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Biomedical subjects

Christian Müller

Publications and source records attributed to Christian Müller.

At least 109 records · Page 6Linked to original sources
PubMed2002

The evolution of the biotechnology industry in Germany.

In the past five years, the climate for commercial biotechnology in Germany has improved significantly and has resulted in an increase in the number of biotechnology companies. On examination of the underlying factors of the evolution of the biotechnology industry in Germany, and against the background of the current situation, it is predicted that many German biotech companies will have to change their business models to focus on product development rather than on platform technologies.

Biotechnology↗
PubMed2002

Elevations in procalcitonin but not C-reactive protein are associated with pneumonia after cardiopulmonary resuscitation.

A possible diagnostic role of procalcitonin (PCT) as a marker for ventilator associated pneumonia (VAP) in patients with an already triggered acute phase response after successful cardiopulmonary resuscitation (CPR) was investigated. In 28 patients with return of spontaneous circulation (ROSC) after out of hospital CPR, measurements of PCT, C-reactive protein (CrP), white blood cell count (WBC) and body temperature were compared with the clinical course of the patients. In this setting, PCT was the only marker to differentiate between patients with and without VAP (median value on day 1, 6.0 vs. 0.5 ng/ml; P<0.001). Using a cut off value of 1 ng/ml during the first 7 days after ROSC PCT had a sensitivity of 100% and a specificity of 75% to indicate VAP. PCT was elevated a median of 2 days earlier than the clinical diagnosis of VAP. Elevations in PCT can, therefore, indicate bacterial complications in cardiac arrest patients with a non-infectious acute phase response.

Adult↗
PubMed2002

Fluorescence resonance energy transfer (FRET) and competing processes in donor-acceptor substituted DNA strands: a comparative study of ensemble and single-molecule data.

We studied the fluorescence resonance energy transfer (FRET) efficiency of different donor-acceptor labeled model DNA systems in aqueous solution from ensemble measurements and at the single molecule level. The donor dyes: tetramethylrhodamine (TMR); rhodamine 6G (R6G); and a carbocyanine dye (Cy3) were covalently attached to the 5'-end of a 40-mer model oligonucleotide. The acceptor dyes, a carbocyanine dye (Cy5), and a rhodamine derivative (JA133) were attached at modified thymidine bases in the complementary DNA strand with donor-acceptor distances of 5, 15, 25 and 35 DNA-bases, respectively. Anisotropy measurements demonstrate that none of the dyes can be observed as a free rotor; especially in the 5-bp constructs the dyes exhibit relatively high anisotropy values. Nevertheless, the dyes change their conformation with respect to the oligonucleotide on a slower time scale in the millisecond range. This results in a dynamic inhomogeneous distribution of donor/acceptor (D/A) distances and orientations. FRET efficiencies have been calculated from donor and acceptor fluorescence intensity as well as from time-resolved fluorescence measurements of the donor fluorescence decay. Dependent on the D/A pair and distance, additional strong fluorescence quenching of the donor is observed, which simulates lower FRET efficiencies at short distances and higher efficiencies at longer distances. On the other hand, spFRET measurements revealed subpopulations that exhibit the expected FRET efficiency, even at short D/A distances. In addition, the measured acceptor fluorescence intensities and lifetimes also partly show fluorescence quenching effects independent of the excitation wavelength, i.e. either directly excited or via FRET. These effects strongly depend on the D/A distance and the dyes used, respectively. The obtained data demonstrate that besides dimerization at short D/A distances, an electron transfer process between the acceptor Cy5 and rhodamine donors has to be taken into account. To explain deviations from FRET theory even at larger D/A distances, we suggest that the pi-stack of the DNA double helix mediates electron transfer from the donor to the acceptor, even over distances as long as 35 base pairs. Our data show that FRET experiments at the single molecule level are rather suited to resolve fluorescent subpopulations in heterogeneous mixture, information about strongly quenched subpopulations gets lost.

Carbocyanines↗
PubMed2002

Lack of evidence for involvement of fetal microchimerism in pathogenesis of primary biliary cirrhosis.

