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Biomedical subjects

H Frank

Publications and source records attributed to H Frank.

At least 19 recordsLinked to original sources
PubMed1992

Genetically engineered V79 Chinese hamster cells for stable expression of human cytochrome P450IA2.

V79 Chinese hamster cells were genetically engineered for stable expression of human P450IA2. Full length cDNA, encoding human P450IA2, was inserted into an SV40 early promoter containing eukaryotic expression vector and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to the neomycin derivative G418) into V79 Chinese hamster cells. The recombinant expression vector was introduced into two different V79 sublines, one expressing an endogenous acetyltransferase (V79-NH), the other not (V79-MZ). The presence of human cytochrome CYP1A2 cDNA in the G418 resistant V79 cell clones was confirmed by Southern blotting. The transcription of the cDNA into mRNA was detected by Northern blotting and the translation into an authentic cytochrome P450IA2 protein was shown by Western blotting. The enzymatic activity in these cells was determined by the cytochrome P450IA2-dependent methoxy-, ethoxy-, benzoxy-, and pentoxyresorufin dealkylation activity.

Animals↗
PubMed1992

Acetylene, a mammalian metabolite of 1,1,1-trichloroethane.

1,1,1-Trichloroethane (TCE) is a widely used industrial solvent of low acute toxicity. It is slowly oxidized to trichloroethanol and trichloroacetic acid by cytochrome P-450-dependent mono-oxygenases. Increased inhalative uptake by rats under hypoxia and spin-trapping experiments indicate that TCE is also reductively metabolized to a radical intermediate. Acetylene is formed as a metabolite, suggesting transfer of an additional electron to form the corresponding carbene. Hypoxia and induction of mixed-function mono-oxygenases accelerate the formation of acetylene. Experiments performed in vitro with rat liver microsomal fractions yield analogous results.

Acetylene↗
PubMed1992

Quinone reduction and redox cycling catalysed by purified rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase.

A highly active preparation of rat liver dihydrodiol/3 alpha-hydroxysteroid dehydrogenase was obtained using a newly developed, rapid purification scheme involving affinity chromatography on Red Sepharose. Depending on the coenzyme present, the purified enzyme was found to catalyse the oxidation of dihydrodiols and steroids or the reduction of substrates with carbonyl or quinone moieties. Using a wide range of synthetic quinones derived from polycyclic aromatic hydrocarbons (PAHs), we observed a pronounced regioselectivity of the quinone reductase activity. Good substrates were the o-quinones of phenanthrene, benz(a)anthracene, chrysene and benzo(a)pyrene with the quinonoid moiety in the K-region which were reduced at rates of 1-10 mumol/min.mg enzyme. 1,4-Benzoquinone, naphthalene-1,2-quinone and benz(a)anthracene-8,9-quinone were also reduced at high rates. In contrast, alkyl-substituted quinones such as duroquinone and menadione were poor substrates for the enzyme. During the enzymatic reduction of several o-quinones, but not 1,4-benzoquinone, we observed the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. Thus, the reduction of quinones of PAHs may lead to a facilitated conjugation and excretion of these highly lipophilic compounds, but may also initiate toxic processes due to the formation of reactive oxygen species.

Animals↗
PubMed1992

Uses and misuses of oxygen in hospitalized patients.

