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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 235 records · Page 13Linked to original sources

Radiotherapy of the rhabdomyosarcoma R1H of the rat: postoperative radiotherapy.

Rhabdomyosarcoma R1H of the rat was excised aiming for a complete macroscopic local excision. Adjuvant radiotherapy was performed from the third postoperative day on. Former tumor sites were locally irradiated with 200 kVp X rays 4 times per week over a period of 6 weeks. Total doses of 0, 15, 30, 45 and 60 Gy were applied. The tumor volume was measured and the time to regrow to initial volume was assessed. The results were compared to the effect of a standard radiotherapy alone with 30 fractions of 2 Gy applied within 6 weeks. All tumors recurred despite of the irradiation treatment. At high total doses (greater than 30 Gy), adjuvant radiotherapy was found to improve short term tumor response considerably, whereas no positive effect was seen at low doses. After a total dose of 60 Gy and long time intervals after start of treatment, radiotherapy alone and a combination of surgery and radiotherapy seem to be isoeffective in our tumor system.

Animals↗

Metastases after fractionated radiation therapy of three murine tumor models.

The incidence of lung metastases after fractionated radiation therapy was compared to single dose irradiation in a retrospective analysis of three murine tumor models. For FSaII and SCCVII 5 or 15 fractions over 5 days were given using curative and subcurative doses and photons and neutrons. Data were pooled from different experiments. In mice with locally controlled FSaII the incidence of lung metastases was the same after all treatments, whereas in mice with locally controlled SCCVII, metastases were enhanced after 15 fractions. Photon and neutron irradiations yielded similar results. Local recurrences were followed by increased metastases. MCaIV was subcuratively irradiated with 9 equal fractions followed by a top-up dose to achieve local control. Metastases were high if doses per fraction were low and interfraction time intervals long. The data on MCaIV indicate increased metastases if clonogenic cells during treatment represent a large proportion of the integral tumor burden. The results on FSaII and SCCVII indicate that fractionated treatments might differently influence distant metastasis in different tumor models.

Animals↗

Autonomic receptors in human prostate adenomas.

Radioligand receptor binding techniques were used to characterize alpha 1 adrenergic, alpha 2 adrenergic and muscarinic cholinergic (MCh) binding sites in human prostate adenomas obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH). Prostate adenoma specimens were obtained from nine men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). A quantitative symptoms score analysis and urinary flow rate determinations documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The mean equilibrium dissociation constants (Kd) and the mean densities of 125I-Heat (alpha 1 adrenergic) and 3H-NMS (MCh) binding sites were similar in tissue homogenates obtained from men with asymptomatic and symptomatic BPH. The mean Kd of 3H-Rauwolscine (3H-Ra) was significantly greater in the prostatectomy specimens obtained from men with symptomatic BPH compared to the specimens obtained from men with asymptomatic BPH (p less than 0.05). The density of 3H-Ra (alpha 2 adrenergic) binding sites was significantly greater in the prostate adenomas obtained from men with symptomatic BPH compared to the prostate adenomas obtained from men with asymptomatic BPH (p less than 0.05). The difference in alpha 2 adrenoceptor density was accounted for by an increased receptor density in the open prostatectomy specimens. There was no significant correlation between alpha 2 adrenergic, alpha 1 adrenergic, and MCh receptor densities and prostate weight or patient age. This study indicates that the development of infravesical obstruction in men with BPH is not related to upregulation or altered binding affinity of alpha 1 adrenergic or MCh receptor binding sites. The significance of the observed upregulation of alpha 2 adrenoreceptors in the prostate adenomas obtained from men undergoing open prostatectomy is unknown, and requires further investigation.

Humans↗

Interleukin 6 is an autocrine growth factor for mesangial cells.