Microchimerism may be involved in the etiopathogenesis of autoimmune diseases such as scleroderma. Primary biliary cirrhosis (PBC) shares some features with scleroderma, including a female predominance and a histologic picture reminiscent of chronic graft-versus-host disease. Our aim was to detect Y-chromosome-specific sequences as a marker for microchimerism in liver tissue of female patients with PBC. Liver biopsies of 105 female patients were investigated (28 patients with primary biliary cirrhosis, 25 patients with chronic hepatitis C, 6 patients with chronic hepatitis B, 9 with autoimmune hepatitis, and 37 patients with other liver diseases) by a sensitive Y-chromosome-specific polymerase chain reaction and/or fluorescence in situ hybridization (FISH) technique for the detection of the Y chromosome on a single cell level. In the liver of 9 (8.6%) female patients Y-chromosome-specific sequences were detected by PCR. Five of the patients had PBC as underlying disease, 2 had chronic hepatitis C, and 2 other liver diseases. No significant difference in the positivity rate for Y-specific sequences in females with PBC and patients with other liver diseases was found (P > 0.05). By FISH, single cells with one Y chromosome were detected in liver specimens from 3 of 21 patients suffering from PBC and from 1 of 13 patients with other liver diseases. In summary, microchimerism can be detected in livers of patients with hepatic diseases. However, in our study we found no evidence for an increased prevalence of microchimerism in the livers of patients with primary biliary cirrhosis. Our data suggest that microchimerism does not play a significant role in the development of PBC.

Biopsy↗
PubMed2002

Liver pathology in compound heterozygous patients for hemochromatosis mutations.

BACKGROUND: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown. AIMS: To evaluate the range of hepatic pathology in C282Y/H63D compound heterozygous patients. PATIENTS: 25 C282Y/H63D compound heterozygous patients with and without known underlying liver disease underwent liver biopsies for evaluation or abnormal liver tests. Eleven cadaveric liver donors with HFE wild type served as controls. METHODS: Mutations in the HFE gene were detected by polyacrylamide gel electrophoresis (PAGE) separation of digested polymerase chain reaction (PCR)-amplificates. The extent of light microscopic changes of liver architecture were studied on haematoxylin, eosin (H. E.) stains. In addition, the extent and the distribution of iron deposition was graded on Prussian blue-stained sections and hepatic iron was quantified by atom absorption spectroscopy. Serum ferritin concentration and the transferrin saturation index were measured using routine laboratory methods. RESULTS: Patients without underlying liver disease (n = 15): Hepatic inflammation was seen in only 8% but fibrosis was found in 36% of compound heterozygous patients. Eighty six percent of those patients had stainable iron predominantly found in Rappaport's zone 1 and 2, but all had a liver iron-index < 1.9. Transferrin saturation was found elevated in 36% of compound heterozygous patients. Patients with liver fibrosis showed significantly higher ferritin levels than patients without liver fibrosis (1110 ng/mL versus 307 ng/mL, p < 0.05). Patients with underlying disease (n = 10): In compound heterozygous patients, 77% had hepatic inflammation and 88% fibrosis. Stainable iron (44%) was less frequently found than in patients without underlying liver disease. Hepatic iron-index in patients with underlying liver disease was always below 1.17; transferrin saturation was elevated in only 22% of the compound heterozygous patients. Histologic hepatic iron-index was significantly lower in patients with underlying disease (median 0.047) as compared to patients without underlying liver disease (median 0.274, P < 0.05). CONCLUSIONS: The underlying liver disease determines the extent of hepatic pathology seen in livers of compound heterozygous patients. However, considerable histologic fibrosis can also be found in compound heterozygous patients without underlying liver disease.

Adolescent↗
PubMed2002

Inhibition of LPS-induced nitric oxide and TNF-alpha production by alpha-lipoic acid in rat Kupffer cells and in RAW 264.7 murine macrophages.

