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G Thiel

Publications and source records attributed to G Thiel.

At least 127 records · Page 7Linked to original sources

Plasma creatinine for the evaluation of recovery of glomerular filtration rate after discontinuation of cyclosporine A in bone marrow transplantation: results of a prospective study.

In clinical practice p-creatinine is used to estimate changes of GFR. Generally, it is believed that recovery of p-creatinine within 10% of initial baseline allows exclusion of relevant nephrotoxic changes. We evaluated whether recovery of GFR after discontinuation of CyA therapy can be adequately predicted by measuring p-creatinine alone. Fifty-four allogenic BMT patients were followed up by p-creatinine and classical inulin clearance (GFR) before BMT and 1, 3, 6, 12, 18, 24 months after BMT. A total of 10 patients fulfilled following three criteria: (1) 24 months total follow-up time; (2) at least 12 months follow-up after discontinuation of CyA therapy (3) no trimethoprim or cimetidine comedication at time of clearance measurement. Time after CyA withdrawal varied between 13 and 21 months (mean +/- standard deviation, 17 +/- 2 months); mean duration of CyA therapy was 8 +/- 2 months (minimum: 3 months, maximum: 11 months). After at least 12 months of CyA stop mean p-creatinine returned to baseline values. In contrast, mean GFR remained about 20% below baseline (paired sample Wilcoxon-test P < .02). Neither creatinine excretion nor body weight nor creatinine clearance changed significantly between baseline and 24 months after BMT. Follow-up of p-creatinine after CyA stop can overestimate the recovery of GFR. A 20% loss of GFR may remain unrecognized. We speculate that this phenomenon is due to tubular hypertrophy in the recovery phase.

Adult↗

Comparative genomic hybridization of human malignant gliomas reveals multiple amplification sites and nonrandom chromosomal gains and losses.

Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue.

Adolescent↗

Modulation of K+ channels in Vicia stomatal guard cells by peptide homologs to the auxin-binding protein C terminus.

Transduction of the auxin stimulus in plants is thought to entail binding of the hormone to a soluble auxin-binding protein (ABP) outside the cell and subsequent interaction between this auxin-protein complex and an integral membrane receptor ("docking") protein that couples the signal across the plasma membrane. To explore the structural requirements for ABP function, synthetic peptides were prepared to the amino acid sequences of the predicted surface domains of ABPzm1, the dominant ABP from Zea. Biological function was assayed under voltage clamp, monitoring the ability of the peptides to evoke auxin-related modulations in inward- (IK,in) and outward-rectifying (IK,out) K+ channel activities of Vicia guard cells in the absence of added auxin. Only the peptide corresponding to the C-terminal domain of ABPzm1 was active. The dominant response was an inactivation of IK,in, although the peptide also evoked an activation of IK,out. Inactivation of IK,in was complete within 20-30 s and was fully reversible, was marked by a slowing of voltage-dependent activation and deactivation, and was dependent on peptide concentration (K1/2, 16 +/- 6 microM). Buffering cytoplasmic-free [Ca2+] with EGTA had no effect on IK,in response to the peptide. However, virtually complete and reversible block of the response was achieved when cytoplasmic pH (pHi) was brought under experimental control using the weak acid butyrate. Parallel measurements of pHi using the fluorescent dye 2',7'-bis(2-carboxyethyl-5(6)-carboxyfluorescein (BCECF) and dual-wavelength laser-scanning confocal microscopy demonstrated that the C-terminal peptide evoked rapid and reversible cytoplasmic alkalinizations of 0.4 +/- 0.1 pHi unit and confirmed the antagonism of the pHi response in the presence of butyrate. These, and comparable results with the auxins indole acetic acid and 1-naphthyleneacetic acid, implicate the C-terminal domain of ABPzm1 in auxin-ABP coupling to pHi and an associated intracellular signaling cascade.

Amino Acid Sequence↗

[C-reactive protein and early diagnosis of kidney transplant rejection].

C-reactive protein (CRP), which is known to rise rapidly in the serum after tissue injuries or inflammation, was measured daily after renal transplantation during hospitalization up to day 28 in 45 consecutive patients. In 16 patients who developed neither an infection nor rejection the CRP level normalized within 3 to 5 days. In 7 out of 14 patients with graft rejection the CRP level rose 1 to 3 days before the clinical signs of rejection. 11 patients with overt infection all had a CRP rise. 6 other patients had a CRP rise: in 5 the clinical situation explained this rise but in the sixth no explanation was found. We conclude from our results that periodic measurement of CRP (for example twice a week), even under aggressive immunosuppression, can help in the early diagnosis of graft rejection after renal transplantation. In the event of infection CRP loses its usefulness with respect to graft rejection and the daily measurements have no further point.

C-Reactive Protein↗

Age-related nonrandom chromosomal abnormalities in human low-grade astrocytomas.

