Biomedical subjects

M Tóth

Publications and source records attributed to M Tóth.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Adrenomedullin under physiologic and pathologic conditions].

Adrenomedullin (AM) is a novel 52-aminoacid-peptide hormone, originally isolated from human phaeocromocytoma. Adrenomedullin acts as a local autocrine and/or paracrine vasoactive hormone and has vasodilator and blood lowering properties, but its exact role is still uncertain. Adrenomedullin is considered to play an important endocrine role in various tissues maintaining the electrolyte and fluid homeostasis. Its normal plasma concentration is low. In hypertension, chronic renal failure and congestive heart failure its plasma concentration increases parallel to the seriousness of the disease. It is assumed that this peptide may be important under pathologic conditions compensating the effects of the vasoconstrictor molecules. Till now, investigations have proved that in diabetic angiopathies the levels and the production of vasoconstrictor factors and adrenomedullin were increased, while, those of other relaxing substances including nitrogenoxid were decreased. It is still uncertain whether increased release of adrenomedullin in diabetes is a compensatory mechanism or a coincidental event. Although, the precise role of adrenomedullin in the pathogenesis of diabetic complications is still to be elucidated, the elevated concentration of adrenomedullin in diabetes--which influences the vascular functions--let us speculate that there might be a certain interaction between adrenomedullin induction and vascular functions in diabetes. Thus, the induction of vascular adrenomedullin could be a new target of a therapeutic approach to the diabetic complications.

Adrenomedullin↗

PubMed2001

[Significance of trypsinogen gene mutations in the etiology of hereditary pancreatitis].

Hereditary, chronic pancreatitis is an autosomal dominant genetic disorder, frequently associated with two point mutations in the cationic trypsinogen gene. The mutations result in characteristic changes in the amino-acid sequence of trypsinogen: an arginine residue at position 117 is changed to histidine (Arg117-->His) or an asparagine residue at position 21 is replaced by isoleucine (Asn21-->Ile). Current opinion on the pathogenesis of hereditary pancreatitis suggests that the mutations lead to increased trypsin activity in the pancreatic tissue as a result of enhanced autoactivation of trypsinogen or decreased autocatalytic degradation (autolysis) of trypsin. To investigate the relationship between the altered properties of mutant trypsinogens and the pathomechanism of pancreatitis, wild-type and two mutant forms of recombinant human cationic trypsinogen were produced and autoactivation of trypsinogens and autolysis of trypsins were studied. The results indicate that trypsin stabilization (i.e. decreased autolysis) caused by the Arg117-->His mutation may contribute to the development of pancreatitis, however, the Asn21-->Ile mutation has no such effect. In contrast, enhanced autoactivation of mutant trypsinogens may contribute to the pathogenesis of both forms of hereditary pancreatitis. This notion is strongly supported by the clear correlation between the autoactivation rates of mutant trypsinogens and the severity of clinical symptoms.

Arginine↗

PubMed2001

Allelic variation at the interleukin 1beta gene is associated with decreased bone mass in patients with inflammatory bowel diseases.

BACKGROUND: Interleukin 1beta (IL-1beta) and its natural antagonist have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Both cytokines influence bone formation. IL-1beta stimulates osteoclast activity while interleukin 1 receptor antagonist (IL-1ra) enhances bone formation. AIMS: To determine whether the decreased bone mass in IBD is related to gene polymorphisms coding for IL-1beta and IL-1ra, and thus identify patients with an increased risk. METHODS: Bone mineral densitometry was performed at the femoral neck, lumbar spine, and the distal third of the radius in 75 IBD patients (34 men/41 women; 40.3 (1.6) years) and in 58 healthy controls (HC; 28 men/30 women; 32.4 (1.2) years). Values were correlated with the TaqI and AvaI gene polymorphisms in the IL1B and the variable number of tandem repeats gene polymorphism in the IL1RN gene. RESULTS: In IBD patients, but not in HC, carriers of allele 2 at the AvaI gene polymorphism (IL1B-511*2) had significantly lower Z scores at the lumbar spine (-0.82 (0.13) v -0.29 (0.21) p=0.03) and the femoral neck (-0.59 (0.14) v 0.15 (0.19); p=0.003) than non-carriers. These patients also had a higher risk for osteopenia or osteoporosis at the femoral neck (odds ratio 3.63 (95% confidence interval 0.95-13.93)). No association was found between bone mass and the other gene polymorphisms analysed in IBD patients or in HC. CONCLUSIONS: Our results suggest that genetic variability may be a major determinant of bone loss in IBD. Carriers of IL1B-511*2, who are hypersecretors of IL-1beta, have a higher risk of presenting with low bone mass in IBD. Screening for this allele may contribute to determination of the risk of bone loss at the time of disease onset.