The activation of Kupffer cells represents a central mechanism of inflammatory liver injury involving the production of two important inflammatory mediators, nitric oxide and TNF-alpha. The aim of this study was to investigate the effect of the hepatoprotective compound alpha-lipoic acid (thioctic acid) on the production of nitric oxide and TNF-alpha in isolated rat Kupffer cells and RAW 264.7 macrophages. Isolated rat Kupffer cells or RAW 264.7 were either untreated, treated with alpha-lipoic acid (500 micro g/mL), or activated with 1 micro g/mL of lipopolysaccharide in the presence or absence of alpha-lipoic acid (0.2-500 micro g/mL). After 20 h the accumulation of nitrite was measured by the Griess assay. Tumour necrosis factor-alpha secretion was quantified after 4 h by L929 bioassay. Cell viability was determined by mitochondrial reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) DNA binding activity by gelshift assays. Treatment of Kupffer cells and RAW 264.7 with alpha-lipoic acid alone had no effect on basal nitric oxide production. However, alpha-lipoic acid significantly inhibited lipopolysaccharide-induced nitrite accumulation. alpha-Lipoic acid did not alter basal TNF-alpha secretion in Kupffer cells, whereas it significantly inhibited lipopolysaccharide-induced TNF-alpha production. alpha-Lipoic acid attenuated the activation of nuclear factor-kappaB and AP-1, two transcription factors pivotal in induction of inducible nitric oxide synthase and TNF-alpha. alpha-Lipoic acid significantly inhibits lipopolysaccharide-induced macrophage production of nitric oxide and TNF-alpha via an attenuated activation of NF-kappaB and activator protein-1. The reduced production of nitric oxide and TNF-alpha in Kupffer cells may be involved in the hepatoprotective action conveyed by alpha-lipoic acid.

Animals↗
PubMed2002

Dengue hemorrhagic fever in a British travel guide.

A 44-year-old female British travel guide suddenly had fever, nausea, vomiting, and diarrhea develop during her stay in South India. Four days later she was transported to our hospital. At admission she had a high temperature, impaired respiration, and abdominal pain. Clinical examination revealed bilateral pleural effusion, hepatomegaly, and ascites. Two days later the patient showed a generalized macular rash with a conspicuous sparing of small islands of normal skin. Hemorrhagic erythema on the palms and soles as well as focal petechiae on the hard palate and scleral and conjunctival bleeding were also observed. Hypotension and renal insufficiency developed 1 week after the illness started. Laboratory investigations revealed highly elevated levels of hepatic enzymes, severe hemolytic anemia, decreased platelet counts, and abnormal coagulation values. The presumptive clinical diagnosis of dengue hemorrhagic fever was supported by serologic testing that disclosed sustained high titers of hemagglutination inhibition antibodies. Symptomatic therapy with substitution of volume and albumin, blood transfusions, and administration of antipyretics resulted in complete recovery within 6 weeks.

Adult↗
PubMed2002

Proacrosin-deficient mice and zona pellucida modifications in an experimental model of multifactorial infertility.

In humans, male and female partners contribute more or less equally to the infertility problem. In approximately 20% of infertile couples, the concurrence of male and female factors is suggested to be responsible for infertility. Neither of these factors are known nor is there a model system to prove this assumption. We present such a model system in the mouse, in which the lack of acrosin in the male and modifications of the zona pellucida (ZP) in the female result in a significant reduction of the fertilization rate in vitro. We generated mice carrying a deletion in the proline-rich region (PRR) of the proacrosin gene, resulting in the absence of proacrosin in the homozygous PRR(-/-) male mouse. Under normal conditions, sperm from the proacrosin-deficient mice are still capable of ZP penetration and fertilization. In this study, modifications of the ZP of oocytes after superovulation were achieved by treatment with dimethylsulphoxide or aroclor-1254 or by in-vitro ageing. It is known that under these conditions, a time-dependent hardening of the ZP occurs. The rates of fertilization in vitro of treated and aged oocytes using sperm from PRR(-/-) mice were found to be significantly reduced when compared with those reached with wild-type sperm. The relevance of the acrosin status and ZP condition for fertilization success were further substantiated by the finding that the fertilization rate with PRR(-/-) sperm is affected by the thickness of the ZP. Our results demonstrate that the lack of acrosin in sperm in combination with modifications to the ZP can affect fertility and can be an experimental model for the study of unexplained infertility in human couples in which both male- and female-derived factors are suggested to be the underlying causes.

Acrosin↗
PubMed2002

Altering the expression of two chitin synthase genes differentially affects the growth and morphology of Aspergillus oryzae.

