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Biomedical subjects

A Leövey

Publications and source records attributed to A Leövey.

At least 19 recordsLinked to original sources

Superoxide anion production and intracellular free calcium levels in resting and stimulated polymorphonuclear leukocytes obtained from healthy and arteriosclerotic subjects of various ages.

It has been established that phagocytic cells are integral components of advanced arteriosclerotic plaques but their role in plaque formation remains unclear. Therefore, toxic agents, such as superoxide anion produced by polymorphonuclear leukocytes (PMNLs) were studied in a clinically defined group of arteriosclerotic patients suffering from obliterative arteriosclerosis of the lower legs. Owing to a close correlation between O2- generation and calcium, the intracellular free calcium concentrations of PMNLs were measured in a resting state and after stimulation with various agents, for example, opsonized zymosan (OZ), the chemotactic peptide f-met-leu-phe (FMLP), and the calcium ionophore A23187. Healthy aged-matched controls were employed. The patients were divided into two age groups: 30-59 years and 60-80 years. We found that in the younger group of arteriosclerotic patients, superoxide anion production and intracellular free calcium concentrations were increased even in the resting state, and only a slight increase was observed after stimulation compared with healthy controls. Granulocyte responses seemed to be similar, independent of the patient's age, to those found in healthy elderly subjects. Arteriosclerosis appears to be associated with an early aging process expressing marked alterations that are greater than those associated with normal aging.

Adult

Lymphocytes resided in the thyroid are the main source of TSH-receptor antibodies in Basedow's-Graves' disease?

The source of TSH-receptor antibodies (TRAb) in Basedow's-Graves' disease is still under debate. Previous studies by other groups had found TRAb levels in the thyroid vein higher than or equal to that in the peripheral vein. The aim of the present work was to investigate the suspected presence of this TRAb gradient in 14 Graves' patients who underwent surgery. Interestingly, in 6 patients higher levels of TRAb were measured in the antecubital vein when compared to the thyroid vein, in another 6 there was no gradient and 2 exhibited higher TRAb levels in their thyroid veins. A clear gradient of thyroid hormones in favour of the thyroid vein was also present, while no gradient of TSH, anti-thyreoglobulin and anti-microsomal antibodies, total IgG, IgA and IgM levels and no differences of the CD4+/CD8+ cell ratios were found between the two sampling sites. We conclude that cells other than lymphocytes residing in the thyroid gland must also be involved in TRAb production.

Adult

Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages.

Serum and granulocyte elastase-type protease activities were determined simultaneously with their main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic (ATS) subjects. The age-related associations of these parameters were also investigated. Serum elastase-type protease activity increased, but not statistically significantly, with aging in both control and ATS subjects. The enhancement of elastase-type protease activity in sera of ATS patients was significantly (p less than .02) greater than control subjects only in the case of the elderly. The granulocytes' elastase activity was significantly greater in granulocytes derived from both middle-aged and elderly ATS patients (p less than .03 and p less than .06) compared to age-matched control subjects. Alpha-1-antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was significantly lower in sera of ATS subjects compared to age-matched control subjects (p less than .01). The conclusion is that increased elastase-type activity and decreased antiproteinase activity should be considered as potential factors in atherosclerotic arterial wall damage. The similarity of the results in the elderly and the ATS subjects suggest that atherosclerosis is an early aging process.

Adult

Sera but not immunoglobulins of ophthalmic Graves' patients stimulate human embryonal fibroblasts' biosynthetic activity in culture.

The retroocular connective tissue changes in the ophthalmopathy of Graves' disease are known, however, the mechanism which leads to the increase in fibroblast number and activity is poorly understood. Using human embryonal fibroblast monolayers, fibroblast biosynthetic activity in the presence of sera, immunoglobulin deprived sera or immunoglobulins of Graves' patients with and without ophthalmopathy has been measured. Both sera and immunoglobulin deprived sera of the ophthalmic Graves' patients caused a marked increase of protein synthesis and a moderate increase of the sulphated glycosaminoglycan synthesis of fibroblasts. The same stimulatory effect was not found when immunoglobulin in fetal calf serum was used instead of sera, though anti-fibroblast IgG-s were present both in the sera and separated immunoglobulin fractions, as it has been demonstrated in an ELISA system. We conclude that the sera of ophthalmic Graves' patients contains a factor which stimulates human embryonal fibroblasts' biosynthetic activity in culture; this factor is not an immunoglobulin. The system described here seems to be suitable for studying the accompanying connective tissue changes in Graves' disease.

