Soluble HLA class I serum concentrations increase with transplant-related complications after liver transplantation.
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Biomedical subjects
Publications and source records attributed to W Vogel.
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Human biglycan is a small proteoglycan that is expressed at high levels in the growing skeleton and in human skin at the cell surface of differentiating keratinocytes. The human gene for biglycan (BGN) has previously been mapped by in situ hybridization to the Xq27-q28 region. Employing somatic hybrid cell lines with human X chromosome breakpoints within this region, we performed a fine mapping of the gene within Xq28. Our results indicate that the biglycan gene is proximal to the red/green cone pigment genes, G6PD, and coagulation factor VIII and is distal to DXS304, DXS305, and GABRA3. The biglycan gene precisely maps to a region of the X chromosome, where, by comparative gene mapping, one would expect to find the gene for X-linked dominant chondrodysplasia punctata/ichthyosis/short stature (Happle) syndrome. Hence, BGN is a candidate gene for the Happle syndrome.
The results with two new enucleation prothesis made of Bioverit are presented. After unilateral enucleation 14 rabbits received bioreactive, 14 rabbits biocompatible and 9 rabbits nylon prostheses. Implantation periods: 1-13 months. The tissue surrounding of the prostheses was studied histologically, the ceramic electron microscopically. Of 28 ceramic prostheses, 26 were adapted very well. Bioverit ist excellently suited as orbital prosthetic material, even half-open implants are possible.
The study's objective was to investigate serum levels of interleukin-8 (IL-8) after liver transplantation and to correlate these findings with tumor necrosis factor alpha serum levels and various clinical parameters. This was a prospective observation study conducted at the University Hospital of Innsbruck with 19 patients studied after orthotopic liver transplantation. Serum levels of IL-8 were analyzed by a solid-phase double ligand ELISA method. Serum TNF-alpha concentrations were measured by means of a commercially available radio immunoassay (IRE-Medgenix, Fleurus, Belgium). Three patients with an uneventful recovery after transplantation showed IL-8 levels below the detection limit. IL-8 serum levels markedly increased in patients with acute graft rejection, bacterial infection, and CMV disease. Increments of serum IL-8 preceded clinical complications in all patients. Highest levels were observed in bacterial infection, lowest in acute rejection. A statistically significant positive correlation was demonstrated between IL-8 and TNF-alpha serum levels in the context of bacterial infection and CMV disease. Elevated IL-8 serum levels represent a feature of alloimmune and infectious complications following liver transplantation. IL-8 can thus be considered a further indicator molecule in the heterogenous group of acute-phase reactants that accompany various inflammatory responses and do not permit the underlying clinical complication to be specified.
The study objectives were to investigate serum levels of interleukin-6 and C-reactive protein (CRP) after liver transplantation to correlated measurements with various clinical parameters. Twenty-three patients were studied after orthotopic liver transplantation. Serum IL-6 activity was evaluated by testing its capacity to induce proliferation of the IL-6-dependent hybridoma cell line B9. CRP was assessed by a nephelometric method. Only two of seven patients with acute cellular rejection developed an increase of serum IL-6 and CRP. In contrast to this rejection group, elevated IL-6 levels were observed in 7/9 patients with bacterial infections. Peak values for IL-6 were observed one day and for CRP two days after clinical diagnosis of infection. CMV disease was also associated with markedly increased IL-6 and CRP levels in 5/7 patients. Surprisingly, levels in this condition were approximately in the same range as in bacterial infection. IL-6 and CRP serum levels seen in bacterial infection and CMV disease were significantly higher than those in rejection (P less than 0.001). Serum IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6. Preferential elevations of IL-6 and CRP represent one feature of bacterial and viral infections. Elevation of TNF during rejection as described earlier is only rarely accompanied by increased serum IL-6 levels.