PURPOSE: To document the use/misuse of oxygen therapy as compared with antibiotics in internal medicine inpatients. To determine whether the same care was being taken in the prescription and administration of both forms of therapy. PATIENTS: Ninety-six eligible patients at a university teaching hospital were entered into a study examining the use of oxygen. They were compared with 60 patients for whom antibiotics were prescribed. MATERIAL AND METHODS: Three hundred thirty consecutive newly admitted patients were screened for the presence of either (1) oxygen apparatus at the bedside, (2) physician orders for oxygen, or (3) oxygen orders noted in nursing kardex. Those meeting one of these three criteria were observed on up to four occasions over 48 hours following study entry. Similarly, patients were screened for medical orders or nursing medication kardex notation for antibiotics and were also observed for proper prescription and administration of medication. Procedural errors, determined by kardex audit and direct patient observation, were compared for the individuals with specific oxygen orders and those receiving antibiotics. RESULTS: Oxygen delivery apparatus was found in the room in 17 of 96 patients without it ever having been ordered by the physician or noted in the nursing kardex. In 27 of 96 patients, oxygen was noted in the nursing kardex and administered to patients without a physician order. There were no cases of antibiotic therapy without a physician order. Observations of 47 patients with specific orders for oxygen revealed the following errors: (1) physician order incorrectly transcribed to nursing kardex (16%), (2) flow meter off (34%), (3) oxygen delivery apparatus improperly worn (57%), (4) wrong fractional inspired oxygen concentration (58%). Improper transcription of antibiotic orders occurred on only one occasion (2%), and antibiotics were improperly administered in 5%. Arterial blood gas determinations preceded oxygen orders in 61%, whereas microbiologic cultures preceded antibiotic orders in 87% of the patients. CONCLUSIONS: We conclude that oxygen therapy is neither prescribed nor administered with the same attention that is given to other drugs such as antibiotics. Oxygen prescription and/or delivery is associated with significantly greater error than that seen with antibiotics. Education of medical personnel should stress more prudent prescription and use of oxygen in hospitalized patients.

Anti-Bacterial Agents↗
PubMed1992

[Magnetic resonance tomography in pulmonary hypertension].

We examined 23 patients with pulmonary hypertension of varying aetiology by MRI and compared the results with those of right heart catheterisation. The best correlation was obtained between right ventricular mural thickness and mean pulmonary pressure (R = 0.91, p = 0.001). There was significant correlation (R = 0.85, p = 0.001) for the diameter of the inferior vena cava, which was dilated in all patients with pulmonary hypertension. There was no significant correlation between mean pulmonary pressure and the diameters of the superior vena cava or the main pulmonary artery branches (R = 0.55 and 0.75 respectively, p less than 0.05). Amongst functional measurements there was a correlation between right ventricular ejection fraction and mean pulmonary artery pressure (R = 0.71, p = 0.001). There was no correlation between right ventricular end-systolic and end-diastolic volume. In all patients with pulmonary hypertension, dynamic flow sensitive gradient echo sequences showed the presence of tricuspid insufficiency. A further semiquantitative criterion for the presence of pulmonary hypertension in 4 patients (17%) was an abnormal signal from the main pulmonary artery in early to mid-systole shown on T1-weighted transverse sections.

Adult↗
PubMed1992

Quantitative assessment of aortic regurgitation by magnetic resonance imaging.

Thirty patients with aortic regurgitation and 10 controls were examined using an 0.5 T superconducting magnet with ECG gating. In each case a multislice-multiphase spinecho study in sagittal-coronal double angulated projection (four-chamber equivalent) was performed to assess left and right ventricular volumes, ejection fraction and regurgitation fraction. Additionally, a blood-flow sensitive cine-study (gradient echo, FAME) was performed to visualize direction and area of regurgitant jet. Magnetic resonance imaging (MRI) data were compared with quantitative and qualitative assessment of aortic regurgitation by angiography, Doppler and colour flow mapping. Using the FAME mode MRI, we were able to detect the regurgitant jet as an area of signal loss within the left ventricle in all patients; moderate correlation to jet area was determined by colour flow mapping (R = 0.60, P less than 0.001). Determination of left and right ventricular end-diastolic, end-systolic and stroke volumes by MRI revealed excellent correlation with invasive data (R = 0.94, P = 0.0001). With MRI regurgitant fraction (RF) could be calculated from the difference between right and left ventricular stroke volumes, which showed good correlation with invasively determined RF (R = 0.91, P = 0.001) and with qualitative Sellers' scoring (R = 0.70, P less than 0.001), respectively. Thus MRI provides the basis for noninvasive detection and quantification of aortic regurgitation.

Adolescent↗
PubMed1992

Survey of infection control precautions: a comparison to recommended guidelines.