Absorptiometry, Photon↗

PubMed2001

Factors derived from adrenals are required for activation of cardiac gene expression in angiotensin II-induced hypertension.

The mechanisms mediating the activation of cardiac gene expression during pressure overload are not fully understood. We examined whether angiotensin II-induced activation of ventricular gene expression is related to blood pressure and ventricular mass or requires other factors by infusing angiotensin II in sham-operated and adrenalectomized rats. In sham-operated rats, angiotensin II (33 microg/kg x h, sc) produced a significant increase in mean arterial pressure (measured by telemetry) within 3 h. Mean arterial pressure (up to 45 h) and the increase in left ventricular hypertrophy in adrenalectomized rats during angiotensin II infusion were similar to those in sham-operated rats. Angiotensin II produced 3.6-fold (P < 0.01) and 20.4-fold (P < 0.001) increases in ventricular atrial natriuretic peptide mRNA levels at 12 and 72 h, respectively. Angiotensin II infusion for 12 h also significantly increased the ventricular mRNA levels of B-type natriuretic peptide (5.2-fold) and adrenomedullin (1.4-fold). Adrenalectomy either abolished (atrial natriuretic peptide and adrenomedullin) or blunted (B-type natriuretic peptide) the early activation of ventricular gene expression by angiotensin II. The baseline synthesis of atrial natriuretic peptide, B-type natriuretic peptide, and adrenomedullin in the ventricle remained unchanged in adrenalectomized rats. In conclusion, our results indicate that factors derived from the adrenals are required for angiotensin II-induced early activation of cardiac gene expression.

Adrenal Glands↗

PubMed2000

[Celiac disease today: review of the growing knowledge].

Coeliac disease is the most common disorder with malabsorption of the small intestine, caused by the gluten fraction of cereals in genetically predisposed individuals. T-cell mediated autoimmune processes are initiated by gluten exposure, leading to both intestinal and extraintestinal manifestations, therefore coeliac disease is nowadays considered to be a systemic disorder. More and more diseases are proved to be associated with coeliac disease, in these conditions screening is strongly recommended. The studying of the recently explored autoantibodies against tissue transglutaminase brought us further in the understanding of the pathophysiology of coeliac disease. The spreading of reliable serologic methods modified our knowledge on the clinical picture and prevalence of the disease. In case of long-term dietary abuse the most common complications are decreased bone mineral density and development of lymphomas. Sustained glutenfree diet results in clinical and histological restitution, affects the course of associating diseases beneficially and decreases the risk for malignancies.

Celiac Disease↗

PubMed2000

Gain-of-function mutations associated with hereditary pancreatitis enhance autoactivation of human cationic trypsinogen.

Hereditary pancreatitis (HP), an autosomal dominant disorder, has been associated with mutations in the cationic trypsinogen gene. Here we demonstrate that the two most frequent HP mutations, Arg117 --> His and Asn21 --> Ile, significantly enhance autoactivation of human cationic trypsinogen in vitro, in a manner that correlates with the severity of clinical symptoms in HP. In addition, mutation Arg117 --> His inhibits autocatalytic inactivation of trypsin, while mutation Asn21 --> Ile has no such effect. The findings strongly argue that increased trypsinogen activation in the pancreas is the common initiating step in both forms of HP, whereas trypsin stabilization might also contribute to HP associated with the Arg117 --> His mutation.

Catalysis↗

PubMed2000

[Effects of growth hormone replacement therapy in adults with severe growth hormone deficiency].