Interleukin 6 (IL-6) induces the acute phase response, differentiation of B cells, proliferation of T cells, thymocytes, hematopoietic progenitors, hybridoma and plasmacytoma cells. Monocytes, T cells, fibroblasts, epithelial and endothelial cells secrete IL-6. Since IL-6 responsive cell-types may participate in the pathogenesis of glomerular inflammation, we studied the secretion of IL-6 by rat MCs, using the IL-6 dependent hybridoma cell line B9. The results of our studies indicate that MCs secrete IL-6 with a molecular weight of 17-42 kDa and isoelectric point of 4.0 to 5.3 MC-IL-6 activity could be blocked by a polyclonal antimurine-IL-6 antibody. MC express IL-6 mRNA as determined by Northern blot. Furthermore, our data demonstrate that IL-6 acts as an autocrine growth factor for MC. Incubation of subconfluent MC with recombinant IL-6 results in a dose-dependent increase of 3H-thymidine incorporation and number of MCs. Moreover, reverse phase HPLC fractions of MC-CM containing IL-6 activity increase 3H-thymidine incorporation by MC. In addition to its possible paracrine role in mediating the immune response in the glomerulus, MC-IL-6 may also be one of the autocrine signals leading to mesangial cell proliferation in vivo.

Animals↗

Flow cytometric determination of the time of metastasis during fractionated radiation therapy of the rat rhabdomyosarcoma R1H.

A technique is presented for determining the time of metastasis during fractionated radiation therapy of the rat rhabdomyosarcoma R1H by flow cytmetric DNA index measurements. The DNA index is the relative DNA content of the tumour cells compared with normal cells. The DNA index of the highly hyperploid R1H tumour decreases linearly during radiation therapy dependent on the total dose applied, with a rate of 0.22% per Gy. Since metastatic cells escape further irradiation, their DNA index should correspond to the DNA index at time of spread. If so, cells disseminated late during a course of fractionated irradiation are expected to produce symptoms later and to have a lower DNA index compared with cells that metastasized at the start of treatment. The results obtained fitted these expectations, showing that timing of metastases by DNA flow cytometry, in principle, is possible. A first application of this method indicates that the risk per clonogenic R1H tumour cell to matastasize increases during fractionated irradiation.

Animals↗

Subglottic stenosis in Wegener's granulomatosis: development during cyclophosphamide treatment with response to carbon dioxide laser therapy.

A patient with Wegener's granulomatosis rapidly developed a circumferential subglottic stenosis while on a cyclophosphamide regimen that had caused resolution of systemic symptoms and pulmonary infiltrates. The stenosis developed in the area of previously noted tracheal ulceration and responded satisfactorily to carbon dioxide laser therapy.

Adult↗

[Laser-induced occlusion of corneal blood vessels with variable emission and absorption].

Laser light has repeatedly been proposed for the occlusion of corneal neovascularizations. Priority has to be given to minimize laser energy in order to limit side effects such as corneal burns. We investigate the influence of variable emission wavelength using a dye laser or dye-enhanced absorption with intravenous sodium fluorescein. Laser energy can be reduced using intravenous dyes at vessel diameters less than 50 microns. Permanent occlusion is achieved in 43% instead of 28% without dye-enhanced absorption. Vessels measuring greater than 50 microns in diameter can be occluded best at lowest laser energy levels when 575 nm laser light is used, which approximates the absorption maximum of hemoglobin.

Absorption↗

The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer.

The diagnostic validity of the glycolytic enzyme phosphohexose isomerase (PHI) as a serum tumor marker was evaluated. For this purpose the sensitivity of PHI was determined in 435 patients with histopathologically defined, malignant gastrointestinal, kidney, and mammary tumors prior to primary treatment. To assess the specificity, PHI serum activities were measured in 181 patients with benign diseases and disorders from an internal practice. In gastrointestinal and kidney cancer, PHI reached an overall diagnostic sensitivity of about 70%, and a specificity of 92% was obtained. Even in early stages without metastasis, elevated PHI serum levels were found in about 60% of the patients. In mammary cancer, however, a sensitivity of only 40% was observed. PHI activity can be measured without the need for highly technical skills and equipment, in a short time and at low cost. These data suggest that serum PHI can be a useful indicator in the preventive checkup of gastrointestinal and renal cancer in medical practice.

Biomarkers, Tumor↗

Production of interleukin 6 by hepatoma cells.