In Aspergillus oryzae, one full-length chitin synthase (chsB) and fragments of two other chitin synthases (csmA and chsC) were identified. The deduced amino acid sequence of chsB was similar (87% identity) to chsB from Aspergillus nidulans, which encodes a class III chitin synthase. The sequence obtained for csmA indicated that it had high similarity to class V chitin synthases. chsB and csmA disruption strains and a strain in which chsB transcription was controlled were constructed using the nitrite reductase (niiA) promoter. The strains were examined during hyphal growth by Northern analysis, analysis of the cell-wall composition and growth in the presence of Calcofluor white (CFW). The chsB disrupted strain and the uninduced p(niiA)-chsB strain exhibited hyperbranching, they had a lower level of conidiation than the wild-type and were sensitive to CFW at 50 mg l(-1). When chsB transcription was induced in the strain containing the p(niiA)-chsB construct, the strain displayed wild-type morphology on solid medium and at sub-maximum growth rates but the wild-type morphology was not fully restored during rapid growth in batch cultivation. The csmA disruption strain displayed morphological abnormalities, such as ballooning cells, intrahyphal hyphae and conidial scars. The growth was severely inhibited in the presence of 10 mg CFW l(-1). In none of the constructed strains did the cell-wall composition differ from the wild-type. Northern analysis indicated no change in the transcription of the chitin synthase genes csmA and chsC when chsB expression was altered, and there was no change in the transcription of chsB and chsC when csmA was disrupted.

Aspergillus oryzae↗
PubMed2002

Metabolic engineering of the morphology of Aspergillus oryzae by altering chitin synthesis.

Morphology and alpha-amylase production during submerged cultivation were examined in a wild-type strain (A1560) and in strains of Aspergillus oryzae in which chitin synthase B (chsB) and chitin synthesis myosin A (csmA) have been disrupted (ChsB/G and CM101). In a flowthrough cell, the growth of submerged hyphal elements was studied online, making it possible to examine the growth kinetics of the three strains. The average tip extension rates of the CM101 and ChsB/G strains were 25 and 88% lower, respectively, than that of the wild type. The branching intensity in the CM101 strain was 25% lower than that in the wild type, whereas that in the ChsB/G strain was 188% higher. During batch cultivation, inseparable clumps were formed in the wild-type strain, while no or fewer large inseparable clumps existed in the cultivations of the ChsB/G and CM101 strains. The alpha-amylase productivity was not significantly different in the three strains. A strain in which the transcription of chsB could be controlled by the nitrogen source-regulated promoter niiA (NiiA1) was examined during chemostat cultivation, and it was found that the branching intensity could be regulated by regulating the promoter, signifying an important role for chsB in branching. However, the pattern of branching responded very slowly to the change in transcription, and increased branching did not affect alpha-amylase productivity. alpha-Amylase residing in the cell wall was stained by immunofluorescence, and the relationship between tip number and enzyme secretion is discussed.

Aspergillus oryzae↗
PubMed2002

Gadodiamide as an alternative contrast agent during angioplasty in patients with contraindications to iodinated media.

PURPOSE: To evaluate gadodiamide as an alternative contrast agent for peripheral and renal angioplasty in patients with contraindications to iodinated contrast media. METHODS: Seventeen patients (10 men; mean age 74 years, range 68-83) with contraindication to iodinated contrast media were given gadodiamide as the contrast agent during peripheral and renal intra-arterial digital subtraction angiography (DSA) and subsequent percutaneous interventions (balloon angioplasty, stent placement). RESULTS: The mean volume of gadodiamide used was 136 +/- 46 mL (range 60-200). No serious side effects were observed, especially no change in renal or thyroid function; no exanthema or other allergic reactions were noted. In patients without renal artery intervention, serum creatinine at discharge remained unchanged (2.57 +/- 1.43 mg/dL to 2.40 +/- 1.28 mg/dL, p=NS). In patients undergoing angioplasty/stenting of renal artery stenoses, serum creatinine decreased significantly from 3.53 +/- 1.75 mg/dL to 2.36 +/- 1.15 mg/dL (p<0.01). All but 1 intervention was successful. Using a simple scoring system, 2 judges blinded to the contrast agent graded the quality of the peripheral DSAs as "good," whereas renal DSA images were only "sufficient." CONCLUSIONS: For patients with contraindications to iodinated materials, gadodiamide may be a suitable alternative for renal or peripheral DSA followed by angioplasty.

Aged↗
PubMed2002

Multicenter evaluation of a new immunoassay for intact PTH measurement on the Elecsys System 2010 and 1010.

