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M Arand

Publications and source records attributed to M Arand.

104 records · Page 6Linked to original sources
PubMed1991

An impaired peroxisomal targeting sequence leading to an unusual bicompartmental distribution of cytosolic epoxide hydrolase.

To gain an understanding of the mechanism by which the subcellular distribution of cytosolic epoxide hydrolase (cEH) is directed, we have analyzed the carboxy terminal region of rat liver cEH by means of cDNA cloning to define the structure of its possible peroxisomal targeting sequence (PTS). Purified cEH was subjected to peptide analysis following endoproteinase Glu-C digestion and HPLC-separation of the fragments. The obtained sequence information was used to perform PCR experiments resulting in the isolation of a 680 bp cDNA clone encoding the carboxy terminus of cEH. The deduced amino acid sequence displays a terminal tripeptide Ser-Lys-Ile which is highly homologous to the PTS (Ser-Lys-Leu) found in other peroxisomal enzymes. This slight difference appears to be sufficient to convert the signal sequence into an impaired and therefore ambivalent PTS, directing the enzyme partly to the peroxisomes and allowing part to reside in the cytosol.

Amino Acid Sequence↗
PubMed1991

Post-traumatic radioulnar synostosis after forearm fracture osteosynthesis.

One hundred sixty-seven forearm fractures treated with plate osteosynthesis were analyzed for synostosis occurring between the radius and the ulna. Eleven cases (6.6%) were found, in 7 of which both bones of the forearm had been fractured, while the other 4 were cases of isolated radial or ulnar fracture. Overall there were 89 cases of fracture of both bones; of the 65 cases treated utilizing the two-incision approach, cross-union was seen in only 1, while in a comparable group (12 cases) in which the fractures were stabilized using the Boyd approach, there were 5 synostoses. In 38 cases of isolated ulna fracture, only 2 synostoses were seen one associated with severe soft-tissue trauma and the other arising after treatment with a modified Boyd approach. Among 40 isolated radial fractures, 2 radioulnar synostoses occurred, one in an open fracture and the other after fixation via the Boyd approach. These results emphasize the importance of using two approaches for fractures of both forearm bones. The highest risk of post-osteosynthetic synostosis appears to be in fractures of the proximal third of both radius and ulna.

Adolescent↗
PubMed1991

Selective induction of bilirubin UDP-glucuronosyl-transferase by perfluorodecanoic acid.

Differential effects of perfluorodecanoic acid (PFDA) on rat liver UDP-glucuronosyltransferase isoenzymes have been observed after a single i.p. administration of the compound to young male Sprague-Dawley rats. (1) Bilirubin glucuronidation was induced 2-fold. The induced state was stable for at least 3 weeks. (2) Glucuronidation of 1-naphthol, morphine and testosterone was decreased to half of the control values. These decreases were maximal after 12 days but all three activities returned to normal levels after 3 weeks. (3) Immunoblotting experiments indicated that the differential effects of PFDA on UDP-glucuronosyltransferase activities were due to modulation of enzyme protein concentrations rather than activation/inactivation mechanisms. With respect to its influence on UDP-glucuronosyltransferase isoenzymes, PFDA may be classified as a clofibrate-type inducer. The persistence of the induction after a single application however is unique among peroxisome proliferators and therefore PFDA may be a useful, elective inducer of bilirubin glucuronidation.

Animals↗
PubMed1991

[Cervical spinal injuries in craniocerebral trauma: their x-ray diagnosis on the day of the accident].

To investigate cervical spine injuries and to evaluate cervical radiography 100 patients were reviewed who were referred to computed tomography of the head because of blunt head trauma. 15 sustained cervical injury, 11 were located at the lower level of the cervical spine. Six fractures of the lower cervical spine were detected by additional radiographs. The diagnosis was established by computed tomography in three cases. To rule out cervical injuries in patients with incomplete visualisation of the lower cervical spine, cervical computed tomography should be performed in addition to lateral, anterioposterior, and open-mouth views.

Adult↗
PubMed1991

[Trends in indications and technique of osteosynthesis. Innovations in surgery of the spine].

More understanding of the biomechanics of injured segments, standardized dorsal and ventral accesses to all spinal column levels, and developments in fixation systems specifically conceived for the stabilization of vertebral column lesions have all greatly expanded the operative indications for spinal column injuries. Modern fixation systems should have the following features: short-term application, angular stability, universal suitability for all types of fractures, ability to bear axial loads, thus dispensing with the need for additional external stabilization.

Fracture Fixation↗
PubMed1988

[Injuries of the cervical spine--surgical therapy].

Surgical treatment of unstable cervical spine injuries has justifiably gained acceptance when based on definite indications and methods of internal fixation. Direct anterior screw fixation of the odontoid process is the appropriate procedure for stabilizing articulation fractures. Many instability problems of the upper cervical spine can be solved with posterior transarticular fixation C1/C2 according to Magerl. Of the posterior procedures for the lower cervical spine, hook-plate fixation according to Magerl is preferable to wirings. Plate fixation with hollow titanium screws (Morscher) has proved a successful anterior procedure. The two methods can be combined to treat severe osteoligamentous injuries.