Cells, Cultured

Body composition in hypertensive elderly and middle-aged patients.

The occurrence of hypertension, leading to various life-threatening complications in the elderly is a widely recognized problem. The changes of body composition were determined in 120 control and untreated hypertensive subjects of various ages. In middle-aged hypertensive males, the total blood volume and plasma volume increased significantly compared to those of the healthy controls, while this increase was not significant in the case of hypertensive middle-aged females. In contrast, in the elderly hypertensive male subjects, the volume of all fluid components decreased, except the total body fat and the vascular volumes. There was a slight, statistically non-significant, increase in all the vascular volumes except in the red cell mass. The elderly hypertensive females showed the same tendency compared to the healthy controls of the same age. The vascular compartments seem to be decreased in elderly males, compared to those of the middle-aged males, while slightly increased in elderly females.

Adipose Tissue

Atypical clinical features of hypo- and hyperthyroidism in elderly age.

The clinical features of senile hypothyroidism and hyperthyroidism differ from the general characteristics of these conditions. This may be explained primarily by the changed response of peripheral tissues to thyroid hormones. Because of the atypical clinical symptoms the recognition of these conditions meets difficulties and, in general, occurs late. Therapy raises further special questions considering primarily cardiac complications and other accompanying diseases (for instance arteriosclerosis, osteoporosis, diabetes mellitus.). The authors analyse data of 171 hypothyroid and 219 hyperthyroid patients as a function of age, primary disease, and the most often occurring impulse generation, impulse conduction disorders.

Aged

[Two cases of hyperthyroidism and ophthalmopathy following hypothyroidism].

Two cases of Graves' disease emerging in previously hypothyroid patients are described. After two years of thyroid hormone substitution due to 'idiopathic' hypothyreosis (patient 1) and Hashimoto's thyroiditis (patient 2), the substitution had to be stopped. The persisting clinical and laboratory signs of immune hyperthyreosis, including positivity for TBII and TSAb, were accompanied by the signs of mild ophthalmopathy. The antibody-spectrum changes during the course of the disease are discussed.

Adult

Altered phosphatidylinositol breakdown after K-elastin stimulation in PMNLs of elderly.

The degradation of elastic fibres during atherosclerotic plaque formation in arterial wall is a well known process. The liberated elastin peptides such as K-elastin possess various biological activities: They are chemotactic for monocytes and fibroblasts, stimulate the oxidative burst and the intracellular free Ca2+ mobilisation through the phosphatidylinositol (PIP2) breakdown in PMNLs. It was found that the PIP2 breakdown induced by K-elastin is a pertussis toxin sensitive process in PMNLs of young subjects. In the case of the elderly, the K-elastin-induced oxidative burst, intracellular free Ca2+ elevation was less than in young, and could not be inhibited by pertussis toxin. Studying the K-elastin-induced inositol phosphate (IP) formation in PMNLs of elderly a disturbed PIP2 breakdown was found. K-elastin stimulated the IP formation at a very low level in PMNLs of elderly. This alteration of the second messenger formation (e.g. IP3 and Ca2+) after KE stimulation, might be the consequence of their originally elevated levels in resting PMNLs of elderly.

Age Factors

Disturbed intracellular calcium-related processes of hepatocytes and neutrophils in human alcoholic liver disease.