UNLABELLED: The aim of the study was to analyse the effects of GH replacement therapy (1 year duration) on body composition, carbohydrate metabolism, thyroid hormone metabolism and bone mineral density in 8 adults with growth hormone deficiency (5 women, 3 men; mean age 40 years). Mean maintenance dose of GH was 1.5 IU/day-1.76 IU/day for women and 1.07 IU/day for men, respectively--determined according to individual patient requirements. Serum insulin-like growth factor-I standard deviation score increased from -5.4 to 0.0 (p < 0.001). There was a significant negative relationship between serum insulin-like growth factor-I standard deviation score at the start of therapy and the increase in this score (r = -0.85; p < 0.05). The waist:hip ratio decreased after 12 months by 0.039 (p < 0.05). The glycosylated hemoglobin increased (4.43 +/- 0.56% vs. 5.86 +/- 0.27; p < 0.05), and a negative correlation of the baseline glycosylated hemoglobin to the glycosylated hemoglobin increase was found (r = -0.88; p < 0.01). Both the free triiodothyronine and free triiodothyronine:free thyroxine ratio increased (3.09 +/- 0.22 vs. 4.17 +/- 0.40; p < 0.05, and 0.234 +/- 0.02 vs. 0.324 +/- 0.04; p < 0.01), and a positive relationship was observed between this ratio at the start of therapy and the increase in the ratio (r = 0.76, p < 0.05). The bone mineral density of lumbar spine and femoral neck expressed as z-score increased (-1.18 +/- 0.56 vs. -0.75 +/- 0.48; p < 0.01 and -0.06 +/- 0.60 vs. 0.43 +/- 0.43; p < 0.05), while the bone mineral density of forearm was unchanged. CONCLUSIONS: Growth hormone replacement leads to a decrease in visceral fat, modulates the thyroid hormone levels by increasing peripheral conversion of thyroxine to triiodothyronine and probably is a physiological regulator of peripheral thyroxine metabolism, slightly deteriorates the carbohydrate metabolism, and results in an increase of bone mineral density of lumbar spine and femoral neck.

Adipose Tissue↗

PubMed2000

High-affinity Ca(2+) binding inhibits autoactivation of rat trypsinogen.

The recent discovery that mutation Asn21 --> Ile in the human cationic trypsinogen (Tg) is associated with hereditary pancreatitis has brought into focus the functional role of amino acid 21 in mammalian Tgs. In the present paper, the effect of mutations Thr21 --> Asn and Thr21 --> Ile on the Ca(2+) dependence of zymogen activation was investigated, using the autolysis-resistant rat Tg mutant Arg117 --> His. In the absence of Ca(2+), rat Tg exhibited low but significant basal autoactivation, which was inhibited by micromolar concentrations of Ca(2+) (IC(50) 2.6 microM). Interestingly, basal autoactivation was diminished in both mutants, and no further inhibition by micromolar Ca(2+) was detectable. Millimolar Ca(2+) concentrations markedly and comparably stimulated autoactivation of wild-type and mutant zymogens (EC(50) 1.7-2.4 mM). The results indicate that rat Tg is subject to dual regulation by Ca(2+), allowing zymogen stabilization in a low-Ca(2+) environment and efficient activation in a high-Ca(2+) milieu.

Animals↗

PubMed2000

[Glucocorticoid-induced osteoporosis].

Chronic glucocorticoid treatment is the most frequent cause of secondary osteoporosis. The direct inhibitory effect of glucocorticoids on osteoblasts results in decreased bone formation. Increased osteoclastic bone resorption due to low concentrations of gonadal steroid hormones and glucocorticoid-induced direct suppression of intestinal calcium absorption also contribute to the decrease of bone mass in these patients. Bone loss is rapid, particularly in the first months of glucocorticoid therapy. Bone mineral density of the lumbar spine and proximal femur should be measured in patients who are starting chronic therapy with glucocorticoids. Although glucocorticoid-induced osteoporosis is a severe and nowadays partially preventable disorder, osteoporosis prophylaxis is only rarely prescribed to these patients. Recent randomized, controlled trials proved the therapeutic effects of hormone replacement therapy, as well as of bisphosphonates and active vitamin D analogs in primary and secondary prevention of glucocorticoid-induced osteoporosis.

Bone Density↗

PubMed2000

Comparative analysis of plasma 17-hydroxyprogesterone and cortisol responses to ACTH in patients with various adrenal tumors before and after unilateral adrenalectomy.

