequate standardized surgical technique and identification of the laryngeal nerve, the complication rate is comparable to bilateral subtotal resection.

Female↗
PubMed2001

[Combined liver and kidney transplantation: indications and long-term follow-up].

INTRODUCTION: In patients suffering from chronic liver and kidney disease combined liver-kidney transplantation is the only therapeutic option. However, in these patients, it is mandatory to distinguish between chronic and acute renal failure prior to transplantation, because acute renal failure may recover after successful liver transplantation. In this study we investigated the indications and results of this combined procedure. PATIENTS AND METHODS: We report on 27 patients who underwent liver and kidney transplantation. The underlying diseases were viral hepatitis (n = 12), polycystic liver and kidney disease (n = 9), primary hyperoxaluria (n = 4), and cryptogenic cirrhosis (n = 2) with end-stage renal disease due to glomerulonephritis, diabetic nephropathy or renal failure caused by nephrotoxicity of immunosuppressive therapy after liver transplantation. Nine patients had lymphocytotoxic antibodies and 5/27 patients had a positive crossmatch pretransplant. RESULTS: One patient died due to bleeding complications, two patients lost the kidney graft due to initial non-function or technical problems. The incidence of acute and steroid-resistant rejections was 60% and 20% in patients with a positive cross-match compared to 32% and 14% in negative cross-match transplants. Only two patients experienced a rejection episode of the kidney (3.7%). No hyperacute rejection of the kidney graft occurred. Long-term patients and graft survival was not impaired in the presence of a positive cross-match. The 1- and 5-year survival rates of patients who underwent combined transplantation was 97% and 93% versus 91% and 83% in patients with liver transplantation alone. CONCLUSION: Combined liver-kidney transplantation is a safe treatment for endstage liver and kidney disease even in the face of a positive cross-match.

Adult↗
PubMed2001

3D-reconstruction of craniofacial structures of a human anencephalic fetus. Case report.

It was the purpose of this study to investigate the craniofacial bones, cartilages and major blood vessels of a human anencephalic fetus and to describe the malformations of these structures accompanying this developmental disruption. The head of a 16 week old human fetus with anencephaly was serially sectioned and the craniofacial bones, cartilages and major blood vessels were traced and reconstructed by 3D-computer technology. The sphenoidal, temporal and occipital bones showed severe malformations, whereas the bones of the facial cranium were normally developed. Both internal carotid arteries ended within the cerebro-vascular area with no further branches. The vertebral arteries also ended within the cerebro-vascular area. No arterial circle of Willis was developed. The notochord terminated normally in the sphenoid body. The observations indicate that the possible reason for this malformation was non-closure of the anterior neuropore of the neural tube. The normal termination of the notochord suggests that it had no influence on the pathogenesis of this malformation. The malformations of the temporal and occipital bones are contradictory to the hypothesis of Marin-Padilla (1991) that anencephaly is caused by a maldevelopment of the sphenoidal bone.

Abortion, Induced↗
PubMed2001

Cytotoxic necrotizing factor type 1-positive Escherichia coli causes increased inflammation and tissue damage to the prostate in a rat prostatitis model.

Infection of rat prostates with cytotoxic necrotizing factor type 1 (CNF1)-positive uropathogenic Escherichia coli caused more inflammation-mediated morphological and histological tissue damage than did infection with isogenic CNF1-negative mutants. These striking differences occurred despite the finding that bacterial counts for the strain pairs were indistinguishable. We conclude that CNF1 contributes to E. coli virulence in a model of acute prostatitis. To our knowledge, the results of this study provide the first demonstration of a role for any uropathogenic E. coli virulence factor in acute prostatitis.

Animals↗
PubMed2001

Interlaboratory variation of biochemical markers of bone turnover.

BACKGROUND: Biochemical markers of bone metabolism are used to assess skeletal turnover, but the variability of marker assays is still an issue of practical concern. We describe the results of an international proficiency testing program for biochemical bone markers among clinical laboratories. METHODS: Two serum and two urine pools (normal and increased marker concentrations) were sent on dry ice to 79 laboratories for analysis within 2 weeks of receipt. RESULTS: Data were submitted by 73 laboratories. The within-method interlaboratory CVs (CV(IL)s) were as follows: serum bone-specific alkaline phosphatase (n = 47 laboratories), 16-48%; serum osteocalcin (n = 31), 16-42%; urinary free deoxypyridinoline (n = 30), 6.4-12%; urinary total deoxypyridinoline and pyridinoline (n = 29), 27-28%; urinary N-terminal cross-linked telopeptide of type I collagen (n = 10), 39%; serum C-terminal cross-linked telopeptide of type I collagen (ICTP; n = 8), 22-27%; urinary hydroxyproline (n = 13), 12%. Analytical results showed both systematic and nonsystematic deviations. In identical samples, results obtained for the same marker by the same method differed up to 7.3-fold. In urine-based assays, correction for urinary creatinine slightly increased CVs. CONCLUSION: Even with identical assays and methods, results for most biochemical markers of bone turnover differ markedly among laboratories.

