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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 163 records · Page 9Linked to original sources

[Results of radiotherapy in recurrences of soft tissue sarcomas].

PURPOSE: Published data for radiotherapy in soft tissue sarcomas refer in most of the cases to the use of irradiation for primary tumors. Experiences of radiotherapy in local recurrences are limited. The own treatment results of a multimodal treatment approach in a large number of patients will be analyzed for local tumor control rates, survival rates, side effects and prognostic factors and will be compared to the literature. PATIENTS AND METHODS: At the University Hospital Hamburg-Eppendorf a total of 98 patients with local recurrences of soft tissue sarcomas were irradiated between 1980 and 1993. The median age of the patients was 55 years. There was a large variety of different histologies. Grading was evaluable in 95 cases: G1 24 patients, G2 21 patients and G3 50 patients. Localisation was dominated by the extremities with 64.3%. Recurrences were reclassified: 21 patients had rT1-tumors and 77 patients had rT2-tumors. Twelve cases showed lymph node metastases and 9 patients distant metastases. Generally treatment included surgery and postoperative irradiation. R-classification showed R0 in 25, R1 in 20 and R2 in 48 cases. Neutrontherapy was prefered in 57 cases and neutron- and photontherapy in 22 cases. Local tumor control rates and survival rates were calculated using the Kaplan-Meier method. Side effects were scored using the RTOG/EORTC scoring system. Univariate and multivariate analyses were applied to evaluate prognostic factors. RESULTS: Local tumor control rates at 5 years were 56.4%, for G1 75.2%, G2 52.5%, G3 47.1%, rT1 66.0%, rT2 53.6%, R0 63.4%, R1 42.3% and R2 53.2%, N0 61.1% vs. N1 31.7%. Survival rates at 5 years were 45.2%, for G1 64.8%, G2 66.9%, G3 25.0%, rT1 60.0%, rT2 41.5%, R0 64.2%, R1 49.3% and R2 32.7%. Acute side effects were scored as grade 1 and grade 2. The rate of grade 3 and 4 late effects was about 6%. Lymph node status was a significant factor for local control. Grade, residual tumor status, type of irradiation and the applied neutron dose were significant factors for survival. CONCLUSIONS: Nowadays no standard treatment exists for local recurrences of soft tissue sarcomas. Treatment should be interdisciplinary. Local recurrences should be avoided by the consequent use of surgery and radiotherapy. It is important that local recurrences should be detected early. Neutrontherapy may bring advantages for local control of recurrences with macroscopic tumor residuals.

Adolescent↗

[Nomenclature of modified fractionation protocols in radiotherapy].

BACKGROUND/AIM: During the last few years a number of new, unconventional fractionation protocols have been established for various biological reasons. Recently specific terms, established for these schedules, have frequently been applied inappropriately in oral presentations as well as in publications. Hence, the present work was initiated in order to clarify definitions and, in addition, to illustrate the respective biological basis for the various fractionation designs.

Humans↗

[The efficacy of radiotherapy in vertebral hemangiomas].

AIM: Assessment of the efficacy of radiation therapy for symptomatic vertebral hemangiomas. PATIENTS AND METHODS: Records of 19 patients who were treated from 1969 to 1988 were retrospectively analyzed. Radiation treatment was given at 2 Gy per fraction to 20 Gy (n = 2), 30 Gy (n = 11), or 40 Gy (n = 6). Improvement of symptoms was chosen to determine the efficacy of the treatment. In addition the lesions were controlled radiographically. RESULTS: Symptomatic improvement was achieved in 17 of 19 patients, remission was complete in 7 patients. No dose-response relationship was observed. The median time to improvement of symptoms was 3 months. The radiographic controls did not correlate with the clinical course. CONCLUSIONS: Radiation therapy is an effective treatment for symptomatic vertebral hemangiomas. The aim of the treatment is to ameliorate clinical symptoms, radiographic improvement is of minor importance.

Adult↗

[Lymph- and haemangiosis carcinomatosa--an important prognostic factor in non-small-cell bronchial carcinoma (NSCLC)].