The emergence of acquired immune deficiency syndrome as a new and devastating communicable disease has led to concern among health care workers as to their risk of acquiring human immunodeficiency virus (HIV) in the workplace. Centres for Disease Control, and Health and Welfare Canada guidelines seek to prevent HIV transmission through modification of work practices. A study was performed in the authors' institution to quantitate health care worker compliance with such practice modifications as outlined in the researchers' institutional infection control procedures and to evaluate administrative and engineering controls related to this policy. An infection control program to educate health care workers and modify practices was being implemented prior to commencement of this study. Three areas were studied: emergency room, dental clinic and plastic surgery clinic. Adherence to established procedures was judged as compliant, noncompliant and interpretive compliant. Of 806 observations made on 24 health care workers in the three areas, 31.3% were compliant, 28% were noncompliant and 40.7% were interpretive complaint. The most serious non-compliance was noted in handling and disposal of needles. Use of gloves, eyewear, gowns or masks varied among the three sites. Administrative and engineering controls were lacking for eyewear, gowns, puncture-resistant containers and a written policy in some sites. The lack of compliance with institutional infection control procedures needs to be confirmed in other institutions. If there is generalized compliance failure, then a re-evaluation of the present strategies to reduce risk of HIV infection in health care workers is essential.

Clinical Protocols↗
PubMed1991

Influence of the level of cytosolic epoxide hydrolase on the induction of sister chromatid exchanges by trans-beta-ethylstyrene 7,8-oxide in human lymphocytes.

trans-beta-Ethylstyrene 7,8-oxide, a substrate of cytosolic epoxide hydrolase, and 4-fluorochalcone oxide, an inhibitor of this enzyme, were investigated on induction of sister chromatid exchanges (SCE) in human lymphocytes. Both epoxides enhanced the frequency of SCE. 4-Fluorochalcone oxide at low concentration (2.5 microM) inhibited cytosolic epoxide hydrolase activity towards trans-beta-ethylstyrene 7,8-oxide in lymphocytes by 74% and had no effect on glutathione transferase activity using this substrate. At this concentration it did not induce SCE itself, but it potentiated the effect of trans-beta-ethylstyrene 7,8-oxide several fold. In lymphocytes from different subjects, the number of SCE induced by a low concentration of trans-beta-ethylstyrene 7,8-oxide correlated negatively with the individual cytosolic epoxide hydrolase activity (r = -0.72; -0.73 in two series of experiments). The number of SCE induced by a high concentration of trans-beta-ethylstyrene 7,8-oxide did not correlate with cytosolic epoxide hydrolase activity (r = 0.004; -0.24), but a negative correlation was found with glutathione transferase activity (r = -0.50). This finding is consistent with the results of biochemical studies in lymphocytes in which we determined the relative contribution of cytosolic epoxide hydrolase and glutathione transferase to the metabolism of trans-beta-ethylstyrene 7,8-oxide at varying substrate concentrations. The study demonstrates that the level of genotoxic effects induced in human lymphocytes is influenced by the individual level of detoxifying enzymes. At low concentrations, cytosolic epoxide hydrolase was more important than glutathione transferase activity.

Cells, Cultured↗
PubMed1991

Regiospecific oxidation of polycyclic aromatic dihydrodiols by rat liver dihydrodiol dehydrogenase.

Rat liver dihydrodiol dehydrogenase (DDH, E.C. 1.3.1.20) has recently been shown to oxidize the highly carcinogenic benz[a]anthracene-3,4- dihydrodiol in an NADP(+)-dependent reaction to its corresponding catechol. The present study is a systematic investigation of the substrate specificity of the purified enzyme towards synthetic trans-dihydrodiol metabolites of phenanthrene, benz[a]anthracene, chrysene, dibenz[a, h]anthracene and benzo[a]pyrene. DDH exhibited a remarkable regiospecificity of enzymatic catalysis with regard to the site of the dihydrodiol moiety of the parent hydrocarbon. M-region- and, with lower efficiency, bay-region dihydrodiols were found to be good substrates of the enzyme with maximal velocities between 20-80 nmol/min per mg enzyme and Km values in the micromolar range. K-region dihydrodiols were not accepted as substrates. Dihydrodiols situated at the terminal ring of an anthracene-type structure such as benz[a]anthracene-8,9-dihydrodiol as well as the corresponding dihydrodiol epoxides were also not oxidized by DDH at measurable rates. The results provide evidence for a detoxifying role of DDH in the metabolism of the chemical carcinogens benz[a]anthracene, chrysene and dibenz[a, h]anthracene.