Biomarkers↗
PubMed2001

Inhibition of the helicase activity of HCV NTPase/helicase by 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide-5 '-triphosphate (ribavirin-TP).

In the presented study the ribavirin-TP--an established inhibitor of the NTPase activity of the superfamily NTPase/helicases II--was investigated as an inhibitor of the unwinding activity of the hepatitis C virus (HCV) NTPase/helicase. The kinetics of the reaction revealed that ribavirin-TP reduces the turnover number of the helicase reaction by a mechanism that does not correspond to that of the inhibition of the NTPase activity. Our results suggest that derivatives of ribavirin-TP with enhanced stability towards hydrolytic attack may be effective inhibitors of the enzyme.

Acid Anhydride Hydrolases↗
PubMed2000

Diatom fucoxanthin chlorophyll a/c-binding protein (FCP) and land plant light-harvesting proteins use a similar pathway for thylakoid membrane Insertion.

The light-harvesting proteins in plastids of different lineages including algae and land plants represent a superfamily of chlorophyll-binding proteins that seem to be phylogenetically related, although some of the light-harvesting complex (LHC) proteins bind different carotenoids. LHCs can be divided into chlorophyll a/b-binding proteins found in green algae, euglenoids, and higher plants and into chlorophyll a/c-binding proteins of various algal taxa. LHC proteins from diatoms are named fucoxanthin-chlorophyll a/c-binding proteins (FCP). In contrast to chlorophyll a/b-binding proteins, there is no information so far about the way FCPs integrate into thylakoid membranes. The diatom FCP preproteins have a bipartite presequence that is necessary to enable transport into the four membrane-bound diatom plastids, but similar to chlorophyll a/b-binding proteins there is apparently no presequence present for targeting to the thylakoid membrane. By establishing an in vitro import assay for diatom thylakoids, we demonstrated that thylakoid integration of diatom FCP depends on the presence of stromal factors and GTP. This indicates that a pathway involving signal recognition particles (SRP) is involved in membrane integration just as shown for LHCs in higher plants. We also demonstrate integration of diatom FCP into thylakoids of higher plants and vice versa SRP-dependent targeting of LHCs from pea and Arabidopsis into diatom thylakoids. The similar SRP-dependent modes of thylakoid integration of land plant LHCs and FCPs support recent analyses indicating a common origin of chlorophyll a/b- and a/c-binding proteins.

Amino Acid Sequence↗
PubMed2000

YbRh(2)Si(2): pronounced non-fermi-liquid effects above a low-lyingmagnetic phase transition.

We report the first observation of non-Fermi-liquid (NFL) effects in a clean Yb compound at ambient pressure and zero magnetic field. The electrical resistivity and the specific-heat coefficient of high-quality single crystals of YbRh(2)Si(2) present a linear and a logarithmic temperature dependence, respectively, in more than a decade in temperature. We ascribe this NFL behavior to the presence of (presumably) quasi-2D antiferromagnetic spin fluctuations related to a very weak magnetic phase transition at T(N) approximately 65 mK. Application of hydrostatic pressure induces anomalies in the electrical resistivity, indicating the stabilization of magnetic order.

Journal Article↗
PubMed2000

Helicity dependence of gammap --> Npi below 450 MeV and contribution to the Gerasimov-Drell-Hearn sum rule.

The helicity dependence of the single pion photoproduction on the proton has been measured in the energy range from 200 to 450 MeV for the first time. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam, and a frozen-spin target. The data obtained provide new information for multipole analyses of pion photoproduction and determine the main contributions to the Gerasimov-Drell-Hearn sum rule and the forward spin polarizability gamma(0).

Journal Article↗
PubMed2000

New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis.

The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor induced angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed on vascular endothelial cells and initiate angiogenesis upon activation by VEGF. 1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787 / ZK222584), reversibly inhibit Flt-1 and KDR with IC(50) values < 0.1 microM. CGP 79787D also blocks the VEGF-induced receptor autophosphorylation in CHO cells ectopically expressing the KDR receptor (ED(50) = 34 nM). Modification of the 1-anilino moiety afforded derivatives with higher selectivity for the VEGF receptor tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally well absorbed, these compounds qualify for further profiling and as candidates for clinical evaluation.

Administration, Oral↗