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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 109 records · Page 6Linked to original sources

Dynamics of oscillating erythrocyte doublets after electrofusion.

Erythrocytes were electrofused with multiple rectangular voltage pulses to show an oscillatory movement, divided into swell phases and pump events. During each swell phase, which lasted from 0.5 s to more than 180 s, the fused cells' (doublets') volume increased by colloid osmotic swelling, and the membrane area was expanded until rupture. Membrane rupture initiated the pump event, where the doublets' volume and membrane area decreased with an almost exponential time course and time constants between 2 ms and 8 ms. Simultaneously, a portion of cytosolic hemoglobin solution was ejected into extracellular space ("jet"). Pump event time constants and swell phase durations decreased with rising chamber temperature, indicating that both parts of the oscillatory movements were determined by physical properties of membrane and liquids. Relative volume change developments express a gradual loss of membrane elasticity during the oscillation, decreasing the elastic forces stored in the membrane. Evidence is given that the first rupture causes a weakening of the membrane at the rupture site. Heat treatment up to 45 degrees C had a negligible effect on swell times, pump time constants, and relative volume changes. A heat treatment of 50 degrees C prevented oscillatory movements. The rupture location accorded with theories of potential induced membrane electropermeabilization.

Biomechanical Phenomena↗

Impact of overall treatment time on local control of slow growing human GL squamous cell carcinoma in nude mice treated by fractionated irradiation.

BACKGROUND AND PURPOSE: The impact of overall treatment time of fractionated irradiation on local control of slow growing human GL squamous cell carcinoma (SCC) was determined. MATERIALS AND METHODS: Moderately well differentiated and keratinizing human GL SCC with a volume doubling time of 8 days were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions over 2, 3, 4.5, 6 and 10 weeks. Endpoint of the experiments was local tumor control at day 180 after end of treatment. RESULTS: The tumor control dose 50% (TCD50) increased from 40 to 57 Gy when the treatment time was extended from 2 to 10 weeks. The data can be well described by a linear increase in TCD50 with time. The recovered dose per day (D(r)) was 0.28 Gy (95% confidence interval 0.06; 0.48). The fit to the data was not significantly improved by assuming a biphasic (dog-leg) time course with constant TCD50 values in the initial part of treatment followed by a more rapid increase of TCD50 thereafter. CONCLUSIONS: D(r) in GL SCC was significantly less than the value of 1.0 Gy (0.7; 1.3) previously reported for poorly differentiated, non-keratinizing and fast growing human FaDu SCC (Baumann M, Liertz C, Baisch H, Wiegel T, Lorenzen J, Arps H. Impact of overall treatment time of fractionated irradiation on local control of human FaDu squamous cell carcinoma in nude mice. Radiother. Oncol. 1994:32:137-143), indicating important heterogeneity of the time factor between different tumors of the same histological type.

Algorithms↗

Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia.

To identify residual candidate normal progenitor/stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia (ALL), expression of AC133 and CD117 was analysed on the leukaemic cell clone and on immature B-lineage-negative CD34+CD19- bone marrow cells. 10/25 patients (40%) had no detectable expression of AC133 within the leukaemic cell clone. 24/26 patients (92%) lacked expression of CD117 on the leukaemic blast cell population. In contrast, a distinct AC133-positive cell population was found in 8/8 children with AC133-negative ALL and a CD117-positive cell population could be identified in 12/12 children with CD117-negative ALL, within the CD34+CD19- progenitor/stem cell compartment. These observations provide further evidence that in B-cell precursor ALL, unlike in acute myelogenous leukaemia, it may be possible to distinguish residual normal progenitor/stem cells from the leukaemic cell clone.

AC133 Antigen↗

A new methodology for controlled particle inhalation by small rodents.

In order to investigate the deposition, retention, and clearance mechanisms implicated in particle inhalation under standardized conditions, we developed a continuous negative-pressure ventilation system, whereby the breathing pattern in small rodents could be controlled during exposure to aerosols. Using an on-line open-flow set-up, 19 anesthetized, intubated, and paralyzed Syrian golden hamsters, individually contained within a whole-body box, were artificially ventilated under the said continuous negative-pressure conditions, 1 of 5 different combinations of breathing frequency and tidal volume being established. The animals were then exposed to aerosols containing 6-micron diameter polystyrene spheres, and the deposition of particles in the conducting airways was monitored photometrically. During exposure, the level of respiration (mean lung inflation) was stabilized by means of a negative-pressure vent. Breathing frequency and tidal volume, as well as the compliance of the system, remained virtually unchanged during the course of a single experiment, and in each case, a reproducible deposition of particles was achieved. Our findings indicate that tidal volume, but not breathing frequency, has a marked influence on the particle deposition ratio. Breathing frequency exerts opposing and counterbalancing effects on this latter parameter by enhancing the impaction of particles on the one hand, and by decreasing sedimentation on the other.

Administration, Inhalation↗

Impact of preirradiation of the tumour bed on cell production rate and cell loss of human FaDu squamous cell carcinoma growing in nude mice.

