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Biomedical subjects

K Fischer

Publications and source records attributed to K Fischer.

At least 109 records · Page 6Linked to original sources
PubMed1998

Urokinase induces proliferation of human ovarian cancer cells: characterization of structural elements required for growth factor function.

Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [3H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo19,31 uPA19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF.

Antibodies, Monoclonal↗
PubMed1998

Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89.

In contrast to childhood acute lymphoblastic leukemia (ALL), the cell-biological features, clinical characteristics, and treatment outcome of CD10(-) pro-B ALL have not yet been determined in larger series of adult patients. Therefore, we studied 57 adult patients with newly diagnosed pro-B ALL (median age, 30 years) enrolled in two consecutive German multicenter ALL studies (03/87 and 04/89). Extensive immunophenotypic characterization of leukemic blasts could be performed on all patients, whereas adequate cytogenetic data were available in 33 cases and molecular studies in 18 cases, using reverse transcription-polymerase chain reaction to detect MLL-AF-4 transcripts. Twenty-two patients demonstrated a t(4;11)(q21;q23) and/or MLL-AF-4 rearrangements, and 6 patients had other structural abnormalities, including a t(9;22)(q34;q11) (N = 2). Nine patients had a normal karyotype. Patients with 11q23 abnormalities tended to be younger (median age, 29 years) and were characterized by male predominance (64%), hyperleukocytosis (median leukocyte count, 168 x 10(9)/L), and a frequent coexpression of CD65s (64%) as compared with patients with other cytogenetic abnormalities or a normal karyotype. Twelve of 16 (75%) pro-B ALL patients in study 03/87 and 30 of 41 (73%) in study 04/89 achieved a complete remission (CR). Sixteen of 30 patients in study 04/89 remain in continuous CR (CCR) in contrast to only 2 of 12 patients in study 03/87. Interestingly, all 7 patients treated with high-dose cytarabine and mitoxantrone as consolidation in study 04/89 remain alive and leukemia-free. One patient in study 03/87 and 8 in study 04/89 underwent autologous (N = 2) or allogeneic (N = 7) bone marrow transplantation (BMT). The median remission duration was 420 days for patients in study 03/87 and has not yet been reached in study 04/89. The median survival time of all pro-B ALL patients was 571 days in study 03/87 and 747 days in study 04/89. Among the 22 patients with a t(4;11) and/or MLL-AF-4 rearrangements, 17 achieved a CR and 8 are still in CCR, of whom 4 underwent an allogeneic BMT. Remission duration and overall survival did not differ significantly between pro-B ALL patients with 11q23 abnormalities and those with a normal karyotype or other structural abnormalities. These data indicate that intensification of postremission treatment may improve the prognosis of adult pro-B ALL, including patients with a t(4;11).

Adolescent↗
PubMed1998

Characterization and cloning of the gene encoding the vacuolar membrane protein EXP-2 from Plasmodium falciparum.

As a contribution to the characterization of the parasitophorous vacuolar membrane from Plasmodium falciparum we have begun the identification of vacuolar membrane proteins. Exported protein-2 (EXP-2) is a vacuolar membrane protein exposed into the vacuolar space. To further characterize EXP-2, it was purified, and the 45 N-terminal amino acids were determined by micro-sequencing. Based on this information, partial cDNA and genomic fragments were amplified by PCR and used as probes for the isolation of complete cDNA and genomic DNA clones. The single copy gene is located on chromosome 14, and is transcribed during the ring stage of parasite development. The open reading frame encodes an N-terminal signal sequence which is cleaved from the mature protein. The amino acid composition of EXP-2 is characterized by charged amino acids, with a high abundance of aspartate residues in the C-terminal portion of the protein. In contrast to EXP-1, an integral protein of the vacuolar membrane, EXP-2 lacks a typical hydrophobic transmembrane domain. We suggest that EXP-2 may associate with the vacuolar membrane via an amphipathic helix located in the N-terminal half of the protein.

Amino Acid Sequence↗
PubMed1998

[Argon plasma surgery (APC) in the upper aerodigestive tract. Initial results].