Five rat hepatoma cell lines were shown to secrete hepatocyte-stimulating factors (HSFs) capable of inducing a characteristic spectrum of acute phase genes. Three of these lines, but not normal rat livers or livers from rats with an experimentally induced acute inflammation, produced interleukin 6 (IL6) mRNA. An anti-rat IL6 serum was prepared against synthetic peptides derived from the rat IL6 cDNA sequence. This antiserum cleared authentic rat IL6 and a fraction of the HSF activities secreted by the hepatoma cell lines. After concentration of culture supernatants from FTO2B hepatoma cells, IL6 was detected with the anti-IL6 serum by immuno-blot analysis. Biosynthesis of IL6 in the HTC line was demonstrated by metabolic labeling and immunoprecipitation. Secretion of HSF activities by hepatoma cells was increased by serum factors. These data suggest that different rat hepatoma lines each secrete different characteristic sets of HSF activities and establish unambiguously that IL6 is secreted by at least some of these lines.

Acute-Phase Proteins↗

[Influence of examining temperature on the ultrasound attenuation in testicular tissue].

By means of an ultrasound spectroscopic measurement technique the influence of examining temperature on the ultrasound attenuation was experimentally investigated on formalin-fixed normal and altered testicular tissue. In the examined tissue specimens a temperature-dependent change of ultrasound attenuation (alpha on 6 MHz) was found in the temperature area between 10 and 50 degrees C. In the altered testicular tissue a higher damping decline could be observed. On the measuring points the specimens were examined by light microscopy.

Dysgerminoma↗

[Experimental investigations on the effect of the transducer-specimen distance on the ultrasound attenuation of formalin-fixed testicular tissue].

Additional information on the tissue structure are possible by estimation of sound physical parameters in comparison with normal B-scan ultrasonography, especially the frequency-dependent ultrasound attenuation. The ultrasound attenuation measurements were made on histochemical normal and pathological testicular tissue with changing transducer-specimen distance. No markedly difference in damaging behaviour was found between normal and pathological testicular tissue at different distances.

Fixatives↗

Response of human squamous cell carcinoma xenografts of different sizes to irradiation: relationship of clonogenic cells, cellular radiation sensitivity in vivo, and tumor rescuing units.

The relationship of clonogenic cells, cellular radiation sensitivity at tumor control does in vivo, and tumor rescuing units at different tumor sizes was investigated in the human squamous cell carcinoma FaDu growing in NCr/Sed nude mice. The composition of the tumors was determined in single cell suspensions and compared to tumor control data after single-dose irradiation. To avoid the influence of varying oxygen concentrations in the tumors, all irradiations were performed under clamp hypoxia. Nude mice and animals further immunosuppressed by 6-Gy whole-body irradiation were used to assess the immunological effects. The numbers of total cells, cells excluding trypan blue, host cells, and colony-forming cells increased linearly with the weight of FaDu tumors. Comparable results were obtained for cell suspensions prepared from tumors growing in nude of pretreated nude mice. The radiation dose required to control 50% of tumors (TCD50) of different sizes between 36 and 470 mm3 increased from 52.1 to 60.1 Gy when the tumors were maintained in normal nude mice and from 50.8 to 61.3 Gy in whole-body-irradiated mice. The D0 of FaDu cells in vivo was calculated by regression analysis of TCD50 vs the logarithm of the clonogenic cell number, assuming an oxygen enhancement ratio of 3.0. The resultant D0S of 1.1 and 1.2 Gy in vivo correspond well to the radiosensitivity of FaDu cells in vitro determined previously. Assuming the single-hit multitarget model of cell killing and extrapolation numbers between 2 and 20, the mean number of tumor rescuing units would be 10(5) to 10(6) for a 100-mm3 tumor growing in whole-body-irradiated nude mice. Comparison of the number of tumor rescuing units to the estimated number of clonogenic cells does not conflict with the assumption that every surviving clonogenic cell is able to repopulate FaDu tumors after irradiation; however, it seems more likely that more than one clonogenic cells is necessary. The proportion of tumor rescuing units in the clonogenic cell population is independent of tumor size.

Animals↗

Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum.

The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments.

Epithelium↗

Evidence for the identity of glutathione-dependent formaldehyde dehydrogenase and class III alcohol dehydrogenase.

