Different effects of cyclosporine or tacrolimus on hepatocyte acute phase proteins.
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Acute-Phase Proteins↗
Biomedical subjects
B Krüger
Publications and source records attributed to B Krüger.
Direct detection of premature protease activation in living pancreatic acinar cells.
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Animals↗
[Phenotypic characterization of equine Dermatophilus congolensis field isolates].
In 1993 and 1994 a highly increased occurrence of equine dermatophilosis was observed, and a study was initiated to determine phenotypic heterogeneity among 120 clinical isolates using biochemistry, antibiotic resistance profiles, membrane protein profiles and Western blotting. The biochemical examinations contained 1% equine serum in medium. Moreover, the API ZYM-test from bioMérieux was used. The biochemical reactions were suited to identify Dermatophilus congolensis but did not allow a differentiation among the various isolates. Antibiotic resistance in one or more isolates was observed against polymyxin B, enrofloxacin, oxacillin, neomycin and trimethoprim-sulfamethoxazol. All isolates were sensitive penicillin G, ampicillin, streptomycin, gentamicin, lincomycin, erythromycin, tetracycline, oxytetracycline, bacitracin and ceftiofur. The evaluation of silver-stained and immuno-stained membrane protein profiles showed minor differences among several isolates. In total, all isolates appeared to be closely related and the minor differences observed did not correlate with the geographic origin of the respective isolates.
Actinomycetales↗
[Role of protease activation in pathophysiology of acute pancreatitis].
For over a century it has been assumed that acute pancreatitis represents an autodigestion of the pancreas by its own, physiologically inactive proteases. Whether, how and where digestive proteases are being activated in the pancreas has remained the topic of much controversy and speculation. We review a number of recent studies that have been undertaken to elucidate the mechanisms and identify the initial subcellular localization of this process. These studies suggest that a premature and intrapancreatic protease activation does, indeed, occur early in pancreatitis and can be experimentally induced in vivo and in vitro. Activation begins within minutes of the induction of pancreatitis and is initially confined to cytoplasmic vacuoles at the apical pole of acinar cells. From here trypsin activity as well as its activation peptide are transferred to the cytosol of acinar cells where autodigestion may begin.
Animals↗
Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study.
One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L), and chronic (persistent) hepatic encephalopathy (HE), which developed spontaneously without the existence of known precipitating factors, were enrolled in a randomized, double-blind, placebo-controlled clinical trial of intravenously administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0, West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged number connection test A (NCT-A) time, and manifest HE (grades I and II, West-Haven criteria) were included in the investigation. The trial was planned as a confirmatory clinical trial OA administered in a dose of 20 g/d, as well as placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a period of 4 hours during 7 consecutive days with a superimposed protein load at the end of the daily treatment period. Primary variables were postprandial venous ammonia and NCT-A performance time measured following OA or placebo infusions to evaluate the net effect of the treatment on the prevention of the protein-induced hyperammonemia, and on parameters such as NCT-A influenced by hyperammonemia. Mental state gradation, portal systemic encephalopathy index (PSEI), and fasting ammonia levels were estimated as additional efficacy parameters. The data presented are based on the total study sample (intent-to-treat analysis), which included 63 patients in the placebo group and 63 patients in the OA group. Of the 126 patients, 114 met all the criteria for inclusion and completed the trial and treatment as outlined in the protocol (treated-per-protocol analysis). During baseline, the placebo and treatment groups were homogeneous with regard to mental states, NCT-A performance time, fasting venous blood ammonia levels, and Child-Pugh criteria. Although a slight improvement occurred in the placebo group, NCT-A performance times (P < .001) and postprandial venous ammonia concentrations in the OA-treated group showed improvements in comparison with placebo. In addition, venous fasting blood ammonia concentration (P < .01), mental state gradation (P < .001), and PSEI (P < .01), which includes the mental state gradation, NCT-A time, and postprandial venous ammonia in this trial, improved to a much higher degree in the OA group than in the placebo group. In subgroups retrospectively classified according to their initial mental state gradation, OA showed differential but uniformly significant efficacies in patients with manifest HE with respect to ammonia-lowering, improvement in NCT times, and mental state gradation. In patients with initial SHE, OA revealed differences between the medications in the psychometric test used. Adverse events consisting of mild gastrointestinal disturbances were observed in 3 of the OA-treated patients (5%). OA infusion appears to be a safe, effective treatment of chronic (persistent) manifest HE in cirrhotic patients. Additional investigations are required to assess the efficacy of OA in patients with SHE, as well as in patients with more severe grades of HE.
Adult↗
Expression of sulphonylurea receptors in bovine monocytes from animals with a different metabolic rate.
