Showing papers by "University of Graz published in 1993"

Pathologic correlates of incidental MRI white matter signal hyperintensities

Abstract: We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid: An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas?

Abstract: Background: Topical photodynamic therapy with endogenous porphyrins consists of irradiation of a tumor with visible light after the application of exogenous 5-aminolevulinic acid. Objective: To assess the effectiveness of this modality, patients with precancerous conditions and various skin cancers were treated. Methods: Thirteen patients with 70 skin lesions were enrolled. Standard treatment involved the topical application of 20% 5-aminolevulinic acid in an oil-in-water emulsion. The emulsion was applied under an occlusive dressing for 4 to 8 hours before exposure to photoactivating light. Results: We observed a complete response after a single treatment for all 9 solar keratoses, 5 of 6 early invasive squamous cell carcinomas, and 36 of 37 superficial basal cell carcinomas. Only 1 of 10 noduloulcerative basal cell carcinomas completely resolved. Eight cutaneous metastases of malignant melanoma were therapeutic failures. Conclusion: Topical photodynamic therapy with endogenous porphyrins is effective for superficial epithelial skin tumors.

Lipid peroxidation and its role in atherosclerosis.

Abstract: A crucial step in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low density lipoprotein (LDL). The oxidation of LDL is a free radical driven lipid peroxidation process and the aldehyde products of lipid hydroperoxide breakdown are responsible for the modification of the LDL apoprotein. Aldehyde-modified apoB protein has altered receptor affinity, causing it to be scavenged by macrophages in an uncontrolled manner with the development of foam cells and the initiation of the atherosclerotic lesion. The aldehydic products of lipid peroxidation may also be involved in other aspects of the development of the lesion. The oxidation of LDL may be prevented by its endogenous antioxidant compounds, most prominent of which is alpha-tocopherol. Consequently, an improved antioxidant status may offer possibilities for the prevention of this major disease.

Neuropsychologic correlates of MRI white matter hyperintensities A study of 150 normal volunteers

Abstract: To determine the effects of MRI white matter hyperintensities (WMH) on cognitive functioning, we used neuropsychologic tests and MRI to study 150 elderly volunteers free of neuropsychiatric or general disease. There were 76 (50.3%) individuals without and 74 (49.7%) with WMH. The latter subset was older (61.3 +/- 6.6 years versus 58.5 +/- 5.8 years, p = 0.005), had a higher mean arterial blood pressure (103.7 +/- 11.4 mm Hg versus 99.9 +/- 10.3 mm Hg, p = 0.03), and a larger ventricular-to-intracranial-cavity ratio (6.3 +/- 5.6% versus 4.7 +/- 1.6%, p = 0.02). Individuals with WMH performed worse than their counterparts without such abnormalities on all tests administered. After adjusting for the group differences in age, arterial blood pressure, and ventricular size, we noted statistically significant results on form B of the Trail Making Test (121.8 +/- 37.8 msec versus 100.3 +/- 47.9 msec, p = 0.04), a complex reaction time task (680.8 +/- 104.9 msec versus 607.1 +/- 93.9 msec, p = 0.001), and the assembly procedure of the Purdue Peg-board Test (27.5 +/- 5.8 versus 30.6 +/- 5.9, p = 0.02). Partial correlations did not reveal any relationship between test scores and the semiautomatically assessed total area of WMH. Our data suggest that the presence of WMH exerts a subtle effect on neuropsychologic performance of normal elderly individuals, which becomes particularly evident on tasks measuring the speed of more complex mental processing.

Physiology and pathophysiology of organic acids in cerebrospinal fluid

Abstract: Concentrations of organic acids in cerebrospinal fluid (CSF) appear to be directly dependent upon their rate of production in the brain. There is evidence that the net release of short-chain monocarboxylic acids from the brain is a major route for removing these products of cerebral metabolism. Concentrations of organic acids in blood and CSF are largely independent of each other. Quantitative reference values for the concentrations of organic acids in CSF and plasma as well as ratios of individual organic acids between CSF and plasma were determined in 35 pairs of samples from paediatric patients. Over 25 organic acids were quantifiable in all or in the majority of CSF and/or plasma specimens (limit of detection 1 µmol/L). There were substantial differences in the CSF/plasma ratios between subgroups of organic acids. Metabolites related to fatty-acid oxidation were present in CSF in substantially less amounts than in plasma. Organic acids related to carbohydrate and energy metabolism and to amino acid degradation were present in CSF in the same amounts as or slightly smaller amounts than in plasma. Finally, some organic acids were found in substantially higher amounts in CSF than in plasma, e.g. glycolate, glycerate, 2,4-dihydroxybutyrate, citrate and isocitrate.