We report a cytogenetic investigation of 55 low-grade astrocytomas in 52 patients, 15 children and 37 adults. In addition to numerical aberrations such as trisomy 7 and gonosomal losses, we found structural and/or numerical aberrations of chromosome 1 in eight astrocytomas. There was a striking difference between the rearranged chromosomes in pediatric and adult patients. Whereas the pediatric tumors revealed monosomies 1p with accompanying trisomy 1q, the astrocytomas in adults showed partial or complete monosomies 1q.

Adolescent↗

Changes of telomere lengths in human intracranial tumours.

The termini of human chromosomes comprise stretches of G-rich repeats that are about 5-20 kilobase (kb) in length. The size of the telomeres can be determined by hybridization with probes specific for these (ttaggg)n sequences after digestion of chromosomal DNA with appropriate restriction enzymes and electrophoretic separation of the fragments. Here, probing with the 32P-labelled synthetic (TTAGGG)3 oligonucleotide revealed length changes of the telomeres occurring in intracranial tumours. Among 60 samples, analysed, 41.7% showed telomere elongation, and 21.7% telomere reduction, whereas 36.7% of the tumours exhibited equal lengths compared with the patients' peripheral blood leukocytes. Most of the elongated glioma telomeres exceeded in length those of untransformed astrocytes derived from human fetal tissue.

Adolescent↗

Microscopic elements of electrical excitation in Chara: transient activity of Cl- channels in the plasma membrane.

The plasma membrane of Chara corallina was made accessible for patch pipettes by cutting a small window through the cell wall of plasmolyzed internodal cells. With pipettes containing Cl- as Ca2+ or Ba2+ (50 or 100 mM), but not as Mg2+ or K+ salt, it was possible to record in the cell-attached mode for long periods with little channel activity, randomly interspersed with intervals of transient activation of two Cl- channel types (cord conductance at +50 mV: 52 and 16 pS, respectively). During these periods of transient channel activity, variable numbers (up to some 10) of the two Cl- channel types activated and again inactivated over several 100 msec in a coordinated fashion. Transient Cl- channel activity was favored by voltages positive of the free running membrane voltage (> -45 mV); but positive voltage alone was neither a sufficient nor a necessary condition for activation of these channels. Neither type of Cl- channel was markedly voltage dependent. A third, nonselective 4 pS channel is a candidate for Ca2+ translocation. The activity of this channel does not correlate in time with the transient activity of the Cl- channels. The entire set of results is consistent with the following microscopic mechanism of action potentials in Chara, concerning the role of Ca2+ and Cl- for triggering and time course: Ca2+ uptake does not activate Cl- channels directly but first supplies a membrane-associated population of Ca2+ storage sites. Depolarization enhances discharge of Ca2+ from these elements (none or few under the patch pipette) resulting in a local and transient increase of free Ca2+ concentration ([Ca2+]cyt) at the inner side of the membrane before being scavenged by the cytoplasmic Ca2+ buffer system. In turn, the transient rise in [Ca2+]cyt causes the transient activity of those Cl- channels, which are more likely to open at an elevated Ca2+ concentration.

Cell Membrane↗

Electrocoupling of ion transporters in plants.

In the plasmalemma of plants, the major ion transporters are voltage gated. Hence, they are intrinsically coupled via the membrane voltage. Theoretical predictions and electrophysiological recordings on guard cells demonstrate nonlinear oscillations of a dynamic system which provides long-term osmotic adjustment by switching between periods of net uptake and net release of salt, rather than by a steady-state.

Cell Membrane↗

Characterization of ion channels from Acetabularia plasma membrane in planar lipid bilayers.

Plasma membrane from Acetabularia acetabulum was prepared by aqueous-polymer two-phase partitioning and incorporated into planar 1-palmitoyl-2-oleoyl phosphatidylethanolamine bilayers by stirring in the presence of a (cis:trans) 325:100 mM KCl gradient. Under these conditions five distinct K(+)-selective channels were observed which had unitary chord-conductances (determined between 30 mV either side of the reversal potential) and frequencies of incorporation (in parentheses) of 1,600 pS (26%), 485 pS (21%), 259 pS (53%), 140 pS (37%) and 27 pS (37%). Two Cl(-)-selective channels were also observed, which had unitary chord-conductances of 8 and 48 pS and were present in 21 and 16% of bilayers, respectively. The voltage dependencies of channel open probability (Po), open-state time constant (tau o) and closed-state time constant (tau c) were determined for the 259, 140 and 27 pS K+ channels. The Po of all three channels increased with increasingly positive membrane potentials. Thus, since these channels were oriented with their extracellular face adjacent to the cis chamber, which was grounded, all would exhibit outward rectification in vivo. Changes in Po were effected by modulation of tau c in all channels, which shortened as membrane potentials became more positive, and also of tau o in the 140 and 27 pS channels, which increased as membrane potentials became more positive. Extracellular (cis) KCl concentration (and/or the KCl gradient across the bilayer) affected the Po of all three K+ channels, shifting the Po/membrane potential relationship in the direction of the change in the potassium reversal potential. In all channels this was achieved largely by changes in tau c.

