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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 73 records · Page 4Linked to original sources
PubMed2001

Congenital ovine neuronal ceroid lipofuscinosis--a cathepsin D deficiency with increased levels of the inactive enzyme.

We recently showed that a form of neuronal ceroid lipofuscinosis (NCL) in white Swedish landrace sheep is caused by a missense mutation in the cathepsin D gene resulting in complete inactivation of the enzyme. Despite the lack of cathepsin D activity, the brains of the cathepsin D deficient sheep showed strongly increased staining for cathepsin D in immunohistochemistry. By Western blotting, a 5-10 fold increase in the level of cathepsin D was confirmed. These results indicate that the missense mutation in congenital NCL sheep results in the synthesis of an inactive yet stable cathepsin D.

Animals↗
PubMed2001

Radiobiological hypoxia, oxygen tension, interstitial fluid pressure and relative viable tumour area in two human squamous cell carcinomas in nude mice during fractionated radiotherapy.

Very little is known about the correlation between the radiobiological hypoxic fraction (rHF) and other measures of tumour oxygenation during fractionated irradiation. In the present study the rHF is determined in untreated human FaDu and GL squamous cell carcinoma in nude mice and in tumours irradiated with 10 fractions in 2 weeks and 20 fractions in 4 weeks, using tumour control as the experimental endpoint. The results were compared with measurements of the pO2, the interstitial fluid pressure (IFP) and the relative viable tumour area. In FaDu tumours the radiobiological hypoxic fractions (rHFs) before and during irradiation were not statistically different from 100%. Depending on the assumptions made for D0, the rHFs of GL tumours were between 0.2 and 4% or 30 and 53%. The median pO2 values were 2.8 mmHg for untreated FaDu tumours and 0.2 mmHg for GL tumours (p < 0.001). The median IFP values were 2.6 mmHg in FaDu and 5.3 mmHg in GL tumours (p = 0.01). No important changes in the pO2 and IFP values were observed during fractionated irradiation. The relative viable tumour area during irradiation decreased by 83% in FaDu tumours (p = 0.002) and by 54% in GL tumours (p = 0.003). It is concluded that differences in rHF exist between FaDu and GL tumours before and during fractionated irradiation and that these differences are not reflected by pO2 and IFP values and the relative viable tumour area.

Animals↗
PubMed2001

Impact of the tumour bed effect on microenvironment, radiobiological hypoxia and the outcome of fractionated radiotherapy of human FaDu squamous-cell carcinoma growing in the nude mouse.

PURPOSE: To investigate the impact of the tumour bed effect (TBE) on histological parameters of the micromilieu, radiobiological hypoxic fraction and local control after fractionated irradiation in FaDu squamous-cell carcinoma in the nude mouse. This tumour has previously shown a clear-cut TBE caused by increased necrotic cell loss at a constant cell production rate in the viable tumour compartment. MATERIALS AND METHODS: Human FaDu tumours were studied in the NMRI nude mouse. Tumours were transplanted either into unirradiated subcutaneous (s.c.) tissues (controls) or s.c. tissues pre-irradiated with 12.5 Gy (TBE group). In both groups we measured the volume doubling time (VDT), potential doubling time (T(pot)), relative necrotic area, and in the viable tumour compartment the relative vascular area (9F1 mAb), relative hypoxic area (NITP or pimonidazole), relative perfused area (Hoechst 33342), and the perfused fraction of vasculature. The tumour control dose 50% (TCD 50), radiobiological hypoxic fraction (rHF) and dose-modifying factors (DMF) for the comparison of tumours in the TBE and control groups were determined from local tumour control data after treatment with single doses under ambient conditions or under clamp hypoxia, and after irradiation with 30 fractions under ambient conditions within 6 weeks using maximum-likelihood analysis. RESULTS: A clear-cut TBE (VDT = 4.0 days (95%CI 2.9;4.4) for the control group versus 7.2 days (6.4;8.9) for the TBE group; p <0.0001) caused by increased necrosis (mean relative necrotic area of 12% (5;20)) versus 33% (10;41); p = 0.07) at a constant cell production rate (T(pot) = 2.2 days (1.4;2.3) versus 2.2 days (1.7;2.6); p = 0.30) was confirmed. Histological analysis of the micromilieu within the vital subarea revealed no systematic differences between the TBE and control groups. The rHF of 2% (0.1;27) for control tumours was lower than the 15% (95% CI 2;91) for the TBE group, but this difference was nonsignificant (p = 0.12). Compared with control tumours, the TCD50 for irradiation under clamped hypoxia was in a statistical trend lower for tumours in the TBE group (DMF 1.11 (0.98;1.28), p = 0.09). After fractionated irradiation, tumours of the TBE group were significantly more radiosensitive (TCD50 56.6 Gy (46;70) versus 78.7 Gy (63;100); p = 0.003). CONCLUSIONS: The results on FaDu tumours growing in pre-irradiated tissues indicate that increased necrosis caused by impairment of the vascular supply may increase the radiosensitivity of tumours treated by fractioned irradiation.