Cold knife surgery, electrosurgery and laser surgery all offer techniques, instruments, equipment and systems for resecting and destroying mucosal lesions and for hemostasis in the upper aerodigestive tract. When used in the head and neck, argon plasma surgery (APS) offers a new, contact-free, electrosurgical technique in which high frequency current is applied through ionized, and thus electrically conductive, argon(argon plasma) to the tissue undergoing treatment. Especially noteworthy in APS are its advantages for removing a lesion and controlling bleeding: the technique is easy to control, and the depth of the thermal tissue destruction is limited to a maximum of 3 mm even in wide-area application, so that damage to adjacent or submucosal tissues can be avoided. Initial results with APS in the reduction of hyperplastic nasal turbinates, treatment of hereditary hemorrhagic teleangiectasia (Osler's disease) in the nasal mucosa, and in treating progressive juvenile papillomatosis of the larynx have shown clear advantages for APS over other methods used.

Adolescent↗
PubMed1998

[Trans-pupillary hyperthermia of malignant choroid melanoma. Initial experiences].

UNLABELLED: The purpose of this report is to evaluate the efficacy of transpupillary thermotherapy (TTT) to treat choroidal melanoma. PATIENTS AND METHODS: Twelve patients with choroidal melanoma were treated. Four with small tumors close to the posterior pole received TTT alone; 8 were treated simultaneously with TTT and Ru-106 brachytherapy. To perform TTT a diode laser with a beam diameter of 3 mm was used. Exposure time ranged from 60 to 90 s until the retinal surface became light gray. Follow-up examinations were performed at 1-month intervals. If the tumor was partially regressed, additional TTT was performed to reach the endpoint of a chorioretinal scar. RESULTS: All tumors exhibited a reduction of tumor height in a maximal follow-up period of 6 months. Four cases showed complete regression within 3 months. Side effects were minimal. CONCLUSIONS: Treatment with TTT may be useful as a complementary modality to brachytherapy. A longer follow-up time is necessary for final evaluation.

Adult↗
PubMed1998

The use of the Port-A-Cath in children with haemophilia--a review.

Port-A-Caths have been used increasingly in children with severe haemophilia. In non-inhibitor patients where Port-a-Caths were used to facilitate long-term prophylaxis, the infection rate is rather low and ranges in the various studies from 0 to 29%, with a median follow-up time of about 27 months. Patients that received the Port-A-Cath for the induction of immune tolerance (inhibitor patients) have a high infection rate of 50% to 83%. Although this percentage is high, good venous access is extremely important, especially in this group. The number of both inhibitor and non-inhibitor patients in the studies are very small, and a prospective survey is important to obtain more adequate data.

Catheterization, Central Venous↗
PubMed1998

Physical strain-mediated microtubule reorientation in the epidermis of gravitropically or phototropically stimulated maize coleoptiles.

During gravitropic and phototropic curvature of the maize coleoptile, the cortical microtubules (MTs) adjacent to the outer epidermal cell wall assume opposite orientations at the two sides of the organ. Starting from a uniformly random pattern during straight growth in darkness, the MTs reorientate perpendicularly to the organ axis at the outer (faster growing) side and parallel to the organ axis at the inner (slower growing) side. As similar reorientations can be induced during straight growth by increasing or decreasing the effective auxin concentration, it has been proposed that these reorientations may be used as a diagnostic test for assessing the auxin status of the epidermal cells during tropic curvature. This idea was tested by determining the MT orientations in the coleoptile of intact maize seedlings in which the gravitropic or phototropic curvature was prevented or inversed by an appropriate mechanical counterforce. Forces that just prevented the coleoptile from curving in a gravity or light field prevented reorientations of the MTs. Forces strong enough to overcompensate the tropic stimuli by enforcing curvature in the opposite direction induced reorientations of the MTs opposite to those produced by tropic stimulation. These results show that the MTs at the outer surface of the coleoptile respond to changes in mechanical tissue strain rather than to gravitropic or phototropic stimuli and associated changes at the level of auxin or any other element in the signal transduction chain between perception of tropic stimuli and asymmetric growth response. It is proposed that cortical MTs can act as strain gauges in a positive feed-back regulatory circle utilized for amplification and stabilization of environmentally induced changes in the direction of elongation growth.