Genotoxic properties of 4-hydroxyalkenals and analogous aldehydes.

Abstract: 4-Hydroxynonenal (HNE), one of the major products of lipid peroxidation, has been demonstrated to induce genotoxic effects in the micromolar range. HNE has too structural domains, a lipophilic tail and a polar head with three functional groups: the aldehyde and hydroxy groups and the trans CC double bond. To evaluate their relative importance, the genotoxic effects of HNE were compared with those of the homologous aldehydes 4-hydroxyhexenal and 4-hydroxyundecenal (different lengths of the lipophilic tail), and the analogous aldehydes 2-trans-nonenal (lacking the OH group) and nonanal (lacking the OH group and the trans CC double bond). This investigation was carried out on primary cultures of adult rat hepatocytes in order to further determine the influence of biotransformation- and/or detoxification reactions. A 3-h treatment with HNE induces statistically significant levels of SCE at concentrations > or = 0.1 microM, micronuclei at concentrations > or = 1 microM and chromosomal aberrations at a concentration of 10 microM. Compared to HNE the homologous aldehydes induced a significant genotoxic effect at higher concentrations. Statistically significant increases in SCE frequency were obtained at concentrations > or = 1 microM for 4-hydroxyundecenal and at a concentration of 10 microM for 4-hydroxyhexenal. The induction of chromosomal aberrations was significantly elevated at concentrations of > or = 10 microM and 10 microM for 4-hydroxyhexenal and 4-hydroxyundecenal, respectively. Except for a 4-hydroxyhexenal concentration of 1 microM, both aldehydes did not induce statistically significant levels of micronuclei. The HNE analogous aldehydes 2-trans-nonenal and nonanal induced statistically significant frequencies of SCE at concentrations of > or = 1 microM (nonanal) and > or = 10 microM (2-trans-nonenal). No significant induction of chromosomal aberrations or micronuclei could be demonstrated. The structure of the aldehydes investigated appears to influence the cyto- and genotoxic potential in the following ways. (1) The length of the lipophilic tail has no influence on chromosomal aberration induction, but appears to determine the yield of SCE and micronuclei, and the cytotoxic potential. (2) The lack of the OH group (2-trans-nonenal) reduces the SCE-inducing potential of the aldehyde shifting the dose-effect curve to higher concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Proximal humeral fractures. Management techniques and expected results.

Abstract: During a ten-year period (1978-1988), 143 of 1386 patients with proximal humeral fractures were treated with internal osteosynthesis. Ninety-seven proximal humeral osteosynthesis cases had adequate documentation, and 77 (80%) were available for clinical review. The 97 fractures were graded by the AO/ASIF classification and included 44 Group A, 32 Group B, and 21 Group C fractures. Exercise-stable osteosynthesis using T-plate, cloverleaf plate, or small condylar plate was performed in 70% of patients. In the remaining patients, a less rigid fixation, with Kirschner wires or screws and cerclage wires, was used. Fifty-two percent of the patients had excellent and good results, 15% had fair results, and 33% had poor results. Most poor results occurred in patients with four-part fractures (61% of poor results). Of the cases involving four-part fractures, however, 22% had an excellent result after internal fixation. Displaced four-part fractures or fracture-dislocations should be treated by reconstruction of the proximal humerus, especially in young patients. The use of minimal fixation rather than rigid fixation is considered after careful assessment of the condition of the soft tissue and blood supply of the humeral head fragments. Primary treatment with endoprostheses is required when internal fixation is impractical in AO/ASIF fracture Types C 2/3 and C3 fractures. Improved clinical results may be achieved, particularly in the more severe fracture types, with increased experience in techniques of internal fixation of proximal humeral fractures.