Acetabularia↗

Cyclosporin A-induced transient rise in plasma alkaline phosphatase in kidney transplant patients.

In 1981 cyclosporin A (CyA) became available and replaced azathioprine (Aza) as the immunosuppressive agent in kidney transplantation at the University Hospitals in Basel, Switzerland. Patients on CyA and prednisone (CyA/p) therapy frequently demonstrated an isolated rise in bone-derived serum alkaline phosphatase (aP) concentration, but patients on Aza and prednisone (Aza/p) therapy did not. On the basis of long-term aP concentration and using noninvasive means, the present retrospective study was designed to investigate biochemical markers and radiographic signs of bone disease after successful kidney transplantation in patients on Cya/p treatment. Similar investigations were performed in patients on Aza/p and the results were compared. Follow-up examinations included clinical examination, radiography of the hand, and biochemical analysis of serum and urine. In 139 renal transplant patients on CyA/p, aP increased transiently after successful grafting (at transplantation 84 +/- 43 U/l; on day 90, 112 +/- 82 U/l). In 50 patients aP levels were higher at the time of transplantation (120 +/- 80 U/l) and aP peaked after 8 +/- 6 months, at a mean concentration of 242 +/- 103 U/l. In these patients aP concentrations exceeded the normal range for 16 +/- 10 months. None of the patients on CyA/p showed symptoms of bone disease when aP was increased. Radiological surveys revealed more pronounced osteodystrophy in patients at the time of transplantation, which increased aP to above the normal range after transplantation. Despite this rise in aP, over the long term bone lesions improved radiographically while bone mass remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Complications of immunosuppression].

In the near future several new immunosuppressive substances will be available: Cyclosporin G, IMM125 (both are new derivates of Cyclosporin A), FK506, Rapamycin, Leflunomid, Mycophenolic acid (RS-61443), Bredinin (Mizorinin), Brequinar, Deoxyspergualin and several new monoclonal antibodies (anti-CD4, anti-II-2-Receptor, anti-CD8, anti-CD45, anti-ICAM1 and others). Side-effects of immunosuppressants are classified in 1) relative drug-specific or 2) unspecific effects of over-immunosuppression (infections and malignancies). Nephrotoxicity of Cyclosporin A and guidelines for its prevention are covered in more detail. The authors fear, that the proliferation of new immunosuppressive drugs will make it more difficult, to carefully evaluate their side-effects.

Cyclosporine↗

Synapsin I, synapsin II, and synaptophysin: marker proteins of synaptic vesicles.

The nerve terminal of neurons is filled with small synaptic vesicles, specialized secretory organelles involved in the storage and release of neurotransmitters. The synapsins are a family of four proteins that are the major peripheral proteins on the cytoplasmic face of synaptic vesicles. Synaptophysin is the major integral membrane protein of synaptic vesicles. The characterization of the synapsins and of synaptophysin during the last years has revealed exciting information about their structure, regulation and possible function. To understand the role of the synapsins and synaptophysin in the biology of a nerve cell means to elucidate the fundamental mechanism of brain function, the release of neurotransmitter.

Amino Acid Sequence↗

Atrial natriuretic peptide release and volume regulation following kidney transplantation.

The major stimulus for atrial natriuretic peptide (ANP) release is atrial stretch and increased values are observed in volume overload states such as chronic renal failure. Since successful kidney transplantation restores volume homeostasis, we compared the effects of human cadaveric kidney transplantation on time course and changes of plasma ANP in the early postoperative period in 4 patients with successful and 4 patients with failed transplantation. ANP concentrations were elevated before transplantation in both groups (91 +/- 16 and 70 +/- 32 pmol/l) and decreased after successful (50 +/- 27 pmol/l, day 16) but increased after failed transplantation (146 +/- 45 pmol/l, day 16). Moreover, there was a close correlation between changes of body weight and ANP concentrations. Plasma renin activity decreased and plasma noradrenaline increased non-significantly in both groups, the latter more so after failed transplantation (116 +/- 42 to 194 +/- 156 vs 156 +/- 157 to 425 +/- 287 ng/l). No correlation was found between changes of renin activity or plasma catecholamines and ANP concentrations. The results indicate that the mechanisms governing release of atrial natriuretic peptide are operative in patients with chronic end-stage renal failure and after successful kidney transplantation with a return of atrial natriuretic peptide concentrations towards normal in the latter.

Adult↗