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Biomedical subjects

S Böhm

Publications and source records attributed to S Böhm.

At least 55 records · Page 3Linked to original sources
PubMed1994

The FAR domain defines a new Xenopus laevis zinc finger protein subfamily with specific RNA homopolymer binding activity.

The zinc finger motif defines a large superfamily of nucleic acid binding proteins. Conserved amino acid sequence elements associated with structurally variant zinc finger clusters define subfamilies of zinc finger proteins (ZFPs). The FAR domain (Finger Associated Repeats) is a novel type of repeat element found at the amino-terminus in a subfamily of Xenopus laevis ZFPs. Northern blot analyses of three different members of the FAR subfamily (XFO 6, XFO 9-3 and XFG 68) revealed that each of these genes is transcribed during oogenesis, embryogenesis and in all investigated tissues of adult animals thereby indicating a ubiquitous distribution of transcripts. All FAR-ZFPs tested so far have specific RNA homopolymer binding activity; they associate preferentially with poly(U). The FAR repeats possess limited primary sequence homology with a sequence in the nucleolar shuttling protein NO38, within a region that contains a casein kinase II phosphorylation site.

Amino Acid Sequence↗
PubMed1994

Influence of halothane on the effect of cAMP-dependent and cAMP-independent positive inotropic agents in human myocardium.

Volatile anaesthetics have a variety of effects on the myocardium, namely a negative inotropic effect and a catecholamine sensitizing effect. The present study was designed to see if the hydrocarbon anaesthetics interact specifically with subcellular targets of the myocardial cell, by examining the effects of halothane in the presence of positive inotropic agents with different mechanisms of action. Experiments were performed in isolated electrically driven left ventricular preparations (1 Hz, 37 degrees C, Ca2+ 1.8 mmol litre-1) from human hearts obtained at cardiac surgery. The concentration-response curves of noradrenaline, milrinone, BayK 8644 and Ca2+ were investigated in the absence and in the presence of halothane. Halothane enhanced the efficacy of noradrenaline and milrinone but not of Ca2+ or BayK 8644. The potency of milrinone was also increased by halothane, whereas the potency of BayK 8644 was decreased and those of noradrenaline and Ca2+ were unchanged. Halothane differentially influences the effects of agents with different positive inotropic mechanisms. This experimental approach can be taken as a functional method to localize the mechanisms of action of the inhalation anaesthetics in human myocardium, namely sensitization of cAMP formation and interaction with L-type Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

Adult↗
PubMed1994

[Primary stomach lymphoma. An assessment of the current status].

The gastrointestinal tract represents the most frequent extranodal manifestation of Non-Hodgkin's lymphoma. Primary gastrointestinal lymphoma which are classified according to the concept of MALT (mucosa-associated-lymphoid-tissue) have to be differentiated from lymphoma involving secondarily the digestive tract. Primary gastric lymphoma which appear at an advanced age can be usually diagnosed endoscopic-bioptically. Representing the major prognostic factors options in the therapy of gastric lymphoma are based on the histologic grading and the stage of disease. Surgical resection and radiotherapy allow a good local tumor control while chemotherapy is the treatment of choice in case of disseminated disease or high malignancy. Characterizing the morphology and molecular biology of primary gastric lymphoma of the MALT, evaluating the role of endoscopic ultrasound in the local staging (EI1, EI2 and EII1), and optimating the therapeutic modalities are main topics of an ongoing prospective multicenter trial.

Combined Modality Therapy↗
PubMed1994

[Primary stomach lymphoma of the MALT type. Diagnosis and therapy. Gastrointestinal Lymphoma Study Group].

Primary gastric lymphoma are nowadays considered as a distinct lymphoma entity. Their classification is based on the concept of MALT (Mucosa-associated lymphoid tissue). Within the gastrointestinal tract, the stomach is most frequently involved. In the pathogenesis of gastric lymphoma, Helicobacter pylori-associated gastritis plays an important, conditioning role. Usually, the diagnosis of gastric lymphoma can be established on the basis of endoscopic biopsies. Endoscopic ultrasound seems highly useful for differentiating the depth of lymphoma infiltration and for evaluating the perigastric lymph nodes. Options in the therapy of gastric lymphoma are based on their histological grade and stage of the disease. They include surgical resection and/or radiotherapy for local tumor control as well as chemotherapy in the case of disseminated disease or high malignancy. Currently, special interest focuses on the effect of Helicobacter pylori eradication.