Isolated human hepatocytes and separated neutrophils of 11 patients with alcoholic liver disease (ALD) were used to study some aspects of cellular calcium-related processes compared to nonalcoholic controls. 45Ca2+ efflux from the cells decreased in ALD and the calmodulin-inhibitor trifluoperazine did not influence it further. The intracellular free calcium concentration [( Ca2+]i) of nonstimulated hepatocytes and neutrophils proved to be higher in ALD with the Quin2/AM loading technique. However, the [Ca2+]i rise in hepatocytes and neutrophils, with stimulation by low density lipoprotein (LDL) and N-formyl-methionyl-leucyl phenylalanine (FMLP), respectively, was diminished in ALD compared to appropriate controls. The slower 45Ca2+ extrusion rate, higher basal [Ca2+]i levels, and the diminished [Ca2+]i elevation of activated hepatocytes and neutrophils, suggest disturbed calcium-related intracellular processes in ALD, in particular, impaired regulation of the plasma membrane Ca2(+)-ATPase.

Adult

Cell surface markers, inositol phosphate levels and membrane potential of lymphocytes from young and old human patients.

It is well known that most physiological functions change with aging, including the immune response. Data concerning the aging of lymphocyte subpopulations are conflicting. The antigen density of peripheral blood lymphocytes has been determined by fluorescently tagged OKT-3, OKT-4, OKT-8, OKT-11 and OKM1 monoclonal antibodies in a carefully selected aged (over 87 years) population, and compared to that of young subjects. A substantial difference was found in the percentage distribution of OKT8 and OKM1 subsets. The volume of lymphocytes of the elderly population was significantly less than that of the young. The effect of various monoclonal antibodies on phosphatidylinositol breakdown has also been studied. It was found that only OKT3, acting through the CD3 antigen receptor, was able to induce inositol phosphate formation in both young and elderly, although in the latter population this occurred at a lower level. Because the plasma membrane plays a regulatory role in this process, an important and sensitive functional parameter, the membrane potential, was also monitored and influenced by changing the extracellular K+ concentration. The lymphocytes of the elderly population responded less sensitively to changes in extracellular potassium concentration.

Adult

Incidence of rhythm disorders in hyperthyrosis with special respect of old age form.

Sinus tachycardia and atrial fibrillation are frequent features in hyperthyrosis while sinus node dysfunction is regarded as a rare complication. Bradycardia may cause diagnostic problems mainly in atypical hyperthyrosis of the old age. The authors analysed distribution and age related association of the rhythm disorders in hyperthyrosis. In case of the appearance of Sick Sinus Syndrome (SSS), parameters representing the function of sinus node were studied by electrophysiological investigations. Above the age of 50 years incidences of atrial fibrillation and SSS were significantly increased. The abnormal sinus node function proved to be reversible in a portion of the cases. In old age, in case of occurrence of the symptoms of SSS, possibility of hyperthyrosis also should be considered, especially when indication of permanent pacemaker is established.

Adult

[Bone scintigraphy in uremic osteodystrophy].

99mTc-HEDP bone scan was carried out on 12 long-time haemodialysed patients, suffering from bone pains. X-ray examinations of the bone and laboratory tests (serum calcium, -phosphor, -alkaline phosphatase, -parathormone, -aluminium, -ferritin) were also performed. The scintigrams were evaluated by two semiquantitative scores. Based on diffuse, increased radiopharmacon uptake of the bones and more than five points in the Fogelman score 5 patients most likely had serious and 3 had moderate hyperparathyroidism. In two patients osteomalacy was presumed based on decreased radiopharmacon uptake of the bones, increased uptake of the soft tissues and zero Fogelman score. Mixed or other bone disease was suggested in two other patients. Good correlation was found between the results of bone scans, the parathormone values and the results of histology obtained after parathyreoidectomy of 4 patients and autopsy of two others. This non-invasive examination (ie. bone scan) is helpful in differential diagnosis of uraemic osteodystrophy and its wide use is proposed in domestic nephrological practice.

Adult

Age related impairment in phosphatidylinositol breakdown of polymorphonuclear granulocytes.

It is well known that with aging the immune response decreases. Most of the effector functions occur through specific receptors. Thus, we investigated the effects of various stimulants, acting through receptors or directly through the GTP-binding Gi protein, on phosphatidylinositol breakdown in PMNLs of young and elderly subjects and try to modulate it. A marked decrease in inositol phosphate (IP1, IP2, IP3) formation in PMNLs of elderly was found under FMLP stimulation when compared to that of young subjects. Neither GTP gamma S, nor AIF4- could induce an increase of IP3 in PMNLs of elderly comparable to that of young subjects. The results suggest that at least an alteration exists at the GTP-binding Gi protein level, as well as in the mechanism of linkage of the receptor to the G protein.

