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Biomedical subjects

A Leövey

Publications and source records attributed to A Leövey.

At least 19 recordsLinked to original sources

[Current diagnostic method, prognosis estimation and therapy of papillary thyroid cancer: recommendations of the medical universities and the National Oncologic Institute of Budapest].

Physical examination, cervical ultrasonography (US) and aspiration cytology are the mainstays of the preoperative diagnostics of papillary thyroid carcinoma. For the staging of suspected malignant cases, cervical and mediastinal CT (MRI for inconclusive results) is indicated before any surgery. The end-result of primary treatment is assessed by total-body iodine scintigraphy and the serum human thyroglobulin (hTG) level. For long-term follow-up, physical examination and the serum hTG level are the most reliable tools (6-monthly), supplemented by cervical US and chest X-ray (yearly), and total-body iodine scintigraphy (2-yearly). If these furnish positive results, further examinations may be indicated. In suspected relapses of hTG non-producing and iodine non-accumulating papillary carcinomas, 201thallium chloride or 99mTc-sesta-MIBI (methoxy-isobutyl-isonitrile) scintigraphy, and positron emission tomography with 18fluoro-deoxyglucose or 11C-methionine may be of help. For estimation of the prognosis (cause-specific survival) of the patients, the MACIS score system of the Mayo Clinic is widely accepted, the patients being divided into low-risk and intermediate/high-risk categories. The recommended standard surgical intervention is near-total thyroidectomy (2-4 g residual glandular tissue left at the upper pole of the less-involved lobe), with a central cervical lymph node dissection for diagnostic purposes. In cases of lymph node dissemination, dissection (radical, modified radical, selective or microdissection) of any of the involved compartments (central, right or left cervical, or upper mediastinal) is indicated for therapeutic reasons, the method of which is depending on the extent of the metastatic involvement. Following adequate surgical intervention, no adjuvant radioiodine therapy is indicated for low-risk cases with a tumour of less than 1 cm diameter. For other low-risk or intermediate/high-risk patients, radioiodine ablation (R0N0M0) or a therapeutic radioiodine dosage (R2N1M1) is indicated. In cases at high-risk of local/regional relapse and in radioiodine non-accumulating tumorous cases, external radiotherapy may be applied. Thyroid hormone medication in a TSH suppressive dose is indicated during the first 5 postsurgical years: the goal is to achieve a TSH level below 0.1 (determined by a 3rd generation assay). If no relapse occurs or the case is a low-risk one, following the 5 years, it is enough to maintain the TSH level in a subnormal range (0.1-0.3).

Carcinoma, Papillary

Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G.

OBJECTIVE: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN: Following stimulation with TSI, the level of inositol trisphosphate (IP3) and [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS: Seven out of eleven TSI samples activated PTC through IP3 generation, elevated [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [14C]AA derivates (however, one of the samples was also able to take up Ca2+ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Adult

[Intracellular signal transmission of low density lipoprotein receptors in human monocytes].

The authors found that in human monocytes administered low density lipoprotein in doses of 50 micrograms had optimal inhibition of endogenous cholesterol synthesis which measured by [14C] acetate incorporation. There was not effect of pertussis toxin and phorbol myristate acetate on the inhibiton of endogenous cholesterol synthesis, whereas calcium channel blocker verapamil and phospholipase A2-inhibitor chloroquine decreased it. In contrast, the protein kinase C-stimulant phorbol myristate acetate alone had effects as LDL, but the protein kinase C-inhibitor H-7 had antagonist effect against LDL. Inositol phosphate generation was induced by administration of LDL in doses of 50 micrograms, which was pertussis toxin insensitive. The calcium signal was not also pertussis toxin sensitive, while occurred an intensive protein kinase C activation by administration of LDL. In signal transduction of monocytes activated by LDL may be an important role of the opening of calcium channels and activation of two enzymes, such as phospholipase A2 and protein kinase C.

Calcium Channel Blockers

Treatment possibility of hypercholesterolaemia associated with hypertriglyceridaemia.

Thirty patients were investigated with hyperlipoproteinaemia, 15 patients with non-insulin dependent diabetes mellitus (NIDDM) and 15 with primary hyperlipoproteinaemia. The patients took 250 mg acipimox (5-metyl-pyrazine-carboxylic acid 4-oxide) 3 times per day for 2 months. Serum examinations were performed before and after 1 and 2 months of acipimox administration. After treatment the cholesterol and triglyceride levels decreased in both groups. Patients with NIDDM had 11% increase of high density lipoprotein-cholesterol (HDL-C) level at the end of the first, and 18% increase at the end of the second month, while patients with primary hyperlipoproteinaemia did not change significantly. The low density lipoprotein (LDL) level did not change significantly in either groups of patients. The apolipoprotein A 1 (apo A 1) levels increased significantly during the second month of acipimox administration. Uric acid levels decreased in both groups, but significant change could be detected mainly in the NIDDM group. Serum glucose level did not change in the non-diabetic patients, while it decreased significantly in the NIDDM group.

Apolipoprotein A-I

[Molecular biology of thyroid diseases].

