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Biomedical subjects

M Schmitz

Publications and source records attributed to M Schmitz.

At least 55 records · Page 3Linked to original sources
PubMed2000

Growth inhibitory effects of paclitaxel on human epithelioid sarcoma in vitro: heterogeneity of response and the multidrug resistance phenotype.

BACKGROUND: Epithelioid sarcoma is a highly malignant soft tissue tumor that is largely resistant to conventional chemotherapy and radiotherapy. Because paclitaxel has been proven to be effective in other human malignancies refractory to conventional chemotherapy, the authors analyzed the in vitro growth inhibitory effects of paclitaxel on the human epithelioid-sarcoma cell line GRU-1 and its clonal subpopulations GRU-1A, GRU-1B, and GRU-1C. METHODS: Paclitaxel-induced morphologic alterations were visualized using light microscopy, immunofluorescence microscopy, and transmission electron microscopy. The antiproliferative effects of paclitaxel on the cell lines were determined by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium' bromide (MTT) assay. The extent of paclitaxel-induced apoptosis was determined by light microscopy. The expression and function of P-glycoprotein and the multidrug resistance-associated protein (MRP) were defined by reverse transcriptase-polymerase chain reaction and fluorescence-activated cell sorter analysis. RESULTS: Paclitaxel-induced morphologic alterations such as micronucleus formation and microtubule bundles showed no significant differences between the parental cell line and its clonal subpopulations. A significant (P < 0.05) dose-dependent growth inhibition was observed in GRU-1 and its clonal subpopulations, with the IC(50) (concentration that inhibits 50%) values ranging from 0.04-0.49 microM in the different subpopulations. Paclitaxel-induced growth inhibition was accompanied by a slight increase in apoptosis. All cell lines showed an expression of and an effective function of P-glycoprotein and MRP. CONCLUSIONS: The differential response of GRU-1 and its clonal subpopulations to paclitaxel could not be predicted by the expression and function of P-glycoprotein and MRP, suggesting that other drug resistance mechanisms might be relevant in the heterogenous response observed in the epithelioid sarcoma cell lines in the current study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients.

Antibody reactivity against survivin, a recently identified tumor-associated protein, was determined in sera from patients with lung (n = 51) or colorectal cancer (n = 49). The same collection of sera was tested for the presence of antibodies against p53. Eleven sera from lung cancer patients and four sera from colorectal cancer patients reacted with purified recombinant survivin in an ELISA (21.6% and 8.2%, respectively), whereas four sera from lung cancer patients and nine sera from colorectal cancer patients contained anti-p53 antibodies (7.8% and 18.4%, respectively). The increase in prevalence when anti-survivin and anti-p53 antibodies were determined in parallel was statistically significant (29.4% versus 7.8%, P = 0.005 in lung cancer population; 26.6% versus 8.2%, P = 0.015 in colorectal cancer population). The high prevalence of anti-survivin antibodies makes these antibodies an attractive novel marker for the diagnosis of lung and colorectal cancer, particularly in patients lacking anti-p53 antibodies.

Antibody Formation↗
PubMed2000

Plasmacytoma of the tonsil with AL amyloidosis: evidence of post-fibrillogenic proteolysis of the fibril protein.

We report of a 58-year-old Caucasian man who was referred to the University Hospital with a greatly enlarged left tonsil which showed calcifications on computed-tomography scans. Histopathology revealed a plasmacytoma with secondary AL amyloidosis, ossifications, and multinucleated foreign-body-type giant cells. N-terminal sequencing of amyloid-fibril proteins purified from the formalin-fixed tissue showed the presence of two proteins of different size; these were of lambda-light-chain origin (subgroup V), measured approximately 15.2 kDa and 10.5 kDa, and had identical N-terminal ends (YVLTQPP). When the amyloid deposits were immunolabeled with a polyclonal antibody directed against lambda light chain, they showed two staining patterns: some deposits showed intense immunolabeling while others were not immunoreactive. Immunostaining of amyloid was completely absent after protease pre-treatment. Immunoelectron microscopy with gold-labeled secondary antibodies showed staining that was spatially related to amyloid fibrils and suggested that the antibody probably detected the fibril protein. Therefore, our hypothesis in this case is that the different immunostaining patterns are due to a post-fibrillogenic proteolysis of the fibril protein at the C-terminal end of the light chain, as indicated by the presence of two differently sized lambda-light-chain fragments with identical N-terminal ends.

