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Biomedical subjects

K Fischer

Publications and source records attributed to K Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2002

Association between joint bleeds and Pettersson scores in severe haemophilia.

PURPOSE: To assess and quantify the association of haemophilic arthropathy, measured by the radiological Pettersson score, with the number of joint bleeds suffered by the patient. MATERIAL AND METHODS: In order to quantify the effect of the cumulative number of joint bleeds on the Pettersson score, a study was performed using 295 Pettersson scores obtained in 117 patients with severe haemophilia. The patients were born between 1965 and 1994, and had no history of inhibitors. The number of joint bleeds was determined annually from the entry in the clinic and onwards. The localization of bleeds was not assessed. The patients entered the clinic at a median age of 3.6 years, and received intermediate dose prophylaxis, starting at a median age of 5.3 years. Evaluation of 1643 treatment years showed a mean of 6.8 joint bleeds/year. Pettersson scores were obtained at a mean age of 15.9 years (range 1.7-32.9) and had a median value of 4 points (range 0-50). RESULTS AND CONCLUSION: The Pettersson scores began to rise after the age of 5 years and increased with one point for every 13 joint bleeds (95% confidence interval 11-15). No evidence was found of 'autonomous' progression of Pettersson scores, independent of bleeds.

Adolescent↗
PubMed2001

Immunohistochemical localization and differential expression of cytochrome P450 3A27 in the gastrointestinal tract of rainbow trout.

In mammals the cytochrome P450 3A (CYP3A) subfamily isoforms are primarily expressed in liver and intestines with lesser amounts found in other tissues. The aim of this study was to examine the cellular localization and the expression pattern of CYP3A27 in the gastrointestinal tract (GI tract) of a freshwater teleost species, the rainbow trout (Oncorhynchus mykiss), a fish model used extensively for toxicological and carcinogenesis research. Using an avidin biotinylated enzyme complex and 3,3'-diaminobenzidine staining, strong cytoplasmic immunohistochemical staining was observed for CYP3A27 protein in hepatocytes and in enterocytes of the intestinal ceca and the proximal descending intestine when probed with a polyclonal antibody raised against rainbow trout P450 LMC5, a CYP3A protein. The intensity of epithelial staining decreased distally along the GI tract with faint staining observed in the epithelial cells examined near the vent. Western blot analysis was supportive of the immunohistochemistry results. Northern blot analysis also demonstrated that CYP3A27 mRNA was expressed along the entire GI tract. The major area of CYP3A27 mRNA expression was in the intestinal ceca, followed by the proximal descending intestine, at levels that were about three- to five-fold and two- to four-fold, respectively, greater than seen in the liver of the fish studied. Monooxygenase activities of intestinal ceca microsomes against testosterone and progesterone confirmed the presence of active CYP3A enzyme in this tissue. These results suggest that the intestine of rainbow trout may possesses substantial capacity for first-pass metabolism of xenobiotics by CYP3A27, which makes it an excellent model in which to study the consequence of such metabolism.

Animals↗
PubMed2001

Alteration of radiation-induced hematotoxicity by amifostine.

PURPOSE: To investigate whether amifostine can reduce radiation hematotoxicity. PATIENTS AND METHODS: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5 x 2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m(2) amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n = 501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. RESULTS: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10(3)/mm(3) to 5.8 x 10(3)/mm(3) (difference: 2.3 x 10(3)/mm(3)). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. CONCLUSION: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study.

Amifostine↗
PubMed2001

Mycobacterial lysocardiolipin is exported from phagosomes upon cleavage of cardiolipin by a macrophage-derived lysosomal phospholipase A2.

Pathogenic mycobacteria are able to survive and proliferate in phagosomes within host macrophages (Mphi). This capability has been attributed in part to their cell wall, which consists of various unique lipids. Some of these are important in the host-pathogen interaction, such as resistance against microbicidal effector mechanisms and modulation of host cell functions, and/or are presented as Ags to T cells. Here we show that two lipids are released from the mycobacterial cell wall within the phagosome of infected Mphi and transported out of this compartment into intracellular vesicles. One of these lipids was identified as lysocardiolipin. Lysocardiolipin was generated through cleavage of mycobacterial cardiolipin by a Ca2+-independent phospholipase A2 present in Mphi lysosomes. This result indicates that lysosomal host cell enzymes can interact with released mycobacterial lipids to generate new products with a different intracellular distribution. This represents a novel pathway for the modification of bacterial lipid Ags.

Animals↗
PubMed2001

Differential diagnostic use of interleukin patterns in patients being monitored after transplantation.

