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Biomedical subjects

W Baum

Publications and source records attributed to W Baum.

At least 19 recordsLinked to original sources
PubMed2005

Characterization of the nuclear import of human MutLalpha.

DNA mismatch repair (MMR) is essential for the maintenance of replication fidelity. Its major task is to recognize mismatches as well as insertion/deletion loops of newly synthesized DNA strands. Although different players of human MMR have been identified, the regulation of essential steps of MMR is poorly understood. Because MMR is initiated in the nucleus, nuclear import might be a mechanism to regulate MMR. Nuclear targeting is accomplished by conserved signal sequences called nuclear localization signals (NLS), which represent clusters of positively charged amino acids (aa). hMLH1 contains two clusters of positively charged amino acids, which are candidate NLS sequences (aa 469-472 and 496-499), while hPMS2 contains one (aa 574-580). To study the effect of these clusters on nuclear import, NLS mutants of hMLH1 and hPMS2 were generated and expressed in 293T cells. The subcellular localization of the mutant constructs was monitored by confocal laser microscopy. We demonstrated that missense mutations of two signal sequences, one in hMLH1 and one in hPMS2, lead to impaired nuclear import, which was especially prominent for mutants of the hMLH1 residues K471 and R472; and hPMS2 residues K577 and R578.

Amino Acid Sequence↗
PubMed2003

Indicators of quality of in-patient psychiatric treatment: the patients' view.

OBJECTIVES: The object of this study was to find out from psychiatric in-patients which aspects of care and treatment they considered important and how satisfied they were with these. DESIGN: One hundred and ninety-four in-patients were asked to rate the importance of, and their satisfaction with, 22 different aspects of in-patient care and treatment. The questionnaire, developed for the purpose of the study after a pilot phase including professional care givers and patients, contained 92 items and was returned by 52% of all discharged patients from the Psychiatric university hospital during a 3-month period. RESULTS: Patients made a clear distinction between aspects of treatment they considered important and aspects they were satisfied with. Ranked of highest importance were various therapeutic relationships, and respect for their rights and privileges. They were satisfied with their relationships with clinical staff but dissatisfied with medication. CONCLUSION: A well differentiated assessment of importance and satisfaction has implications for the evaluation of the quality of psychiatric care, for specific methods of treatment, and for the improvement of in-patient psychiatric care.

Health Services Research↗
PubMed2001

Apoptosis regulators and their role in tumorigenesis.

It has become clear that, together with deregulated growth, inhibition of programmed cell death (PCD) plays a pivotal role in tumorigenesis. In this review, we present an overview of the genes and mechanisms involved in PCD. We then summarize the evidence that impaired PCD is a prerequisite for tumorigenesis, as indicated by the fact that more and more neoplastic mutations appear to act by interfering with PCD. This has made the idea of restoration of corrupted 'death programs' an intriguing new area for potential cancer therapy.

Animals↗
PubMed2001

An improved procedure for the generation of recombinant single-chain Fv antibody fragments reacting with human CD13 on intact cells.

A procedure was developed to generate recombinant single chain Fv (scFv) antibody fragments reacting with the extracellular domain of human cell surface antigen CD13 (hCD13; aminopeptidase N) on intact cells. Membrane fractions prepared from a stably transfected hCD13-positive murine NIH/3T3 cell line were used to immunize BALB/c mice, with the intention that hCD13 would be the major immunogenic molecule recognized by the immune system. Spleen RNA from the immunized mice served to generate a combinatorial scFv phage display library. The library was adsorbed against non-transfected NIH/3T3 or Sf21 insect cells to eliminate nonrelevant binders. The supernatant was then used for panning with either hCD13-transfected Sf21 insect cells or a hCD13-expressing human leukemia-derived cell line. Therefore, the key concepts of the procedure were the presentation of hCD13 as the sole human antigen on murine NIH/3T3 cells and a screening strategy where hCD13 was the major common antigen of the material used for immunization and panning. Two different hCD13-reactive phages were isolated and the soluble scFvs were expressed in E. coli and purified. The two scFvs, anti-hCD13-1 and anti-hCD13-3, differed at four amino acid positions in their V(H) regions and both had high affinities for hCD13 as determined by surface plasmon resonance (K(D)=7 and 33x10(-10) M, respectively). Both efficiently recognized hCD13 on intact cells. Therefore, the procedure allowed the production of high affinity scFvs reacting with a desired antigen in its native conformation without requiring extensive purification of the antigen and should be useful for the preparation of scFvs against other conformation-sensitive cell-surface antigens.

