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Biomedical subjects

M Marx

Publications and source records attributed to M Marx.

At least 91 records · Page 5Linked to original sources
PubMed1996

Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea.

In this population-based study, we correlated possible risk factors for rodent-to-human transmission of Lassa virus with markers of Lassa fever in two different regions of the Republic of Guinea (Prefectures of Pita and Gueckedou). Antibody prevalence was 2.6% (6 of 232) in Pita compared with 14.0% (105 of 751) in Gueckedou, with up to 35.0% seropositivity in selected villages of the higher prevalence area. We observed three major risk factors in Gueckedou favoring Lassa virus transmission: rodent infestation was much higher, food was more often stored uncovered and most strikingly, peridomestic rodents were hunted as a protein source by 91.5% of the population as opposed to 0% in Pita. To control for the confounding effects of differences in rodent infestation and food storage, rodent consumption was analyzed as a risk factor for transmission of Lassa virus comparing rodent consumers (RC) and nonconsumers (NC) in Gueckedou only: 14.6% of RC had Lassa virus antibodies versus 7.4% of NC (P = 0.1) and 23.0% of RC reported a history of a febrile illness with hearing loss (the most common sequel of Lassa fever) versus 6.1% of NC (P = 0.003).

Adolescent↗
PubMed1995

Phenytoin free fraction determination: comparison of an improved direct serum injection high-performance liquid chromatographic method to ultrafiltration coupled with fluorescence polarization immunoassay.

Recent developments in restricted-access media (RAM) liquid chromatography make the simultaneous determination of total and free phenytoin concentrations possible by direct injection of drug-containing serum samples. A comparison of phenytoin free fraction determination by ultrafiltration coupled with fluorescence polarization immunoassay (TDX) to an improved direct injection RAM-HPLC method is presented. Our improved method differs from those previously reported with regard to column type, mobile-phase composition, and column temperature. Replicate samples analyzed by each method yielded similar values for serum phenytoin free fraction.

Anticonvulsants↗
PubMed1995

Agmatine and spermidine reduce collagen accumulation in kidneys of diabetic db/db mice.

In the present study, we tested the hypothesis whether agmatine and spermidine, metabolites of arginine metabolism, share the pharmacological activities of arginine reducing collagen accumulation in the diabetic kidney. Eleven db/db mice were administered agmatine and 12 db/db mice spermidine (50 mg/kg body weight). Ten db/db mice received no treatment as negative controls and 10 db/db mice were treated with aminoguanidine (50 mg/kg body weight) as positive controls. Mean kidney OH-proline content reflecting kidney collagen content and mean CML concentration were significantly higher but acid solubility of collagen significantly lower in the untreated group than in the treated groups. Agmatine, although missing the alpha-amino group and the carboxyl group, and spermidine, although missing the guanidino group, thus still revealed the arginine activity. We hypothesize that the strongly nucleophilic structure of polyamines common to all active compounds is able to block reactive carbonyls.

Agmatine↗
PubMed1995

[Acute respiratory failure (ARDS) in a young child after drowning accident: therapy with exogenous surfactant and high frequency oscillatory ventilation].

The adult respiratory distress syndrome (ARDS) in children has a very poor prognosis with a mortality risk of between 55 and 85%, in spite of improvements due to the introduction of positive endexpiratory pressure ventilation. We describe the clinical course of a not yet 3 year-old boy with severe ARDS following near-drowing. Treatment with exogenous surfactant and high frequency oscillatory ventilation, a well-established procedure in neonatology, was responsible for the favorable outcome. The high cost of surfactant therapy, however, is the main limiting factor for this kind of treatment in children beyond the neonatal period, but it may be the last therapeutic resort in the management of severe ARDS.

Child, Preschool↗
PubMed1995

Transformation-resistant mos revertant is unable to activate MAP kinase kinase in response to v-mos or v-raf.

To study the mechanism by which v-mos induces cell transformation, we generated a transformed rat cell line (DTM) containing two functional copies of mos, one encoding the p37v-mos of the m1 wild-type strain of Moloney murine sarcoma virus (Mo-MuSV) and the other the p85gag-mos fusion protein of the ts110 mutant of Moloney murine sarcoma virus. Subsequently, we isolated a revertant cell line (F-1) following transfection of DTM with a mutant retroviral construct (pIC4Neo) carrying a selectable marker. Like DTM, the F-1 revertant contained two integrated copies of v-mos, expressed mos containing viral RNA, and contained rescuable transforming viruses. The revertant did not grow in soft agar, showed a greatly reduced ability to form tumors in nude mice, and exhibited organized tubulin and actin structures similar to those found in normal cells. Revertant cells were resistant to retransformation by v-mos and v-raf but could be retransformed by v-ras. MAP kinase (ERK-2) and MAP kinase kinase (MKK-1) activity, which are constitutively elevated in v-mos- and v-raf-transformed cells, exhibits levels in the F-1 revertant similar to those seen in nontransformed cells. F-1 and normal REF-1 cells express elevated levels of protein phosphatases in comparison to DTM cells. In vivo treatment with okadaic acid, a potent protein phosphatase inhibitor, leads to an increase in MKK-1 and MAP kinase activity in F-1 cells but not in REF-1. The results support the hypothesis that mos acts through the MAP kinase cascade (MKK-1 and ERK-2) to induce cell transformation and that blocking v-mos activation of that cascade (possibly because of increased levels of phosphatase) prevents transformation.