BACKGROUND AND AIM: We investigated how far the determination of selected interleukins in bodily fluids of patients who had received kidney allografts can help to confirm the diagnosis of complications after transplantations. MATERIALS AND METHODS: Levels of soluble interleukin-2-receptor, interleukin 6 and interleukin 8 were determined in serum and urine of 79 patients. According to the type of diagnosis obtained with histological, serological and microbiological methods and to the clinical course, the groups "stable graft function without complication", "allograft rejection", "cytomegalovirus infection", "systemic extrarenal bacterial infection", "urinary tract infection" and "pyelonephritis" were created. RESULTS AND CONCLUSIONS: The activation of the immune system in different ways depending on the trigger substance (alloantigen, virus, bacterium) and the possibility to differentiate systemic and local processes cause typical patterns of interleukin levels in serum and urine in conjunction with the above mentioned complications after kidney transplantation. Cytomegalovirus infections and systemic extrarenal bacterial infections differ from rejection by the unchanged urine interleukins IL 6 and IL 8, the local urinary tract infections differ from rejection by the unchanged serum interleukins. Acute pyelonephritis differs from rejection by the significantly higher serum IL 6 level. During our daily clinical work, the practical interleukin determinations were proven to be an important tool for early and differential diagnosis of complications after kidney transplantation.

Diagnosis, Differential↗
PubMed2001

Ion-pair RP-HPLC determination of sugars, amino sugars, and uronic acids after derivatization with p-aminobenzoic acid.

A new, selective, and sensitive ion-pair RP-HPLC method for the simultaneous determination of three classes of natural organic compounds, i.e., carbohydrates, amino sugars, and uronic acids, in environmental samples is presented. p-Aminobenzoic acid is used for precolumn derivatization of the analytes, enabling fluorescence (lambda(ex) 313 nm, lambda(em) 358 nm) or photometric detection (303 nm). The dependence of the derivatization yield on the reaction conditions is examined. Derivatives of lactose, galactose, glucose, mannose, xylose, arabinose, galacturonic acid, glucuronic acid, N-acetylglucosamine, and glycerinealdehyde were separated on a RP-C18 column with hydrophilic end capping within 35 min, applying TBAHSO4 as the ion-pair reagent. The concentration detection limits range between 20 and 30 microg L(-1) ((1-2) x 10(-7) M) for fluorescence detection and between 30 and 75 microg L(-1) for UV detection. A good linearity is achieved in the concentration range from 50 microg L(-1) to 100 mg L(-1) (r2 > 0.99). The described method has been applied for the determination of mono-/disaccharides, uronic acids, and amino sugars in soil solutions and in landfill leachates.

Journal Article↗
PubMed2001

Age-specific seroprevalence to varicella-zoster virus: study in Swiss children and analysis of European data.

Up to date epidemiological data provide the rationale for potential varicella immunization strategies in Europe. The scope of this study was: (1) to generate new seroprevalence data by evaluating sera of 970 individuals aged 0-16 years for the presence of IgG against Varicella-zoster virus (VZV); and (2) to review existing seroprevalence data. Of 256 individuals >12 years of age, 96.1% (95% confidence interval [CI], 93.7-98.5) were seropositive. Swiss citizens > 12 years of age were less likely to be seronegative than foreign citizens (2.3 vs. 15.4%; odds ratio, 0.17; CI, 0.05-0.58). The age-specific seroprevalence curve demonstrated a peak at 7 years of age (84.9%; CI, 75.2-94.5) followed by lower rates at 8 and 9 years. A peak at 7-10 years of age was found in all previously reported seroprevalence curves (chi(2)-test for trend of pooled data, P = 0.09; Poisson analysis, P < 0.001). It is concluded that: (1) > 90% of individuals in Europe acquire immunity against VZV before adolescence; (2) there is no evidence for a recent upward shift of the age at primary varicella; and (3) there may be a north-to-south gradient of seroprevalence. The peak at 7-10 years may represent a transient loss of detectable antibody by some individuals.

Adolescent↗
PubMed2001

Highly specific tumor binding of a 213Bi-labeled monoclonal antibody against mutant E-cadherin suggests its usefulness for locoregional alpha-radioimmunotherapy of diffuse-type gastric cancer.