Alcohol Oxidoreductases↗
PubMed1991

[Diagnosis of arrhythmogenic right ventricular disease using magnetic resonance tomography].

In our study, 12 patients with ventricular arrhythmias, but without any documented cardiac disease, and 10 healthy volunteers were investigated by spin echo magnetic resonance tomography (MRT) using a 0.5 Tesla magnet. Axial T1-weighted spin-echo sequences, as well as double angulated, multislice-multiphase sequences were acquired. Left- and right-ventricular volumes were then evaluated by outlining the endocardium in an end-systolic and an end-diastolic frame. The right-ventricular free wall and the right-ventricular outflow tract were investigated for myocardial thickness and intramural fat.

Adipose Tissue↗
PubMed1990

The oxidation of the highly tumorigenic benz[a]anthracene 3,4-dihydrodiol by rat liver dihydrodiol dehydrogenase.

Rat liver dihydrodiol dehydrogenase (DDH, EC 1.3.1.20) has been shown to reduce the mutagenicity of benz[a]anthracene (BA) in the bacterial Ames test. BA-3,4-dihydrodiol is a highly mutagenic and tumorigenic metabolite of BA. In order to test the hypothesis that this dihydrodiol may be a substrate of DDH, we established two novel assay systems for the NADP(+)-dependent oxidation of BA-3,4-dihydrodiol by rat liver DDH, an HPLC-based assay procedure and a radiometric assay with specifically labelled [3,4-3H]-BA-3,4-dihydrodiol as substrate. With the HPLC-based assay, the kinetic constants of the enzymatic catalysis were as follows: Km(app) = 21 microM for BA-3,4-dihydrodiol and Vmax = 20.0 nmol/min.mg enzyme. The reaction product was identified by cochromatography, fluorimetry and mass spectroscopy as BA-3,4-catechol, but interconversions between the catechol and the corresponding o-quinone during the analytical procedures were detected. With the radiolabelled substrate, a linear relationship between substrate concentration and reaction velocity was found. The V/K value for labelled substrate was 0.155 ml/min.mg enzyme and a (V/K)H/(V/K)T kinetic isotope effect of 6.7 was observed. The non-labelled substrate acted as a competitive inhibitor of the enzymatic oxidation of tritiated BA-3,4-dihydrodiol with a Ki value of 56.4 microM. The reaction rates determined in this study suggest an important role of DDH activity in the metabolism of BA.

Alcohol Oxidoreductases↗
PubMed1990

[Cine-MR for the quantification of regurgitation defects by a volume method].

We have examined 46 patients with angiographically confirmed regurgitant lesions (26 mitral insufficiency, 20 aortic insufficiency) using a 0.5 Tesla magnet. In each patient, multiplane and multiphase spin-echo sequences were obtained in a plane angled in the sagittal and coronal direction in the long axis of the heart; left and right ventricular volumes, ejection fractions and regurgitation fractions were calculated. In addition, a blood-flow sensitive gradient echo sequence was obtained in order to determine the direction and extent of the regurgitant jet. The data was compared with the results of angiography and echocardiography. By means of the gradient echo technique, MRI was able to show the regurgitant jet in every patient. There was a linear correlation between volumes determined by MRI and angiography. The best agreement was found for left ventricular contraction volume (R = 0.82, p is less than 0.0001). Comparison of the noninvasive and angiographic method showed a linear correlation for AI patients of R = 0.91 (p is less than 0.001), which is somewhat better than for patients with MI (R = 0.84, p less than 0.001). Semiquantitative grading of MI with a gradient echo technique showed a linear correlation with angiography of R = 0.73 (p less than 0.001), for AI there was agreement between both methods in 72% of cases. A comparison between MRI and colour Doppler sonography showed only moderately good correlation R = 0.69 (p less than 0.01).

Adult↗
PubMed1990

Stereoselective metabolism of dibenz(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens.

