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Biomedical subjects

M Stephan

Publications and source records attributed to M Stephan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Time course of high-intensity transient signals in patients undergoing elective heart valve replacement: a prospective study.

BACKGROUND AND AIMS OF THE STUDY: This study was performed to evaluate the time course of intracranial high-intensity transient signals (HITS) in patients undergoing elective heart valve replacement. METHODS: Thirty-three patients were enrolled in this study. The examination protocol included serial (before and at one, five, 90 and 180 days after surgery) monitoring sessions with transcranial Doppler and detailed neurological examination. Monitoring was performed bilaterally over the middle cerebral arteries for one hour per session using 2 MHz probes. Microembolic signals were recognized according to standard criteria and stored on a computer for later evaluation. RESULTS: HITS prevalence increased from 3% preoperatively to 41% on the first postoperative day and remained unchanged during the postoperative period. No influence of the intensity of anticoagulation or valve type on HITS counts was evident. Unilateral monitoring provided adequate results in 83.9% of cases. CONCLUSIONS: The causative role of the valve implant in the pathogenesis of HITS appears certain, since their prevalence dramatically increases following valve implantation. Valve type, duration of valve implant or intensity of anticoagulation did not influence HITS counts. Bilateral monitoring is warranted for accurate evaluation of HITS counts in this patient group.

Aortic Valve↗
PubMed1997

Sequential interleukin-3 and granulocyte-colony stimulating factor prior to and following high-dose etoposide and cyclophosphamide: a phase I/II trial.

Administration of growth factors prior to chemotherapy (priming) may reduce myelosuppression and provide an alternative to the use of stem cell support for the delivery of dose-intensive therapy. It is possible, however, that such priming may worsen aplasia, either by recruitment of progenitors into cell cycle and thereby increasing their sensitivity to chemotherapy or by depleting stem cell pools. We performed a Phase I/II trial of sequential interleukin 3 (IL-3)/granulocyte colony-stimulating factor (G-CSF) prior to and following high-dose etoposide and cyclophosphamide to determine the safety and efficacy of priming. IL-3 was given for 7 days, and then G-CSF was given until the WBC count reached a level of 100, 000/microliter or stopped rising. Chemotherapy was started 48 h after the last dose of G-CSF. Sequential administration of IL-3/G-CSF was repeated beginning 36 h after the last dose of chemotherapy. Twenty-five eligible patients with Hodgkin's disease, non-Hodgkin's lymphoma, or breast cancer were enrolled. Priming was generally well tolerated. The median maximum WBC count and absolute neutrophil count achieved was 66,400 and 57,600/microliter, respectively. Significant decreases in platelet counts were seen during priming with 15 patients having a >/=40% decrease from prepriming values. Hematological recovery of study patients was compared to that of an unprimed historical control group (n = 38) treated with the same chemotherapy followed by G-CSF alone. Neutrophil recovery to 500 and 1000/microliter and platelet recovery to >/=50,000/microliter was significantly faster in the study group compared to that of historical controls (P = 0.03, 0.05, and 0.01, respectively). Sequential IL-3/G-CSF given prior to and following high-dose etoposide and cyclophosphamide is safe and is a feasible strategy to compare in prospective randomized trials to patients treated with only postchemotherapy IL-3 and G-CSF and to patients treated with peripheral blood stem cell support.

Adult↗
PubMed1995

Quantitative lipoxygenase product profiling by gas chromatography negative-ion chemical ionization mass spectrometry.

An assay for the quantitative determination of the hydroxylation profile of long-chain fatty acids is described for gas chromatography negative-ion chemical ionization mass spectrometry and stable isotope dilution using [carboxyl-18O2]-labeled internal standards. The assay has been applied to the study of fatty acids isolated from body fluids, tissue, and cultured cells. Examples for the analyses of biological systems expressing 5-, 8-, 12-, or 15-lipoxygenase activity are given and the most important sources of analytical errors are addressed. Increased specificity compared to analysis by negative-ion chemical ionization, at the cost of sensitivity, can be achieved by the use of positive-ion electron impact ionization for the investigation of hydrogenated pentafluorobenzylester/trimethylsilylether derivatives. The method described provides complete, specific, and quantitative profiles of hydroxylated fatty acids originally present in biological samples or generated in vitro by incubation with polyunsaturated fatty acid substrates such as linoleic or arachidonic acid.

Animals↗
PubMed1995

12-Lipoxygenase isoenzymes in mouse skin tumor development.

