Biomedical subjects
Publications and source records attributed to B Kubat.
A 27 year-old woman died unexpectedly due to a cyst of the pineal gland with a prominent cerebellar tonsillar herniation.
The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18-34 years (n=19) and > or =35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II.
Despite the fact that muscle weakness is a major problem in chronic obstructive pulmonary disease (COPD), detailed information on myopathological changes at the microscopic level in these patients is scarce, if indeed available at all. Vastus lateralis biopsies of 15 COPD weight-stable patients (body mass index (BMI) 23.9+/-1.0 kg x m(-2); fat-free mass index (FFMI) 17.2+/-1.7 kg x m(-2)) and 16 healthy age-matched controls (BMI 26.3+/-0.8 kg x m(-2); FFMI 19.6+/-2.2 kg x m(-2)) were evaluated. Histochemistry was used to evaluate myopathological features. Immunohistochemistry was used for the detection of macrophages and leukocytes, and active caspase 3 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) as markers of apoptosis. Fatty cell replacement and fibrosis were observed in both groups, the latter being slightly, but significantly, more pronounced in COPD. No differences between COPD and controls were found with respect to central nuclei, necrosis, regeneration, or fibre splitting. Signs of mitochondrial abnormalities were absent and normal numbers of inflammatory cells were found. Active caspase 3 positive myocytes were not observed and no difference was found in the number of TUNEL-positive myonuclei between controls and COPD patients (1.1% versus 1.0%, respectively). The cross-sectional area of type-IIX muscle fibres was smaller in COPD than in controls (2,566 versus 4,248 microm2). Except for the I to IIX shift in fibre types, the selective type-IIX atrophy and a slight accompanying increase in fibrosis and fat cell replacement in chronic obstructive pulmonary disease relative to age-matched controls, no other morphological abnormalities were observed in the muscle biopsies of chronic obstructive pulmonary disease patients. Also, in this group of clinically and weight stable chronic obstructive pulmonary disease patients, apoptosis appeared not to be involved in muscle pathology.
Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to proteinuria. This study examines the involvement of xanthine oxidase in this process. Xanthine oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d after induction of PHN, and this was associated with increased glomerular superoxide anion generation. Analysis of glomerular samples by Northern and Western blotting revealed no quantitative changes in xanthine oxidoreductase expression in PHN, suggesting conversion of xanthine dehydrogenase to the oxidase form as the cause of increased activity. Treatment of rats with tungsten, an inhibitor of xanthine oxidase, before induction of PHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased proteinuria by 80% (day 12: 423+/-245 mg/d in PHN versus 78+/-53 mg/d in tungsten-treated PHN animals, P < 0.01). These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.
1. Antioxidant and oxidative enzymes were examined in renal glomeruli and proximal tubules of healthy young rats (10-12 weeks old), and results were related to the superoxide anion generation of these tissues. 2. Activities of superoxide dismutases, catalase, and glutathione peroxidase were 3- to 6-fold higher in proximal tubules than in glomeruli. Similarly, enzyme levels and mRNA levels of superoxide dismutases and catalase were significantly higher in proximal tubules. 3. NADH- and NADPH-dependent oxidase activity and xanthine oxidase activity were not different in glomeruli and proximal tubules. 4. Measurements with lucigenin-enhanced chemiluminescence in vital tissues indicated 10-fold higher rates of superoxide anion in glomeruli than in tubules. 5. Compared with the young rats, tubules of 8-month-old rats had significantly higher superoxide anion rates and lower superoxide dismutase activity, whereas NADH- and NADPH-dependent oxidase activities were unchanged. 6. We conclude that considerable differences in the antioxidant-oxidant balance exist between the glomerulus and proximal tubule. Results from experiments using chemiluminescence in vital tissues suggest that changes in the antioxidant-oxidant balance have an effect on oxygen radical levels. The relevance of the observed differences to glomerular and tubulo-interstitial disease remains to be determined, but a greater susceptibility of the glomerulus to oxidant stress might be anticipated.
A large number of PTCA balloon catheters from different manufacturers were examined following their use. Several of these balloons had been previously used for PTCA for the mere purpose of guide wire support. Each balloon was evaluated starting at 8 atm. The pressure was increased in steps of 1 atm until rupture. This stepwise increase of pressure was documented at each level in a short cine film. During dilatations, balloons were in room air until rupture. None of the balloons ruptured before the rated burst pressure. A few of the balloons tolerated pressures of approximately 27 atm. With increasing pressure the shape of the balloons became distorted. Most assumed a banana shape. Most of the balloons ruptured after developing a small hole. Increasing pressure produced increasing diameter, and, generally, we found a linear increase. Most balloons increased by > 15% in diameter over the nominated diameter before rupture. The burst pressure in all balloons was not influenced by the prior mode of dilation, duration of dilation, maximum pressure applied, or length of the balloon. Balloons with smaller diameter ruptured later than compared to those with larger diameters. Our findings demonstrated that all of the balloons tolerated the manufacturers' recommended inflation pressure supporting the safety in their use.
Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromycin aminonucleoside glomerulopathy. In this study, generation of reactive oxygen species was examined directly in glomeruli isolated from rats in the acute phase of puromycin aminonucleoside nephrosis and related to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, reduced creatinine clearances, and typical changes of glomerular morphology were present. Levels of reactive oxygen species were increased eightfold in glomeruli isolated 15 min after puromycin aminonucleoside injection, returned to baseline levels on days 1 and 5 after injection, and rose again to 14-fold on day 9 after injection, as determined by chemiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin and different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in reactive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species. Despite oxidative stress, antioxidant enzymes were not induced in the course of nephrosis. On the contrary, catalase and glutathione peroxidase activities declined 9 d after puromycin aminonucleoside injection. The results indicate that a transient increase in glomerular reactive oxygen species is sufficient to induce the oxidative glomerular injury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.
The water permeability of collecting ducts is greatly increased by the antidiuretic hormone, vasopressin (VP). Freeze-fracture studies were carried out to test if this permeability increase is associated with the appearance of intramembrane particle (IMP) aggregates and whether increased doses of VP lead to an increase in the number and size of particle aggregates in the luminal membrane of principal cells in the isolated cortical collecting duct. Unstimulated cells expressed 17 +/- 6.5 particle aggregates per 100 microns 2. Stimulation with VP at concentrations of 20 or 200 microU/ml increased the number of particle aggregates significantly to 129 +/- 15.8 and 324 +/- 45.8, respectively. The size of the particle aggregates increased from 0.0012 microns 2 under control conditions to 0.025 microns 2 at 20 microU/ml VP and to 0.063 microns 2 at 200 microU/ml VP. In addition, the total area occupied by the IMP increased from 0.02 microns 2/100 microns 2 (controls) to 3.17% and 20.38% (after 20 and 200 microU ADH/ml, respectively). Particle aggregates were also observed in the luminal plasma membrane of isolated collecting ducts fixed immediately after dissection, resembling the in vivo status. These results demonstrate that a dose-dependent relationship exists between the concentration of the applied VP and the number of particle aggregates, as well as the size of the aggregates. Cytoplasmic tubular vesicles in fusion with the apical membrane were observed.
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