Dibenz(a,h)anthracene (DBA), a carcinogenic, polycyclic aromatic hydrocarbon ubiquitous in the environment, is metabolized by the hepatic microsomal fraction of immature Sprague-Dawley rats pretreated with Aroclor 1254 to 27 ethyl acetate-extractable metabolites. More than half of these metabolites (51%) consisted of trans-1,2-; -3,4-; and -5,6-dihydrodiols including their identified secondary metabolites. The three trans-dihydrodiols (4.9, 15.8, and 0.6% of total metabolic conversion) were highly enriched in their R,R enantiomers (85, 71, and 98%) as determined by high performance liquid chromatography on suitable chiral stationary phases. This is explained on the basis of the stereoselective epoxidation of DBA by cytochrome P-450c (induced by Aroclor 1254) followed by regioselective hydration catalyzed by microsomal epoxide hydrolase. Determination of the bacterial mutagenicity by measuring the reversion rate of histidine-dependent Salmonella typhimurium TA100 to histidine prototrophy revealed marked differences in the mutagenicity of the enantiomers of the trans-dihydrodiols of DBA when activated by the same metabolizing system as used in the metabolism studies. In the case of trans-1,2- and -5,6-dihydrodiol, the S,S enantiomers were converted to more mutagenic metabolites than their corresponding optical antipodes, whereas in the case of trans-3,4-dihydrodiol it was the R,R enantiomer that produced the stronger mutagens. Therefore, both regio- and stereoselectivity of the metabolizing enzymes attribute to the dominant role of trans-3,4-dihydrodiol in the mutagenicity of DBA.

Animals↗
PubMed1990

[Examples for using capillary gas chromatography with wide bore columns in occupational health].

Wide bore capillary columns (0.4-0.75 mm ID) can be easily and inexpensively installed in packed column GCs. The analytical advantages cause an expanding market for such capillaries and interconverting hardware kits. It is illustrated with some examples that often individual exposition levels can be determined exactly only by using capillary columns: ethylbenzene may be separated from the C8-isomers also in complex mixtures, the marker PBN for rubber smoke expositions can be determined with 30 min sampling time, the detection sensitivity of the FID is sufficient also for chlorinated pesticides and the analyses of high-boiling compounds profit by the high phase ratio of wide bore capillary columns. A single capillary column substitutes a variety of different packed columns, so saving time and money and protecting the analyst from failures and frustrating compromises.

Air Pollutants, Occupational↗
PubMed1990

[Long-term follow-up of pulmonary hypertension of unknown etiology].

Since 1967, 166 patients with primary pulmonary hypertension of unknown etiology have been followed-up at the Department of Cardiology at the University of Vienna. Although an exact etiopathogenetic differentiation was not possible, three groups of patients were identified clinically: patients with so-called primary pulmonary hypertension (PPH)--group 1; patients with pulmonary hypertension induced by anorexipens (aminorex fumarate)--group 2; and patients with pulmonary hypertension due to emboli in the large pulmonary vessels--group 3. In addition to non-invasive echocardiographic assessment of pulmonary pressures, regular cardiac catheterizations were carried out, which revealed right atrial mean pressure, cardiac output, and mixed venous saturation to be prognostic predictive factors. Patients with anorexigen-induced pulmonary hypertension have a clearly better life expectancy than those with PPH. Owing to the temporally limited effect of the pulmonary hypertension-inducing agent, aminorex fumarate (Menocil), patients with anorexigen-induced pulmonary hypertension may be considered a model group for drug-induced vascular pathology.

Aminorex↗
PubMed1989

Mass spectrometric detection of cross-linked fatty acids formed during radical-induced lesion of lipid membranes.

A mass spectrometric method is described for the quantitative determination of dimers of polyunsaturated fatty acids (PUFA) formed in the hepatic endoplasmic reticulum of rats upon inhalation of tetrachloromethane. The results show that dimers account for a considerable fraction of microsomal PUFA which disappear during CCl4 metabolism. Cross-linking of the membrane lipids of the endoplasmic reticulum seems to be a significant process with respect to cell toxicity.

Animals↗