Cutaneous immunocytomas: a clinicopathologic study of 26 cases

Abstract: The clinical and histological features of 16 patients with a primary cutaneous immunocytoma and 10 patients with a secondary cutaneous immunocytoma are reported. In all cases the diagnosis was based on the presence of monotypic plasma cells or lymphoplasmacytoid cells. Our data show that primary cutaneous immunocytomas are a distinct type of cutaneous lymphoma, characterized by (a) the presence of solitary or localized skin lesions (13 of 16 cases); (b) preferential localization on arms and legs (15 of 16 cases); (c) excellent response to local treatment (15 of 16 cases) and (d) a favourable prognosis. Histologically, these primary cutaneous immunocytomas are characterized by the presence of nodular or diffuse infiltrates with monotypic lymphoplasmacytoid/plasma cells located at the periphery of the infiltrates. Important clinical and histological differences were noted between primary and secondary immunocytomas. In the latter group more widespread skin disease was seen, often in the presence of paraproteins and/or autoimmune diseases. In contrast with the peripheral localization of the monotypic cells in primary cutaneous immunocytomas the monotypic lymphoplasmacytoid/plasma cells in secondary immunocytomas formed diffuse infiltrates or these cells were found dispersed throughout the infiltrate. There were no differences in clinical presentation or course between the different subtypes of cutaneous immunocytomas (lymphoplasmacytic, lymphoplasmacytoid and polymorphic immunocytomas). The differential diagnosis between primary cutaneous immunocytomas and cutaneous plasmacytomas, primary follicular centre cell lymphomas and cutaneous ‘pseudolymphomas’ is discussed.

Immunostaining of human autopsy aortas with antibodies to modified apolipoprotein B and apoprotein(a).

Abstract: A systematic immunohistochemical study of different stages of atherosclerosis in human aortas was performed using several antibodies. Because oxidation of lipoproteins could be a key event in atherogenesis, an antibody against apolipoprotein B (apoB) from low-density lipoprotein (LDL) modified with the lipid peroxidation-specific aldehyde, 4-hydroxynonenal (4-HNE) (anti-4-HNE-apoB), was raised in rabbits. This antibody recognizing 4-HNE protein adducts was used in concert with an antibody to apo(a) from lipoprotein(a), considered also potentially atherogenic, as well as with an antibody and a monoclonal antibody (mAb) to apoB. Autopsy material from 12 corpses was investigated. The immunohistochemical investigation by the alkaline-phosphatase technique included control specimens regarding postmortem artifacts by autolysis and oxidation. The results from six specimens from five corpses are presented. A positive staining with the antibody to apoB but not with anti-4-HNE-apoB was seen in the normal intima. The thickened intima of early, transitional, and advanced atherosclerotic lesions and atheromata showed a predominantly extracellular staining with all antibodies and the applied mAb. To test the specificity of the staining, antibodies preadsorbed by the appropriate antigens and nonimmune sera were used, giving negative results. These findings indicated a colocalization of epitopes derived from lipid peroxidation of polyunsaturated fatty acids and epitopes specific for apoB and apo(a) during atherogenesis in humans.

A regional blood circulation alternative to in-series two compartment urea kinetic modeling.

Abstract: Assuming that the clearance of urea from total body water (TBW) is flow limited, the authors developed a parallel flow model using physiologic data. Organ systems with a blood flow to water volume ratio of greater than 0.2 min-1 were allocated to the high flow system. Remaining organs were represented in the low flow system. In end-stage renal disease patients with minimal renal blood flow, the high flow system contained 20% TBW and received 70% of the systemic blood flow. The authors used this flow heterogeneity to predict the post-dialysis urea rebound (R) in 12 patients after 1 hr of hemodialysis. Dialyzer clearance was 248 +/- 14.5 ml/min (mean +/- SEM) Access recirculation was obviated by returning cleared blood into a central vein. In these patients, R at 1, 3, 5, 7, 10, and 15 minutes. after slowing dialyzer blood flow (Qb) from 383 +/- 18 to 50 ml/min was 3.8 +/- 2.9, 6.2 +/- 3.4, 7.6 +/- 3.1, 8.8 +/- 3.9, 9.0 +/- 4.1, and 9.9 +/- 4.4%, respectively. CO and QAc were modeled with values of 5.5 and 0.5 L/min, respectively. The modeled TBW was 35 L. Total body water derived by nomogram was 38.1 +/- 2.0 L. Our results suggest that the parallel-flow model for urea transport can be used to explain the amount and time course of post dialysis R on a physiologic basis.

Assessment of MRI criteria for a diagnosis of MS

Abstract: To test the reliability of four previously proposed MRI criteria for the diagnosis of MS, we reviewed 1,500 consecutive brain scans for the presence, number, size, and location of areas of increased signal (AIS) on proton-density and T2-weighted images, unaware of the patients' clinical presentations and ages. This series included 134 subjects with a clinical diagnosis of MS. Relying exclusively on the presence of at least three or four AIS for a positive diagnosis of MS resulted in high sensitivity (90% for three AIS and 87% for four) but inadequate specificity (71% for three AIS and 74% for four) and positive predictive value (23% for three AIS and 25% for four). If one of these lesions was required to border the lateral ventricles, specificity was 92% and positive predictive value was 50% at a sensitivity of 87%. Using the Fazekas criteria (at least three AIS and two of the following features: abutting body of lateral ventricles, infratentorial lesion location, and size > 5 mm) led to a further highly significant improvement of specificity (96%; p = 0.0000) and increase of the positive predictive value (65%) at the expense of a less significant decrease in sensitivity (81%; p < 0.01).