Between 1 Jan 1984-1 Jan 1990, 199 patients underwent curative (R0) surgery for non-small cell lung cancer. The pathohistological findings showed that a carcinomatous lymphangiosis and haemangiosis (L/H pos.) were present in 26 patients. In six patients, no lymph node metastases were detected. The median (22 mo. vs. 74 mo.) and 5-year survival (25% vs. 41%) were significantly (p < 0.001) higher compared to patients with and without lymphangiosis and haemangiosis carcinomatosa (L/H neg.). There were also significant (p < 0.05) differences in the survival time between pNO L/H neg. and pNO L/H pos. patients (median 74 mo. vs. 15 mo.-5 years 43% vs. 0%).

Capillaries↗

Apolipoprotein E increases the fibrillogenic potential of synthetic peptides derived from Alzheimer's, gelsolin and AA amyloids.

Apolipoprotein E (apoE) has been found in association with several different types of systemic and cerebral amyloid deposits and the presence of the epsilon 4 allele constitutes a risk factor for Alzheimer's disease. It has been shown that apoE binds and promotes the fibrillogenesis in vitro of Alzheimer's amyloid beta-peptide, suggesting an important role for apoE in the modulation of amyloidogenesis. Due to the co-localization of apoE with several biochemically distinct amyloid deposits, it has been proposed that apoE plays a general role modulating and/or participating in amyloidosis. In the present study, we show for the first time that apoE, isolated from human plasma, increases fibril formation of synthetic peptides comprising the amyloidogenic sequences of gelsolin amyloid related to familial amyloidosis Finnish type, and amyloid A found in secondary amyloidosis and familial Mediterranean fever. Our results suggest that apoE acts as a general pathological chaperone in various amyloidoses by enhancing the transition from soluble peptides into amyloid-forming, pathological molecules.

Alzheimer Disease↗

Sphingolipid activator proteins (SAPs) are stored together with glycosphingolipids in the infantile neuronal ceroid-lipofuscinosis (INCL).

The storage material isolated from the brains of patients with infantile neuronal ceroid-lipofuscinosis (INCL) contains, on average, 43% protein and 35% lipids on a dry weight basis. Recently we identified the major storage proteins as sphingolipid activator proteins (SAPs) A and D by direct sequencing. In the present study we used monospecific anti-sap-B-, anti-sap-C, and anti-sap-D-antisera in immunohistochemical and Western analyses to show that sap-D is, indeed, an integral component of the storage bodies. In contrast, no (or little) immunoreactivity for sap-B or sap-C was detected in the INCL storage granules. This observation is of interest for an understanding of the pathogenesis because the four SAPs are produced from a single precursor protein by proteolytic cleavage. Furthermore, we analysed the stored lipids on high performance thin layer chromatography combined with different staining techniques. In this preliminary analysis we found two glycosphingolipids, yet to be identified, to be common for all INCL patients.

Adolescent↗

In vivo radiation sensitivity of glioblastoma multiforme.

PURPOSE: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. METHODS AND MATERIALS: The TCD50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. RESULTS: The TCD50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 +/- 6.4. The difference between the average TCD50 of GBM and SCC was not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD50 in vivo and the SF2 or D0 in vitro. CONCLUSIONS: Our data on GBM xenografts showed a wide range of sensitivities to single dose irradiation in vivo, which does not correlate with the almost invariably fatal clinical outcome of these patients. No correlation was observed between the TCD50 in vivo and the in vitro SF2/D0 of the corresponding cell lines. Our in vivo and in vitro data on GBM suggest that radiation sensitivity alone does not explain the cause of the poor clinical response of GBM to radiation, and other factors could contribute to this response.

Animals↗

Sphingolipid activator proteins in the neuronal ceroid-lipofuscinoses: an immunological study.

The molecular defects underlying neuronal ceroid-lipofuscinoses (NCL) are still unknown. However, more data exist on the composition of the hydrophobic storage material characteristic of NCL. Accumulation of subunit c of the mitochondrial ATP synthase has been shown in most forms of human NCL with the exception of the infantile NCL (INCL) for which we have recently demonstrated storage of sphingolipid activator proteins (SAP). In the present study we raised an antiserum against storage cytosomes purified from INCL brain. Using the anti-INCL antiserum and monospecific SAP antisera, we studied storage material isolated from the brains of patients affected with NCL by Western analysis, and found a 12-kDa protein showing a SAP-like immunoreactivity not only in INCL, but also in all the childhood forms of NCL. Furthermore, using the anti-sap-D antiserum for immunohistochemistry, we observed strong immunoreactivity of the storage cytosomes in all major forms of NCL, and also in tissues of non-neuroectodermal origin. From these data we conclude that the presence of SAP within the storage bodies is a phenomenon common to all major forms of human NCL.

