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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 181 records · Page 10Linked to original sources

The effect of particle inhalation on macrophage number and phagocytic activity in the intrapulmonary conducting airways of hamsters.

The number and functions of macrophages in the lungs are crucial factors for prevention and development of lung disease caused by inhaled particles. To examine whether airway macrophages are attracted to the site of particle deposition and what proportion of these macrophages is involved in phagocytosis, aerosols of 6-microns polystyrene particles (PSP) were inhaled by Syrian Golden hamsters under controlled conditions through an inhalation tubule and their lungs were fixed by intravascular perfusion within 20 min (PSP-1, PSP-1a), 40 min (PSP-2), and 24 h (PSP-3) after the beginning of the inhalation. The number and the phagocytic activity of airway macrophages were studied in situ with a fractionator, a stereologic method, on light microscopic sections. No significant increase in macrophage number was detected for the groups PSP-1 and PSP-1a. The increase for group PSP-2 was, however, between 2- and 3-fold, whereas for group PSP-3 the increase was between 1.5- and 2.5-fold with respect to control animals, which had inhaled ambient air through an intubation tubule (C-2) and whose lungs had been fixed after 40 min. There were no significant differences among the four groups with respect to the proportion of airway macrophages that had phagocytized polystyrene microspheres. Twelve to fifteen percent of the macrophages were found to be involved in phagocytosis. In the case of the mean number of particles per phagocytizing macrophage, there was a significant decrease for the PSP-3 group with respect to the pool of the three groups PSP-1, PSP-1a, and PSP-2 taken together. These studies demonstrate (1) that airway macrophages are rapidly recruited to the sites of particle deposition and (2) that only a small proportion of very active macrophages contributes to the clearance of particles, suggesting a great potential of airway macrophages to interact with many more particles than the hamsters were exposed to in this study.

Administration, Inhalation↗

Present results of neutron therapy. The German experience.

Results of fast neutron therapy are reviewed with special reference to the main indications for this type of treatment and the experience of five German centers. Neutron therapy seems beneficial compared to conventional radiotherapy in advanced salivary gland tumors, inoperable or unresectable soft tissue sarcomas, some bone tumors, prostate cancer stage C and some rare low-grade tumors. About 3,000 patients with malignancies have been treated with neutrons at the German centers Berlin/Rossendorf, Essen, Hamburg, Heidelberg and Münster. Treatment results and treatment-related morbidity depend on the treatment techniques and the physical selectivity of the neutron machines. A critical appraisal suggests that fast neutrons are of advantage in about 5% of all radiotherapy patients.

Carcinoma, Non-Small-Cell Lung↗

Impact of tumor stroma on expression of the tumor bed effect in R1H rat rhabdomyosarcoma.

The impact of intratumoral stroma on the expression of the tumor bed effect was studied in R1H rat rhabdomyosarcoma. For this, either R1H tumors growing in subcutaneous tissues (in situ) were irradiated at median volumes of 40 mm3 with a single exposure of 15 Gy (200 kVp X rays), or fresh tumor fragments or cloned tumor cells cultured in vitro were transplanted into subcutaneous tissue 2 days after preirradiation with 15 Gy. The tumor bed effect was evaluated by the time necessary for experimental tumors to grow from 0.1 cm3 to 10 cm3. When irradiated in situ, R1H tumors expressed a clear-cut tumor bed effect. The growth rate was decreased by a factor of 1.8 +/- 0.2 compared to controls. A significant decrease in growth rate by a factor of 1.7 +/- 0.2 was also observed when cultured tumor cells were transplanted into preirradiated tissue. However, when tumor fragments were transplanted into preirradiated sites, no significant decrease in growth rate occurred in two independent experiments (1.0 +/- 0.1; 1.2 +/- 0.2). Our results indicate that vessels originating from the intratumoral stroma can modulate the expression of the tumor bed effect in R1H tumors.

Animals↗

Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin.