Amyloidosis↗
PubMed2000

Exploring ADHD age-of-onset criterion in Brazilian adolescents.

OBJECTIVE: To explore age-of-onset criterion for the diagnosis of attention-deficit hyperactivity disorder (ADHD) in a school sample of young Brazilian adolescents. METHODS: 191 students aged 12 to 14 years were evaluated using DSM-IV ADHD criteria, measures of ADHD symptoms and global impairment. RESULTS: Both adolescents with ADHD (n = 30) and adolescents who fulfilled all DSM-IV ADHD criteria, except age of onset of impairment criterion (ADHD w/o age-of-onset, n = 27) had significantly higher scores on Attention Problems, Delinquent and Aggressive Behavior scales of the Child Behavior Checklist (CBCL) and lower scores on the Child Global Assessment scale (CGAS) than non-ADHD adolescents (n = 134). Adolescents with ADHD and youths with ADHD w/o age-of-onset did not differ significantly in any measure assessed. CONCLUSION: These results concur with recent literature proposing revision of the age-of-onset criterion for the diagnosis of ADHD.

Adolescent↗
PubMed2000

Solution structure and metal-ion binding of the P4 element from bacterial RNase P RNA.

We determined the solution structure of two 27-nt RNA hairpins and their complexes with cobalt(III)-hexammine (Co(NH3)3+(6)) by NMR spectroscopy. The RNA hairpins used in this study are the P4 region from Escherichia coli RNase P RNA and a C-to-U mutant that confers altered divalent metal-ion specificity (Ca2+ replaces Mg2+) for catalytic activity of this ribozyme. Co(NH3)3+(6) is a useful spectroscopic probe for Mg(H2O)2+(6)-binding sites because both complexes have octahedral symmetry and have similar radii. The thermodynamics of binding to both RNA hairpins was studied using chemical shift changes upon titration with Mg2+, Ca2+, and Co(NH3)3+(6). We found that the equilibrium binding constants for each of the metal ions was essentially unchanged when the P4 model RNA hairpin was mutated, although the NMR structures show that the RNA hairpins adopt different conformations. In the C-to-U mutant a C.G base pair is replaced by U.G, and the conserved bulged uridine in the P4 wild-type stem shifts in the 3' direction by 1 nt. Intermolecular NOE cross-peaks between Co(NH3)3+(6) and RNA protons were used to locate the site of Co(NH3)3+(6) binding to both RNA hairpins. The metal ion binds in the major groove near a bulge loop, but is shifted 5' by more than 1 bp in the mutant. The change of the metal-ion binding site provides a possible explanation for changes in catalytic activity of the mutant RNase P in the presence of Ca2+.

Endoribonucleases↗
PubMed2000

Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells.

We investigated the ability of both acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cells (DC) in vitro. Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) were performed. Mononuclear cells out of peripheral blood or bone marrow containing between 60% and 90% leukemic blasts were cultured for eight days using different growth factor combinations. The highest yield of CD1a(+)/CD14(-) cells could be obtained with stem cell factor, transforming growth factor-beta, tumor necrosis factor-alpha, GM-CSF, and FLT-3-ligand. In the AML samples the median content of CD1a(+)/CD14(-) cells after eight days of culture was 3.5% (r = 0%-82%). In five informed patients CD1a(+)/CD14(-) cells were sorted by fluorescence-activated cell sorting or immunomagnetic separation. Cytogenetic and polymerase chain reaction analyses showed known primary chromosomal aberrations (monosomy 7 and inversion 16) in the sorted fractions, respectively. Dendritic cells (DC) could be generated out of leukemic blasts in 68% of AML patients. Leukemic DC showed no phagocytosis of latex beads, but stimulated allogeneic naive cord blood-derived T cells more efficiently than did uncultured blasts. In ALL patients the median percentage of CD1a(+)/CD14(-) cells was 1.2% (r = 0.7%-3.8%) after culture. The sorted CD1(+)/CD14(-) fractions were BCR/ABL-negative when analyzed with fluorescence in situ hybridization, indicating their nonleukemic origin. Leukemic DC can be generated out of leukemic progenitors in patients with AML. These cells might become relevant for autologous and allogeneic immunotherapy in selected patients. BCR/ABL-positive lymphoblasts could not be transformed into cells with an early dendritic phenotype with the cytokines used in our experiments.