Patients with non-hyperfunctioning adrenal adenomas often have an increased plasma 17-hydroxyprogesterone response to ACTH stimulation. The effects of adrenal surgery on this abnormality have rarely been investigated. One hundred and sixty-one patients with unilateral adrenal tumors (non-hyperfunctioning adenomas, 78; cortisol-producing adenomas, 8; aldosterone-producing adenomas, 37; adrenal cysts, 12; pheochromocytomas, 26) were studied. Patients before and after adrenal surgery as well as 60 healthy subjects underwent an ACTH stimulation test using 2 mg synthetic ACTH(1-24) (Cortrosyn Depot, Organon). Basal and ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations are reported. Before adrenal surgery, the basal plasma 17-hydroxyprogesterone concentrations were normal in patients with all types of tumors. However, the ACTH-stimulated plasma 17-hydroxyprogesterone levels were abnormally increased in 53% and 31% of patients with non-hyperfunctioning adenomas and aldosterone-producing adenomas, respectively. In addition, a few patients with adrenal cysts and pheochromocytomas also showed an increased ACTH-stimulated 17-hydroxyprogesterone response. After unilateral adrenalectomy, this hormonal abnormality disappeared in most, although not all patients with adrenal tumors. In patients with non-hyperfunctioning adrenal tumors, ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations significantly correlated with the size of the tumors. These results firmly indicate that the tumoral mass itself may be responsible for the increased plasma 17-hydroxyprogesterone and cortisol responses after ACTH stimulation in patients with non-hyperfunctioning and hyperfunctioning adrenal adenomas.

17-alpha-Hydroxyprogesterone↗

PubMed2000

Are there systemic changes in the arterial biomechanics of intracranial aneurysm patients?

Current theories on the development of intracranial aneurysm suggest that there is a general weakness of vascular connective tissue. Potential systemic alterations in arterial wall biomechanics were tested in the present study. A three-dimensional in vitro stress-strain analysis was made in the 0-200-0 mmHg pressure range on cylindrical segments excised from the anterior cerebral artery, the radial artery and from the arteria dorsalis pedis of aneurysm patients and of control cadavers. In the anterior cerebral artery from aneurysm patients (intracranial artery segments directly not affected by the aneurysm or by the subarachnoid bleeding), we found the wall thickness to be larger (0.1480+/-.019 versus 0.091+/-0.004 mm), the radius/wall thickness ratio smaller (9.7+/-1.4 versus 14.1+/-1.2), and the tangential wall stress lower [(0.122+/-0.019)x10(6) versus (0.181+/-0.016)x10(6) N/m2 at 100 mmHg] than in control subjects. Reduced radius was found in the extremity arteries studied. Elastic parameters, as incremental distensibility and elastic modulus, were remarkable similar. Our study demonstrates changes in the geometry of walls of arteries not directly affected by aneurysm formation, and it thus confirms systemic vascular pathology in this disease. At the same time, these data show that the molecular and morphological defects of arterial connective tissue formation generally thought to induce intracranial aneurysms will probably not affect the components responsible for the passive elastic properties of the vascular wall.

Adult↗

PubMed2000

Regulation of nitric oxide synthase activity by tetrahydrobiopterin in human placentae from normal and pre-eclamptic pregnancies.

The possible regulatory role of tetrahydrobiopterin (BH(4)) in Type III nitric oxide synthase (NOS III) activity of human placentae from first trimester, term and pre-eclamptic pregnancies was investigated. In homogenates of first-trimester or term placentae, BH(4)stimulated NOS III activity up to 2.5-fold in a concentration dependent manner from 20 n m to 1 microm BH(4), and half-maximal stimulation (EC(50)) was observed at 100-110 n m. No significant further stimulation was detectable over an extended concentration range from 1 microm to 50 microm BH(4). NOS III present in microsomal and gel-filtered cytosol fractions exhibited similar BH(4)-activation patterns, with an identical EC(50)value of 50 n m. Remarkably, tissue concentrations of BH(4)showed a marked decrease in term placentae (57+/-23 n m, mean+/-s.d., n=26) relative to first-trimester placentae (189+/-79 n m, mean+/-s.d., n=17), suggesting that alterations in cellular BH(4)concentrations may play a more significant role in the regulation of NOS III activity in late pregnancy. Placental homogenates from 10 pre-eclamptic pregnancies exhibited two distinct types of response to BH(4). In seven placental homogenates, addition of physiological concentrations of BH(4)(20 n m to 1 microm) elicited no increase whatsoever in basal NOS III activity, and only high BH(4)concentrations (50 microm) caused notable stimulation (BH(4)resistant group). In contrast, in three of 10 placental homogenates both physiological and 50 microm BH(4)concentrations stimulated NOS III to levels similar to that of normal placentae (BH(4)responsive group). There were no appreciable differences in the clinical presentation of pre-eclampsia between the two groups. Importantly, BH(4)concentrations in pre-eclamptic placentae were comparable with those of normal, control placentae. Taken together, the observations suggest that BH(4)controls NOS III activity in the human placenta, and a defect in BH(4)regulation of NOS III may contribute to the development of pre-eclampsia. A model implicating the malfunction of placental NOS III rather than its actual tissue level in the pathogenesis of pre-eclampsia is discussed.