The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only been reported on cells of myeloid and monocytic origin. In the present study, we analyzed 62 childhood acute lymphoblastic leukemias (ALLs) and seven surface immunoglobulin positive (sig+) B-cell lines for the expression of the CEA family members CEA, NCA-50/90, NCA-95, NCA-160, CGM1 and CGM7. We demonstrated that members of the CEA family were present in 76% of childhood ALLs of B- and T-cell origin. In ALLs of B-cell origin, 82% of the samples expressed at least one CEA subgroup member: 38% NCA-50/90 (CD66c), 31% NCA-160 (CD66a), and 13% both. Six of seven B-cell lines solely expressed NCA-160. In seven ALL of T-cell origin, sole NCA-160 expression was present in 29% of the cases. CEA and CGM1 were not expressed in childhood ALLs or in the sIg+ B-cell lines. In 15 ALLs and seven B-cell lines which could be analyzed for CGM7 expression, the antigen was not detected. NCA-95 was not expressed in 91% of the B-lineage ALLs, in T-lineage ALLs and in the B-cell lines. However, five B-lineage ALLs showed conflicting data on the binding patterns of two, on leukocytes specifically NCA-95 recognizing antibodies suggesting either expression of unknown forms of NCA-95 or NCA-50/90 or of a yet unknown member of the CEA family in these ALL cells. The expression of CEA subgroup members in childhood ALL cells might have prognostic impacts, as an inverse correlation exists between NCA expression on leukemic blasts and the risk factor white blood count at diagnosis.

Adolescent↗

[Problems of radiotherapy in Germany after the recent events in Hamburg].

BACKGROUND: During the 3rd Symposium on "Experimental Radiotherapy and Clinical Radiobiology" (Hamburg, March 1994) the consequences of the recent events in the Department of Radiotherapy of the University-Hospital in Hamburg for daily radiotherapy practice in Germany were discussed. The following topics were covered: information of the patient, choice of therapy, development of new treatment modalities, ethics committee, follow-up and role of radiobiology. DISCUSSION AND RESULTS: Information of the patient: Due to the insecure juridical situation in Germany there is a tendency to inform patients excessively, which is rather confusing for them. Adequate information of patients is a difficult task for physicians considering their daily workload. Choice of therapy: Unfortunately in Germany radiotherapists are often not initially involved in planning of the overall treatment strategy for individual cancer patients. The recent events in Hamburg led to a decreased referral of cancer patients for radiotherapy. This might even hold for tumor entities where radiotherapy is an essential part of therapy. Another problem is that dose might be reduced inadequately. This would reduce complications but also significantly increase local failure. Development of new treatment modalities: There are no special juridical problems with the conduction of clinical studies for optimization of radiation treatments. Ethics committee: Ethics committees are not only meant to safeguard patients but also protect physicians and institutions from the consequences of questionable research. FOLLOW-UP: Only radio-oncologists are adequately trained for follow-up after radiation treatment. Nevertheless, because of administrative, financial, legal and political problems many patients in Germany are not regularly seen by the radiation oncologist after end of radiation treatment. Always when new treatment strategies are established, careful follow-up is of special concern. Role of radiobiology: The main obligation of clinical radiobiology is to introduce radiobiological knowledge into clinical practice. This may be best promoted by a period of radiobiological research during residency. However, close collaboration between radiotherapists and radiobiologists is only possible at very few centres in Germany, because the institutes of radiobiology are dismantled systemically.

Aftercare↗

[Acute management and face reconstruction in severe open facial injury].

Authors describe the acute treatment and the reconstruction of the face in the severe, multiple combined fracture of the facial bones. After the primary definitive care further reconstructive operations were performed. After one and half year treatment the functional and esthetic results are good.

Accidents, Occupational↗

[Radiation tolerance of the human spinal cord].