Adolescent↗
PubMed2000

Multidrug resistance phenotype and paclitaxel (Taxol) sensitivity in human renal carcinoma cell lines of different histologic types.

We compared the effects of paclitaxel (Taxol) in human renal cell carcinoma (RCC) of different histologic types. The growth inhibitory effects of paclitaxel on 34 human RCC cell lines of strictly defined different histologic types were determined by 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazoliumbromide (MTT) assays. Paclitaxel-induced morphologic alterations were visualized by light and immunofluorescence and by transmission electron microscopy. The expression and function of P-glycoprotein and multidrug resistance-associated protein (MRP) were defined by reverse transcriptase polymerase chain reaction and fluorescence-activated cell sorting (FACS) analysis, respectively. Modulation of P-glycoprotein function was performed by verapamil or Cremophor EL. A significant (p < 0.05) dose-dependent paclitaxel-induced growth inhibition could be demonstrated in all cell lines, with the effects of paclitaxel dissolved in Cremophor EL/ethanol (= Taxol) exceeding the effects of paclitaxel dissolved in dimethyl sulfoxide. The extent of response markedly varied between the different cell lines, although chromophilic RCCs exhibited a more pronounced response to Taxol (IC50: 0.03-0.38 microM) than clear cell RCCs (IC50: 0.01-36.69 microM). Exposure to paclitaxel/Taxol induced an increase of microtubule bundles in the clear cell and the chromophobe RCCs but not in the chromophilic RCCs. The expression of the MRP was low in RCC cell lines and was not found to be related to paclitaxel/Taxol sensitivity. In contrast, the expression level of P-glycoprotein was much more pronounced and showed a positive correlation (p < 0.05) with the response to paclitaxel. Reversal of P-glycoprotein function by verapamil or Cremophor EL enhanced the growth inhibitory effects of paclitaxel and further supported the role of P-glycoprotein for paclitaxel sensitivity of human RCCs. Paclitaxel/Taxol effectively inhibits proliferation of human RCCs in vitro, irrespective of their histologic types. Moreover, expression and function of P-glycoprotein markedly contribute to paclitaxel responsiveness, although other as yet undefined drug resistance mechanisms are effective in human RCCs as well.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Quality of life of the mentally ill].

Object of this research project was to study the subjective quality of life of psychiatric patients. The vulnerability of 424 out- and inpatients was assessed. The Vulnerability Index, composed of: marital status, income, health, life conditions, occupation, and risk factors in childhood was used. According to their vulnerability, two groups of patients were differentiated: patients with high and low vulnerability. We compared these objective criteria of vulnerability with the subjective quality of life (Q-LES-Q). Quality of life was also compared with diagnosis, severity of illness, and treatment (first contact/long-term contacts). Quality of life of 250 patients was analysed after one year follow up. Patients with a low vulnerability score are more satisfied with 'social relations' than patients with a high vulnerability score. In-patients are more satisfied with 'social relations' than out-patients. Out-patients are more satisfied with their 'physical health', 'subjective feelings', 'leisure time activities', and 'overall life satisfaction' than in-patients. Patients with a mild affective disorder have a better 'life satisfaction' than patients with severe affective disorder. Quality of life of schizophrenics and of patients with anxiety and adjustment disorders has improved significantly after one year.

Adaptation, Psychological↗
PubMed2000

[Expectations of psychiatric patients from their outpatient and inpatient treatment].

OBJECTIVE: This study describes patient evaluations about treatment interventions and the subjective value of specific treatment expectations. METHOD: A random sample of 425 out-patients and in-patients was assessed to evaluate importance of treatment interventions and specific expectations of psychiatric treatment. RESULTS: Preferences regarding treatment interventions varied among diagnostic groups. Psychiatric patients ranked medication and supporting therapeutic conversations the highest. Sociodemographic characteristics, numbers of previous hospitalizations, quality of life and social abilities influenced treatment expectations. A patient's perception of dissatisfying quality of life and high social vulnerability increased the need for social assistance. CONCLUSION: Subjective treatment expectations of psychiatric patients should be the start-out for every treatment-regime. Socially vulnerable patients should be identified and specific treatment plans should be developed at treatment-start.