BACKGROUND AND OBJECTIVE: The determination of parathyroid hormone (PTH) is of great clinical relevance in the assessment of calcium metabolic disorders. Although PTH was one of the first hormones measured by immunoassays, there are still many difficulties in its determination due to the low concentration of the hormone in blood and due to the heterogeneity of PTH resulting from different circulating hormone fragments. The aim of our multicenter-study was to evaluate the technical performance and the clinical validity of a new immunoassay for intact PTH measurement on the Elecsys Systems 2010 and 1010. METHODS AND RESULTS: The multicenter evaluation was performed in 11 clinical laboratories. The Elecsys PTH assay is a one step sandwich electrochemiluminescence immunoassay based upon the streptavidin-biotin technology. Two monoclonal antibodies are used in the assay providing detection of intact PTH. The imprecision study yielded within-run and between-days coefficients of variation of 3.1% - 6.6% and 3.4% - 15.6%, respectively using a three level control (PreciControl Bone, Roche Diagnostics) and human pool sera at two different concentrations (HS-low: 20 - 60 pg/ml, HS-high > 65 pg/ml). The analytical sensitivity calculated as the mean value plus 2 standard deviations of a within-run imprecision was below 2.70 pg/ml using zero calibrator matrix. Dilution linearity was observed up to 4890 pg/ml using zero calibrator matrix or human pool sera. Recoveries ranged between 85% - 115%. Serum, EDTA- and heparin plasma were evaluated for PTH measurement. Due to a better analyte stability (48h at 21 degrees C; 3d at 4 degrees C) EDTA plasma was recommended for PTH measurement. Results of the Elec sys PTH immunoassay correlated well (r = 0.926 - 0.994) with three different immunoradiometric assays (N-tact PTH SP, DiaSorin; Nichols Allegro Intact PTH, Nichols Institute Diagnostics; ELSA-PTH, CISBio International) and two different immunochemiluminometric assays (PTH-Intact-Immulite, DPC Biermann; Nichols Advantage Intact PTH, Nichols Institute Diagnostics) in technical and clinical method comparisons. The Passing/Bablok regression analysis yielded slopes of 0.692 - 1.729 and intercepts of -13.982 - +15.763 pg/ml. Deviations from slope 1.0 and intercept 0.0 were not unexpected due to differences in immunoassay standardization and probably due to the presence of different PTH fragments and a variable affinity of the used antibodies to these PTH fragments. Highly similar PTH concentration pattern of the Elecsys immunoassay and the Quick-Intraoperative Intact PTH immunoassay (Nichols Institute Diagnostics) obtained from specimens taken intraoperatively support the applicability of the Elecsys immunoassay to monitor the success of parathyroid resection. A reference range of 12.3 - 56.0 pg/ml calculated from PTH values of 43 apparently healthy individuals confirms reference limits published in the literature. The partition of collectives according to age showed, that individuals > 50 years have slightly higher PTH concentrations, independently of gender. This shift could be due to age itself or to an increased prevalence of individuals without obvious calcium metabolic disorders in this collective. CONCLUSION: The Elecsys PTH assay is a useful and reliable tool for determination of intact PTH. Our data support the intended use of the assay in clinical applications related to disorders of calcium metabolism.

Adolescent↗
PubMed2002

Revision surgery in pelvic discontinuity: an analysis of seven patients.

The technical aspect and clinical outcome of seven patients with pelvic discontinuities in acetabular revision surgery after a mean followup of 96 months were analyzed. The surgical treatment consisted of three consecutive steps beginning with mechanical stabilization of the two acetabular columns, followed by bony acetabular reconstruction by filling the osteolytic defect with allograft chips covered with autologous bone to achieve a contained defect after healing of the autograft, and anchorage of the cup using an acetabular reinforcement ring (five with a hook, two without a hook). Complications included a partial ischial nerve lesion, one intraoperative femoral shaft fracture, and one recurrent dislocation. One patient had revision surgery 12 months after the first revision surgery because of aseptic loosening, and in one patient two prominent screws had to be removed. The clinical improvement according to the Harris hip score was 40.1 points on average (preoperative, 33 points; postoperative, 73.1 points). At the final followup all acetabular components were stable and the pelvic discontinuity had healed. Despite the technical feasibility of such revisions and the acceptable clinical results, the complication rate is high. Early diagnosis of acetabular loosening to minimize the osteolytic loss of bone stock is important.

Acetabulum↗
PubMed2002

Mast cells and inflammation.