Recent developments in molecular biology and the accessibility of techniques for clinical research have led to a better understanding of the background of common thyroid diseases. The cloning and sequencing of the thyroid stimulating hormone receptor, thyroid peroxidase and thyroglobulin, and the characterization of the protein-DNA interaction during thyroid hormone action, as well as the discovery of intracellular signal transduction pathways were the most important steps which resulted in new diagnostic and therapeutic approaches. New explanations of thyroid autoimmune processes are being investigated.

Genes, Tumor Suppressor

Parameters of respiratory burst and arachidonic acid metabolism in polymorphonuclear granulocytes from patients with various thyroid diseases.

The oxidative processes (oxygen consumption, superoxoid anion generation, arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained from patients suffering from thyroid disorders of autoimmune origin (Graves' disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma) were investigated. All Graves' and toxic adenoma patients were hyperthyroid. Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched volunteers served as controls. The results are as follows: 1) In PMNs from both hyperthyroid groups (Graves' disease and toxic adenoma), independently from the autoimmune origin of the disease, a significantly increased Antimycin A sensitive mitochondrial oxygen consumption and a slightly increased superoxide anion generation were detected. 2) In both autoimmune thyroid disease groups (Graves' disease and Hashimoto's thyroiditis)--depending on the functional state of the thyroid gland--a significantly altered intracellular killing activity was measured. 3) An increased arachidonic acid cascade--triggered by opsonized zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin treatment. 4) The PMNs from both autoimmune thyroid diseases produced large amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc receptors but the synthesis of prostagalandins (PGs) has not changed. There are no data indicating local, specific effects of circulating leukotriens in the thyroid gland itself, but based on authors' data, their general, regulating role on both the endocrine-- as well as on the immune system--seems to be plausible.

Adenoma

[Clinical significance of nodular goiter].

The clinical characteristics of nodular goitres: relatively frequent (4-7%), diagnostic difficulties deriving from heterogeneity as well as the marked difference of treatment and prognosis. In the case of nodules the possibility of malignancy must always be considered, though the incidence is less than 5%. The pathogenesis of multinodular goitres has been discussed and the different endogen and exogen factors which are important in the development of autonomies. The different diagnostic possibilities, especially the fine-needle biopsy, ultrasonography and thyroid scan examinations have been made known. Besides treatment of toxic and non-toxic multinodular goitres as well as toxic adenoma and the practical tasks according to cold and hot nodules has been discussed.

Age Factors

Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes.

The granulocyte-macrophage colony stimulating factor (GM-CSF) is an important in vivo regulator of granulopoiesis and neutrophil functions. It is well-known that the immune response and the transmembrane signalling in immune cells change with aging. We wished to elucidate the effects of GM-CSF in itself and in priming the activities of other inflammatory agents on neutrophils of elderly persons. Neutrophils of 20 healthy elderly (aged 60-90 years) and 20 healthy young (aged 20-25 years) subjects were studied for superoxide anion production, intracellular free calcium mobilization, antibody dependent cellular cytotoxicity (ADCC) and intracellular killing activities. It was found that GM-CSF is unable to prime neutrophils of elderly subjects to the action of FMLP, metenkephalin or opsonized zymosan. By the use of Pertussis toxin and H7 it was demonstrated that a different signal transduction pathway in neutrophils of elderly subjects is activated by GM-CSF or FMLP if compared to that of young subjects. These results suggest that the lack of priming could contribute to the greater susceptibility of the elderly to infections and that the change of the signal transduction mechanism in neutrophils of elderly subjects might partly explain this phenomenon.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

[Definition and clinical importance of thyroiditis].

Regarding the different forms of thyroiditis our knowledge has so significantly grown in the last two decades that their clinical importance has been reevaluated. To-day they are ranged among the most often endocrinological disorders. Namely, it became obvious that the most often causes of the temporary hyper- and hypothyroidism are the most recent recognized forms of subacute thyroiditis, and that producing of permanent hypothyroidism the postpartum form also joined with Hashimoto's thyroiditis as the most often endogenous aetiological factor. The most accepted classification of the large group of thyroiditis is the following: acute, subacute and chronic forms. Beyond these rigorous frames of terminology the individual forms overstep the conventional boundaries relating to time, histology and clinical symptoms; they can overlap of follow each other, even they can appear together at the same time. These can be better understood and explained by the disturbance of immunoregulation, which is detectable or supposed in the majority of discussed disorders. The diagnostic and therapeutical characteristics of different forms of thyroiditis have been made known.

Acute Disease

[Effect of acipimox on diabetes mellitus-associated hyperlipoproteinemia].

The authors give summary on the pathogenesis of hyperlipoproteinaemia in patients with diabetes mellitus. They investigated the effects of acid nicotinic derivate acipimox on lipid metabolism in these patients. They treated with acipimox 15 patients who suffered from non-insulin-dependent diabetes mellitus, as well as II/B, IV type hyperlipoproteinaemia by Fredrickson. They investigated the effect of acipimox on the lipoprotein content and quality in the sera and uric acid and carbohydrate metabolism. The authors found decreased cholesterol, triglyceride, apolipoprotein-B, glycosilated haemoglobin, glucose and uric acid levels in the sera and they found that the atherogenic index decreased too. During the treatment they could not recognise a change in the low-density lipoprotein level of the sera while the high density lipoprotein and apo-A1 level increased.

Adult

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