Clinical and Molecular Analysis of Five Inv Dup(15) Patients

Abstract: Five patients with inv dup(15) chromosomes were investigated with molecular probes on proximal 15q to determine the parental origin and extent of the duplicated segment. Cytogenetic investigation showed that four patients carried one and a fifth patient had two extra chromosomes derived from number 15 in all cells. In situ hybridization with a chromosome 15 library and a centromere 15 probe confirmed that the entire inv dup chromosomes were derived from chromosome 15. Molecular analysis using probes mapping in the region deleted in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients implied that in at least two patients the extra chromosomes were asymmetric with one copy of the PWS region on the extra marker chromosome but two copies of the region centromeric to the PWS region. Three other cases had an inv dup(15) with two extra copies of the PWS region, but in one of these, heteromorphisms clearly demonstrated that the two centromeres derived from two different chromosomes. The inv dup(15) presumably resulted from an illegitimate recombination event between two different chromosomes 15 in most or all of these cases. All patients showed a maternal origin of the duplicated chromosome. The clinical severity appears to be associated with dosage of the PWS/AS region rather than with differences in the extent of the duplicated segment.

An on-line scheduling heuristic with better worst case ratio than Graham's list scheduling

Abstract: The problem of on-line scheduling a set of independent jobs on m machines is considered. The goal is to minimize the makespan of the schedule. Graham’s List Scheduling heuristic [R. L. Graham, SIAM J. Appl. Math., 17(1969), pp. 416–429] guarantees a worst case performance of $2 - \frac{1} {m}$ for this problem. This worst case bound cannot be improved for $m = 2$ and $m = 3$. For $m \geqslant 4$, approximation algorithms with worst case performance at most $2 - \frac{1}{m} - \varepsilon _m $ are presented, where $\varepsilon _m $ is some positive real depending only on m.

Novel actions of methylene blue.

Abstract: Methylene blue has been frequently used as an inhibitor of soluble guanylyl cyclase. We found that endothelium-dependent relaxations of isolated blood vessels were considerably more sensitive to inhibition by methylene blue than relaxation induced by direct activators of soluble guanylyl cyclase. Similar data were obtained in the presence of superoxide dismutase, indicating that the diverse potencies of methylene blue were not due to superoxide-induced inactivation of nitric oxide (NO). Subsequent experiments revealed that methylene blue is an inhibitor of purified NO synthase. Conversion of L-arginine to L-citrulline was inhibited by the dye in a concentration-dependent fashion with half-maximal effects observed at 5.3 microM and 9.2 microM in the absence and presence of superoxide dismutase, respectively. Purified soluble guanylyl cyclase, however, was far less sensitive to methylene blue. When the enzyme was maximally stimulated with S-nitroso-glutathione, cyclic guanosine monophosphate, (cGMP) formation was reduced by 50% at approximately 60 microM methylene blue; 1 mM produced maximal inhibitions of about 70%. Our data indicate that methylene blue is only a poor inhibitor of soluble guanylyl cyclase. The dye seems to act primarily via inhibition of NO synthase, with enzyme-bound heme being a possible target in its inhibitory action.

Chicken oocyte growth : receptor-mediated yolk deposition

Abstract: During the rapid final stage of growth, chicken oocytes take up massive amounts of plasma components and convert them to yolk. The oocyte expresses a receptor that binds both major yolk lipoprotein precursors, vitellogenin (VTG) and very low density lipoprotein (VLDL). In the present study, in vivo transport tracing methodology, isolation of coated vesicles, ligand- and immuno-blotting, and ultrastructural immunocytochemistry were used for the analysis of receptor-mediated yolk formation. The VTG/VLDL receptor was identified in coated profiles in the oocyte periphery, in isolated coated vesicles, and within vesicular compartments both outside and inside membrane-bounded yolk storage organelles (yolk spheres). VLDL particles colocalized with the receptor, as demonstrated by ultrastructural visualization of VLDL-gold following intravenous administration, as well as by immunocytochemical analysis with antibodies to VLDL. Lipoprotein particles were shown to reach the oocyte surface by passage across the basement membrane, which possibly plays an active and selective role in yolk precursor accessibility to the oocyte surface, and through gaps between the follicular granulosa cells. Following delivery of ligands from the plasma membrane into yolk spheres, proteolytic processing of VTG and VLDL by cathepsin D appears to correlate with segregation of receptors and ligands which enter disparate sub-compartments within the yolk spheres. In small, quiescent oocytes, the VTG/VLDL receptor was localized to the central portion of the cell. At onset of the rapid growth phase, it appears that this pre-existing pool of receptors redistributes to the peripheral region, thereby initiating yolk formation. Such a redistribution mechanism would obliterate the need for de novo synthesis of receptors when the oocyte's energy expenditure is to be utilized for plasma membrane synthesis, establishment and maintenance of intracellular topography and yolk formation, and preparation for ovulation.

