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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 253 records · Page 14Linked to original sources
PubMed1989

Contractile properties of human prostate adenomas and the development of infravesical obstruction.

The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 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). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.

Aged↗
PubMed1989

Evidence for a respiration-modulated cholinergic action on the activity of medullary respiration-related neurons in the rabbit. An iontophoretic study.

Effects of the iontophoretically administered cholinergic agonists acetylcholine, bethanechol and DMPP on the activity of medullary respiration-related neurons were examined in urethane-anaesthetized rabbits. Inhibitory effects prevailed over excitatory effects. Analysis of cholinergic effects by cycle-triggered averaging revealed three major types of neuronal responses: (i) constant alterations of spike-density throughout the whole period of activity ("constant effects"), (ii) effects increasing during the progression of the burst of discharge or effects restricted to a particular fraction of the burst ("phasic effects") and (iii) effects which were characterized by an excitation during one respiratory phase and an inhibition during the other phase ("bi-phasic effects"). The latter type of effects was observed in phase-spanning respiration-related neurons. Phasic effects were mainly observed in inspiration-related neurons which were predominantly inhibited by stimulation of muscarinic receptors. Inspiratory R beta-neurons in no case were phasically affected by cholinergic agents. The mean muscarinic inhibition of inspiration-related neurons increased with the progression of inspiration. The mean nicotinic inhibition of expiration-related neurons decreased with the progression of expiration. Results suggest that the efficacy of (i) a central inspiration terminating mechanism and (ii) the onset of discharge of expiratory neurons is modulated by acetylcholine.

Acetylcholine↗
PubMed1989

Comparison of muscarinic cholinergic and alpha adrenergic receptors in canine ileum, colon, intestinal urinary reservoirs and bladder.

The muscarinic cholinergic (MCh) and alpha 2 adrenergic receptor densities in canine ileum, colon, ileal and colonic urinary reservoirs and bladder were determined using radioligand receptor binding methods in order to provide a rational basis for pharmacologic management of urinary incontinence following bladder replacement with intestinal segments. Muscarinic cholinergic and alpha 2 adrenergic receptor binding sites were studied in these tissues using saturation experiments with 3H-NMS and 3H-rauwolscine, respectively. The mean equilibrium dissociation constants for 3H-NMS binding (0.13 to 0.17 nM) in these tissues were similar (p greater than 0.05) indicating homogeneity of muscarinic cholinergic binding sites. The mean equilibrium dissociation constants for 3H-rauwolscine binding (1.27 to 1.98 nM) in these tissues were also similar (p greater than 0.05). A substantial density of MCh (1.06 to 1.22 fmol/mg. wet wt.) and alpha 2 adrenergic (0.47 to 1.11 fmol/mg. wet wt.) binding sites was identified in the intestinal tissues assayed. The density of ileal and colonic MCh and alpha 2 adrenergic binding sites was not altered following construction of urinary intestinal reservoirs. The presence of a substantial density of MCh and alpha 2 adrenergic binding sites in the intestinal tissues suggests that MCh and alpha 2 adrenergic analogs may be utilized for the management of urinary incontinence following bladder replacement with intestinal urinary reservoirs.

Animals↗
PubMed1989

Muscarinic cholinergic receptors in normal pediatric and myelodysplastic bladders.

