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M. Herrmann and G. Winkler

ABSTRACT

Male guinea pigs were simultaneously treated with cortisone and oestradiol-dipropionate. Observations were made on the nuclear volumes of the cells of the zona fasciculata of the adrenal cortex, the urinary 17-hydroxycorticoids and the haemorrhagic necrosis after intoxication with diphtheria-toxin.

The comparatively long restitution phase of the adrenals following the long-term pretreatment with cortisone only may be considerably reduced by application of oestradioldipropionate, which is shown by the following results: the nuclear volumes of fasciculata cells of the adrenal cortex stay normal or show higher values after termination of the pretreatment. Haemorrhagic necrosis in the adrenal cortex after intoxication with diphtheria-toxin is observed on the 2nd day after long-term pretreatment with cortisone and oestradioldipropionate. In animals treated with cortisone only this tissue lesion is observed at first on the 8th day after termination of the pretreatment. The excretion of 17-hydroxycorticoids does not correspond with this accelerated reaction of the adrenal cortex.

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G. Winkler, H. H. Janssen, G. Kolig and K. Huhnstock

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G. BARGSTEN, D. GRUBE, W.G. FORSSMANN and H. WINKLER

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W. Rick, G. Winkler, E. Koch and H. Bohn

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RB Kovacs, J Foldes, G Winkler, M Bodo and Z Sapi

OBJECTIVE: Malignant tumors of the thyroid gland exhibit a variety of histopathologies and clinical behavior. Immune markers are gaining more and more importance in diagnostic pathology, especially in the differential diagnostics and in the grading of thyroid gland tumors. DESIGN: The Authors investigated the immunohistochemical reaction of galectin-3 (gal3) in patients with various thyroid gland diseases. They tested the diagnostic value of gal3 in determining the benign or malignant nature of various lesions, especially in lesions of follicular origin, because previous results have indicated nearly 100% specificity and sensitivity in this regard. METHODS: Gal3 immunoperoxidase reaction was carried out on 91 sections of thyroid gland samples fixed in formalin and embedded in paraffin. RESULTS: While gal3 expressed itself strongly and diffusely in papillary carcinomas (19 of 20 cases), in other malignant lesions it showed weaker, focal or variable positivity. Focal positivity was found in four of 19 follicular adenomas, and negativity was found in three of 10 follicular carcinomas. In all cases of inflammation a focal positivity was observed (eight of eight cases). All nodular goiter and normal thyroid tIssue were negative (25 of 25 cases). CONCLUSIONS: Based on our results, the gal3 immunohistochemical reaction seems to be reliable in the diagnosis of papillary carcinomas. However, in the case of solitary thyroid nodules and follicular lesions, although it is still a useful supplementary marker, it is not of absolute value (as stated in previous studies) in determining whether a tumor is benign or malignant.

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G Speer, K Cseh, G Winkler, P Vargha, E Braun, I Takacs and P Lakatos

OBJECTIVE: We studied the significance of BsmI restriction enzyme polymorphism of the vitamin D receptor (VDR) gene and the XbaI and PvuII polymorphisms of the estrogen receptor (ER) gene in patients with type 2 diabetes (n=49), android type obesity with normal carbohydrate metabolism (n=29) and healthy controls (n=138). METHODS: The distribution of genotypes in the study groups, as well as their relationship to fasting and 1 h postprandial serum C-peptide levels were analyzed. RESULTS: Postprandial serum C-peptide levels of BB genotypes were significantly higher in the diabetes and obese groups (6.18+/-5.09 ng/ml) compared with other genotypes (2.71+/-2.45 vs. 1.72+/-1.97 ng/ml, respectively, P=0.05). Among patients with type 2 diabetes and obese subjects, the XX allelic variant of the ER gene was more frequent (P=0.00015). Postprandial C-peptide levels of subjects exhibiting XX genotype were significantly lower compared with those with Xx genotype (1.67+/-2.16 vs. 3.8+/-3.72 ng/ml, P=0.021). The BBXx allelic combination of the VDR/ER receptor genes was less frequent in diabetic patients than in healthy subjects or in obese patients. The BBXx genotype was associated with significantly elevated postprandial C-peptide levels in all subjects compared with other combinations (9.65+/-3.14 vs. 1.35+/-2.82 ng/ml, P=0.003). No difference was found in the distribution of the PvuII polymorphism of the ER gene or in the association with the C-peptide levels among study groups. CONCLUSION: Polymorphisms of the VDR/ER receptor genes might play a role in the pathogenesis of type 2 diabetes by influencing the secretory capacity of beta-cells.

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N. STAHNKE, P. HAUPT, R. P. WILLIG, G. SINNECKER and K. WINKLER

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L Kalabay, K Cseh, A Pajor, E Baranyi, GM Csakany, Z Melczer, G Speer, M Kovacs, G Siller, I Karadi and G Winkler

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

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G Winkler, S Kiss, L Keszthelyi, Z Sapi, I Ory, F Salamon, M Kovacs, P Vargha, O Szekeres, G Speer, I Karadi, M Sikter, E Kaszas, O Dworak, G Gero and K Cseh

OBJECTIVE: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. DESIGN: A cross-sectional case-control study was used. PATIENTS: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI>27 kg/m(2)) and 15 lean people (BMI<25 kg/m(2)), all of them undergoing planned surgical operation, participated in the study. METHODS: Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein. Serum TNF-alpha, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. RESULTS: TNF-alpha protein was expressed in adipocytes of both depots. The expression was evaluated visually and found to be greater in the obese patients. Significantly higher serum TNF-alpha (5.58+/-0.87 pg/ml vs 4.21+/-0.55, mean+/-s.d., P<0.01, Mann-Whitney) and sTNFR-2 levels (7.84+/-3.56 ng/ml vs 4.59+/-1.35, P=0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r=0.49, P=0.003; and r=0.74, P=0.001) and the C-peptide/ blood glucose ratio (r=0.47, Spearman, P=0.005; and r=0.70, P=0.001). The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients (subcutaneous: r=0.52, P=0.0003; r=0.69, P<0.0001; visceral: r=0.65, P<0.0001; r=0.63, P<0.0001) and in both subgroups. CONCLUSIONS: Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha, sTNFR-2 production and obesity-linked insulin resistance.