Cell Transformation, Neoplastic↗
PubMed1994

Sensitization of adenylate cyclase by halothane in human myocardium and S49 lymphoma wild-type and cyc- cells: evidence for inactivation of the inhibitory G protein Gi alpha.

Halothane has been reported to sensitize the myocardium towards the effects of exogenous catecholamines in patients and laboratory animals. This study was aimed at investigating the catecholamine-sensitizing effects of halothane as well as the underlying subcellular mechanisms in human myocardium. Halothane augmented the positive inotropic effect of isoprenaline but not of Ca2+. The increase of the effect of isoprenaline by halothane was more pronounced in failing myocardium, with increased Gi, than in nonfailing donor hearts. Halothane (1%) increased basal as well as isoprenaline-, NaF-, cholera toxin-, and guanylylimidodiphosphate [Gpp(NH)p]-stimulated adenylate cyclase in human myocardial membranes (p < 0.05). Treatment of membranes with pertussis toxin increased adenylate cyclase by 40% and abolished the effect of halothane. Halothane had no effect on forskolin-stimulated adenylate cyclase. The same results, i.e., a pertussis toxin-sensitive increase of adenylate cyclase stimulation by halothane, were obtained in S49 cyc-, wild-type, or recombinant Gs alpha-reconstituted cyc- cell membranes. Carbachol-stimulated guanosine-5'-O-(3-[35S]thio)triphosphate binding was not influenced by halothane, but halothane attenuated the inhibition of adenylate cyclase by Gpp(NH)p in S49 cyc- cells. These data show that halothane stimulates adenylate cyclase and sensitizes adenylate cyclase after stimulation by beta-adrenoceptor agonists and guanine nucleotides due to an impairment of Gi alpha function. This mechanism may play a role in the halothane sensitization of myocardial adenylate cyclase towards catecholamines.

Adenylyl Cyclases↗
PubMed1993

The predominant mRNA class in HPV16-infected genital neoplasias does not encode the E6 or the E7 protein.

Human papillomavirus (HPV) type 16 is strongly implicated in the development of progressive neoplasias of the uterine cervix. Its oncogenic potential is decisively determined by the activity of the early gene products E6 and E7. To look for changes in the expression of these genes during tumour progression we cloned subgenomic fragments of HPV16 into RNA expression vectors, which allowed the generation of 35S-labelled riboprobes specific for distinct mRNA classes. Four constructs were made to differentiate between transcripts starting upstream of the E6 ORF or the E1 ORF, and one probe was specific for unspliced E6/E7 region transcripts. Five other constructs were used to identify transcripts covering the E1, E2, E4, L1 and L2 regions. With the help of these constructs, we analyzed by in situ hybridization 2 low-grade intraepithelial neoplasias of the vulva, 1 high-grade neoplasia of the cervix as well as 4 vulvar and 3 cervical carcinomas. Transcripts from the E1, E2, E4, L1 and L2 region that were consistently detected in the differentiated layers of benign lesions were variably expressed in precancers and carcinomas. None of the investigated cases revealed detectable amounts of unspliced E6/E7 transcripts with a coding potential for a full-length E6 protein. In benign lesions, the E7 transcripts were confined to isolated nuclei of differentiated cells, whereas high-grade lesions and invasive cancers showed elevated levels of equally distributed E7-specific signals in the cytoplasm of all tumour cells. The most abundant transcripts observed in intraepithelial neoplasias and in invasive cancers appear to initiate within ORF E7 and therefore have no coding potential for full-length E6 and E7 proteins. Our data show that the actual level of E7-specific transcripts in cancers is lower than anticipated from earlier studies using an ORF E6/E7-specific probe that hybridizes with the 5'-ends of the abundant mRNA class.

Base Sequence↗
PubMed1993

Color-Doppler ultrasound in ovarian masses: anatomo-pathologic correlation.