Radioligand receptor binding experiments and in vitro muscle contractile studies were performed to determine the binding and functional properties of detrusor muscarinic cholinergic receptors in control and myelodysplastic bladders. Control bladder tissue was obtained from 8 children with primary vesicoureteral reflux undergoing ureteral reimplantation and 1 child at the time of organ transplant harvesting. Bladder specimens also were obtained from 10 children with myelomeningocele undergoing augmentation cystoplasty. Preoperative cystograms revealed that all children with vesicoureteral reflux had a smooth-walled bladder with normal capacity, whereas those with myelomeningocele undergoing augmentation cystoplasty had a small capacity bladder with trabeculations. Experiments were performed on detrusor tissue obtained from the bladder body in all cases. Radioligand receptor binding experiments with the 3H-N-methylscopolamine revealed that the equilibrium dissociation constant in control and myelodysplastic bladders was 0.44 +/- 0.09 and 0.40 +/- 0.10 nM., respectively. The equilibrium dissociation constant was similar in control and myelodysplastic bladders. The muscarinic cholinergic receptor density (Bmax) in control and myelodysplastic bladders was 0.66 +/- 0.12 and 0.24 +/- 0.03 fmol. per micrograms, protein, respectively. The significantly lower density of muscarinic cholinergic receptors in the myelodysplastic bladders may be explained by either a down regulations or by the histologically observed development of fibrosis. Concentration response experiments were performed on 7 control and 6 myelodysplastic bladders using carbachol and potassium chloride. The carbachol and potassium chloride concentrations producing half of the maximal response were similar in the control and myelodysplastic bladders, suggesting that detrusor dysfunction in myelodysplasia is not associated with detrusor supersensitivity. The maximal response (Emax) for potassium chloride was less in the myelodysplastic bladders than in the control bladders but the carbachol Emax was not significantly different. Concentration inhibitory experiments with oxybutynin and imipramine demonstrated that the myelodysplastic and control bladders were identically inhibited by these antagonists. Radioligand receptor binding studies and in vitro contractile experiments indicate that the detrusor dysfunction associated with myelomeningocele is not mediated by changes in the binding or functional properties of detrusor muscarinic cholinergic receptors.

Child↗
PubMed1989

Muscarinic cholinergic receptors in the normal and neurogenic human bladder.

Bladder dysfunction secondary to neurologic conditions occurs in all age groups and is associated with significant morbidity. The role of neuroreceptors in the development of detrusor dysfunction has not been studied previously. Control bladder tissue specimens were obtained from eight children with ureterovesical reflux undergoing ureteral reimplantation and 14 adults with bladder carcinoma undergoing cystectomy. Neurogenic bladder specimens were obtained from 10 children with myelomeningocele and five adults with neurogenic bladder dysfunction undergoing augmentation cystoplasty. Saturation experiments using 3H-N-methylscopolamine (3H-NMS) were performed in these control and neurogenic bladder homogenates. The mean equilibrium dissociation constants in the neurogenic and control bladders were 0.41 nM and 0.55 nM, respectively. The mean density of muscarinic cholinergic (MCh) receptor binding sites in the neurogenic and control bladders was 0.34 fmol/mg wet wt. and 0.65 fmol/mg. wet wt., respectively. Competitive binding experiments with 3H-NMS and various unlabelled MCh antagonists indicated that the pharmacology of MCh binding sites was similar in neurogenic and control bladders. Age was not significantly correlated with MCh receptor density in the control and neurogenic bladders. Muscarinic cholinergic binding sites are homogeneous in neurogenic and control bladders. The lower density of MCh receptors in the neurogenic bladders may represent down regulation of MCh receptors or a replacement of smooth muscle by fibrosis.

Adult↗
PubMed1989

Clinical interest in determinations of cellular radiation sensitivity.

Determinations of cell sensitivity in terms of survival fraction after doses employed in clinical radiation therapy, say 1-3 Gy, are of increasing interest to clinicians as they provide direct experimental data which can be employed without reference to models of cell inactivation. SF2 values are expected ultimately to prove valuable as response predictors. Even so, SF2 values would surely be combined with other predictors also under development to give the best feasible estimate of response of tumor and normal tissue. There are, however, several concerns with the SF2 data currently available. These include: SF2 depends upon the cell system employed (established cell lines vs primary cultures) and the method of assaying survival fraction (colony formation vs population growth); dose-response curves for inactivation of tumors characterized by the reported distribution of SF2 values are, in many instances, not close to those judged to obtain in clinical practice; the broad distribution of SF2 values indicates a rather flatter dose-response curve for tumor control or normal tissue than seems true from clinical experience. There appears to be a potential for clinical gain by determination of sensitivity of normal tissues in order to identify patients who are of increased sensitivity (for example heterozygotes for AT, 5-oxoprolinuria, etc.). Although the absolute SF2 values obtained by current technologies of culturing human cells often appear to be poorly related to values expected from observed radiation response in patients, intensive research on cell viability assays will almost certainly yield more realistic results.

