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Biomedical subjects

A Pataki

Publications and source records attributed to A Pataki.

At least 19 recordsLinked to original sources

Quantitative radiographic diagnosis of osteo-arthritis of the knee-joint in the C57BL mouse.

Comparative histopathological and radiographic investigations in the C57BL mouse model of spontaneous osteo-arthritis of the knee-joint indicate that there is a relation between quantitative radiographic diagnosis and semiquantitative histopathological diagnosis. Statistical analysis based on a set of quantitative radiographic parameters of the mouse knee-joint shows that the greater part of the radiographic information reflecting the histopathological degree of the osteo-arthritis is contained in the projection areas of the lateral and medial meniscus: progression of the osteo-arthritic process is accompanied with enlargement of the menisci. On the basis of these observations, a radiography score for the osteo-arthritis has been constructed, which consists of a weighted sum of the - suitably transformed - projection areas of the lateral and medial meniscus. In addition to the size of the menisci, the width of the joint space is also a useful quantitative parameter of osteo-arthritis of the mouse knee-joint.

Animals

Spontaneous osteo-arthritis of the knee-joint in C57BL mice receiving chronic oral treatment with NSAID's or prednisone.

In a statistically planned study based on quantitative radiography, treatment for 25-26 weeks with the 2 NSAIDs, diclofenac sodium, or indomethacin (both 0.5 and 1.5 mg/kg p.o. daily), or prednisone (6 mg/kg p.o.) had no influence on the progression of spontaneous osteo-arthritis of the knee-joint of the C57BL mouse, by comparison with placebo-treated controls.

Animals

Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466.

The effects of GYKI 52466, a new 2,3-benzodiazepine with muscle relaxant and anticonvulsant properties, were investigated and compared to those of midazolam in electrophysiological experiments. The effects of the drugs on the reflex potentials evoked by afferent nerve stimulation and recorded from the spinal roots in unanesthetized spinal cats were studied. GYKI 52466 exerted a strong inhibitory effect on the monosynaptic as well as the polysynaptic ventral root reflexes, while the dorsal root responses decreased slightly. In contrast, midazolam markedly enhanced the dorsal root responses, did not modify the monosynaptic reflex and partially inhibited the polysynaptic reflex. The spontaneous firing of cerebellar Purkinje cells was depressed by midazolam, but not by GYKI 52466. These results suggest strongly that, contrary to the classical 1,4-benzodiazepines, potentiation of the GABA-A receptor-mediated inhibition does not play a significant role in the pharmacological actions of GYKI 52466.

Animals

Arthritis induced by continuous infusion of hr-interleukin-1 alpha into the rabbit knee-joint.

Continuous infusion of 200 ng/day hrIL-1 alpha for 14 days into knee-joints of rabbits leads to a severe arthritis of low aggressivity. This arthritis shows simultaneously characteristics of acute (serous and fibrinous exudation, polymorph infiltration, etc.) as well as chronic (synovial cell proliferation and fibrosis, pannus formation, cartilage and bone erosion, etc.) inflammation. The arthritis was associated with a distinct loss of metachromasia of the articular cartilage. These results indicate that IL-1 might play an important role in the induction and maintenance of arthritis.

Animals

Induction of erosive arthritis in mice after passive transfer of anti-type II collagen antibodies.

The passive transfer of concentrated immunoglobulins or affinity-purified anti-collagen antibodies from sera of mice with type II collagen-induced arthritis can induce erosive arthritis in recipient animals. In both cases, the incidence of arthritis was over 60% and the inflammation persisted for at least two weeks. Radiography revealed bone destruction and apposition of a newly formed material while histologic examination showed cartilage and bone degradation, accompanied with synovitis and periarthritis. Inflammatory infiltrates were composed of polymorphonuclear leucocytes and lymphocytes, and were associated with a proliferation of connective tissue cells.

Animals

Qualitative radiographic diagnosis of osteo-arthritis of the knee joint in the C57BL mouse.

Experiments were performed to assess the diagnostic value of radiography in osteo-arthritis (OA) of the knee joint in C57Bl mice. Comparative histological and radiographic examination of knee joints from 96 animals showed that if the classical diagnostic criteria (narrowing of the joint space, sclerosis of the subchondral bone, deformation of the joint epiphyses) are applied, OA is not readily detectable by radiography. If these criteria are extended to include radiographic changes in the menisci (enlargement, deformation, increased and/or heterogeneous density), the frequency of detection is much improved. However, except in the severest forms of OA, radiography does not afford a satisfactory means of distinguishing between various degrees of severity. The qualitatively evaluated data nevertheless do suggest that quantitative radiographic diagnosis of OA of the murine knee joint may be useful, both for improving the detection rate and for discriminating various degrees of OA.