A monoclonal antibody (E-cadherin delta 9-1) directed against a characteristic E-cadherin mutation (in-frame deletion of exon 9), found in diffuse-type gastric cancer but not in any normal tissue, was conjugated with the high linear energy transfer alpha-emitter 213Bi and tested for its binding specificity in s.c. and i.p. nude mice tumor models. After intratumoral application in s.c. tumors expressing mutant E-cadherin, the 213Bi-labeled antibody was specifically retained at the injection site as shown by autoradiography. After injection into the peritoneal cavity, uptake in small i.p. tumor nodules expressing mutant E-cadherin was 17-fold higher than in tumor nodules expressing wild-type E-cadherin (62% injected dose/g versus 3.7% injected dose/g). 78% of the total activity in the ascites fluid was bound to free tumor cells expressing mutant E-cadherin, whereas in control cells, binding was only 18%. The selective binding of the 213Bi-labeled, mutation-specific monoclonal antibody E-cadherin delta 9-1 suggests that it will be successful for alpha-radioimmunotherapy of disseminated tumors after locoregional application.

Animals↗
PubMed2001

Vascular grafts in the rat model: an anatomic study.

Vascular grafts in animal models have been used extensively in the microsurgical laboratory, and the rat offers an excellent source of graft to meet these needs. In this study, we compiled a list of vessels that were previously identified in experimental literature for use as vascular grafts in the rat model. We then dissected and measured both arterial and venous grafts taken from these sites in 12 adult rats. The surgical procedure for approaching each vascular graft was recorded. The diameter and harvestable length, the start and end points, and the number of branches of the graft were tabulated. We believe that these data will provide valuable insight applicable to the use of the rat vascular graft in microsurgical research and training.

Animals↗
PubMed2001

Primary structure of the Plasmodium vivax crk2 gene and interference of the yeast cell cycle upon its conditional expression.

The cdc2 gene product, a 34-kDa protein kinase, plays a universal role in the M phase of the eukaryotic cell cycle. To study the cell cycle regulation in malarial parasites, we have characterized a cdc2-related gene from the most widely distributed human malaria, Plasmodium vivax (Pvcrk2). The full-length Pvcrk2 revealed 90--99% homology with Crk2 proteins from other Plasmodium species and approximately 60% homology with p34(cdc2) proteins from higher eukaryotes. We used the temperature-sensitive Schizosaccharomyces pombe cdc2 mutant (cdc2-33(ts)) for gene complementation studies. Expression of the full-length 33-kDa PvCrk2 protein, a truncated 27-kDa version, and two chimeric proteins in which we exchanged the N- and C-terminal regions of PvCrk2 with their S. pombe counterparts at the restrictive temperature in the mutant cdc2-33(ts) did not complement the cell cycle defect. However, conditional expression of the Pvcrk2 genes or the chimera containing the C terminus from Spcdc2 in mutant cdc2-33(ts) cells produced cell-cycle-arrested phenotypes only in the induced state and at the permissive temperature. Our results thus provide the first compelling genetic evidence that the plasmodial Crk2 gene product(s) is capable of interfering with the well-conserved eukaryotic cell cycle machinery.

Amino Acid Sequence↗
PubMed2001

Fibroblast growth factor inhibits expression of neural markers in cultures of zebrafish early embryo cells.

Basic fibroblast growth factor (FGF) regulation of developmental markers in cell cultures derived from early zebrafish embryos was examined with the goal of in vitro culture of zebrafish embryonic stem cells and gaining an understanding of extracellular influences on early embryonic development. Markers were stem/primordial germ cell markers pou-2 and vas, neural markers zp-50, pax[zf-a], en-3, and wnt-1, and mesodermal markers gsc and myoD. Previously we had shown that FGF prevents the development of zebrafish pigment cells in vitro. In our culture system, FGF reduced expression of neural-specific markers, possibly implicating the FGF family in suppression of early neural cell development. Exposure to FGF for 24 hours at the time of seeding the cells was sufficient to suppress neural marker expression for a subsequent 4 days of culture, while absence of FGF for the first 24 hours of culture nullified the effect of FGF added subsequently. FGF predictably increased expression of gsc and myoD. Vas expression was unaffected, while pou-2 expression decreased with time in culture in the presence or absence of FGF. However, in situ hybridization identified a subpopulation of cells expressing pou-2, suggesting the possible continued existence of undifferentiated stem cells in the cultures.

Journal Article↗
PubMed2001

Prediction of many new exons and introns in Plasmodium falciparum chromosome 2.

The current prediction of genes in the Plasmodium falciparum genome database relies upon a limited number of specially developed computer algorithms. We have re-annotated the sequence of chromosome 2 of P. falciparum by a computer-assisted manual analysis, which is described here. Of 161 newly predicted introns, we have experimentally confirmed 98. We regard 110 introns from the previously published analyses as probable, we delete 3, change 26 and add 135. We recognise 214 genes in chromosome 2. We have predicted introns in 121 genes. The increased complexity of gene structure on chromosome 2 is likely to be mirrored by the entire genome.

Algorithms↗
PubMed2001

The sequence of a 200 kb portion of a Plasmodium vivax chromosome reveals a high degree of conservation with Plasmodium falciparum chromosome 3.