Cotyledon↗
PubMed1998

Molecular characterization of a carbon transporter in plastids from heterotrophic tissues: the glucose 6-phosphate/phosphate antiporter.

Plastids of nongreen tissues import carbon as a source of biosynthetic pathways and energy. Within plastids, carbon can be used in the biosynthesis of starch or as a substrate for the oxidative pentose phosphate pathway, for example. We have used maize endosperm to purify a plastidic glucose 6-phosphate/phosphate translocator (GPT). The corresponding cDNA was isolated from maize endosperm as well as from tissues of pea roots and potato tubers. Analysis of the primary sequences of the cDNAs revealed that the GPT proteins have a high degree of identity with each other but share only approximately 38% identical amino acids with members of both the triose phosphate/phosphate translocator (TPT) and the phosphoenolpyruvate/phosphate translocator (PPT) families. Thus, the GPTs represent a third group of plastidic phosphate antiporters. All three classes of phosphate translocator genes show differential patterns of expression. Whereas the TPT gene is predominantly present in tissues that perform photosynthetic carbon metabolism and the PPT gene appears to be ubiquitously expressed, the expression of the GPT gene is mainly restricted to heterotrophic tissues. Expression of the coding region of the GPT in transformed yeast cells and subsequent transport experiments with the purified protein demonstrated that the GPT protein mediates a 1:1 exchange of glucose 6-phosphate mainly with inorganic phosphate and triose phosphates. Glucose 6-phosphate imported via the GPT can thus be used either for starch biosynthesis, during which process inorganic phosphate is released, or as a substrate for the oxidative pentose phosphate pathway, yielding triose phosphates.

Amino Acid Sequence↗
PubMed1998

Multifunctional potential of the plasminogen activation system in tumor invasion and metastasis (review).

Tumor cell migration and invasion into the surrounding tissue depend on the invasive capacity of cells leading to the loosening of cell-cell and cell-substratum contacts via cell surface associated proteolytic enzyme systems. Plasmin is one of the enzymes involved in these complex events. It is generated by the cleavage of the proenzyme plasminogen upon the action of the urokinase-type plasminogen activator (uPA). uPA is synthesized and secreted by tumor cells and normal cells and interacts with a specific cell surface receptor (uPAR) thereby focalizing enzymatic activity to the cell surface. The activity of uPA is controlled by plasminogen activator inhibitors type-1 and type-2. A strong statistically independent prognostic impact has been attributed to uPA and its inhibitor PAI-1 in a variety of malignancies. Besides its proteolytic activity, uPA in concert with uPAR exert biological effects characteristic for molecules with signal transducing properties including chemotaxis, migration/invasion, adhesion, and mitogenesis.

Cell Adhesion↗
PubMed1997

Hair concentrations and self-reported abuse history of 20 amphetamine and ecstasy users.

Hair samples of 20 volunteers of the techno-music scene, who more or less regularly consumed ecstasy tablets and speed and anonymously reported their abuse history, were analyzed in one to seven 3 cm segments for amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethamphetamine (MDE) and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butylamine (MBDB) by digestion in 1 M NaOH, subsequent extraction with C18 Bond Elut columns, derivatization with pentafluoropropionyl anhydride and GC/MS-SIM measurements using deuterated standards of A, MA, MDA and MDMA. The concentrations were in the regions 0.1 to 4.8 ng/mg for A (17 samples), 0.05 to 0.89 ng/mg for MDA (16 samples), 0.1 to 8.3 ng/mg for MDMA (16 samples), 0.12 to 15 ng/mg for MDE (13 samples) and 0.21 to 1.3 ng/mg for MBDB (2 samples). MA was not detected. For comparison the frequency and the concentration of these drugs in 124 different ecstasy tablets were determined by HPLC. The drug concentration in the hair segments were compared with the volunteers' reports. Despite the enormous interindividual differences qualitatively an increase of the total concentration of MDA, MDMA and MDE in the proximate 3 cm segments with increasing ecstasy abuse frequency during the last three month before sampling is recognized. In the individual comparison with the chronological consumer reports in most cases a longer interruption or a change of the abuse intensity is not clearly seen at the segment concentrations. As a reason the incorporation of the drugs from sweat into elder hair regions and the slow removal by washing are discussed.