Cell Line↗
PubMed1989

Susceptibility of Rhodobacter sphaeroides to beta-lactam antibiotics: isolation and characterization of a periplasmic beta-lactamase (cephalosporinase).

Thirteen strains of the gram-negative, facultative phototrophic bacterium Rhodobacter sphaeroides were examined fro susceptibility to beta-lactam antibiotics. All strains were sensitive to the semisynthetic penicillins ampicillin, carbenicillin, oxacillin, cloxacillin, and methicillin, but 10 of the 13 strains were resistant to penicillin G, as well as a number of cephalosporins, such as cephalothin, cephapirin, and cephalosporin C. A beta-lactamase (EC 3.5.2.6) with strong cephalosporinase activity was detected in all of the resistant strains of R. sphaeroides. With strain Y-1 as a model, it was shown that the beta-lactamase was inducible by penicillin G, cephalosporin C, cephalothin, and to some minor extent, cephapirin. The beta-lactamase was located in the periplasmic space, from which it could be extracted by osmotic shock disruption. By using this fraction, the beta-lactamase was purified 34-fold to homogeneity by steps involving batch adsorption to and elution from DEAE-Sephadex A50, chromatography on Q-Sepharose, and preparative polyacrylamide gel electrophoresis. The molecular masses of the native and denatured enzymes were determined to be 38.5 kilodaltons by gel filtration and 40.5 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively, indicating a monomeric structure. The isoelectric point was estimated to be at pH 4.3. In Tris hydrochloride buffer, optimum enzyme activity was measured at pH 8.5. The beta-lactamase showed high activity in the presence of the substrates cephalothin, cephapirin, cephalosporin C, and penicillin G, for which the apparent Km values were 144, 100, 65, and 110 microM, respectively. Cephalexin, cepharidine, and cephaloridine were poor substrates. The beta-lactamase was strongly inhibited by cloxacillin and oxacillin but only slightly inhibited by phenylmethylsulfonyl fluoride or thiol reagents such as iodoacetate and p-chloromercuribenzoate.

Anti-Bacterial Agents↗
PubMed1989

Enhanced myelopoiesis in long-term cultures of human bone marrow pretreated with recombinant granulocyte-macrophage colony-stimulating factor.

Long-term bone marrow culture (LTBMC) for human hemopoiesis supports continuous proliferation and differentiation within the myeloid progenitor population by the formation of an adherent stromal monolayer. LTBMC represents the most suitable in vitro model for the study of regulatory mechanisms in human hemopoiesis. We investigated the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) on bone marrow of normal donors in LTBMC. The cells (2 x 10(6)/ml) were incubated with 100 ng/ml rhuGM-CSF for 24 h in culture medium supplemented with 10% fetal calf serum. After the preincubation, LTBMCs were started and maintained over a period of 10 weeks. After 1 week in culture we observed a statistically significant difference with a 1.5-fold higher number of nonadherent cells in the LTBMCs containing the bone marrow preincubated with rhuGM-CSF (p less than 0.05). This increase was due to an expansion of the mature myeloid cells. At the same time point the number of GM colony-forming units (CFU-GM)/ml in the LTBMCs with rhuGM-CSF-preincubated bone marrow was slightly increased compared to the controls without reaching a statistically significant level. We conclude that rhuGM-CSF at a saturation dose is a potent stimulator of in vitro myelopoiesis stem cell pool. This in vitro result is of relevance for the clinical use of rhuGM-CSF in patients undergoing bone marrow transplantation. The incubation of donor bone marrow prior to transplantation might be a new approach to facilitate the engraftment and to shorten the phase of pancytopenia.

Bone Marrow↗
PubMed1988

Purification and characterization of phosphohexose isomerase from human gastrointestinal carcinoma and its potential relationship to neuroleukin.