BACKGROUND AND AIMS: In the radiologic assessment of ovarian masses, the major difficulty consists in the late recognition and lack of parameters for a differential diagnosis between benign and malignant lesions, especially in the post-menopause when the incidence of cancer is higher. The use of a transvaginal probe and the color-Doppler examination have recently improved the study of the female pelvis. This study is aimed to verify the possibility of the color-Doppler imaging to differentiate between malignant and benign ovarian lesions during transvaginal echographies, on the basis of the qualitative and quantitative characteristics of the vascular pattern of the ovarian lesions. RESULTS: Twenty-six expansive ovarian lesions were studied: 8/26 showed no vascular signals and were considered benign as confirmed at histology. In the remaining lesions with some vascularization, the resistance index (RI) was evaluated: those with RI > 0.40 were considered benign, those with RI < 0.40 malignant. In 8/9 benign lesions and 7/9 malignant neoplasms, the results of color-Doppler were coherent with histology. The results showed a sensibility of 87.5% and a specificity of 88.8% for the transvaginal examination. CONCLUSIONS: The main advantages of the color-Doppler transvaginal examination are: the high frequency of visualization of the ovaries, even in postmenopausal patients; the definition of small lesions; the visualization of small parenchymal vessels, both physiologic and pathologic, and their quantitative analysis. The importance of the RI cutoff was critical for the differential diagnosis between benign and malignant lesions; we think that a cutoff of 0.50, instead of 0.40 proposed by other authors, would be far more appropriate.

Adult↗
PubMed1993

Expression of the different viral mRNAs of human papilloma virus 6 in a squamous-cell carcinoma of the bladder and the cervix.

The prevalence of HPV6 and HPV11 in benign condylomata or mild dysplasias has led to the view of HPV6/11 as rather harmless viruses in relation to carcinogenesis. However, the detection of HPV6/11 DNA in a number of individual cases of squamous-cell carcinomas of the anogenital/urinary tract could also point to a possible contribution of these viruses in the development of certain malignancies. Recently we have shown that the transcription of the E6 and E7 genes of HPV6 in benign anogenital condylomata is strictly confined to the basal cell layers of the epithelium, which express c-fos mRNA. This report describes the in situ hybridization analysis of individual mRNA species of HPV6 in 2 malignant tumours. A consistent feature of both carcinomas was the lack of detectable amounts of E6 mRNA, while the E7 mRNA was the major transcript observed. In situ hybridization with a riboprobe for c-fos revealed an expression pattern similar to that detected with the E7 probe. Hybridization with a probe specific for mRNA with a coding potential for a full-length E2 protein yielded weak signals in both carcinomas. Using restriction-enzyme analysis, we compared the long control region of HPV6 amplified by polymerase chain reaction from both tumours with already known HPV6 subtypes. In contrast to previous reports suggesting a correlation between genetic alterations in the long control region of HPV6 and increased malignant behaviour, our data do not support this hypothesis.

Base Sequence↗
PubMed1993

Evidence for an interaction of halothane with the L-type Ca2+ channel in human myocardium.

BACKGROUND: The present study was aimed at investigating the underlying mechanisms for the cardiac depressant effect of halothane. To test the hypothesis, whether there is an interaction of halothane with the L-type Ca2+ channels in human myocardium and whether this interaction has functional consequences for force generation in the human myocardium, effects of halothane were studied in human myocardial membranes and isolated cardiac preparations. METHODS: The experiments were performed on isolated, electrically driven ventricular preparations (1 Hz, 37 degrees C) and cardiac membranes with radioligand binding experiments using 3H-PN 200-110. Myocardium from human failing and non-failing hearts was obtained at cardiac surgery. RESULTS: Halothane produced a negative inotropic effect, which was similar in nonfailing and failing myocardium. Halothane shifted the concentration-response curve for the positive inotropic effect of the L-type Ca2+ channel agonist BayK 8644 to the right. The density of dihydropyridine receptors as judged from 3H-PN 200-110 radioligand binding experiments was similar in nonfailing and failing myocardium, whereas the density of beta-adrenoceptors was reduced. Halothane concentration dependently reduced the binding of 3H-PN 200-110, an antagonist at the 1,4 dihydropyridine receptor site of the Ca2+ channel, to myocardial membranes. Furthermore, halothane produced a rightward shift of the competition curve of BayK 8644 for binding of 3H-PN 200-110 to cardiac membranes. CONCLUSIONS: In human ventricular myocardium, halothane exhibits an interaction with the L-type Ca2+ channel by interfering with its dihydropyridine binding sites. This may explain, at least in part, the observed negative inotropic effect of this agent and could hypothetically play a general role in its anesthetic effects.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Effects of halothane on beta-adrenoceptors and M-cholinoceptors in human myocardium: radioligand binding and functional studies.