Cell kinetics of chorionic villi (CV) were studied by BrdUrd-incorporation detected by fluorescence-plus-Giemsa and BrdUrd-antibody techniques, and by DNA flow cytometry. Growth characteristics of long-term cultures of CV resembled fibroblasts with a total cell cycle time of 26 h, final S phase of 9 h, penultimate S phase of 16 h and G2/M phase of 3-4 h. Especially useful for a quick routine diagnostic approach, Ultroser RG, a commercially available serum supplement, significantly increased cell proliferation and stabilized cell cycle lengths to a total cell cycle time of 14 h, final S phase of 7 h, penultimate S phase of 6 h and G2/M phase of 4 h. Moreover, mitotic activity steadily increased in cultured CV, when studying six successive subculturings. This reflects adaptation to the culture conditions rather than an inherent response of cultured CV cells of increasing passage numbers. Native villi exposed to BrdUrd immediately after biopsy show lower rates of uptake than do aliquots after overnight incubation. As shown by BrdUrd-pulse labelling studies, more than 7 h are required to overcome the proposed 'biopsy stress'. This correlates with routine diagnostic techniques, in which many more metaphase cells are observed in short-term cultures than in direct preparations.
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Biglycan (PG-I, DS-PG-1, PG-S1) is a small cellular or pericellular matrix proteoglycan that is closely related in structure to two other small proteoglycans, decorin (PG-II, PG-S2, DS-PG2, or PG-40) and fibromodulin. The core protein is made up predominantly of a series of 11 tandem repeats that appear to have been used throughout evolution for protein-protein, protein-cell, or cell-cell interactions. The function of biglycan is unclear at this time, but it has been shown to bind transforming growth factor beta in vitro. We have cloned and partially sequenced the approximately 8-kilobase pair human biglycan gene. The gene consists of eight exons including one in the sequence that encodes the 5'-untranslated region of the mRNA. The first and seventh introns are approximately 1 kilobase pair, while the remainder are shorter. With the exception of the first two introns, all of the introns are spread throughout the hydrophobic repeat domain. The 500-base pair 5' to the start of transcription contains several elements that strongly suggest that it contains a significant amount of the gene promoter. The elements include one AP2 and five SP1 consensus sequences. Like in many other genes, the biglycan gene promoter lacks both a CAAT and TATA box but is rich in GC content. Using 3H-labeled cDNA and in situ hybridization and autoradiography of human chromosomes, the human gene was localized to the end of the long arm of the X chromosome (Xq27-ter). The relationship of biglycan to a number of other proteins containing the leucine-rich repeats is discussed with respect to homologies of cysteine regions immediately adjacent to the repeat sequences.
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Three cases of unusual chromosomal mosaicism are reported for which the cytogenetic data show inconsistent findings between CVS and AC or fetal tissue, and which cannot be explained simply by non-disjunction. For case 1, in CVS the karyotype was 46,XY, whereas lymphocytes and fibroblasts revealed 69,XXY. DNA fingerprinting indicated one paternal and two maternal chromosome sets, the latter most probably due to omission of maternal meiosis II. For case 2, in CVS mos 46,XX/47,XX,+ mar de novo was observed. Amniotic fluid cells had the karyotype 46,XX. The origin of the marker chromosome might be explained by at least two events of unknown order (a somatic chromosome/chromatid deletion and non-disjunction of the homologous chromosome). In case 3 (CVS: mos 46,XY/46,XY,19q+ de novo; amniotic fluid cells, lymphocytes, and fibroblasts: 46,XY), the surplus of chromosome material in 19q+ might be explained on the basis of a somatic translocation. The idea of a chimera is less convincing, as the mosaic finding is restricted to one tissue. Furthermore, there was no hint of a vanishing twin. Hitherto, no case of structural chromosome mosaicism in CVS has been reconfirmed in fetal tissues.
In accordance with observations by other groups direct CVS preparations reveal only a few mitoses, whereas semi-direct cultures (overnight incubation) give good results. By monitoring the BrdU uptake with an immunological method, a delay in the proliferation activity in native villi could be observed up to 7 h after biopsy.
Profound biological changes occur in patients treated with interferon. Observations of endocrine changes prompted us to examine the effects of subcutaneous alpha-interferon administration in single doses on circulating levels of thyroid stimulating hormone, total thyroxine, and total triiodothyronine in 10 volunteers (5 healthy subjects and 5 patients with hepatitis C). Blood samples were taken on an out-patient basis immediately before and 2, 12, 24, 48, and 72 h after administration of 1, 3, or 5 x 10(6) units of recombinant alpha-interferon. Application of the different dose levels was randomly assigned. Plasma samples were stored at -80 degrees C; after collection of samples had been completed hormone levels were measured using commercially available test kits. At all time points before and after injection of alpha-interferon, standard deviations of measured hormone levels of healthy control subjects and patients overlapped to a considerable extent. At a dose level of 5 x 10(6) units, alpha-interferon significantly increased cortisol levels as described, and decreased the level of thyroid stimulating hormone in the group receiving alpha-interferon as compared to placebo-treated healthy volunteers. The effects occurred 12 h after injection. Maximum suppression of thyroid stimulating hormone levels was observed 24 h after injection, when serum levels of thyroxine and triiodothyronine also were significantly reduced. We conclude that subcutaneous alpha-interferon treatment with doses as low as 5 x 10(6) units affects the control of thyroid function.