PURPOSE: Chronic myelopathy is among the most serious sequelae of high dose radiation treatment. Therefore medical and forensic reasons warrant detailed knowledge of the radiation tolerance of the human spinal cord. PATIENTS AND METHODS: This paper reviews published data on the incidence of radiation myelopathy in patients treated with megavoltage radiation. RESULTS AND CONCLUSIONS: Two years after completion of radiation treatment with daily fractions of approximately 2 Gy development of radiation myelopathy is expected in 1% of the patients at 50 to 55 Gy. An incidence of 5% is estimated to occur at approximately 55 to 60 Gy. At higher doses the risk of spinal cord damage increases steeply. Interpretation of these data has to consider that the incidence of radiation myelopathy increases with increasing time of follow-up. Even after two years no clearcut plateau is observed. High doses per fraction are poorly tolerated by the spinal cord, the alpha/beta-ratio appears to be approximately 1 Gy. Accelerated schedules with < or = 2 Gy per fraction but daily doses greatly exceeding 2 Gy may result in a higher risk of radiation myelopathy than conventionally fractionated treatments. This observation seems, at least in part, to be due to a slow component of repair of sublethal radiation damage in the spinal cord.

Humans↗

Surfactant and inhaled particles in the conducting airways: structural, stereological, and biophysical aspects.

We have investigated the displacement into the sol phase of inhaled particles deposited in the intrapulmonary conducting airways. Hamsters inhaled an aerosol of monodisperse polystyrene particles of 6 microns diameter. Their lungs were fixed by intravascular perfusion, and light and electron microscopy was used to study the epithelial coating. The surfactant film at the wall-air interface was investigated by measuring its surface tension. The number of particles retained was determined stereologically. In addition we investigated the displacement of spherical particles in vitro on a DPPC monolayer in a Langmuir-Wilhelmy surface balance and determined the surface tension in vivo in the horse trachea by video bronchoscopy, applying the droplet spreading method. We found that particles deposited onto a surfactant film were pulled into the aqueous subphase, and we concluded that surface forces due to the airway surfactant likely displace deposited particles into the periciliary fluid (sol phase). Comparing lungs fixed immediately after inhalation with lungs fixed 24 hr after inhalation revealed that 86% of the particles retained in the intrapulmonary conducting airways immediately after inhalation had been cleared within 24 hr. One-third of the particles of the lungs fixed immediately after inhalation was phagocytized. The combination of structural and stereological analyses with in vitro and in vivo measurements has led to new insights into the role of airway surfactant with respect to the fate of inhaled particles, which may have important consequences regarding the effects of hazardous particles. These studies may also help to evaluate the deposition pattern and clearance of therapeutic particles, with important implications for their therapeutic use.

Administration, Inhalation↗

Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation.

Amphoterin is a heparin-binding protein that is developmentally regulated in brain and functionally involved in neurite outgrowth. Unexpectedly, amphoterin has a high mobility group 1 (HMG1)-type sequence. In the present study we have expressed amphoterin cDNA in a baculovirus vector and produced antibodies against the recombinant protein and several synthetic peptides. It was found that the amphoterin cDNA encodes the 30-kDa form of the protein isolated from tissues, whereas the co-purifying 28- and 29-kDa proteins (p28 and p29) have closely related but distinct primary structures. Partial amino acid sequencing shows several local changes in the sequences of p28 and p29 compared with amphoterin, suggesting the occurrence of a multigene family that encodes at least three different HMG1-type sequences in the rat. Studies using the probes that discern amphoterin from the other HMG1-type proteins indicate a high level expression in various transformed cell lines. Immunostaining of cells with the amphoterin-specific antibodies indicates a cytoplasmic localization that becomes remarkably enriched at the leading edges in spreading and motile cells. An extracellular localization is suggested by immunostaining of nonpermeabilized cells and by a plasminogen-dependent degradation of amphoterin in the substratum-attached material of cells. Tissue-derived and recombinant amphoterins strongly enhance the rate of plasminogen activation and promote the generation of surface-bound plasmin both by tissue-type and urokinase-type plasminogen activators. The results suggest an extracellular function for amphoterin in the leading edge of various invasive cells.

Amino Acid Sequence↗

Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis.

We have isolated storage cytosomes from brain tissue of patients with infantile neuronal ceroid-lipofuscinosis. The purified storage bodies were subjected to compositional analysis which revealed a high content of proteins, accounting for 43% of dry weight. Saposins A and D, also known as sphingolipid activator proteins (SAPs), were shown to constitute a major portion of the accumulated protein using gel electrophoresis and sequence analysis. This is the first time that saposins have been found to be stored in any form of neuronal ceroid-lipofuscinosis.