Cervical Vertebrae↗
PubMed1988

[Cross stabilization of the internal fixator of the spine].

The "Internal Fixator" for stabilizing the dorso-lumbar spine represents an effective and meanwhile established device to neutralize flexion-bending and sagittal shearing forces. Because of the possible movement of the Schanz' screws in the bone and within the connection clamps, this device does not withstand torsional and frontal plane shearing forces after postinjury or postlaminectomy instability. Therefore, a cross-link device, adaptable to the "Internal Fixator" has been developed. Biomechanical testing against torsion and frontal plane bending moments have shown very low stability resulting in lateral displacement of the fixation device without cross-linking. The diagonal bracing with two wire cerclages does not significantly increase the stability. The recently developed cantilever cross-link device completes the two longitudinal bars to a frame construction and increases therefore the torsional and frontal plane stability for over 70%. This supplementary device is easy to apply to the "Internal Fixator" and has been successful in clinical practise.

Biomechanical Phenomena↗
PubMed1987

A fluorometric assay for quantitating phenol sulfotransferase activities in homogenates of cells and tissues.

A new, rapid, and sensitive method for assaying phenol sulfotransferase activity toward 2-naphthol is described. The product 2-naphthyl sulfate is quantitated fluorometrically. Optimal wavelengths for excitation and emission were determined by recording the three-dimensional fluorescence spectra of the substrate and the product. The new method is applicable to crude cell or tissue homogenates as well as to further purified preparations. A comparison to another widely used method is given to point out the advantages provided by the new procedure. In particular, sensitivity and accuracy of both methods are evaluated and the influence of interfering substances on both systems is compared. These results clearly indicate the superiority of the new method.

Arylsulfotransferase↗
PubMed1987

A time-course investigation of vitamin A levels and drug metabolizing enzyme activities in rats following a single treatment with prototypic polychlorinated biphenyls and DDT.

Xenobiotics previously characterized as selective inducers of drug-metabolizing enzymes were chosen to probe possible relationships between enzyme induction and vitamin A metabolism. Liver, kidney and serum retinol and retinyl palmitate levels were investigated in male Sprague--Dawley rats receiving a single i.p. injection of the polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumol/kg) or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) (150 mumol/kg). While 2,2',5,5'-tetrachlorobiphenyl, a weak or non-inducer, and 2,2',4,4',5,5'-hexaclorobiphenyl and DDT, phenobarbital-type inducers of cytochrome P-450, led to no reduction in total vitamin A content of liver or kidney during the 7 day time-course, administration of 3,3',4,4'-tetrachlorobiphenyl, a toxic PCB and a potent 3-methylcholanthrene-type inducer of cytochrome P-450, resulted in progressively lowered liver vitamin A levels (to 40% of control values by day 7). During this time, kidney total vitamin A content increased 3-fold. The increase in kidney vitamin A (due primarily to increased retinol content) was only equal to 1/40 of total vitamin A which had disappeared from the liver. Although 3,3',4,4'-tetrachlorobiphenyl specifically induced certain drug-metabolizing enzyme activities, e.g. aryl hydrocarbon hydroxylase and UDP-glucuronosyltransferase (toward 4-nitrophenol), no highly significant correlations were found among the vitamin A levels and drug-metabolizing enzyme activities in the liver (aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aldrin epoxidase, microsomal epoxide hydrolase, UDP-glucuronosyltransferase toward 4-nitrophenol, glutathione transferase toward 1-chloro-2,4-dinitrobenzene and cytochrome P-450 content) as determined by multiple linear regression analysis.

Animals↗
PubMed1986

cis- and trans-1,2-diphenylaziridines: induction of xenobiotic-metabolizing enzymes in rat liver and mutagenicity in Salmonella typhimurium.

trans-Stilbene imine (trans-1,2-diphenylaziridine) is the nitrogen analog of trans-stilbene oxide, a potent inducer of several microsomal and cytosolic xenobiotic-metabolizing enzymes. Although the acute toxicity of cis- and trans-stilbene imines prevents their application at the usual dose for trans-stilbene oxide (400 mg/kg/day), it is apparent that the imines nevertheless potently induce several xenobiotic-metabolizing enzymes in rat liver. The IP administration of trans-stilbene imine resulted in statistically significant increases in the activities of aminopyrine N-demethylase, microsomal epoxide hydrolase, glutathione transferase (toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene and delta 5-androstene-3,17-dione) and UDP-glucuronosyltransferase (toward testosterone). cis-Stilbene imine was less potent in inducing these activities. Although trans-stilbene imine (total dose = 400 mg/kg) was more potent than trans-stilbene oxide (total dose = 1200 mg/kg) in inducing the activities of glutathione transferase (toward 1-chloro-2,4-dinitrobenzene) and UDP-glucuronosyltransferase (toward testosterone), both compounds belong to the class of substances which are more potent inducers of conjugating (phase II) enzymes. Because of their structural similarity with K-region arene imines which are potent mutagens, cis-stilbene imine and trans-stilbene imine were investigated for mutagenicity (reversion of his- strains of Salmonella typhimurium). cis-Stilbene imine and trans-stilbene imine were direct mutagens in the strain TA100. This result, and the finding that acenaphthene 1,2-imine efficiently reverts various strains of Salmonella typhimurium, demonstrates that not only K-region arene imines, but also other aziridines substituted at the two carbons with aromatic moieties, are mutagenic.