An attempt was made to reduce the risk of infection following liver transplantation by means of selective bowel decontamination with tobramycin, polymyxin E and amphotericin B, as well as short-term systemic antibiotics with cephotaxim and tobramycin. After 53 consecutive orthotopic hepatic transplants performed in 51 patients between 1985 and 1987, a total of eight pneumonias occurred as the clinically most significant infection. Two pneumonias were caused by cytomegalovirus, one by Pneumocystis carinii, one by Candida and the remaining four by various bacteria. In 6 patients, bacteria were cultured from the blood, but only in one case was an indwelling catheter identified as the source of the septicemia. Taking all samples together, Streptococcus faecalis was the bacterium most frequently cultured, which was not covered by the prophylactic antimicrobial regime applied. Pseudomonas, however, and gram-negative bacteria were demonstrated much less frequently. Vaginal and oral Candida infections, as well as oral and genital herpes simplex infections, responded well to topical therapy with fungicide and aciclovir, respectively. Three patients developed cytomegalovirus (CMV) hepatitis. All five CMV infections were successfully treated with ganciclovir and hyperimmunoglobulin, as well as reduction of prophylactic immunosuppression. Out of 15 patients transplanted for posthepatitic cirrhosis, 7 developed a recurrence of the infection (5 hepatitis B virus) 2 hepatitis C virus) in the graft. Two died of the cirrhosis, three are still alive with cirrhosis but sufficient graft function, and one patient is suffering from chronic active hepatitis. One patient grafted for acute hepatic failure was able to clear the delta virus within 1 year post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
Two types of metabolically regulated K channels have been identified for the first time in enzymatically demyelinated fibres of amphibian sciatic nerve using the patch-clamp technique. A maxi K channel with a single-channel conductance of 132 pS (105 mM K on both sides of the membrane, 15 degrees C) is activated both by micromolar concentrations of internal Ca and by depolarization. A second type of K channel with a conductance of 44 pS is inhibited by intracellular adenosine 5'-triphosphate (ATP) with a half-maximal inhibitory concentration (IC50) of 35 microM. It is blocked by submicromolar concentrations of external glibenclamide. Both channels are sensitive to external tetraethylammonium chloride (IC50 = 0.2 mM for the maxi K channel and 4.2 mM for the ATP-sensitive channel). They may be part of a complex feedback system regulating axonal excitability under various metabolic conditions.
This study was designed to investigate acute effects of various doses of the cytokines IFN-alpha, IFN-gamma, Interleukin 2 and tumor necrosis factor alpha on white blood cell differential counts. Before initiation of phase II trials, a dose-determination phase was performed, where three different dose levels of each cytokine were applied as a single dose. White blood cell differential counts were assessed immediately before and 2, 12, 24, 48 and 168 h after injection. Patients enrolled suffered from metastatic cancer or chronic active hepatitis. In addition, IFN-alpha was administered to five healthy volunteers. Results indicate that cytokines cause rapid and transient changes in the numbers of leukocyte subsets. Hematologic changes were cell-type- and cytokine-specific: transient lymphopenia was observed after administration of all four cytokines, reaching a nadir 12 to 24 h after subcutaneous injection. Administration of TNF-alpha and IFN-gamma also caused transient monocytopenia. Neutrophilia developed after administration of Interleukin 2, IFN-alpha and TNF-alpha. We conclude that cytokines play a key role in the regulation of peripheral blood cell traffic by their capacity to influence homing patterns of peripheral blood leukocytes.
We describe a full-term immunocompetent neonate who developed jaundice at 3 weeks of age. Physical examination disclosed no abnormalities. Laboratory investigations showed direct reacting hyperbilirubinaemia and elevated liver enzymes. Liver biopsy revealed a non-caseating granulomatous hepatitis. The patient made an uneventful recovery within 4 weeks without therapy. Bacille Calmette-Guérin hypersensitivity reaction is suggested as the reason for this neonatal hepatitis.