Animals

Arthritis in MRL/LPR mice and in collagen II sensitized DBA-1 mice and their use in pharmacology.

For assessment of anti-arthritic drugs, we used mice of the autoimmune MRL/lpr strain and DBA-1 mice sensitized with collagen type II. Our studies showed that in these two mouse arthritis models, unlike the classical rat adjuvant arthritis, the nonsteroidal antiinflammatory compounds tested were either ineffective or minimally affected a chosen number of humoral parameters and the incidence and severity of arthritis. Interestingly, both arthritis models showed a distinct pharmacological pattern in response to the slow-acting anti-rheumatic drugs, whereas steroids and cyclophosphamide inhibited both arthritic processes. Therefore, these two mouse models are useful for studying the immunopathological events operating in chronic inflammation and could potentially serve the characterization of new antirheumatic drugs.

Animals

Polyarthritis in MRL lpr/lpr mice.

Mice of the inbred strain MRL/MpJ-lpr/lpr are affected by a systemic autoimmune disease and a spontaneously occurring polyarthritis. To characterize the arthritis a histopathological study was performed on the joints of the four limbs and of the spinal column of 7, 16, 22 and 28-week-old animals of both sexes. Polyarthritis, the severity of which increased with age was detected in all mice. Proliferation of the synovial lining cells, already evident in 7-week-old animals, was the initial lesion. In the majority of cases infiltrates containing lymphocytes with a few plasmocytes, histiocytes, polymorphonuclear neutrophils and eosinophils were detected later on. The most pronounced changes were observed in the hind-paws, the fore-paws, the knee and hip joints, paired articulations being symmetrically involved. A pannus was seen at the most in 10% of the joints leading to limited and superficial destruction of the cartilage. Rheumatoid nodules were not seen. From 16 weeks of age deposits of unknown nature, often surrounded by phagocytosing macrophages and/or neutrophils, were observed in the articular and/or extra-articular connective tissue and in the vessels. There was a positive correlation between their presence and the intensity of the arthritis. The articular lesions in our study differ from those in rheumatoid arthritis because they lacked the specific and characteristic histological features of the human disease.

Age Factors

Serum amyloid P component and autoimmune parameters in the assessment of arthritis activity in MRL/lpr/lpr mice.

The concentration of immunoglobulins, anti-ssDNA, anti-dsDNA, anti-TNP antibodies, IgM rheumatoid factor, C3, immune complexes and serum amyloid P component (SAP), in the serum were measured in 68 male and female MRL/lpr/lpr mice, a strain affected with a systemic autoimmune disease. The degree of lymphoproliferation was assessed by the spleen weight. Spontaneous secretion of immunoglobulins and anti dsDNA antibodies were measured in spleen cell cultures. All mice presented age related increases or decreases (C3) in the level of measured parameters. Inflammatory lesions were detected, by light microscopy in the joints of all mice. There was a significant correlation, in both sexes between the serum level of SAP and the severity of the polyarthritis, as assessed by light microscopy. In female mice the levels of anti-dsDNA antibodies, immunoglobulins, either measured in serum or in the spleen compartment, and circulating immune complexes also showed correlation with the activity of the arthritis, but neither of these variables correlated as closely with arthritis scores as did serum SAP.

Age Factors

Age-related histochemical and histological changes in the knee-joint cartilage of C57B1 mice and their significance for the pathogenesis of osteoarthrosis. I. Oxidative enzymes.

For a better understanding of the part played by the aging of cartilage in the pathogenesis ofosteoarthrosis, we attempted to detect functional age-related changes in the knee-joint cartilage of C57B1 mice using histochemical methods and to correlate these changes with the concomitant histological changes. A comparison of 57- and 97-week-old mice revealed a statistically significant age-related focal loss of activity for a number of oxidative enzymes of the chondrocytes. There was an associated significant increase in regressive changes of the chondrocytes. A relation probably exists between these two changes, inasmuch as the focal loss of enzyme activity precedes and possibly gives rise to the regressive changes. A comparison with the changes described in the articular cartilage of other species including man suggests that the phenomena observed are inherent age-related changes. The loss of activity of all the enzymes investigated indicates a far-reaching derangement of cellular metabolism, leading to impaired synthesis of proteoglycans. Since these compounds are major determinants of the physical properties of articular cartilage, the changes described might render the cartilage more vulnerable and might thus play a major part in the pathogenesis of osteoarthrosis.