Animals↗
PubMed1994

Addition of oral clonidine to postoperative patient-controlled analgesia with i.v. morphine.

Using a randomized, double-blind, placebo-controlled design, we have investigated, in 40 patients undergoing major abdominal surgery, the effect of oral clonidine 300 micrograms, 1 h before and 12 h after surgery on postoperative morphine requirements (evaluated by PCA). During the 24 h of the study, pain scores measured every 6 h did not differ significantly. Morphine requirements tended to be reduced in the clonidine group but the difference was not significant. There were no significant differences also in mean arterial pressure, ventilatory frequency and the incidence of pruritus and nausea. Heart rate was significantly lower until 18 h after surgery and sedation was significantly more pronounced in patients receiving clonidine. We cannot recommend routine oral administration of clonidine before surgery to improve postoperative analgesia.

Administration, Oral↗
PubMed1994

Differences in intravenous and subcutaneous application of recombinant human erythropoietin: a multicenter trial.

The aims of this clinical study were to compare the maintenance doses for intravenous (i.v.) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under i.v. and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end-stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1-week pretreatment phase, a subsequent 8-week double-blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol.% was 33 U/kg body weight three times a week in the i.v. group compared with 22 U/kg in the SC group (i.e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the i.v. group. During the maintenance phase, there was no essential difference between the two groups.

Adult↗
PubMed1994

Functional and biological properties of an avian variant long terminal repeat containing multiple A to G conversions in the U3 sequence.

We previously reported that infection of chicken embryonic neuroretina cells with Rous-associated virus type 1 leads to the frequent occurrence of spliced readthrough transcripts containing viral and cellular sequences. Generation of such chimeric transcripts constitutes a very early step in oncogene transduction. We report, here, the isolation of a c-mil transducing retrovirus, designated IC4, which contains a highly mutated U3 sequence in which 48% of A is converted to G. Functional analysis of this variant U3 indicated that these mutations do not impair viral transcription and replication; however, they abolish functioning of its polyadenylation signal, thus allowing readthrough transcription of downstream cellular sequences. On the basis of these results, we designed a nonreplicative retroviral vector, pIC4Neo, expressing the neomycin resistance (Neo(r)) gene under the control of the IC4 long terminal repeat. Infection of nondividing neuroretina cells with virus produced by a packaging cell line transfected with pIC4Neo occasionally resulted in sustained cell proliferation. Two independent G418-resistant proliferating cultures were found to express hybrid RNAs containing viral and cellular sequences. These sequences were characterized by reverse transcription-PCR and were identified in both cultures, suggesting that proliferation was correlated with a common integration locus. These results indicate that IC4Neo virus functions as a useful insertional mutagen and may allow identification of genes potentially involved in regulation of cell division.

Adenine↗
PubMed1994

L-arginine reduces heart collagen accumulation in the diabetic db/db mouse.

BACKGROUND: Diabetic cardiomyopathy presents with significant collagen accumulation; decreased solubility, increased glucose-mediated abnormal cross-linking, free radical cross-linking, or glucose-induced increased transcription of collagen is incriminated. In a previous study, we reduced collagen accumulation in the kidneys of diabetic mice by treatment with oral arginine. This observation led us to examine the effect of arginine on cardial fibrosis. METHODS AND RESULTS: Twenty-nine db/db spontaneously diabetic mice were used in the experiments. Sixteen were given L-arginine (free base, in tap water, 50 mg/kg body wt per day) for 4 months. At the end of the experiment, we determined total collagen content of total ventricular tissue, acid solubility, carboxymethyllysine, O-tyrosine, glutathione, blood glucose, and fructosamine as parameters for glycemic control. Heart collagen level was significantly (P = .0001) reduced in the experimental group (mean, 0.24 +/- 0.05) compared with the control group (mean, 0.49 +/- 0.10 mumol hydroxyproline per 100 mg heart tissue). Significantly more collagen could be eluted from heart samples of the experimental group (P = .02). Carboxymethyllysine and O-tyrosine did not differ when related to heart weight. Glutathione level was significantly higher in the untreated group (P = .003). Parameters of glycemic control did not differ between the groups. CONCLUSIONS: Our findings clearly indicate that L-arginine reduced total heart collagen and increased acid solubility of heart collagen. Both findings are compatible with the cross-linking hypothesis. The data for carboxymethyllysine, O-tyrosine, and glutathione would rule out the glycoxidation hypothesis and, therefore, free radical cross-linking. The postulated mechanism of action is most likely the blocking of reactive carbonyl functions by L-arginine in analogy to aminoguanidine activity. Correlations of collagen with glycemic control, however, point to an association of glucose with collagen metabolism, a phenomenon documented in cell cultures at the transcriptional level.