PURPOSE: To explore whether the tumour bed effect (TBE) in FaDu squamous cell carcinoma growing in nude mice is caused by a reduced tumour cell production rate and/or by increased tumour cell loss. MATERIALS AND METHODS: Human FaDu tumours were studied in NMRI nude mice. The volume doubling time (VDT) between 100 and 400 mm3 was determined for tumours in unirradiated subcutaneous (sc) tissues (group 1), tumours in sc tissues preirradiated with 12.5 Gy (group 2), tumours irradiated in situ with 12.5 Gy (group 3), and tumours from group 3 re-transplanted into unirradiated sc tissues (group 4). Labelling index (LI), potential doubling time (Tpot), relative necrotic area and apoptotic index (AI) were evaluated in tumours from groups 1 and 2. RESULTS: The median VDT were 2.6 days (95% CI 2-4) in group 1 and 7.0 days (4-15) in group 2 (p<0.001). The VDT were not significantly different between groups 2 and 3, and group 1 and 4. In groups 1 and 2, the Tpot values (3.1 +/- 0.6 days (SD) versus 2.9 +/- 0.5 days) and the LI were identical (10 +/- 1.5%). The median relative necrotic area was significantly larger in group 2 (37% [23-42]) compared with group (6% [0.3-27]). The apoptotic index was low (0.2%) and did not differ between groups 1 and 2. CONCLUSIONS: The results indicate that the TBE in FaDu squamous cell carcinoma is not caused by a reduced cell production rate in the viable tumour compartment. Rather, the TBE reflects a decreased viable tumour cell compartment due to increased cell loss. Necrosis appears to be the major component of the tumour bed induced cell loss in FaDu tumours, whereas apoptosis has no impact on the TBE in this model.

Animals↗

Phospholipid transfer protein (PLTP) causes proteolytic cleavage of apolipoprotein A-I.

Plasma phospholipid transfer protein (PLTP) is a factor that plays an important role in HDL metabolism. In this study we present data suggesting that PLTP has an inherent protease activity. After incubation of HDL3 in the presence of purified plasma PLTP, the d < 1.25 g/ml particles (fusion particles) contained intact 28.2 kDa apoA-I while the d > 1.25 g/ml fraction (apoA-I-PL complexes) contained, in addition to intact apoA-I, a cleaved 23 kDa form of apoA-I. Purified apoA-I was also cleaved by PLTP and produced a similar 23 kDa apoA-I fragment. The cleavage of apoA-I increased as a function of incubation time and the amount of PLTP added. The process displayed typically an 8-10 h lag or induction period, after which the cleavage proceeded in a time-dependent manner. This lag-phase was necessary for the development of the cleavage activity during incubation at 37 degrees C. The specific apoA-I cleavage activity of different PLTP preparations varied between 0.4-0.8 microg apoA-I degraded/h per 1000 nmol per h of PLTP activity. The 23 kDa apoA-I fragment reacted with monoclonal antibodies specific for the N-terminal part of apoA-I, indicating that the apoA-I cleavage occurred in the C-terminal portion. The apoA-I cleavage products were further characterized by mass spectrometry. The 23 kDa fragment yielded a mass of 22.924 kDa, demonstrating that the cleavage occurs in the C-terminal portion of apoA-I between amino acid residues 196 (alanine) and 197 (threonine). The intact apoA-I and the 23 kDa fragment revealed identical N-terminal amino acid sequences. The cleavage of apoA-I could be inhibited with APMSF and chymostatin, suggesting that it is due to a serine esterase-type of proteolytic activity. Recombinant PLTP produced in CHO cells or using the baculovirus-insect cell system caused an apoA-I cleavage pattern identical to that obtained with plasma PLTP. The present results raise the question of whether PLTP-mediated proteolytic cleavage of apoA-I might affect plasma HDL metabolism by generating a novel kinetic compartment of apoA-I with an increased turnover rate.

Amino Acid Sequence↗

[Diagnosis of health in a population and humanitarian actions: a practical guide].

The identification of priority public health problems is the objective of a population health diagnosis. We propose four stages for its development. 1. A description of the situation gives information about the socio-demographic characteristics, sociological, economic, and health indicators, and cultural and economic determinants that influence the health of the population in question. 2. The analysis of consultations among the population and professionals gives indications as to the existence, or lack, of significant collective health problems (diagnosis of perception). 3. From the available statistics, the study of epidemiological data may corroborate the previously obtained results (objectified diagnosis). 4. The outcome of these two approaches may lead to a combination of the diagnosis of perception and the objectified diagnosis and permits, with the help of priority criteria, to determine the priority problems. The approach and the tool presented here were tested among thirty teams responsible for humanitarian programmes and are the result of three years of collaboration with Médecins du Monde. The objective of this approach is to provide the base for conceptual reflection on humanitarian interventions as community action and to propose some elements of methods.

Altruism↗

Orphanin FQ stimulates prolactin and growth hormone release in male and female rats.