Adolescent↗
PubMed1997

Construction and characterization of a Plasmodium vivax genomic library in yeast artificial chromosomes.

Here we describe the construction of a representative YAC library for the human malarial parasite Plasmodium vivax. As P. vivax cannot be maintained continuously under laboratory conditions, the P. vivax DNA necessary for the library construction was isolated from a single human patient presenting himself with vivax malaria to a local hospital in the Brazilian Amazon. Thus, this YAC library is the first of its kind to be generated from patient-derived material. The YAC library consists of 560 clones with an average insert size of 180 kb. Of 9 published P. vivax genes, 8 were found to be present in the library. In addition, 12 P. vivax telomeric YAC clones were identified.

Animals↗
PubMed1997

11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis.

Deletions of the long arm of chromosome 11 (11q) are one of the most frequent structural chromosome aberrations in various types of lymphoproliferative disorders. However, in most conventional chromosome banding studies of B-cell chronic lymphocytic leukemia (B-CLL), 11q deletions were not identified as a frequent aberration. The objective of this study was to analyze the frequency and clinical impact of 11q deletions in B-CLL by interphase cytogenetics using fluorescence in situ hybridization (FISH). Mononuclear cells from 214 patients with B-CLL were studied by FISH using the yeast artificial chromosome (YAC) clone 755b11 from chromosome region 11q22.3-q23.1; we previously showed that this clone was contained within a 2- to 3-Mb sized segment of 11q commonly deleted in lymphoproliferative disorders. Forty-three of the 214 (20%) tumors exhibited 11q deletions; 11q deletions were the second most frequent chromosome aberration following 13q14 (RB1 and/or D13S25) deletions (45%); they were more frequent than trisomy 12 (15%) or deletion of 17p (TP53 gene) (10%). Patients with 11q deletions were younger (P = .01) and had more advanced clinical stages (P = .01). 11q deletions were associated with extensive peripheral, abdominal, and mediastinal lymphadenopathy (P < .001). Patients with 11q deletions had a more rapid disease progression as shown by a shorter treatment-free interval (9 months v 43 months; P < .001). The prognostic effect of 11q deletion on survival strongly depended on the age: in patients less than 55 years old, the median survival time was significantly shorter in the deletion group (64 months v 209 months; P < .001), whereas in patients > or = 55 years old there was no significant difference (94 months v 111 months; P = .82). 11q deletions identify a new clinical subset of B-CLL characterized by extensive lymph node involvement. In younger B-CLL patients, this aberration is an important predictor of survival.

Adult↗
PubMed1997

Molecular cytogenetic delineation of deletions and translocations involving chromosome band 7q22 in myeloid leukemias.

Loss of chromosome 7 (-7) or deletion of its long arm (7q-) are recurring chromosome abnormalities in myeloid disorders, especially in therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML). The association of -7/7q- with myeloid leukemia suggests that these regions contain a novel tumor suppressor gene(s) whose loss of function contributes to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified: one in band 7q22 and a second in bands 7q32-q35. We analyzed bone marrow and blood samples from 21 patients with myeloid leukemia (chronic myeloid leukemia, n = 2; de novo MDS, n = 4; de novo AML, n = 13; t-AML, n = 2) that on chromosome banding analysis exhibited deletions (n = 19) or reciprocal translocations (n = 2) of band 7q22 using fluorescence in situ hybridization. As probes, we used Alu-polymerase chain reaction products from 22 yeast artificial chromosome (YAC) clones that span chromosome bands 7q21.1-q32, including representative clones from a panel of YACs recognizing a contiguous genomic DNA fragment of 5 to 6 Mb in band 7q22. In the 19 cases with deletions, we identified two distinct commonly deleted regions: one region within band 7q22 was defined by the two CML cases; the second region encompassed a distal part of band 7q22 and the entire band 7q31 and was defined by the MDS/AML cases. The breakpoint of one of the reciprocal translocations was mapped to 7q21.3, which is centromeric to both of the commonly deleted regions. The breakpoint of the second translocation, which was present in unstimulated bone marrow and phytohemagglutinin-stimulated blood of an MDS patient, was localized to a 400-kb genomic segment in 7q22 within the deletion cluster of the MDS/AML cases. In conclusion, our data show marked heterogeneity of 7q22 deletion and translocation breakpoints in myeloid leukemias, suggesting the existence of more than one pathogenetically relevant gene.