Adult↗

PubMed2000

Enhanced accumulation of pericardial fluid ferritin in patients with coronary artery disease.

BACKGROUND: Ferritin is a storage protein for iron that can either represent a source of iron or perform a cytoprotective action as an iron sequestrant. OBJECTIVE: To compare the concentrations of ferritin in pericardial fluid of patients with valvular heart disease, serving as controls, and in patients with coronary artery disease. DESIGN: We studied a total of 59 consecutive male patients undergoing elective heart valve replacement (group 1: n = 22, mean +/- SD age 55 +/- 11 years) or elective coronary artery bypass grafting (group 2: n = 37, mean +/- SD age 59 +/- 9 years). METHODS: Iron status indicators, total protein and albumin concentrations, and lactate dehydrogenase activities were determined in pericardial fluid and serum samples obtained from patients during surgery. RESULTS: Pericardial fluid concentrations of ferritin in both patient populations were significantly (P < 0.001) greater than the concentrations in sera: group 1, 375 (107-2030) micrograms/l compared with 146.5 (21-407) micrograms/l; group 2, 1115 (226-2500) micrograms/l compared with 152.0 (16-398) micrograms/l (median (range)), respectively. Moreover, pericardial fluid ferritin concentration was significantly (P < 0.01) greater in patients undergoing coronary artery bypass grafting than in those undergoing heart valve replacement, whereas serum ferritin concentrations did not differ between the two patient populations. CONCLUSIONS: As pericardial fluid reflects the composition of the myocardial interstitium, we suggest that ferritin released can serve as a potential source of iron in the cardiac interstitium that may promote the generation of oxygen free radicals. Conversely, we presume that induction of ferritin synthesis, representing an important mechanism by which tissue adapts to hypoxic damage, can afford myocardial cytoprotection.

Adult↗

PubMed2000

Circulating plasma endothelin-1, plasma lipids and complications in Type 1 diabetes mellitus.

UNLABELLED: The damage of endothelial integrity is an important step in the atherogenic process. To evaluate the role of circulating endothelin-1 (ET-1) in Type 1 diabetes mellitus (T1DM), plasma ET-1 levels were evaluated in T1DM patients either with (n=9) or without hyperlipidaemia (n=11), or with (n=9) and without (n=11) late diabetic complications, in non-diabetic hyperlipidaemic patients (n=17) and in healthy volunteers. Groups were matched for age, sex and body mass index. RESULTS: Serum total cholesterol and apolipoprotein B were significantly higher in the diabetic group (p<0.05). Plasma ET-1 level was similar in controls and in non-diabetic hyperlipidaemic subjects (5.77+/-1.74 ng/l vs 4.97+/-1.58 ng/l); however, diabetic hyperlipidaemic patients had a significantly higher plasma ET-1 concentration compared to control subjects (6.67+/-2.44 ng/l vs 4.97+/-1.58 ng/l, p<0.05). Diabetic patients with vascular complications had a significantly higher plasma ET-1 concentration than found in diabetic patients without complications (6.99+/-2.17 ng/l vs 4.74+/-1.27 ng/l, p<0.01) and in controls (6.99+/-2.17 ng/l vs 4.97+/ 1.58 ng/l, p<0.01). Patients with diabetic complications also had a significantly higher apolipoprotein B level compared to healthy controls (0.94+/-0.37 g/l vs 0.66+/-0.12 g/l, p<0.005). CONCLUSION: The susceptibility of T1DM patients to the development of atherosclerosis might be attributed to the relationship between elevated lipid levels and ET-1.

Adolescent↗

PubMed1999

[Effective demeclocycline therapy in a patient with over-secretion of antidiuretic hormone following head trauma].

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a common cause of hyponatremia. In this study a case of SIADH caused by head trauma is reported, in which severe hyponatraemia, escorted by life-threatening neurological symptoms was observed that could only be managed by parenteral sodium chloride infusions. Severe hyponatraemia was accompanied by elevated urinary sodium excretion, a characteristic sign of SIADH. After introducing the therapy with demeclocycline, a tetracycline type antibiotic that inhibits the renal action of antidiuretic hormone, serum sodium levels began to rise gradually, and the urinary sodium excretion slowly decreased. These observations show the effectiveness of demeclocycline in the treatment of SIADH.