Intracerebroventricular administration of Orphanin FQ (5.5, 55 or 550 pmol) caused a dose-related increase in prolactin secretion in both male and female rats and stimulated GH secretion in males. The magnitude of the prolactin secretory response was greater in females than in males. These effects of OFQ on prolactin and growth hormone release are the same as the stimulatory effects of the endogenous opioid peptides.

Analysis of Variance↗

Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor.

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is essential for the immortalization of human B cells and is linked etiologically to several human tumors. LMP1 is an integral membrane protein which acts like a constitutively active receptor. It binds tumor necrosis factor (TNF)-receptor-associated factors (TRAFs), activates NF-kappaB and triggers the transcription factor AP-1 via the c-Jun N-terminal kinase (JNK) cascade, but its specific contribution to B-cell immortalization has not been elucidated fully. To address the function of LMP1, we established B cell lines with a novel mini-EBV plasmid in which the LMP1 gene can be regulated at will without affecting the expression of other latent EBV genes. We demonstrate here that continuous expression of LMP1 is essential for the proliferation of EBV-immortalized B cells in vitro. Re-induction of LMP1 expression or activation of the cellular CD40 receptor both induce the JNK signaling cascade, activate the transcription factor NF-kappaB and stimulate proliferation of these B cells. Our findings strongly suggest that LMP1 mimics B-cell activation processes which are physiologically triggered by CD40-CD40 ligand signals. Since LMP1 acts in a ligand-independent manner, it replaces the T cell-derived activation signal to sustain indefinite B-cell proliferation.

B-Lymphocytes↗

[The results of radiotherapy in meningiomas with a high risk of recurrence. A retrospective analysis].

AIM: Retrospective assessment of the efficacy of radiation therapy for meningiomas with high risk for local recurrence. PATIENTS AND METHODS: Records of 67 patients with meningiomas treated from 1974 to 1995 at 2 centres were analyzed. Follow-up time ranged from 0.8 to 213 months (median: 61 months). Radiation therapy was given either after local failure or after biopsy or subtotal resection. The ratio between malignant (n = 20) and benign (n = 47) meningioma was 1:2.4. Median age of the patients was 55 years (7 to 77 years). Radiation treatment was given at 1.5 to 2 Gy per fraction to 36 to 79.5 Gy. Survival rates were calculated by the Kaplan-Meier method. Statistical comparisons were performed with the log-rank test and the Cox proportional hazards model. The Bonferroni method was used to correct for multiple comparisons. RESULTS: Five- and 10-year disease-free survival rates were 82% +/- 5% (standard error) and 70% +/- 9%. Local control rates at 5 and 10 years were 78% +/- 5% and 68% +/- 9%. In uni- and multivariate analysis histology, sex, total dose and center showed no significant influence on the results. Patients age was significant for local control (univariate p = 0.02; multivariate p = 0.03) and disease-free survival (univariate/multivariate p = 0.04). The postoperative tumor burden had a significant influence of disease-free survival (multivariate p = 0.04). After Bonferroni correction no significant influence was observed. We did not observe late side effects, especially brain necrosis. CONCLUSIONS: Despite of the negative selection of our patients we observed high survival- and local control rates after radiation therapy. This underscores the role of radiation therapy in the treatment of meningiomas with high risk of local failure.

Aged↗

Comparison of the response of human FaDu squamous cell carcinoma in nude mice after hypofractionated-accelerated regimens and "curative" fractionation schedules.

BACKGROUND: It has been suggested that tumors respond differently after irradiation with 10 or more fractions than with less fractionated regimens and that extrapolation from experiments with only a few fractions to "curative" regimens may be invalid. To test this hypothesis, we compared hypofractionated-accelerated treatments with "curative" fractionation schedules in human squamous cell carcinoma in nude mice. MATERIAL AND METHODS: FaDu tumors were transplanted subcutaneously into the hindleg of NMRI nu/nu mice. TCD50 values, i.e., the dose necessary to control 50% of the tumors locally, were determined after irradiation under ambient blood flow conditions with 5 and 10 fractions in 5 days, 10 fractions in 10 days, and 30 fractions in 15 days, 6 weeks or 10 weeks. RESULTS: TCD50 values of the hypofractionated regimens were not significantly different and varied from 41 to 46 Gy. The number of fractions given in the same overall time had no measurable effect on local tumor control. The TCD50 after 30 fractions in 6 weeks was 30 Gy higher than after the hypofractionated regimens. This effect was caused by a substantial increase of TCD50 with overall treatment time, the dose recovered per day was 0.82 Gy (95% CI 0.66; 0.96). alpha/beta eff determined from all data was 58 Gy (13; infinite). CONCLUSIONS: The results of the present study compare well with our previous findings after different "curative" fractionation schedules in the same tumor. Thus, our study does not support that tumors respond differently after application of 10 or more fractions compared to less fractionated regimens. The biological mechanisms that govern the radiation response of FaDu tumors appear to be the same for hypofractionated-accelerated and "curative" regimens. Since only one tumor was investigated, these results cannot be generalized at the present time.

Animals↗