Formaldehyde dehydrogenase (EC 1.2.1.1) is a widely occurring enzyme which catalyzes the oxidation of S-hydroxymethylglutathione, formed from formaldehyde and glutathione, into S-formyglutathione in the presence of NAD. We determined the amino acid sequences for 5 tryptic peptides (containing altogether 57 amino acids) from electrophoretically homogeneous rat liver formaldehyde dehydrogenase and found that they all were exactly homologous to the sequence of rat liver class III alcohol dehydrogenase (ADH-2). Formaldehyde dehydrogenase was found to be able at high pH values to catalyze the NAD-dependent oxidation of long-chain aliphatic alcohols like n-octanol and 12-hydroxydodecanoate but ethanol was used only at very high substrate concentrations and pyrazole was not inhibitory. The amino acid sequence homology and identical structural and kinetic properties indicate that formaldehyde dehydrogenase and the mammalian class III alcohol dehydrogenases are identical enzymes.

Alcohol Dehydrogenase↗

Human gelatinase/type IV procollagenase is a regular plasma component.

Gelatin zymograms revealed in human plasma a constant 66 kDa proteolytically active polypeptide. In most plasma samples other major proteolytic activities were seen at Mr 92,000, 130,000 and 225,000. All four proteases were Ca2+-dependent metalloproteases and bound quantitatively to gelatin-Sepharose. Immunoblotting results indicated that the 66 kDa protease was the human fibroblast gelatinase/type IV procollagenase and that the other three proteases were macrophage/granulocyte-derived gelatinase components. The 66 kDa protease did not bind to conA- nor lentil lectin-Sepharose allowing its separation from the 92, 130 and 225 kDa proteases. During the isolation procedure the plasma gelatinase/type IV procollagenase tended to form a proteolytically active spontaneous disulfide-bonded dimer and a 62 kDa component that could also be obtained by digestion with trypsin. The same polypeptide changes occurred also in stored preparations of the corresponding protease isolated from fibroblast culture medium while the freshly purified protein contained only the 66 kDa proform.

Collagenases↗

Isolation of a human hepatic 60 kDa aspartylglucosaminidase consisting of three non-identical polypeptides.

We have characterized the properties of human aspartylglucosaminidase (EC 3.5.1.26), the lysosomal enzyme which is deficient in the human inherited disease aspartylglucosaminuria. The purification procedure from human liver included affinity chromatography, gel filtration, strong-anion- and strong-cation-exchange h.p.l.c., chromatofocusing and reverse-phase h.p.l.c. In a denaturing SDS/polyacrylamide-gel electrophoresis, the 6600-fold purified enzyme was shown to be composed of three non-identical inactive polypeptide chains of molecular masses 24, 18 and 17 kDa. In a native polyacrylamide-gel electrophoresis, these polypeptide chains ran as one active enzyme complex. As judged from the elution position of the native enzyme in a Biogel P-100 gel filtration, the approximate molecular mass of this complex was 60 kDa. The enzyme had a pI of 5.7, a pH optimum at 6, of 0.48 mM and a specific activity of 200,000 nkat for the substrate 2-acetamido-1-beta-(L-aspartamido)-1,2-dideoxy-D-glucose. The enzyme showed a 57% loss of activity at 60 degrees C after 45 h but was practically inactive after incubation at 72 degrees C for a few minutes. The molecular structure, Km and specific activity as well as the thermostability of the enzyme described here are different from those reported previously for human aspartylglucosaminidase.

Amidohydrolases↗

Effects of warm and cold ischemia on mitochondrial functions in brain, liver and kidney.

The purpose of this work was to study the effects of warm (37 degrees C) and cold (4 degrees C) ischemia on different mitochondrial functions in rat brain, liver and kidney. After 10 to 60 minutes of ischemia at 37 degrees C the energy coupled respiration as well as the ADP-induced malate-aspartate shuttle activity in brain and liver mitochondria or the rate of mitochondrial ATP synthesis in kidney were significantly decreased. However, the respiratory rates and the shuttle activity in the absence of ADP remained unchanged. These data suggest that ischemia primarily affects electron transport in the respiratory chain rather than the hydrogen shuttle and the energy coupling system. When the temperature during the indicated ischemic periods was decreased to 4 degrees C, in brain and liver no significant alterations of these mitochondrial functions were found in comparison with the non-ischemic controls. When rat kidneys were stored for 36 hours at 4 degrees C according to Collins mimicking transplantation conditions, the mitochondrial respiration and ATP synthesis were only slightly decreased. It therefore appears that hypothermia can prevent effectively mitochondrial dysfunction due to ischemia.

Adenosine Triphosphate↗