12-lipoxygenase-catalyzed arachidonic acid metabolism in normal and neoplastic mouse epidermis was assessed by cDNA cloning of the epidermal 12-lipoxygenases and by studying their expression patterns, enzyme activities, and product levels. Papillomas and squamous cell carcinomas induced by the initiation/promotion protocol contained 50- to 60-fold more 12-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) than normal epidermis. The ratio of S to R enantiomers was 9:1. This indicates that most of this eicosanoid was of enzymatic origin. Accordingly, cell-free preparations of the tumors exhibited about fivefold elevated 12-lipoxygenase activities. A papilloma-derived cDNA library was screened with human platelet-type 12-lipoxygenase cDNA probes. Two cDNA clones encoding the platelet-type and the leukocyte-type isoforms of murine 12-lipoxygenase were isolated, demonstrating the coexpression of the isoenzymes in the same tissue and species. When expressed in COS-7 cells, the recombinant enzymes showed the characteristic substrate selectivity and product profile, with the leukocyte-type enzyme metabolizing linoleic and arachidonic acid to 13-hydroxy-9,11-octadecadienoic acid and to 12- and 15-HETE, respectively, and the platelet-type enzyme oxygenating exclusively arachidonic acid to 12-HETE. In epidermis in vivo and in keratinocytes in culture, only the platelet-type 12-lipoxygenase (mRNA and protein) was detectable. In mouse epidermis both isoenzymes were induced transiently by phorbol esters. Most tumors showed constitutive overexpression of platelet-type mRNA, whereas leukocyte-type specific transcripts were detectable only in a few tumors. These data suggest that the platelet-type enzyme is the 12-lipoxygenase isoform of keratinocytes that is responsible for the generation of most of the 12-HETE found in neoplastic epidermis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Possible involvement of arachidonic acid and eicosanoids in metamorphic events in Hydractinia echinata (Coelenterata; Hydrozoa).

Upon induction of metamorphosis, larvae of the marine hydroid Hydractinia echinata release [14C]-arachidonic acid from previously labeled endogenous sources. The lipoxygenase inhibitors nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid inhibited metamorphosis induced by Cs+ and 1,2-sn-dioctanoylglycerol, whereas the inhibitors of cyclooxygenase, indomethacin, and acetylsalicylic acid were ineffective, suggesting a role for lipoxygenase metabolites of arachidonic acid in induction of metamorphosis. Lipoxygenase products in Hydractinia echinata were isolated and identified by gas chromatography/mass spectrometry. 8- and 12-HETE were the most abundant metabolites. In cytosolic fractions from larvae activity of an arachidonic acid metabolizing enzyme, presumably a lipoxygenase, was found. The metabolic product was identified by 1H-NMR and chiral phase HPLC as 8(R)-HETE. Its production was strongly inhibited by NDGA, but not by indomethacin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Hemorrhagic varicella: a case report and review of the complications of varicella in children.

The case of a previously healthy child who developed progressive systemic varicella with purpura is reported. The clinical course of this patient is outlined, and the range of potential complications of chickenpox in children is reviewed. Familiarity with the usual uncomplicated natural history of primary varicella infection should alert the clinician to signs and symptoms that signal significant systemic involvement.

Bacterial Infections↗
PubMed1993

Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis.

Hyperkalemic periodic paralysis (HYPP), one of several inheritable myotonic diseases, results from genetic defects in the human skeletal muscle Na+ channel. In some pedigrees, HYPP is correlated with a single base pair substitution resulting in a Met replacing Thr704 in the fifth transmembrane segment of the second domain. This region is totally conserved between the human and rat channels. We have introduced the human mutation into the corresponding region of the rat muscle Na+ channel cDNA and expressed it in human embryonic kidney 293 cells. Patch-clamp recordings show that this mutation shifts the voltage dependence of activation by 10-15 mV in the negative direction. The shift results in a persistent Na+ current that activates near -70 mV; this phenomenon could underlie the abnormal muscle activity observed in patients with HYPP.

Amino Acid Sequence↗
PubMed1992

Profiling assay for lipoxygenase products of linoleic and arachidonic acid by gas chromatography-mass spectrometry.

A method for determination of the lipoxygenase products of linoleic acid (9- and 13-hydroxyoctadecadienoic acid; 9-HODE, 13-HODE) and of arachidonic acid (5-, 8-, 9-, 11-, 12-, and 15-hydroxyeicosatetraenoic acid; 5-, 8-, 9-, 11-, 12-, and 15-HETE) is described. The method combines solid-phase extraction, derivatization to the corresponding fully hydrogenated methylester/trimethylsilylether derivatives and capillary gas chromatography coupled with electron impact mass spectrometry. Each regioisomeric HODE and HETE shows a unique pair of mass spectrometric fragment ions originating from fission of the fatty acid carbon chain at the hydroxylated position. The carboxyl-terminal fragment is used for quantification relative to a carboxyl-18O2-labeled analogue added as internal standard and the methyl-terminal fragment is monitored for confirmation. The assay can be extended for quantification of the complete hydroxylation profile of linoleic and arachidonic acid. Applications of this assay are demonstrated for the quantification of HODEs and HETEs in normal, hyperplastic, and neoplastic mouse epidermis. In mouse epidermis papilloma, the tissue levels of 8- and 12-HETE were found to be increased by one to two orders of magnitude compared to levels in normal epidermis.