Within a 199,866 base pair (bp) portion of a Plasmodium vivax chromosome we identified a conserved linkage group consisting of at least 41 genes homologous to Plasmodium falciparum genes located on chromosome 3. There were no P. vivax homologues of the P. falciparum cytoadherence-linked asexual genes clag 3.2, clag 3.1 and a var C pseudogene found on the P. vivax chromosome. Within the conserved linkage group, the gene order and structure are identical to those of P. falciparum chromosome 3. This conserved linkage group may extend to as many as 190 genes. The subtelomeric regions are different in size and the P. vivax segment contains genes for which no P. falciparum homologues have been identified to date. The size difference of at least 900 kb between the homologous P. vivax chromosome and P. falciparum chromosome 3 is presumably due to a translocation. There is substantial sequence divergence with a much higher guanine+cytosine (G+C) content in the DNA and a preference for amino acids using GC-rich codons in the deduced proteins of P. vivax. This structural conservation of homologous genes and their products combined with sequence divergence at the nucleotide level makes the P. vivax genome a powerful tool for comparative analyses of Plasmodium genomes.

Animals↗
PubMed2001

Long-term outcome of individualized prophylactic treatment of children with severe haemophilia.

The development of arthropathy is a serious complication of severe haemophilia. With the use of prophylaxis, bleeds can be prevented and arthropathy delayed. We investigated whether an individually tailored prophylactic regimen can prevent arthropathy and whether it had a similar effect on orthopaedic outcome compared with that of a high-dose regimen. Efficacy was determined clinically and by radiographs of six major joints. Prophylaxis was started in 70 patients at a mean age of 4.1 years. Mean follow-up was 15.6 years (range 8-24.5 years). The mean factor VIII consumption was 2319 IU/kg/year. The mean number of joint bleeds was 3.5/year and the mean clinical score (maximum score 90) was 1.0, with a mean Pettersson joint score (maximum score 78) of 3.0 at a mean age of 13.5 years. In conclusion, long-term, early-onset, individualized prophylaxis in haemophilia is feasible and prevents arthropathy.

Adolescent↗
PubMed2001

Purity of factor VIII product and incidence of inhibitors in previously untreated patients with haemophilia A.

It has been suggested that ultrapure clotting factor products carry a greater risk for inhibitor development in patients with haemophilia. We compared the incidence of inhibitors in 59 previously untreated patients (PUPs) with severe haemophilia (endogenous factor VIII < 0.01 U L-1) A, who were initially treated with cryoprecipitate or intermediate purified products, with that in 22 patients exclusively treated with monoclonally purified and recombinant factor VIII. Persistent inhibitors were those with 1 Bethesda unit per mL or more, on more than one occasion, combined with a decrease in recovery. Incidences of persistent inhibitors were 17% (10/59) for patients who were treated with cryoprecipitate or intermediate-purity products and 9% (2/10) for monoclonally purified and recombinant factor VIII. Transient inhibitors appeared to develop earlier during treatment with ultrapure products as compared to treatment with intermediate/low-purity products. In conclusion, ultrapure products appear not to carry a higher risk for inhibitor development.

Adult↗
PubMed2001

Changes in treatment strategies for severe haemophilia over the last 3 decades: effects on clotting factor consumption and arthropathy.

A cohort study was performed among 214 patients with severe haemophilia, born 1944-1994, to describe changes in treatment over the last 3 decades and its effects on clotting factor consumption and haemophilic arthropathy. Data on treatment strategy, clotting factor consumption, and outcome were collected for 3567 patient years (from 1972 to 1998), and 493 Pettersson scores were analysed. Median follow up was 17 years (range 6-27 years), and median age in 1998 was 27.6 years. Since 1965, replacement therapy, prophylaxis, and home treatment have been used and treatment intensified. Over the last 3 decades, annual clotting factor consumption increased by 260%, for both prophylactic and on-demand treatment. Annual clotting factor consumption kg-1 increased during childhood and appeared to stabilize in early adulthood for patients born 1965-79, who were treated with early replacement therapy or early prophylaxis. In contrast, clotting factor consumption increased continuously for patients born before 1965, who had had no access to replacement therapy during the early years of their life. The annual number of joint bleeds decreased over the years. Arthropathy as measured by the Pettersson score generally became apparent around the age of 15 years and was lowest in patients treated with primary prophylaxis. In conclusion, clotting factor consumption has increased and haemophilic arthropathy has decreased due to the intensification of treatment for severe haemophilia over the last 3 decades. Annual clotting factor consumption stabilizes in adulthood for patients who receive early intensive treatment.

Adolescent↗