Adolescent↗

Purification of membrane proteins using a micropreparative gel electrophoresis apparatus: purification of subunits of the integral membrane protein Bacillus subtilis aa3-type quinol oxidase for low level amino acid sequence analysis.

We have developed a continuous elution micropreparative gel electrophoresis system in which small amounts of proteins, e.g., 1-10 micrograms, are continuously eluted from one-dimensional polyacrylamide gel columns in either native or denatured form. Depending on the electrophoretical parameters proteins are separated according to their size and/or net charge. The system is based on a simple modification of the Mini-Protean II 2D unit from Bio-Rad Inc. The apparatus is connected on-line to a high-performance liquid chromatograph allowing accurate delivery of the elution solvent and direct analysis of the separated samples by uv detection. The high resolution of the apparatus allows the purification of individual proteins, even from complex mixtures, in only one step, with overall recoveries of approximately 70%. In addition to standard proteins the system has been applied to the purification of the membrane-bound and thus highly hydrophobic subunits I and II from Bacillus subtilis aa3-type quinol oxidase. The hydrophobic character of these subunits has hindered their purification by other conventional methods. Isolated subunits were collected directly into a buffer suitable for proteolytic digestion and automated amino acid sequence analysis. The internal amino acid sequences determined could all be found in the DNA sequence recently reported by Santana et al. (J. Biol. Chem. 267, 10225-10231, 1992), thereby confirming the expression of such an oxidase.

Amino Acid Sequence↗

Failure of the circulatory system limits exercise performance in patients with systemic sclerosis.

OBJECTIVE: To determine the mechanisms for exercise impairment in symptomatic patients with systemic sclerosis (SSc) using breath-by-breath expired-gas analysis with incremental exercise testing. DESIGN: Prospective, open trial. PATIENTS AND METHODS: Fifteen consecutive patients with SSc seen at the Medical University Hospital (a tertiary referral center) with complaints of exercise intolerance underwent pulmonary function testing (spirometry, helium dilution lung volumes, and diffusing capacity of carbon monoxide) and incremental exercise testing on a cycle ergometer measuring oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (R), oxygen saturation, blood pressure, and heart rate (HR). Values for oxygen uptake at anaerobic threshold (VO2AT) were derived graphically by blinded clinicians experienced in exercise testing, and the results were averaged. Ventilatory reserve and oxygen pulse were calculated from measured values, and all data were subjected to analysis by standard clinical algorithms. MEASUREMENTS AND MAIN RESULTS: Of 15 patients studied, 14 had either restrictive lung disease or normal results of spirometry on pulmonary function testing. One patient with a history of tobacco use had evidence of airways obstruction. Three patients were unable to exercise maximally (as determined by maximum respiratory exchange ratio [Rmax] greater than 1.09 or maximum heart rate [HRmax] greater than 85% predicted), and exercise testing was terminated in one with Mobitz type II atrioventricular block. The following data (mean +/- SEM) were obtained from 11 maximally exercising patients: VO2max 795 +/- 75 mL oxygen (O2)/min, R 1.34 +/- 0.05, VO2AT/VO2max predicted 0.21 +/- 0.02, O2 pulse 5.1 +/- 0.4 mL O2/beat, ventilatory reserve 0.52 +/- 0.06, and tidal volume/forced vital capacity ratio 0.46 +/- 0.02. Of the 11 patients completing breath-by-breath expired-gas analysis, all had circulatory impairment to exercise, as determined by low O2 pulse and low VO2 at anaerobic threshold, and circulatory impairment was limiting in 9 of 11 patients. Of those nine patients, four had evidence of impaired gas exchange compatible with pulmonary vascular disease. Arterial oxygen desaturation occurred in 2 of 11 patients. CONCLUSION: Circulatory impairment to exercise is common in SSc patients with exercise intolerance. Restrictive lung disease, although also common, does not limit exercise tolerance in patients capable of maximal effort.

Adult↗