Adult

Blood laboratory parameters of carefully selected healthy elderly people.

Hematological and biochemical parameters were measured in carefully selected healthy elderly (50 males and 50 females, aged 60-97 years) and young (10 males and 10 females, aged 18-23 years) populations. Most of the parameters measured did not show any age-related variations. It means that any deviation from the present normal ranges established for healthy young subjects should be considered as pathologic in the case of elderly, too. Some parameters showed age-specific changes and hence there is a possibility that their actual normal ranges might be extended towards the upper limit (globulin, IgG, IgA, CIC, C3, BUN, AP for females), or towards the lower limit (creatinine clearance, albumin). Verification of these modifications may indicate that a lot of unnecessary investigations in the case of elderly could be avoided.

Adolescent

Euthyroid infiltrative ophthalmopathy: clinical-immunological characteristics.

The thyroid hormone titres of the sera of 25 euthyroid infiltrative ophthalmopathic patients was examined, TRH test was performed, and thyroid-stimulating antibodies were studied by membrane receptor assay and TRAK assay. Previously, other diseases causing exophthalmos could be excluded by ophthalmological, radiological examinations, orbital ultrasonography and/or CT. Following TRH administration, 18 out of 25 patients showed abnormal TSH response, 16 of them were TSI - positive. Five of them became hyperthyroid 2-2.5 years later. After TRH administration 7 patients produced normal TSH response, none of them became hyperthyroid in the subsequent 2-4 years follow-up period. In the 7 TRH-negative patients, four were found to have higher hTG and an antithyroid microsome antibody titre. In those patients the fine needle biopsy verified chronic lymphocytic thyroiditis. In three patients there was no evidence of a pathological change of the thyroid gland. Based on our results, the patients could be divided into three groups. The prognostic and therapeutic differentiation of these groups seems to be justified.

Adult

Detectability of thyroid anti-microsomal antibodies, changes in thyroid-stimulating immunoglobulins (TSI) and thyrotropin-binding-inhibiting immunoglobulins (TBII) during methimazole treatment of Graves' disease patients.

The prognostic value of determination of different antibodies in Graves' disease patients is questionable. The authors simultaneously assessed the generation of cAMP, the TSH-receptor binding inhibitory assay and the detectability of anti-microsomal antibodies by indirect immuno-fluorescence. The tests were performed before, during and after methimazole treatment. During a 12 months' medication all 22 patients became euthyroid. Six months after withdrawal of the drug, 15 patients were still euthyroid (Group A); 7 relapsed (Group B). Patients showing enhanced activities by all three methods, relapsed (5 out of 7 cases of Group B). The results indicate that simultaneous determination of TSI, TBII and anti-microsomal antibodies are of high prognostic value for relapses. These data should be taken into consideration for the further therapy.

Autoantibodies

A non-isotopic screening test for antibodies to TSH receptor: dot immunobinding assay.

A dot immunobinding assay (DIBA) for thyrotropin (TSH) receptor antibodies is described. The method depends on the detection of antibody binding to highly purified thyroid plasma membrane attached to nitrocellulose solid support by horse-radish peroxidase - conjugated anti-human IgG. The method can detect down to 0.75 mU LATS standard and 1/1000 dilution of Graves' serum or immunoglobulin fraction. The interaction is inhibited dose-dependently by bTSH but not by insulin or human chorionic gonadotropin. The DIBA results show close correlation to those of TRAK (TBII) but not to cyclic AMP generation assay. DIBA is reproducible when tested monthly for 4 months. Sera and immunoglobulins gave virtually the same results. The method has a sensitivity of 90%, validity of 90% and specificity of 80% for both. We have, thus developed a sensitive and reliable method for screening for TSH receptor antibodies which can be performed in routine clinical laboratories.

Animals