Aging

[The influence of aging, post-mortem delay until isolation of the tissue and duration of agony on some glycolytic enzymes in human autoptic brain tissue (author's transl)].

The influence of aging and pre- and post-mortem conditions on the activities of glycolytic enzymes and of the ATPases was determined in samples of autoptic human cerebral cortex and putamen. These results were compared with results obtained from an aging collective of rats (four groups ranging from 20 to 120 weeks of age). The results revealed an interlinked significant age-related increase in soluble hexokinase (HK) and a significant decrease in phosphofructokinase (PFK) activity in human autoptic tissue, whereas no significant age-dependent differences could be observed in rat brain. Subdivision of the cases according to duration of agony and other pre-mortem conditions revealed reduced variance and therefore statistically more significant PFK age-dependence in cases with a short agony. All other cases are not dependent on age. In addition to the pre- and post-mortem effects, the age-dependence of PFK and soluble HK can be clearly demonstrated in human autoptic brain tissue.

Adenosine Triphosphatases

Micropreparation techniques in quantitative histochemistry - density gradient centrifugation, manual microdissection and laser microbeam preparation of tissue.

Each quantitative histochemical problem needs its specific method for tissue preparation. In this connection two of the most important preparation methods, density gradient centrifugation and microdissection of freeze-dried tissue slices, are described. Density gradient centrifugation is a very effective procedure for preparative separation of cell particles such as cell nuclei. The details of the preparation of glial and neuronal cell nuclei are described. The in vitro phosphorylation of histone in the chromatin in relation to age is given as a practical example of the quantitative histochemical application to a preparation of cell nuclei. Other techniques of tissue preparation are the manual tissue microdissection according to Lowry and the Laser microbeam preparation. Advantages and disadvantages of both methods are compared. It is shown, that the introduction of Laser microbeam dissection technique, as alternative to manual microdissection, add new dimensions to Lowry's ultramicrochemical methods. One has greater freedom in the choice of the sample size and the number of samples dissected from the same slice. Furthermore, the need for a well-trained person for the preparation is eliminated. The preparation is also considerably less time consuming and easier to perform than the manual free hand preparation. Two quantitative histochemical methods used for the investigation of microdissected tissue samples are described: the gas-chromatography-massfragmentography (GC/MS)-method for determination of transmitters and its metabolites as well as the enzymatic cycling technique of Lowry. The GC/MS-method is explained with an example of noradrenaline and dopamine determination. The enzymatic cycling technique is demonstrated in combination with the Oil-Well-Technique for determination of the NADP-cycle.

Cell Fractionation

Enzyme histochemistry of rat folic acid nephropathy.

One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently.

Acid Phosphatase

The relevance of drug-induced organ pigmentation in animals.

Postmortem examination of animals from long-term safety evaluation studies often reveals pigment deposition in tissues. A review of several such observations is given and the possible chemical backgrounds of their origin are described, in an attempt to aid the determination of relevance in individual cases. It is suggested that one may be fairly broad-minded in the interpretation of the relevance of such pigments, especially if they are found only in one species, and have no influence on the function of the organs involved. A final answer comes only after administration of the particular drug to man, although he is normally dosed at all events one should not overvalue the relevance of pigmentation found in long-term animal studies.

Animals

The automation of microspectrophotometry of tissue sections.

A system for quantitative microspectrophotometry with automatic data acquisition is described. It is relatively simple and less expensive than presently-available equipment. Fitted with the appropriate software, the system permits various types of probe selection, with both selection and measurement made under individual optimal conditions.

Computers

Histochemical study of monoamine oxidase latency in the liver of the rat.

In a histochemical test system with adrenaline as substrate and nitroblue tetrazolium (NBT) as electron acceptor, an increase of NBT reduction in rat liver sections was found microspectrophotometrically following short hypotonic treatment. Investigations with iproniazide, a monoamine oxidase inhibitor, and non-enzymatic NBT reduction showed that the increased formazan formation was related to the presence of monoamine oxidase. It is suggested that the reason for the observed increase of formazan formation is due to increased permeability of the inner mitochondrial membrane to NBT. Consequently, the increase of monoamine oxidase observed in the histochemical test system does not represent mobilization of a latent activity, but rather complete assessment of activity that is normally present.

Animals