The aim of this study was to investigate the relationship between expression of sulphonylurea receptors (SUR) and metabolic rate (MR). SUR on monocytes and cells from muscle tissue were detected using fluorescent glibenclamide and flow cytometry. Transmembrane potential differences were detected by oxonol dye fluorescence measurements. A bovine model was used to induce differences in the MR by exposure to different ambient temperatures (4 degrees C and 18 degrees C), by different feeding levels (1.0- and 1.6-fold the metabolizable energy requirement for maintenance) and by alpha2-adrenergic stimulation. We found that cells from skeletal muscle (m. semimembranosus), immunochemically identified as smooth muscle cells, skeletal muscle fibres and monocytes, responded in comparable fashions to glibenclamide and ATP, i.e. with a depolarization, and to cromakalim with a polarization, suggesting that monocytes are useful indicators of regulatory events occurring in muscle cells. Glibenclamide fluorescence was assumed to represent SUR associated with KATP channels. Significant differences were detected in the percentage of depolarized monocytes in the different variants of the model. A linear correlation between monocytes that bound fluorescent glibenclamide and the MR was evident (with a coefficient of determination of 0.94) and was reproducible following reduction of the MR, by alpha2-adrenergic stimulation, suggesting that expression is involved in the regulation of whole-body energy expenditure.
ATP-Binding Cassette Transporters↗
Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.
PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.
Adolescent↗
[Psychosis in the early stage of HIV infection].
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AIDS Dementia Complex↗
Effects of stress-related signal molecules on cells associated with muscle tissue.
OBJECTIVE: To elucidate the physiologic background that makes muscle hypertrophy, especially that due to strenuous exercise, often parallel to stress sensitivity and signs of acute phase immune response. STUDY DESIGN: We used an animal model: lines of mice with hypertrophied (H) and normally developed (N) hind leg muscles, six in each case. Functional and receptor tests on cells from digested muscle tissue were made and analyzed by microplate cytofluorimetry and flow cytometry. RESULTS: Higher percentages of cells with a phagocyte marker (> 2-fold) and with opioid (about 1.3-fold) receptors were found, whereas the portion of glucocorticoid receptor-bearing cells tended to differ only among H and N. Naloxone, an opioid receptor antagonist, failed only in H to exert a suppressive effect on dihydrorhodamine 123 oxidation. CONCLUSION: These results and differences in responses of lipid trafficking and proteolytic activities to cortisol, naloxone and adrenergic receptor agonists suggest that not only the cell population associated with muscle tissue but also receptor-mediated responses that are known to be related to stress coping are different between H and N.
Adrenergic alpha-Agonists↗
[Bronchopulmonary carcinoids: surgical therapy and prognosis].
From 1976 to 1996 sixty patients with bronchopulmonary carcinoid were operated on at our institution. Post-operative histologic examination revealed typical carcinoid tumors in 50 cases and atypical carcinoid tumors in 10 cases. Preoperative diagnosis was correct in 32 cases (53%) and wrong in 11 cases (18%). In 17 cases (29%) we carried out a diagnostic thoracotomy. Resection was potentially for cure in 55/60 patients. Five-year-survival rates were 100% for patients with typical carcinoid tumors and 97% and 92% at 10 and 15 years, respectively. Regional lymphatic tissue was involved in typical (12%) as well as in atypical carcinoid tumors (20%). Furthermore distant metastasis occurred in both types of tumors, 4% in typical and 11% in atypical carcinoid tumors. There was no relationship between lymph node involvement and distant metastasis. Local recurrence was seen in 2/60 patients. Both patients suffered from atypical carcinoid tumors. Patients in whom only incomplete resection due to advanced tumor stage was possible showed no benefit from operative therapy.
Adolescent↗
Disassembly of rat pancreatic acinar cell cytoskeleton during supramaximal secretagogue stimulation.
In vivo stimulation of the exocrine pancreas with concentrations of secretagogue in excess of a maximally stimulating dose causes a marked disturbance of the intracellular segregation, transport, and exocytosis of digestive enzyme zymogens. Under physiological conditions elements of the cytoskeleton, most notably microtubules and microfilaments, are involved in the regulation of these intracellular events. We infused caerulein, a peptide analogue of cholecystokinin, at a supramaximal dose (10 micrograms.kg-1.h-1 for up to 6 h) intravenously in rats. To study the ultrastructural alterations of acinar cell microfilaments and microtubules by immunogold labeling, we used monoclonal antibodies directed against actin and beta-tubulin. As early as 30 min after the start of the secretagogue infusion we found a progressive disassembly of microtubules and microfilaments in exocrine cells. In immunoblot studies this disassembly of the cytoskeleton was paralleled by a degradation of its structural proteins actin and beta-tubulin. Our results indicate that the earliest morphological events during supramaximal secretagogue stimulation of the pancreas involve the disassembly and degradation of microtubules and microfilaments. This cell biological phenomenon offers an explanation for the disturbances of segregation, transport, and exocytosis of digestive enzymes, which are known to be associated with supramaximal stimulation of the pancreas and experimental models of pancreatitis.