3T3 Cells↗
PubMed2001

Gp130 and ras mediated signaling in human plasma cell line INA-6: a cytokine-regulated tumor model for plasmacytoma.

INTRODUCTION: Cytokines of the gp130-family, particularly interleukin(IL)-6, play a crucial role in the propagation of malignant plasma cells. MATERIALS AND METHODS: The role of IL-6 and other gp130-cytokines was studied in the human plasma cell line INA-6 in vitro and in INA-6 xenografts. The proliferative response to gp130-cytokines was evaluated and activated components of gp130-signaling pathways were identified by Western blotting and DNA binding studies. Specifically, expression of IL-6 and receptors for IL-6 and leukemia inhibitory factor were analysed by RT-PCR and ELISA. RESULTS: The plasma cell line INA-6 was cultured for several years remaining strictly dependent on exogenous IL-6. Other gp130-cytokines had no significant effect on INA-6 cell proliferation in vitro. Due to an activating mutation in the N-ras gene, mitogen-activated protein kinases (MAPK) were constitutively phosphorylated. In contrast, signal transducer and activator of transcription(STAT)-3 activation was dependent on stimulation with IL-6. Blocking of either one of these pathways resulted in a significant decrease of INA-6 cell proliferation. Remarkably, INA-6 xenografts did not require exogeneous IL-6 for proliferation in vivo. Instead, an autocrine IL-6 loop and, in certain tumor sublines, responsiveness to additional gp130-cytokines was induced during in vivo growth. CONCLUSION: Activation of the gp130 signal transducer is mandatory for INA-6 cell growth in vitro and in vivo. Both the MAPK and the Jak/STAT pathway are operative in malignant plasma cells and either one is essential for plasma cell growth. The INA-6 cell line provides a preclinical model to study growth regulation of human plasmacytoma cells and to evaluate novel therapeutic strategies.

Aged↗
PubMed2000

A novel protein (Fbf-1) that binds to CD95/APO-1/FAS and shows sequence similarity to trichohyalin and plectin.

The Fas/Apo-1/CD95 cell surface receptor belongs to the TNF receptor family of cell death inducing molecules. A number of cytosolic adapter proteins that mediate signal transduction of CD95 have been characterized, but some features of the molecular mechanisms of CD95-induced cell death remain elusive. We describe here a novel protein that can interact with the cytosolic domain of the murine CD95 receptor in a yeast two-hybrid assay. This novel protein was termed Fbf-1 for Fas binding factor and bears no sequence similarity to the known CD95 adapter proteins. Fbf-1 is 1173 aa long and has a theoretical molecular weight of around 130 kDa. The protein is expressed in a wide variety of tissues and is localized in the cytoplasm. Fbf-1 is a very hydrophilic protein, highly conserved between mouse and human and bears a carboxyterminal leucine heptad repeat reminiscent of leucine zipper protein interaction domains. In addition, it shows sequence similarity to trichohyalin and plectin pointing to a function as a structural protein.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell ALL.

Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission. Similarly, in SCID mice with advanced disease a significant prolongation of survival was seen. The therapeutic effects were dependent upon dose and affinity of the antibody. TH-69 is a high-affinity antibody (7.6 x 10(9) M-1) that rapidly induced modulation during treatment. The Fc-portion of the antibody was required for effective tumour cell killing. Complement deposition was found on tumour sections after TH-69 treatment and in part may account for tumour destruction. There was no evidence for antibody-dependent cellular cytotoxicity (ADCC). The kinetics of tumour disappearance suggested the initiation of a programmed cell death (PCD), despite the lack of significant DNA fragmentation. Unmodified high-affinity antibodies to the T-cell antigen CD7 have potential for T-cell ALL therapy.