Mast cells have long been recognized as potent producers of a large panel of biologically highly active mediators such as biogenic amines, arachidonic acid metabolites, cytokines and chemokines, but most of their biological functions have been elusive and speculative. By taking advantage of mast cell-deficient mice, the role of mast cells in a variety of experimental settings can now be studied in detail and such approaches have dramatically altered and enlarged our knowledge about mast cell biology and function. Herein we will focus on the role of mast cells in inflammatory reactions of diverse origin, such as delayed type hypersensitivity, atopy, immune complex-mediated inflammation and innate immune responses. From the current standpoint, there is no doubt that the most outstanding and beneficial feature of mast cells is their recently discovered ability to induce a life-saving inflammatory response rapidly upon encountering microbes and microbial constituents. Nevertheless, the picture is also emerging that mast cells are deeply involved in the induction and maintenance of a variety of severe allergic and autoimmune diseases. However, a deeper understanding of their activation and immune-modulatory capacity might open a new window for the development of curative strategies.

Animals↗
PubMed1999

Study of the glucoamylase promoter in Aspergillus niger using green fluorescent protein.

An Aspergillus niger strain expressing a red-shifted green fluorescent protein (GFP) in the cytoplasm under the control of the glucoamylase promoter (PgIaA) was characterized with respect to its physiology and morphology. Although xylose acted as a repressor carbon source during batch cultivations, PgIaA-driven GFP expression by the glucoamylase promoter could be demonstrated in xylose-limited continuous cultures. In these cultivations, the xylose concentration was therefore too low to cause repression. Transient experiments initiated with a maltose pulse did not further induce red-shifted GFP production in xylose-limited continuous cultures. Maltose induction under conditions of xylose repression was microscopically observed and quantified in a flow-through chamber. Red-shifted GFP was first produced after 5 h induction. Finally the strain was characterized in glucose-limited continuous cultures, and here the area of the mycelium stained with cytoplasmic GFP increased with increasing specific growth rate, indicating that GFP can be used as a marker of cellular activity in this type of cultivation.

Aspergillus niger↗
PubMed1994

[Bioreactor for long-term maintenance of differentiated hepatic cell functions]

A culture model and a bioreactor construction for hepatocyte in vitro culture is described. The reactor is based on capillaries for hepatocyte immobilisation. Four discrete capillary membrane systems, each serving different purposes, are woven to create a three-dimensional framework for decentralized cell perfusion with low metabolite gradients and decentralized oxygenation and CO2 removal. The biochemical performance of reactors initially seeded with 2.5 x 109 pig hepatocytes was evaluated (pig albumin synthesis, midazolam- and lidocaine/MEGX metabolism, galactose elimination, enzymeleakage). The specific construction of the reactor enables a use in pharmacology alternatively to animal experiments.

Journal Article↗
PubMedDate not supplied

Determination of alpha-1 acid glycoprotein in patients with Ph+ chronic myeloid leukemia during the first 13 weeks of therapy with STI571.

The tyrosine kinase activity of the BCR/ABL fusion protein is required for the transformation in patients with chronic myeloid leukemia. The tyrosine kinase inhibitor STI571 inhibits the BCR/ABL and ABL kinase activity and consequently inhibits growth of BCR/ABL-positive cells. However, resistance to STI571 has been demonstrated in Ph+ cell lines and in CML patients and can be explained in some cases by point mutations within the ATP-binding pocket or amplification of the bcr/abl gene. In previous investigations using a nu/nu mouse model, the binding of STI571 to elevated levels of the plasmaprotein -1 acid glycoprotein (AGP) was identified as an additional mechanism of resistance to this therapeutic approach. Here we provide data on the expression of AGP in CML patients under therapy with STI571. Patients received 400 or 600 mg STI571 daily and apart from clinical parameters we determined AGP and C-reactive protein (CRP) plasma levels as well as the quantitative expression of both BCR/ABL and AGP mRNA in peripheral blood cells. Our data suggest that despite elevated AGP levels in 52% of our patients, no upfront resistance against STI571 was present. In conclusion, we demonstrated that during the first 13 weeks of STI571 therapy (i) plasma AGP levels in CML patients correlate with white blood cell count and stage of disease; (ii) patients with elevated AGP responded less rapidly to STI571; (iii) elevated AGP and CRP levels normalized in patients during treatment with STI571, although mRNA levels of AGP remained stable; (iv) initially normal levels of AGP remained in the normal range during treatment with STI571, indicating that STI571 does not trigger AGP expression in humans; and (v) in relapsed patients, elevation of AGP levels is present prior to hematological progress.

Aged↗