Phosphohexose isomerase (PHI) derived from human gastrointestinal tumor tissue was isolated by specific elution from a cation exchanger. The identity of three PHI variants in the purified preparation could be demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing analysis. By preparative IEF the variants could be resolved to high homogeneity. The monomer of the common major variant with a pI of 9.1 revealed a molecular weight of 60,000, whereas for the cancer-associated variants with a pI of 8.9 and 8.6, a molecular weight of 57,000 and 56,000, respectively, was determined. The results obtained support the hypothesis that those variants are due to a specific intracellular cleavage of the enzyme in the malignant cells. Since it has been shown that the Mr 56,000 protein neuroleukin exhibits a strikingly high degree of homology with PHI (M. Chaput et al., Nature (Lond.), 332: 454-455, 1988; P. Faik et al., Nature (Lond.), 332: 455-456, 1988), the described specific cleavage of PHI might be responsible for the conversion of an enzyme to a trophic factor.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

Variants of phosphohexose isomerase in gastrointestinal and mammary carcinoma: isoelectric focusing patterns of normal and tumor tissues derived from surgical specimens of the same patient.

The occurrence of charge variants of phosphohexose isomerase was elucidated in cancerous and, for comparison, in noncancerous tissues obtained from the same organ. Surgical specimens from 35 patients with gastrointestinal and mammary carcinoma were studied by means of the isoelectric focusing (IEF) technique. Differences in the IEF pattern could be demonstrated in 90% of the patients with gastric cancer. Corresponding values for the patients with colorectal and mammary carcinoma were 50 and 73%, respectively. Almost all normal specimens proved to be monomorphic, revealing only the major basic band with a pI of 9.1. In most of the tumors, additional bands of pI 8.9 and 8.6 were found. This "typical" IEF pattern in tumor tissues was observed in 60% of gastric and 73% of mammary tumors, but in only 36% of colorectal tumors. The results obtained suggest that the IEF pattern of phosphohexose isomerase in tumor tissue might be a useful tool for tumor diagnosis.

Breast↗
PubMed1988

Phosphohexose isomerase in hypernephroma. Significance as serum tumor marker, comparison to other glycolytic enzymes and isozyme patterns in normal and tumor tissue.

In hypernephroma an overall diagnostic sensitivity of 72% and a specificity of 87% was found for the serum tumor marker phosphohexose isomerase (PHI). Both in early stage disease and in well differentiated tumors a sensitivity of about 60% was reached. In contrast the sensitivity of three other glycolytic enzymes tested was found to be less than 20%. Since the cancer induced elevation of PHI activity in the tumor was found to be comparable to those of the other test enzymes, elevated PHI serum activities cannot be attributed to overproportional PHI synthesis and unspecific cell-lysis. In 6 of 10 cases studied differences in the PHI isozyme pattern between the tumor and the normal tissue were found suggesting the occurrence of cancer associated structural alterations of PHI.

Biomarkers, Tumor↗
PubMed1988

[Significance of pancreatic and duodenal secretions for the protection of gastrointestinal anastomoses following stomach resection--an animal experiment study].

The consequences of deviation of pancreatic juice and bile after gastric resection were studied in an experimental animal model in 66 rats. After hemigastrectomy and Billroth I resp. Billroth II anastomoses papilla vateri was transplanted into a deep jejunal limb in a B I and a B II group each. Absence of alkaline secretions of Papilla vateri was followed by a marked increase in acidity in the gastric remnant and connected intestine. Especially in the Billroth II operated stomach we found an increased ulcer risk under these circumstances. With additional histamine-stimulation frequency of ulcer was 75% in Billroth II but only 33% in Billroth I animals. When alkaline reflux was preserved the ulcer rate ranged from 15 to 40% in all groups. These results confirmed the protective property of postresectional reflux for the integrity of anastomoses after gastric resection. The increased resistance of Billroth I anastomoses in spite of deficient luminal acid buffers could be explained by the mucus-bicarbonate-barrier of the duodenal mucosa.

Anastomosis, Surgical↗