Adolescent↗

Immunological studies on sphingolipid activator proteins in the neuronal ceroid-lipofuscinoses.

The neuronal ceroid-lipofuscinoses constitute an important group of progressive encephalopathies leading to severe psychomotor retardation, blindness, and early death. They are characterized by accumulation of autofluorescent, electron-dense storage bodies within the cytoplasm of neurons and many other cell types. We have recently identified sphingolipid activator proteins A and D as major components of the storage cytosomes in the infantile form of NCL. Using an immunological approach we have shown that sphingolipid activator proteins also constitute an integral component of the storage bodies in the other major forms of the disease.

Blotting, Western↗

Efficiency of airway macrophage recovery by bronchoalveolar lavage in hamsters: a stereological approach.

Macrophages play a central role in the defence of the respiratory tract against deposited particles. In addition to the well-studied alveolar macrophages, airway macrophages have been recognized as an important clearance factor. Bronchoalveolar lavage (BAL) has been used for functional and morphological investigations of macrophages in vitro, assuming that all macrophages are removed with equal probability from the lung surface. Airway macrophages have been found in close contact with the epithelial cells. These macrophages may not be easily removed by lavage, and they might constitute a functionally different macrophage population. We have tested the hypothesis that there exists a population of macrophages in the conducting airways that resists removal by lavage. We lavaged the lungs of four hamsters and fixed the lungs, thereafter, by intravascular perfusion. The number of macrophages in the intrapulmonary conducting airways was estimated with an unbiased stereological technique, the fractionator, and compared to the number of macrophages in the airways of four hamsters whose lungs had not been lavaged prior to fixation. This in situ study revealed that, in hamster lungs, 42% of the airway macrophages were not removed by BAL and that about 5% of all macrophages in the BAL fluid were airway macrophages. Additionally, ultrastructural alterations of the airway epithelium were found. It is concluded that there exists a population of airway macrophages that resists lavage. This is an aspect which has to be considered in studies performed with macrophages obtained by BAL, since they could represent a functionally different macrophage population.

Animals↗

Purification of the channel component of the mitochondrial calcium uniporter and its reconstitution into planar lipid bilayers.

The purification of the channel-forming component of the mitochondrial calcium uniporter and its channel properties are described. After ethanol and 50% ethanol-water extraction of mitochondria from beef heart or perfused rat liver, the extract was passed through thiopropyl-Sepharose 6B column, and absorbed components were eluted with 2-mercaptoethanol, followed by gel-filtration on Sephadex G-15. The last fraction eluted (M(r) about 2000) was then subjected to reverse-phase high-performance liquid chromatography. Of the more than 10 distinct peaks, only one showed specific Ca(2+)-channel activity in BLM with properties similar to earlier, less extensively purified preparations, i.e., conductance of 20 pS and multiples thereof, clustering of channels, participation of 2 or more subunits in channel formation, and sensitivity to 1 microM ruthenium red. Voltage sensitivity and cooperativity between channels are described. The Ca(2+)-binding glycoprotein with which the peptide was associated was found to have high homology with human acid alpha 1-glycoprotein (orosomucoid) and to show identity with beef plasma orosomucoid in the Ouchterlony immunodiffusion test.

Amino Acid Sequence↗

Immunoscintigraphy with a new indium-111-labeled monoclonal antibody (MAb 1A3) in patients with colorectal cancer.