We investigated whether a postsynaptic sensitization by halothane for beta-adrenoceptor-mediated effects occurs in diseased human myocardium. In addition, we hoped to achieve further insights into the cellular mechanism and, in particular, the role of M-cholinoceptors and beta-adrenoceptors. The experiments were performed on isolated, electrically driven atrial and ventricular preparations and membranes isolated from human hearts obtained at cardiac surgery. Halothane concentration-dependently reduced binding of [3H]quinuclidinylbenzilate ([3H]QNB) to M-cholinoceptors but had no effect on equilibrium saturation binding of 125-iodocyanopindolol (125I]Cyp) to beta-adrenoceptors. High-and low-affinity states of agonist binding of carbachol to M-cholinoceptors were not affected, but halothane inhibited high-affinity binding of isoprenaline to beta-adrenoceptors. In contrast, halothane augmented the potency and efficacy of the positive inotropic effect of isoprenaline in atrial and ventricular myocardium. The "direct" negative inotropic effect in atrial and the "indirect" negative inotropic effect in ventricular myocardium by M-cholinoceptor stimulation with carbachol was unchanged by halothane. We conclude that in human atrial and ventricular myocardium a sensitization to catecholamines is induced by halothane, the mechanism of which is likely to be located at the postsynaptic level of the sympathetic neuroeffector junction. Facilitated coupling of beta-adrenoceptors or an uncoupling of M-cholinoceptors with reduced negative inotropic effects of agonist does not play a role. We showed that sensitization of this system apparently is due to direct actions of halothane on the G-protein-coupled adenylate cyclase complex.

Catecholamines↗
PubMed1992

Peripheral neurotoxicity following high-dose cisplatin with glutathione: clinical and neurophysiological assessment.

The use of high-dose cisplatin is limited by development of severe peripheral neurotoxicity and gradual worsening of renal function. In an ongoing study of high-dose cisplatin glutathione has been employed with the aim of preventing major cisplatin-induced toxicities. Neurotoxicity was examined in detail in 32 patients with ovarian cancer treated with cisplatin (160 mg/m2) and cyclophosphamide (600 mg/m2) every 3-4 weeks for five courses. In addition to serial complete neurological examination, sensory action potentials (SAPs) and motor conduction velocities (MCVs) were also assessed. We confirmed the development of a predominant sensory involvement, characterized by mild distal paresthesias and decrease in vibratory sensibility and in deep tendon reflexes, with a slight reduction of SAPs, observed after three courses of treatment. After five courses, distal paresthesias and disesthesias, decreased proprioception and loss of vibratory sensibility with ataxic signs, absence of deep tendon reflexes, unobtainable SAPs and only moderately reduced MCVs were seen. We did not observe any case of disabling neuropathy. There was a tendency to a more severe involvement of peripheral nerves in patients aged more than fifty. The 3 patients presenting the most serious neuropathy were the oldest in the whole group. Low degree of neurotoxicity observed in this study supports a glutathione protection against cisplatin-induced neurotoxicity. As the urinary excretion of platinum indicated no changes in the renal clearance of cisplatin following repeated courses, the lack of drug accumulation and high plasma peak due to preserved renal function might explain the reduced neurotoxicity observed.

Adult↗
PubMed1992

Isolated rat pancreatic acini as a model to study the potential role of lipase in the pathogenesis of acinar cell destruction.

We have recently reported that lipase may play a role in the pathogenesis of acute pancreatitis by its ability to release fatty acids from triglycerides. The aim of this study was to further investigate the effect of lipase and its various digestive products on the integrity of isolated pancreatic rat acini. Pancreatic acini were prepared by collagenase digestion and their newly synthesized proteins labeled with 35S-methionine. Acini were later incubated in buffer to which various factors were added: Products of lipolytic digestion, such as various fatty acids and monoglycerides, fat tissue, nonactivated or trypsin activated homogenized pancreatic tissue, and a specific lipase inhibitor (THL, tetrahydrolipstatin). Cellular destruction was quantified by the degree of radiolabeled proteins released. Short chain fatty acids and monoglycerides (up to C-12) caused cellular destruction, whereas long chain fatty acids and their respective monoglycerides were not harmful. With regard to unsaturated fatty acids, long chain fatty acids (C-18 to C-22) were also able to destroy cells. The degree of cellular necrosis correlated with incubation time and fatty acid concentration. The cellular damage caused by incubation of acini with either inactive or trypsin activated pancreatic homogenates together with triglycerides could be completely inhibited by the specific lipase inhibitor THL. Bile alone caused no damage. When bile was combined with activated-pancreatic homogenates, about 25% of newly synthesized proteins were released by acini within 30 min. Incubation with a combination out of bile activated pancreatic homogenates and triglycerides resulted in the most pronounced damage. This acinar destruction could only be partly inhibited by THL. These studies suggest that both lipase and phospholipase-A2 may play an important role in the pathogenesis of acinar cell destruction.

Animals↗