Craniocerebral Trauma↗

PubMed1999

Trypsinogen stabilization by mutation Arg117-->His: a unifying pathomechanism for hereditary pancreatitis?

Mutations Arg117-->His and Asn21-->Ile of the human cationic trypsinogen have been recently identified in patients affected by hereditary pancreatitis (HP). The Arg117-->His substitution is believed to cause pancreatitis by eliminating an essential autolytic cleavage site in trypsin, thereby rendering the protease resistant to inactivation through autolysis. Here we demonstrate that the Arg117-->His mutation also significantly inhibits autocatalytic trypsinogen breakdown under Ca(2+)-free conditions and stabilizes the zymogen form of rat trypsin. Taken together with recent findings demonstrating that the Asn21-->Ile mutation stabilizes rat trypsinogen against autoactivation and consequent autocatalytic degradation, the observations suggest a unifying molecular pathomechanism for HP in which zymogen stabilization plays a central role.

Animals↗

PubMed1999

Effects on substrate profile by mutational substitutions at positions 164 and 179 of the class A TEM(pUC19) beta-lactamase from Escherichia coli.

We investigated the effects of mutations at positions 164 and 179 of the TEM(pUC19) beta-lactamase on turnover of substrates. The direct consequence of some mutations at these sites is that clinically important expanded-spectrum beta-lactams, such as third-generation cephalosporins, which are normally exceedingly poor substrates for class A beta-lactamases, bind the active site of these mutant enzymes more favorably. We employed site-saturation mutagenesis at both positions 164 and 179 to identify mutant variants of the parental enzyme that conferred resistance to expanded-spectrum beta-lactams by their enhanced ability to turn over these antibiotic substrates. Four of these mutant variants, Arg(164) --> Asn, Arg(164) --> Ser, Asp(179) --> Asn, and Asp(179) --> Gly, were purified and the details of their catalytic properties were examined in a series of biochemical and kinetic experiments. The effects on the kinetic parameters were such that either activity with the expanded-spectrum beta-lactams remained unchanged or, in some cases, the activity was enhanced. The affinity of the enzyme for these poorer substrates (as defined by the dissociation constant, K(s)) invariably increased. Computation of the microscopic rate constants (k(2) and k(3)) for turnover of these poorer substrates indicated either that the rate-limiting step in turnover was the deacylation step (governed by k(3)) or that neither the acylation nor deacylation became the sole rate-limiting step. In a few instances, the rate constants for both the acylation (k(2)) and deacylation (k(3)) of the extended-spectrum beta-lactamase were enhanced. These results were investigated further by molecular modeling experiments, using the crystal structure of the TEM(pUC19) beta-lactamase. Our results indicated that severe steric interactions between the large 7beta functionalities of the expanded-spectrum beta-lactams and the Omega-loop secondary structural element near the active site were at the root of the low affinity by the enzyme for these substrates. These conclusions were consistent with the proposal that the aforementioned mutations would enlarge the active site, and hence improve affinity.

Amino Acid Substitution↗

PubMed1999

[Ret-protooncogene mutation, verified by molecular genetic methods, in a Hungarian MEN Type 2a family].

Multiple endocrine neoplasia Type 2 (MEN2) is a hereditary tumour syndrome characterized by the association of medullary thyroid cancer, phaeochromocytoma and hyperparathyroidism. It is inherited as an autosomal dominant trait. During the past few years the cloning of the gene responsible for the syndrome, the ret protooncogene, made the molecular genetic diagnosis of the disease possible. In this study we demonstrate the results of the MEN2 mutation analysis performed in three members of a Hungarian MEN2A family. The mutation analysis was carried out according to the method of Dr. W. Hoppner's Laboratory (Hamburg) that is the main centre for MEN2 genetic diagnosis in Germany. Two Members of the family are affected, one suffered from both medullary thyroid cancer and phaeochromocytoma, the other (the first patient's daughter) had only medullary thyroid cancer. We found a ret exon 11 codon 634 mutation, that resulted in the change of TGC to TAC, a cysteine-tyrosine amino acid exchange. We found no mutation in the youngest member of the family. This result is of great clinical significance, because the carrier status of this individual can thus be excluded and, therefore, there is no need for prophylactic thyroidectomy and further clinical screening tests. As molecular genetic diagnosis of MEN2 becomes possible, the uncertain clinical examinations used for MEN2 diagnosis seems to be less important.

Adult↗