Animals↗
PubMed1994

Modulation of platelet-derived growth factor receptor expression in microvascular endothelial cells during in vitro angiogenesis.

Microvascular endothelial cells in vivo exhibit a plastic phenotype, forming a nonproliferative, differentiated capillary network, while retaining their ability to respond to injury by proliferation, migration and neovascularization. The presence of PDGF receptors and PDGF responsiveness in microvascular endothelial cells and the significance of PDGF isoforms in the control of endothelial cell growth and differentiation remain controversial. Since culture of microvascular endothelial cells in a three-dimensional (3D) system induced cell differentiation and angiogenesis and inhibited proliferation, the present study investigates the role of different extracellular matrix environments in inducing different microvascular endothelial cell phenotypes on microvascular endothelial cell PDGF receptor expression and PDGF responsiveness. In conventional two-dimensional (2D) culture, microvascular endothelial cells expressed both PDGF receptor alpha and beta chains. Suramin treatment demonstrated continuous downregulation of the alpha receptor surface expression. PDGF BB and, to a lesser extent, PDGF AB were mitogenic in 2D-culture, PDGF AA failed to induce any proliferative response despite inducing receptor autophosphorylation. During in vitro angiogenesis induced by 3D-culture, both PDGF receptors were rapidly downregulated. Assessment of cell proliferation showed quiescent cells and PDGF unresponsiveness. We conclude that the induction of a differentiated phenotype during in vitro angiogenesis (tube formation) driven in part by the spatial organization of the surrounding matrix is associated with a downregulation of PDGF receptors. Identification of the molecular cell-matrix interactions involved in this receptor regulation may allow for targeted manipulation of cell growth in vivo and lead to novel therapeutic applications for PDGF.

Adipose Tissue↗
PubMed1994

Steps and mechanisms of oncogene transduction by retroviruses.

Oncogene transduction, the process by which a cellular gene is captured by a retrovirus was mainly described in vivo. We have developed a biological system allowing stepwise analysis of transduction mechanisms in tissue culture. Avian neuroretina (NR) cells dissected at the 8th day of embryonic development rapidly cease to divide and differentiate in culture. Serial passaging of a retrovirus that does not carry an oncogene on such cultures leads with a high frequency to the emergence of new viruses that have transduced oncogenes from the mil/raf family of serine/threonine kinases. These viruses have been selected by their ability to induce NR cell division. This experimental system allowed the isolation of the following molecular intermediates generated during the successive steps of oncogene transduction: a chimeric transcript containing viral and cellular sequences joined together by an alternative splicing mechanism; then a complete retrovirus with a 5' end identical to that of chimeric RNA; finally, a retrovirus that has acquired additional gag sequences and consequently, an increased replicative capacity. Structural analysis of these molecules led us to propose a general model for oncogene transduction in which the key step is the synthesis of chimeric RNAs. This model also explains generation of the vast majority of acutely transforming retroviruses isolated in vivo.

Animals↗
PubMed1994

[Comparison of surgical techniques and various suture materials for correction of aortic isthmus stenosis].

UNLABELLED: Clinical examination and Doppler ultrasound were performed in 31 children after repair of coarctation of the aorta. Median postoperative follow-up period was 4.5 years. The aim of our study was a comparison of different operation techniques and suture materials. In 16 infants subclavian flap repair had been performed using polydioxanone absorbable sutures (PDS) in 8 cases and polypropylene (Prolene) sutures in the other 8 cases. Resection and end-to-end repair had been carried out in 8 infants using PDS and in 7 using Prolene sutures. Doppler-echocardiographically derived gradients across the reconstructed aorta were significantly lower in infants operated with the subclavian flap technique (p < 0.05). The length of the arm on the side of the subclavian flap operation was shorter (median 1.2 cm), but there were no signs of ischaemic complications. Using PDS sutures the aortic arch and the aortic isthmus were each morphologically significantly wider in both operation techniques. Noninvasive two-dimensional echocardiography demonstrated good anatomical repair and no anastomotic aneurysm formation after aortic repair using polydioxanone. CONCLUSION: Regarding the doppler-echocardiographically derived gradients in the anastomotic region this intermediate follow-up study reveals better results using the subclavian flap technique; absorbable polydioxanone sutures favour normal growth of the anastomotic site without vascular complications.

Anastomosis, Surgical↗