Actin Cytoskeleton↗
Etofibrate therapy and effect of added low-dose cholestyramine in patients with combined hyperlipidaemia.
Patients with cardiovascular risk factors often have combined hyperlipidaemia which can be effectively treated with fibrate drugs. Resins can be added when further cholesterol reduction is necessary. In this clinical study, after an initial 4-week placebo prephase, 40 high-risk patients with combined hyperlipidaemia were treated with 2 x 500 mg etofibrate per day for five months to reduce blood lipids according to the intervention guidelines. Low-dose cholestyramine was added when further cholesterol reduction was needed. In 23 patients it was found that total cholesterol and LDL cholesterol could be significantly and sufficiently reduced by 30% (p < 0.05), and by 28.8% (p < 0.05) with etofibrate therapy alone. Additional cholestyramine treatment was necessary in 17 patients, resulting in significant total reductions of 37.6% (p < 0.05) in total cholesterol and 36.7% (p < 0.05) in LDL cholesterol by 4 g cholestyramine per day. Triglyceride reductions (22.8% and 25.0%) and fibrinogen reductions (11.2% and 13.4%) were similar in both treatment groups, showing no influence of the addition of cholestyramine. Tolerance and safety data revealed no negative effects for either treatment. Thus etofibrate, either alone or in combination with low-dose cholestyramine, proved to be an effective and well-tolerated therapeutic regime in combined hyperlipidaemia.
Adult↗
[Ornithine aspartate in hepatic encephalopathy: an established new therapeutic approach. Overview and results of current randomized studies].
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Ammonia↗
Immunohistochemical detection of lactoferrin in different human glandular tissues with special reference to the exocrine pancreas.
The immunohistochemical detection of lactoferrin was carried out with the PAP technique on pancreatic tissue samples of 23 patients, operated for acute (13) or chronic (4) pancreatitis as well as for adenocarcinomas (6). In order to control our immunohistochemical technique and the antisera produced by us we studied some tissue samples of human mammary gland and parotis. We detected lactoferrin in the glands of parotis and mammae as well as of their secretions. In the pancreatic tissue we found a positive reaction only in granulocytes of inflammatory areas with the exception of a luminal reaction on the surface of acinar cells in one case of pancreatic adenocarcinoma. We would like to interpret our results with the hypothesis of granulocytic origin of immunochemically detectable lactoferrin in the pancreatic juice of patients, especially in cases of chronic pancreatitis.
Adenocarcinoma↗
The glycosylation as source of the variability in prolactin patterns of individual human amniotic fluids.
Whilst it is known that prolactin has size heterogeneity in human amniotic fluid, no studies exist concerning the heterogeneity between individual amniotic fluids and the molecular properties of the prolactin forms which are connected with such a variability. To elecit this, prolactin forms from amniotic fluid taken from 6 full-term deliveries and processed separately, were fractionated by ConA-Sepharose, and characterized by SDS-PAGE, immunoblotting, and glycan detection of blotted prolactins. Recording the absorbance at 280 nm, dimers in the wash of the ConA-Sepharose column and in the elution with methyl-alpha-D-glucoside were evident in 3 fluids. The proteins of the chromatographically more rapid and retarded migrating fractions, generating the first dimer, of unbound material consisted on average of 74-83% and 85-90% of prolactin forms. The eluted fractions (bound material) contained 10-27% of the prolactin amount of the unbound fractions. The electropherograms using 12.5% gels indicated identical patterns of bands in repeated experiments per fluid but variability between the charges. Thus, the apparent molecular masses (kDa) and the proportions to the total prolactin (%) were 14.5-16 (8-12%), 20-23 (3-5%), 24 (4-8%), 25 (6-10%), 27 (19-25%), 28-29 (6-9%), 39-43 (0.5-1.0%), 60-64 (12-19%), 87-90 (8-11%) and 117-140 (2-7%) in nonreducing electrophoretical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Amniotic Fluid↗
Prolactin heterogeneity: a limitation on the evaluation of results from prolactin assays due to differences in immunoassays and the different bioactivities of prolactin forms.