PURPOSE: This study was designed to evaluate a new anticolorectal carcinoma monoclonal antibody (1A3), conjugated with the bifunctional chelating agent N,N'-bis(2-hydroxybenzyl)1(4-bromoacetamidobenzyl)1,2-ethylenediam ine-N,N'- diacetic acid and labeled with indium-111, in a Phase I/II study involving 38 patients with localized or advanced colorectal cancer. METHODS: Patients were injected with indium-111-N,N'-bis(2-hydroxybenzyl) 1(4-bromoacetamidobenzyl)1,2-ethylenediamine-N,N'-diacetic acid-monoclonal antibody 1A3 (1-50 mg, 1-5 mCi) and imaged at two or three sessions one to five days later. Scintigraphic findings were compared with radiologic, pathologic, surgical, and other clinical findings to assess the accuracy of radioimmunoscintigraphy. RESULTS: At least one known tumor site was clearly defined by planar scintigraphy in 29 (76 percent) patients. Increased radioactivity was seen in 40 of 63 known tumor sites (37/43 abdominal-pelvic, 3/15 hepatic, and 0/5 pulmonary sites) without any apparent dose-related effects. Nineteen previously undetected sites were considered positive by imaging, and, of these, six were biopsy-proven tumor sites, four were probable tumor sites, three were definitely false positive sites, and six were probable false positive sites. Radioimmunoscintigraphy detected proven tumor in 15 of 16 patients with negative or equivocal computed tomography results. Of of the 28 patients with rectosigmoid cancer, 25 (89 percent) had positive studies with 34 of 47 tumor sites showing definite uptake on the scintigrams. This included 3 of 9 hepatic metastases. The only adverse reaction occurred in one patient who developed transient hives. Human anti-mouse antibody responses occurred in approximately one-half of the patients injected with doses of 10 or 50 mg. CONCLUSION: This study shows that radioimmunoscintigraphy with this indium-111-labeled monoclonal antibody is safe, it can detect most nonhepatic abdominal-pelvic tumors with a positive predictive value of 83 (44/53) percent, and it should prove to be useful, particularly in the diagnosis of recurrent rectal carcinoma.

Adenocarcinoma↗

Impact of overall treatment time of fractionated irradiation on local control of human FaDu squamous cell carcinoma in nude mice.

A series of experiments were performed to determine the impact of overall treatment time on local control of human FaDu squamous cell carcinoma irradiated with 30 fractions under ambient conditions in nude mice. The TCD50 increased with treatment time between 15 days and 10 weeks from 43 Gy to 102 Gy. The data can be well described by a single linear function. The dose recovered per day is 1.0 Gy. However, the data can also be adequately fitted by two components with an initial delay of about 30 days followed by a steep increase at a rate of 1.5 Gy per day. Assuming that the increase of TCD50 is solely caused by repopulation of clonogenic tumor cells, and that the cellular radiation sensitivity in vitro reflects the radiation sensitivity of FaDu cells in vivo, the doubling time of clonogenic tumor cells during treatment is estimated to be approximately 1.8 days for the one-component model and, after an initial delay, approximately 1.2 days for the two-component model. Both values are shorter than the doubling time of clonogenic cells in untreated FaDu tumors and similar to the potential doubling time determined by flow cytometry after BrdUrd labelling. It is concluded that the dose necessary to control FaDu squamous cell carcinoma increases considerably with increasing time of a fractionated radiation treatment. It appears most likely that this increase is caused by repopulation of clonogenic tumor cells; however, other mechanisms such as an increasing fraction of hypoxic tumor cells can not be ruled out at present.

Animals↗

Lipopolysaccharide smooth-rough phase variation in bacteria of the genus Chlamydia.

In two strains of Chlamydia psittaci and in Chlamydia trachomatis serotype L1, we have detected a so-far-unknown antigen which (i) is resistant to heat and proteolytic digestion, (ii) can be extracted with phenol-water into the water phase, (iii) gives a ladder-like banding pattern in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (iv) is immunogenic in rabbits and mice, and (v) contains immunoreactivity of lipid A, a common and characteristic component of gram-negative lipopolysaccharides (LPS). Thus, chlamydiae contain, in addition to the known rough-type LPS, another LPS type which is phenotypically smooth (S-LPS). S-LPS was observed preferentially in chlamydiae grown in the yolk sac of embryonated eggs; it was, however, also detected by immunofluorescence in tissue culture-grown chlamydiae with a monoclonal antibody against S-LPS.

Animals↗