Adult↗
PubMed2000

[Utilization of psychiatric treatment. Who drops out, who comes back and who stays?].

OBJECTIVE: The aim of this study is the prediction of specific factors associated with utilization patterns of mental health care. METHOD: Course of treatment of 272 out-patients and in-patients was observed for one year. Patients were asked five times (baseline, 1 month, 3, 6, and 12 months) about their utilization behavior. RESULTS: 71% of the patients continued treatment, 6% ended treatment in agreement with their therapists, and 23% dropped out of treatment. 24 patients of those who dropped out, i.e. 38% of this subgroup, returned to treatment during the one year period. Multivariate analyses indicate that continuity of treatment is associated with referrals from other institutions, male gender, the diagnosis of functional psychosis, high subjective well-being, and poor social functioning. First-time use of the corresponding institution, in-patient status, and living alone are predictors of treatment-dropout. Patients who ended treatment in agreement with their therapists are the best socially integrated group. Drop-outs who returned to treatment during the one year period have more unfavorable clinical premises, and are less well integrated socially than drop-outs who do not take up their treatment again. CONCLUSIONS: Therapeutic interventions, such as permanent efforts towards the maintenance of a supportive therapeutic relationship, motivate psychiatric patients to keep a continuing treatment-alliance. Well functioning communication between, or rather coordination of out-patient and in-patient treatment increases the chance of a continuous course of treatment.

Adult↗
PubMed2000

[Social vulnerability, social isolation of chronic psychiatric patients].

Social vulnerability and social isolation as to different, light and severe grades of chronically ill psychiatric patients were evaluated. A social vulnerability index, composed out of marital status, income, health, living conditions, occupation, and risk factors in childhood was used. The vulnerability of 64 severely chronically ill patients and of 84 chronically ill patients was assessed. According to their vulnerability, the patients were divided into a group of highly vulnerable and a group of less vulnerable patients. The social isolation of the two groups (severely chronically und chronically ill patients) was compared and assessed. We used objective criteria (such as living alone, no friends, no contact to family members) and subjective criteria (feeling isolated). Social Vulnerability and social isolation are higher in severely chronically ill patients compared to chronically ill patients. The severely sick group is significantly more affected by objective and/or by subjective isolation than the less sick group. In both groups patients have more difficulties in social relationships than non-isolated patients. There is no significant correlation between objective isolation and subjective isolation.

Adolescent↗
PubMed1999

Modified vaccinia virus Ankara for delivery of human tyrosinase as melanoma-associated antigen: induction of tyrosinase- and melanoma-specific human leukocyte antigen A*0201-restricted cytotoxic T cells in vitro and in vivo.

Vaccination with tumor-associated antigens is a promising approach for cancer immunotherapy. Because the majority of these antigens are normal self antigens, they may require suitable delivery systems to promote their immunogenicity. A recombinant vector based on the modified vaccinia virus Ankara (MVA) was used for expression of human tyrosinase, a melanoma-specific differentiation antigen, and evaluated for its efficacy as an antitumor vaccine. Stable recombinant viruses (MVA-hTyr) were constructed that have deleted the selection marker lacZ and efficiently expressed human tyrosinase in primary human cells and cell lines. Tyrosinase-specific human CTLs were activated in vitro by MVA-hTyr-infected, HLA-A*0201-positive human dendritic cells. Importantly, an efficient tyrosinase- and melanoma-specific CTL response was induced in vitro using MVA-hTyr-infected autologous dendritic cells as activators for peripheral blood mononuclear cells derived from HLA-A*0201-positive melanoma patients despite prior vaccination against smallpox. Immunization of HLA-A*0201/Kb transgenic mice with MVA-hTyr induced A*0201-restricted CTLs specific for the human tyrosinase-derived peptide epitope 369-377. These in vivo primed CTLs were of sufficiently high avidity to recognize and lyse human melanoma cells, which present the endogenously processed tyrosinase peptide in the context of A*0201. Tyrosinase-specific CTL responses were significantly augmented by repeated vaccination with MVA-hTyr. These findings demonstrate that HLA-restricted CTLs specific for human tumor-associated antigens can be efficiently generated by immunization with recombinant MVA vaccines. The results are an essential basis for MVA-based vaccination trials in cancer patients.

Animals↗