Animals↗
PubMed1992

Decreased function of the class B tetracycline efflux protein Tet with mutations at aspartate 15, a putative intramembrane residue.

The aspartate 15 residue within the first predicted intramembrane helix of the tetracycline efflux protein Tet has been conserved in four tetracycline resistance determinants from gram-negative bacteria. Its replacement in class B Tet by tyrosine, histidine, or asparagine resulted in a 60 to 85% loss of tetracycline resistance and a similar loss of tetracycline-proton antiport. The tyrosine and histidine substitutions lowered the Vmax of the efflux system by some 90% but did not alter the Km. The asparagine substitution raised the Km over 13-fold, while the Vmax was equal to or greater than that of the wild type. Therefore, although the nature of its role is unclear, aspartate 15 is important for normal Tet function.

Aspartic Acid↗
PubMed1992

Kinetics of CO uptake and diffusing capacity in transition from rest to steady-state exercise.

In the transition from rest to steady-state exercise, O2 uptake from the lungs (VO2) depends on the product of pulmonary blood flow and pulmonary arteriovenous O2 content difference. The kinetics of pulmonary blood flow are believed to be somewhat faster than changes in pulmonary arteriovenous O2 content difference. We hypothesized that during CO breathing, the kinetics of CO uptake (VCO) and diffusing capacity for CO (DLCO) should be faster than VO2 because changes in pulmonary arteriovenous CO content difference should be relatively small. Six subjects went abruptly from rest to constant exercise (inspired CO fraction = 0.0005) at 40, 60, and 80% of their peak VO2, measured with an incremental test (VO2peak). At all exercise levels, DLCO and VCO rose faster than VO2 (P less than 0.001), and DLCO rose faster than VCO (P less than 0.001). For example, at 40% VO2peak, the time constant (tau) for DLCO in phase 2 was 19 +/- 5 (SD), 24 +/- 5 s for VCO, and 33 +/- 5 s for VO2. Both VCO and DLCO increased with exercise intensity but to a lesser degree than VO2 at all exercise intensities (P less than 0.001). In addition, no significant rise in DLCO was observed between 60 and 80% VO2peak. We conclude that the kinetics of VCO and DLCO are faster than VO2, suggesting that VCO and DLCO kinetics reflect, to a greater extent, changes in pulmonary blood flow and thus recruitment of alveolar-capillary surface area. However, other factors, such as the time course of ventilation, may also be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Monoxide↗
PubMed1991

Characterization of an 8-lipoxygenase activity induced by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin in vivo.

An enzymatic activity has been found in cytosolic preparations from mouse epidermis which catalyzes the formation of 8-hydroperoxyeicosatetraenoic acid/8-hydroxyeicosatetraenoic acid (8-HPETE/8-HETE) from arachidonate. In contrast to 12-lipoxygenase this enzyme activity was not detectable in normal (untreated) mouse skin but only after in vivo treatment with the phorbol ester tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). The induction showed a maximum at 24 h after TPA treatment strictly depended on the age of the mice and the TPA dose and was prevented by cycloheximide. The primary product formed from arachidonic acid was 8-HPETE, and the enzyme seems not to possess a significant peroxidase activity. This result as well as studies with specific inhibitors and its cytosolic localization indicates this enzyme to be a member of the lipoxygenase family. Most of the 8-lipoxygenase activity is located in cells of the suprabasal compartment of the epidermis. In spite of being a cytosolic enzyme 8-lipoxygenase appeared to be lipophilic to some extent and was activated by lecithin. The enzyme did not require calcium ions or ATP and showed a pH optimum at 7.5-8.0. 8-HPETE/8-HETE levels in mouse epidermis in vivo were determined by gas chromatography-mass spectrometry and found to be strongly increased after phorbol ester treatment, in agreement with the induction of 8-lipoxygenase observed.

Aging↗
PubMed1991

Voltage-sensitive Na+ channels: motifs, modes and modulation.

Much recent progress has been made in understanding the structural organization and functional properties of voltage-dependent Na+ channels, in particular in the areas of activation, ion conductance, and inactivation. At the same time, however, electrophysiological studies have revealed new, more complex functional properties in the form of at least two gating modes and the existence of as yet unidentified modulatory factors.

Action Potentials↗
PubMed1990

Rhizomelic chondrodysplasia punctata and survival beyond one year: a review of the literature and five case reports.

Rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder, is considered to be a lethal neonatal autosomal recessive chondrodysplasia. We report five patients, three of whom survived beyond 1 year, and we summarize the findings in 21 patients from a literature review who survived beyond 1 year. In those patients that survive, there is a high association of spasticity, psychomotor retardation, growth failure, seizures, thermoregulatory instability, feeding difficulty, and recurrent otitis media and pneumonia. Three of our five patients had no radiographic evidence of vertebral body clefts, a finding which has previously been considered invariable in RCDP. Three of our patients had distinctive facies that differ from the classic Conradi-Hunermann facies.

Bone and Bones↗