Animals↗
PubMed2001

Faulty design resulting in temporary pacemaker failure.

A 77-year-old man became asystolic 3 days after aortic valve replacement and coronary artery bypass surgery. A dual-chamber temporary pacemaker generator was turned on but failed to discharge; instead, an obscure error message appeared on the liquid crystal display of the pacemaker. The intensive-care nurses and physicians were unable to activate the pacemaker. We describe the pacemaker design that led to this instance of pacemaker failure. This case is important because it illustrates how a medical equipment design flaw can turn a human error into a potentially catastrophic event.

Aged↗
PubMed2001

[Aid tool for the assessment of health measures performance: the example of the program for alcoholism prevention in Lorraine].

From "alcohol primary prevention program in Lorraine", the authors developed a tool for an evaluation of performance: a card index to assess each action of the program. This tool can be applied to various programs, in particular health regional ones. Before presenting the tool, the authors specify conceptual frameworks to which they refer and present the evaluation of performance step which is declined in "evaluation of the results" and "evaluation of the processes". This assessment combine an understanding and a data based approaches. They show how those two kinds of assessment meet different and complementary aims. The tool presented includes 9 cards. The first 8 cards joined together in a booklet make possible a description and evaluation of each contributive action to the program. A ninth card gives a synthesis view to follow and assess the entire program in comparison with the starting reference frame. The publication of this perfectible tool is a call to practices exchanges between professionals in load of health programs.

Alcoholism↗
PubMed2000

[Long-term outcome after coronary emergency intervention].

BACKGROUND AND OBJECTIVE: Coronary angioplasty (CAG) has become an acceptable method of treating an acute coronary syndrome (myocardial infarction [MI] or unstable angina [UA]). It was the aim of this study to determine whether the results of such emergency treatment differed from those after elective CAG. PATIENTS AND METHODS: Results of emergency CAG in 581 patients (aged 60 +/- 11 years; 77% males) admitted to the authors' hospital between July 1994 and December 1996 were compared with those of elective CAG in 2,460 patients (aged 61 +/- 10, admitted during the same period. Follow-up information was obtained after 22.4 +/- 11 months in 93.2% of the patients by examination, written answers to annual questionnaires, data being collected on survival, repeat cardia catheterizations, other interventions, aorto-coronary bypass, occurrence of myocardial infarction, the patients' general state and drugs received. RESULTS: 19 of 517 patients (3.7%) of the group who had undergone elective CAG had died during the follow-up period, compared with 107 of 2436 of the emergency cohort (4.4%; not significant). There were also no significant differences regarding repeat cardiac catheterization, interventions, coronary bypass or re-admission. The proportion of subsequent emergency CAG among all CAGs was 16.8% in the emergency cohort, 8.8% after elective angiography (p < 0.001). CONCLUSION: Coronary angiography performed in patients with an acute coronary syndrome has no prognostic significance regarding mortality and morbidity after the acute phase of the disease.

Aged↗
PubMed2000

Cell heterogeneity and subpopulations in solid tumors characterized by simultaneous immunophenotyping and DNA content analysis.

BACKGROUND: Heterogeneity in human malignant tumors is a well-described phenomenon and of interest with regard to subpopulations with differences in clonality, metastatic potential, and response to therapy under different treatment regimes. The aim of this study was the simultaneous characterization of surface markers and DNA content of solid tumors to identify tumor cell subpopulations and to study the association between the expression of antigens and DNA content. METHODS: In the present study, six different malignant tumors grown as xenografts in nude mice were characterized by five-parameter flow cytometry. Immunophenotyping was performed using a variety of direct fluorescence-conjugated antibodies. In all cases, simultaneous detection of DNA content was done after staining with 7-aminoactinomycin D. RESULTS: Tumor cells were characterized by light scatter properties, antigen expression, and DNA content. Tumor cell heterogeneity, subpopulations, and DNA content-dependent antigen expression were identified. CONCLUSIONS: This method offers the possibility of characterizing solid tumors according to their immunophenotype and DNA content. The results obtained can be used to identify changes in immunophenotypic and DNA profiles of tumor cell populations before and after therapy and might be useful to define parameters predictive for response to therapy.