Prolactin exists in biological fluids in several molecular forms. This raises two questions: (1) whether the assay of prolactin by immunotechniques is valid and reliable and (2) whether the different forms have different physiological roles, which might be exploited to improve diagnostic accuracy and data interpretation by the use of appropriate methods. To investigate these questions, prolactin from human amniotic fluid was separated, by concanavalin A-Sepharose affinity chromatography, into bound, retarded and unbound fractions (bound prolactin fraction, retarded prolactin fraction, unbound prolactin fraction), which were characterized by electrophoresis, immunoblotting and glycan detection blot. Virtually no contamination was found in the bound prolactin fraction, and the unbound prolactin fraction and retarded prolactin fraction were 74-83% pure according to densitometry of the electrophoretic and immunoblot patterns. High variability was found among the individual patterns. Glycan detection in the blotted fractions revealed that the bound prolactin fraction bands corresponding to M(r)25,000-29,000 were weakly glycolysated, whereas the bands of M(r)60,000-64,000 were significantly glycan-positive. Immunoreactive bands of unbound prolactin fraction and retarded prolactin fraction also stained positively for glycans. Using two commercial prolactin kits, the bound prolactin fraction forms were virtually undetectable. To demonstrate that the prolactin forms may depend on the hypothalamic state, two behaviourly different breeds of cattle were used as an animal model for studying hypothalamic activities. The number of immunoreactive bands, representing the prolactin forms, and the change of the forms in response to thyroliberin differed strikingly among the groups. The bioactivity of the forms was examined in bovine granulosa, oviductal, endometrial and spleen cells, and in murine splenocytes, the latter being activated by concanavalin A or allogeneically to create in vitro conditions that may have relevance for situations in vivo. The rate of incorporation of [3H]thymidine in murine splenocytes was dose-dependently enhanced only by bound prolactin fraction. The increase was abolished by purified anti-prolactin antiserum. However, the standard prolactin from the kits inhibited the proliferation even in low dose (1.25 microgram/l) and the inhibition was abolished in part by bound prolactin fraction. Thymidine incorporation into the bovine cells was significantly increased by low concentrations (2 micrograms/l) of unbound prolactin fraction and retarded prolactin fraction. Oviduct epithelial cells and splenocytes were stimulated by unbound prolactin fraction but not by retarded prolactin fraction in a dose of 16 micrograms/l. Thymidine incorporation into granulosa cells was inhibited by retarded prolactin fraction (16 micrograms/l) but not by unbound prolactin fraction.(ABSTRACT TRUNCATED AT 400 WORDS)
Amniotic Fluid↗
Structural elements of bactopterin from Pseudomonas carboxydoflava carbon monoxide dehydrogenase.
Bactopterin is a novel pterin occurring in bacterial molybdoenzymes as the organic portion of the molybdenum cofactor. Its structure is investigated here. The compound contains a single pterin ring and carries a side chain at carbon atom 6 of the pterin nucleus as indicated by the formation of pterin-6-carboxylic acid upon alkaline permanganate oxidation. Studies with phosphate-cleaving enzymes revealed the presence of two monophosphoric acid monoesters. The affinity of reduced bactopterin for thiol-Sepharose points to the presence of thiol(s) in active bactopterin.
Aldehyde Oxidoreductases↗
The pterin (bactopterin) of carbon monoxide dehydrogenase from Pseudomonas carboxydoflava.
Radioactively labeled carbon monoxide (CO) dehydrogenase has been obtained in good yield and purity from Pseudomonas carboxydoflava grown in the presence of [32P]phosphate. One enzyme molecule contained an average of 8.32 molecules of phosphate. The entire phosphate content was confined to 2 molecules of FAD and 2 molecules of a pterin. These were noncovalently bound. Molybdoenzyme cofactors could be extracted into N-methyl formamide; pterins were isolated by thin-layer chromatography. CO dehydrogenase contained a novel pterin, different from molybdopterin, which was also resolved in other bacterial molybdoenzymes. Therefore, it was tentatively named bactopterin. The characteristic features of bactopterin were as follows. A relative molecular mass, Mr, of 730 which was much greater than that of molybdopterin (330) (Mr values refer to molybdenum-free forms of the cofactors; presumably, the latter were also devoid of the sulfhydryl groups contained in the native compounds). A content of 2 molecules of phosphate/molecule compared to only 1 phosphate in molybdopterin. Bactopterin was three times less susceptible to air oxidation than molybdopterin. Native bactopterin was cleaved by perchloric acid into two phosphorous-containing fragments with Mr of 330 and 420. The smaller one is believed to be very similar to molybdopterin, the larger one was not a pterin but probably contained an aromatic structure.
Aldehyde Oxidoreductases↗