Environmental and Biological Constraints for the Evolution of Long-Range Signalling and Hearing in Acoustic Insects

Abstract: A number of insects use sound signals for the attraction of mates and in aggressive interactions between males. I discuss two constraints which may have shaped both the design of long-range signals, and the structure and physiology of the ear and nervous system of the receiver. Properties of the transmission channel for sound will impose limitations on long-range transfer of information, which may be compensated for by adapting either the signal or the behaviour of the sender or receiver. I describe properties of the nervous system which force the sender to produce more conspicuous signals. I suggest that the evolutionary past may represent a constraint on the communication system, where conservative features of the sensory and nervous system would now appear to be maladaptive for intraspecific communication.

Characterization of endothelial cell amino acid transport systems involved in the actions of nitric oxide synthase inhibitors.

Abstract: N omega-Substituted analogues of L-arginine have proven useful as specific inhibitors of nitric oxide formation in various biological systems. In the present study we describe the characteristics of amino acid transporters that mediate uptake of N omega-methyl-L-arginine (L-NMA) and N omega-nitro-L-arginine (L-NNA) into cultured porcine aortic endothelial cells. The transport of L-[14C]NMA showed biphasic kinetics, with Km values of 4 and 368 microM, and was inhibited by L-arginine, L-homoarginine, L-lysine, and L-ornithine but not by L-leucine or L-isoleucine. Similar transport kinetics (Km values of 6 and 609 microM) and substrate specificities were obtained for L-[3H]arginine uptake, indicating that L-arginine and L-NMA are transported by the same system. In contrast to L-arginine and L-NMA transport, uptake of L-[3H]NNA was monophasic (Km = 617 microM) and was inhibited by L-leucine and L-isoleucine but not by L-arginine, L-homoarginine, L-NMA, L-lysine, or L-ornithine. Uptake studies with L-[3H]leucine revealed that the transport of this amino acid occurred in a manner very similar to that of L-[3H]NNA transport, suggesting that the uptake of both compounds may be mediated by the same system. In additional experiments, we determined the effects of L-NMA and L-NNA on the A23187-induced accumulation of intracellular cGMP, to establish to what extent these transport systems are involved in the actions of nitric oxide synthase inhibitors. L-Lysine and L-ornithine, which both inhibited L-NMA uptake, increased the IC50 of L-NMA from 7.8 microM to 57 microM but did not reduce the inhibitory effects of L-NNA. In the presence of L-leucine or L-isoleucine, however, which both inhibited L-NNA uptake, the IC50 of L-NNA was increased from 1.2 microM to 37 microM but the inhibitory actions of L-NMA remained unaffected. These data demonstrate that the endothelial transport systems for L-arginine and L-leucine mediate the biological effects of L-NMA and L-NNA, respectively.

Solitary myofibroma in adults: clinicopathological analysis of a series

Abstract: Solitary myofibroma is a recently described, benign neoplasm of superficial soft tissue, which represents the adult counterpart of infantile myofibromatosis and is poorly recognized. Eleven new cases are presented herein. The patients were mostly adults with ages ranging from 13-64 years. They presented with a solitary, usually painless nodule of variable duration in the skin or oral cavity. Histologically, each lesion had a biphasic pattern with spindle cells forming fascicular or whorled areas and rounded, more primitive cells arranged around small vessels, forming haemangiopericytoma-like areas. The characteristic zonation of infantile myofibromatosis was often less marked in adult lesions and there was a haphazard arrangement of the fascicular and pericytic areas in some cases. Hyalinization, especially of the peripheral spindle-celled areas, was frequent. Immunohistochemically, the spindle cells were desmin negative but muscle actin (HHF-35 and IA4) positive. The rounded cells were both desmin and actin negative. Electronmicroscopy confirmed the myofibroblastic/fibroblastic nature of tumour cells in two cases. Although vascular invasion was seen in two cases, solitary adult-type myofibroma pursues a benign clinical course.