Animals↗
PubMedDate not supplied

Metabolic detoxification: implications for thresholds.

The fact that chemical carcinogenesis involves single, isolated, essentially irreversible molecular events as discrete steps, several of which must occur in a row to finally culminate in the development of a malignancy, rather suggests that an absolute threshold for chemical carcinogens may not exist. However, practical thresholds may exist due to saturable pathways involved in the metabolic processing, especially in the metabolic inactivation, of such compounds. An important example for such a pathway is the enzymatic hydrolysis of epoxides via epoxide hydrolases, a group of enzymes for which the catalytic mechanism has recently been established. These enzymes convert their substrates via the intermediate formation of a covalent enzyme-substrate complex. Interestingly, the formation of the intermediate proceeds faster by orders of magnitude than the subsequent hydrolysis, ie, the formation of the terminal product. Under normal circumstances, this does not pose a problem, since the microsomal epoxide hydrolase (mEH), the epoxide hydrolases with the best documented importance in the metabolism of carcinogens, is highly abundant in the liver, the organ with the highest capacity to metabolically generate epoxides. Computer simulation provides evidence that the high amount of mEH enzyme is favorable for the control of the steady-state level of a substrate epoxide and can keep it extremely low. However, once the mEH is titrated out under conditions of extraordinarily high epoxide concentration, the epoxide steady-state level steeply rises, leading to a sudden burst of the genotoxic effect of the noxious agent. This prediction of the computer simulation is nicely supported by experimental work. V79 Chinese hamster cells that we have genetically engineered to express human mEH at about the same level as that observed in human liver are completely protected from any measurable genotoxic effect of the model compound styrene oxide (STO) up to a dose of 100 microM in the cell culture medium (toxicokinetic threshold). In V79 cells that do not express mEH, STO leads to the formation of DNA strand breaks in a dose-dependent manner with no toxicokinetic threshold observable. Above 100 microM, the genotoxic effect of STO in the mEH-expressing cell line parallels the one in the parental cell line. Thus, the saturable protection from STO-induced strand breaks by mEH represents a typical example of a practical threshold. However, it must be pointed out that even in the presence of protective amounts of mEH, a minute but definite level of STO is present that does not contribute sufficiently to the strand break formation to overcome the background noise of the detection procedure. As pointed out above, absolute thresholds probably do not exist in chemical carcinogenesis.

Animals↗
PubMedDate not supplied

Tibial shaft fractures: assessment of fracture healing with computed tomography.

OBJECTIVE: To assess the capability of CT in assessing stability of tibial shaft fractures with planimetry. MATERIALS AND METHODS: Eighteen patients with fracture of the tibial shaft were treated by external fixator. All patients underwent CT 1, 6, 12, and 18 weeks postoperatively to assess the fracture healing. The callus formation and compacta were determined with planimetry. Fractometry, a noninvasive method to measure stability, was used as the gold standard to determine the stability of the fracture. RESULTS: The patients were divided into three groups according to different periods of time for removal of external fixation. Twelve patients with stable fractures showed a steady increase of callus, which was 50% higher after 12 weeks. Three patients with delayed fracture healing demonstrated an increase of callus of > 50% after 18 weeks. Three patients with unstable fractures obtained only callus formation of < 20% after 15-18 weeks. The external fixator was removed and endomedullary nails were used for stabilization. CONCLUSION: The CT data allow quantification of callus and compacta formation and are able to determine the stability of tibial shaft fractures.

Adolescent↗
PubMedDate not supplied

Endoprosthetic treatment of metastatic pathological fractures.

Due to a prolonged time of survival patients with lowrisk skeletal dissemination may develop a local relapse after surgical treatment of a pathological fracture. In a series of 180 patients with bone metastases of breast cancer, a local metastatic recurrency was observed 8-36 months after operative treatment in 12 patients. All of them had a receptor-positive primary and were free from visceral metastases; only one had received radiotherapy postoperatively. Patients with low-risk disease therefore should undergo more radial surgical procedures than patients with poor prognosis, in whom reconstitution of stability represents the most important therapeutic goal. In cases with low-risk disease and histologically proven residual tumour a postoperative irradiation should be administered as a rule.

Adult↗