Animals↗
PubMed1990

A delta pH clamp method for analysis of steady-state kinetics of photophosphorylation.

An instrumental device is described which allows steady-state kinetic measurements of photophosphorylation at a desired proton gradient which can be maintained throughout the course of the experiment ('delta pH clamp'). This is achieved by electronic regulation of light intensity using the calibrated 9-aminoacridine fluorescence signal as sensor of the gradient. The instrument is suitable for determination of kinetic parameters of the proton-translocating ATPase in isolated envelope-free chloroplasts under defined conditions. At clamped delta pH, phosphorylation as a function of substrate concentration shows Michaelis-Menten kinetics. The true Michaelis constants and the dissociation constants for phosphate and ADP are reported. The Michaelis constants are not affected by the magnitude of the proton gradient in the investigated range. The significance of these results is discussed.

Aminacrine↗
PubMed1984

Preservation of the helper and suppressor/cytotoxic T-lymphocyte phenotype in continuous culture.

The objective of the present investigation was to culture helper or suppressor/cytotoxic T cell subsets after extensive purification in interleukin 2-containing medium to determine whether phenotype changes for OKT4/91d6- or OKT8/Leu-2a-defined antigens do occur with prolonged culture. Repeated and sequential analysis of such polyclonally activated cultured T cells documented stability of the OKT4/91d6+ and OKT8/Leu-2a+ phenotype. Both populations could be considerably expanded in culture. However, mixing experiments revealed a growth advantage of the OKT8/Leu-2a+ subset. A significant number of cells expressing both phenotypic markers was not detectable. While cultured T cells promoted on interleukin 2 were stable for expression of these functionally important differentiation markers, additional studies on activation antigens revealed high numbers of Tac+ cells at an early time of culture and decreasing numbers during further incubation. The expression of Tac antigen preceded the exponential expansion of the culture. In contrast, the number of cells bearing Ia determinants steadily increased with prolonged culture.

Antibodies, Monoclonal↗
PubMed1977

[Amoxicillin and its excretion into bronchial secretion (author's transl)].

Various dates on amoxicillin (resorption, distribution, elimination, tissue passage, urinary excretion) are presented. The bacterial spectrum is more fully discussed. Amoxicillin is compared with ampicillin. Dosage and therapeutical results are presented. Within repeated bronchoscopic examinations necessary on account of bronchopulmonary affections determination of germs were done in 88 children. At the same time examination of ampicillin levels in bronchial secretions were performed after amoxicillin therapy with different high doses (3 x 125 mg to 3 x 750 mg) for 7 days. It could be shown that good antibiotic levels could be found in secretion specimens above all obtained 2 to 4 hours after the last amoxicillin administration. They could be found too, if there did not exist any purulent secretion or stronger inflammation. There are relations between the amount of dosage, the level in secretion as well as the influence on germs.

Adolescent↗
PubMed1976

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)].

Doxycyclin is one of the first efficacious depot antibiotics. It is used in two applications as Vibramycin (R) (peroral and Vibravenös (R) (parenteral). Doxycyclin has a favourable effect not only on different gram-positive and gram-negative bacteria but also on a lot of other germs as mycoplasms, rickettsias, protozoons and large viruses. The tissue invasions is a good one, because there is only a low fraction of free Doxycyclin and further a high lipid activity. Pharmacokinetic investigations of different age-groups show that good serum-levels can be reached because of the sensitivity of numerous germs. The levels are higher, as our experiences demonstrate, if the dose of 4 mg/kilo/weight is injected in two single doses. Our investigations are reported on 49 patients with diseases of the respiratory tract and on 25 patients with diseases of the urogenital tract. Doxycyclin was very useful especially in different forms of pneumonias. The results in infects of the urogenital tract are not so good ones. The compatibility of Doxycyclin can be characterised as very good for children.

Adolescent↗