Animals↗
PubMed2000

[Anal fissure--a new therapy concept].

The anal fissure is one of the most frequent causes for anal pain. Conservative treatment usually consists of laxatives, local anesthetics and nitroglycerin cream. These therapies have a high recurrency rate. Surgical interventions, i.e. manual dilatation and sphincterotomy are fraught with the danger of fecal incontinence. The completely reversible effect of botulinum toxin injection opens new possibilities in the treatment of anal fissures. Its use is discussed as part of a 3-stage therapeutic regimen.

Administration, Topical↗
PubMed2000

A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration.

The neuronal ceroid lipofuscinoses (NCLs) constitute a group of neurodegenerative storage diseases characterized by progressive psychomotor retardation, blindness and premature death. Pathologically, there is accumulation of autofluorescent material in lysosome-derived organelles in a variety of cell types, but neurons in the central nervous system appear to be selectively affected and undergo progressive death. In this report we show that a novel form of NCL, congenital ovine NCL, is caused by a deficiency in the lysosomal aspartyl proteinase cathepsin D. A single nucleotide mutation in the cathepsin D gene results in conversion of an active site aspartate to asparagine, leading to production of an enzymatically inactive but stable protein. This results in severe cerebrocortical atrophy and early death, providing strong evidence for an important role of cathepsin D in neuronal development and/or homeostasis.

Amino Acid Sequence↗
PubMed2000

The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators.

The propagation of herpesviruses has long been viewed as a temporally regulated sequential process that results from the consecutive expression of specific viral transactivators. As a key step in this process, lytic viral DNA replication is considered as a checkpoint that controls the expression of the late structural viral genes. In a novel genetic approach, we show that both hypotheses do not hold true for the Epstein-Barr virus (EBV). The study of viral mutants of EBV in which the early genes BZLF1 and BRLF1 are deleted allowed a precise assignment of the function of these proteins. Both transactivators were absolutely essential for viral DNA replication. Both BZLF1 and BRLF1 were required for full expression of the EBV proteins expressed during the lytic program, although the respective influence of these molecules on the expression of various viral target genes varied greatly. In replication-defective viral mutants, neither early gene expression nor DNA replication was a prerequisite for late gene expression. This work shows that BRLF1 and BZLF1 harbor distinct but complementary functions that influence all stages of viral production.

Cell Line↗
PubMed2000

Ca(2+)-modulated phosphorylation of a low-molecular-mass polypeptide in rat liver mitochondria: evidence that it is identical with subunit c of F(0)F(1)-ATPase.

A 3.5-kDa polypeptide associated with the inner membrane of rat liver was found to be phosphorylated by [gamma-(32)P]ATP, presumably via a cAMP-dependent kinase. The phosphorylation was modulated by [Ca(2+)] in the physiological range, with a minimum at 1 microM and rising fourfold toward lower (10 nM) and higher (10 microM) concentrations. Further characterization of the 3.5-kDa component showed that the polypeptide has the same electrophoretic mobility as subunit c of F(0)F(1)-ATPase and that it selectively binds to antibodies against subunit c.

Adenosine Triphosphate↗
PubMed2000

[What do we know about the mechanisms of the time factor in oncological therapy?].

BACKGROUND: Experimental studies and prospective randomized clinical trials have demonstrated a detrimental effect of prolongation of overall treatment time on local tumor control. METHODS: In a brief review of the literature, possible mechanisms of the time factor are discussed. RESULTS AND CONCLUSIONS: The mechanisms of the time factor in cancer treatment are complex and, at present, not fully understood. In experimental tumors, rapid proliferation of clonogenic cells during fractionated irradiation and treatment gaps has been determined as a major cause of the time factor in radiotherapy. Also, chemotherapy can stimulate repopulation of experimental tumors by clonogenic cells. Besides repopulation of clonogenic tumor cells, other factors such as the deterioration of the tumor vasculature with increasing tumor hypoxia might contribute to the time factor.

Animals↗