Acute Disease↗
PubMed1997

Study of structure and function of recombinant pea root plastid porin by biophysical methods.

Pea root plastid porin (Fischer et al. (1994) J. Biol. Chem. 269, 25754-25760), which belongs to the family of mitochondrial (eukaryotic) porins, was expressed in Escherichia coli in high amounts using the pQE expression system. The recombinant protein was reconstituted into lipid bilayer membranes, and its characteristic properties were compared to those of the native porin isolated from pea root plastids. No significant difference was found between the native and the recombinant form when the protein was preincubated in detergent and sterol. The recombinant porin seems to be a valuable model system for the study of eukaryotic porins by spectroscopic methods, in which high amounts of protein are needed. CD spectroscopy was performed to determine the secondary structure of the porin under different conditions. It was found to have a high degree of beta-sheet structure in the nonionic detergent Genapol X-80 and in lipid vesicles. The more polar detergent sodium dodecyl sulfate (SDS) induced a large amount of alpha-helix structure in the protein. Addition of sterol to the porin in Genapol buffer did not influence its secondary structure to any measurable extent, whereas it had a strong influence on channel forming activity in black lipid bilayers. First refolding experiments performed in decreasing urea concentrations are discussed together with the results of the other measurements with regard to protein folding and channel formation.

Circular Dichroism↗
PubMed1997

[Importance of mycoses in intra-abdominal infections].

Although there is a 20% yeast colonization in the gastrointestinal tract of the population, fungal infections appear only rarely in secondary peritonitis. The risk of severe mycosis increases after a major operation and when a patient is taking broad-spectrum antibiotics, is on total parenteral nutrition, is catheterized, and/or is immune-suppressed. In the past years the incidence of nosocomial fungal infections (usually Candida spp.) has risen significantly. Five percent of CAPD-related peritonitis is caused by fungi. In enteral anastomosis breakdown, invasive mycosis occurs more often, with an accompanying lethality of up to 80%. In severe pancreatitis, up to 5% of peripancreatic necrosis is infected with fungi. The clinical course of severe mycosis, like the septic syndrome, is associated with fungemia in up to 50% of cases. As most of the facultative pathogenic fungi are part of the physiological flora, it is difficult to interpret mycological cultures. In order to diagnose invasive fungal infections, histopathological techniques and serologic tests for antigens and antibodies are available. Three antifungal agents (amphotericin B, flucytosine, fluconazole) are available for intravenous administration. Amphotericin B is given at doses of up to 1 mg/kg per day, in liposomal galenism up to 3 mg/kg per day. Combining amphotericin B with flucytosine (150-200 mg/kg per day) a synergistic effect is reached. Fluconazole at a dosage of 200-800 mg per day represents an alternative with similar antifungal activity and lower side effects.

Antifungal Agents↗
PubMed1997

Construction and rapid screening of a representative yeast artificial chromosome library from the Plasmodium falciparum strain Dd2.

Large genomic DNA fragments from the Plasmodium falciparum clone Dd2 have been cloned as artificial chromosomes in yeast (YAC). The resulting library has a 10-fold redundancy for single-copy genes and consists of 1440 individual clones, including 240 telomeric clones, with an average insert size of 150 kb. A novel hybridization method was developed for the rapid and cost-effective screening of protozoan YAC libraries. The Dd2 YAC clones will facilitate a positional approach to the parasite's genes and aid in the dissection of genetic loci associated with the virulence and pathogenicity of P. falciparum.

Animals↗