Biomedical subjects

A Gessl

Publications and source records attributed to A Gessl.

At least 19 recordsLinked to original sources

PubMed2006

Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia.

It is currently not known which level of pentagastrin-stimulated calcitonin serum concentration indicates medullary thyroid carcinoma in patients with chronic kidney disease (CKD). We examined CKD stage 3-5 patients who had total thyroidectomy because of a pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and tested the diagnostic performance of basal and pentagastrin-stimulated calcitonin levels for differentiating medullary thyroid carcinoma and C-cell hyperplasia in this patient population. A total of 180 CKD patients presented with an elevated calcitonin level and had a pentagastrin stimulation test. Forty patients showed a maximum pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and 22 patients had a total thyroidectomy. Seven of these 22 patients presented with a medullary thyroid carcinoma, all other patients showed C-cell hyperplasia. Patients with medullary thyroid carcinoma showed higher unstimulated (212 pg/ml (36-577) vs 42 pg/ml (17-150); P < 0.001) and higher maximum pentagastrin-stimulated calcitonin concentrations (862 pg/ml (431-2423) vs 141 pg/ml (102-471); P < 0.001) as compared to patients with C-cell hyperplasia. The sensitivity (100%) and specificity (93%) estimates suggested that a maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml indicates the presence of medullary thyroid carcinoma in patients with CKD. Receiver-operating characteristic (ROC) analysis revealed an area under the ROC plot of 0.99 for maximum pentagastrin-stimulated calcitonin concentrations. A maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml appears to be a clinically meaningful threshold for thyroidectomy.

Adolescent↗

PubMed2006

Non-suppressible TSH in a patient thyroidectomized due to follicular thyroid carcinoma.

Poor compliance or drug malabsorption are the most common reasons why an adequate TSH suppression is not achieved with oral levothyroxin in patients with hypothyroidism or thyroid carcinoma. When these conditions are excluded rare causes have to be considered. We report a female patient with follicular thyroid carcinoma in whom, under intended levothyroxin suppression therapy, a TSH-PRL-producing pituitary adenoma manifested by failure to achieve adequate TSH suppression, subtle signs of hyperthyroidism,and finally symptoms of elevated PRL.

Adenocarcinoma, Follicular↗

PubMed2005

High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease.

Anderson-Fabry disease is a rare lysosomal storage disorder. It results from a deficiency of the lysosomal alpha-galactosidase A and leads to progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. Some of the typical clinical findings such as tiredness, dry skin, myalgia and arthralgia as well as vague gastrointestinal complaints are also symptoms of hypothyroidism. Therefore, we studied the thyroid function in patients with Anderson-Fabry disease. Thyroid function was studied in 11 patients (6 female, 5 male) with Anderson-Fabry disease by measuring thyroid-stimulating hormone (TSH) and free thyroxine serum levels. Nine patients had chronic kidney disease with stage 1 and two with stage 5. Subclinical hypothyroidism (normal serum free thyroxine concentrations along with elevated serum TSH levels) was found in 4 of 11 patients (36.4%). Subclinical hypothyroidism was observed in both male and female patients as well as in patients with stage 1 and stage 5 kidney disease. Subclinical hypothyroidism is a common finding in patients with Anderson-Fabry disease, showing an excess prevalence as compared to the normal population. The high frequency seems to be relevant regarding the potential consequences of a hypothyroid state.

Adult↗

PubMed2005

Hormonal profile and fertility in patients with Anderson-Fabry disease.

Anderson-Fabry disease is a glycosphingolipid storage disorder with an X-linked recessive inheritance. The alpha-galactosidase A deficiency leads to a progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. The kidney, heart and brain are predominantly affected. Reports on endocrine function and fertility rates in patients with Anderson-Fabry disease are sparse. In the present study, we assessed ovarian, testicular and adrenal function in a cohort of patients with Anderson-Fabry disease. Plasma follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, sex hormone-binding globulin, somatotropin, insulin-like growth factor-I and serum cortisol were measured in 13 patients (six female and seven male), currently observed in an outpatient clinic. The profile revealed an undisturbed hormonal function and a normal fertility rate in both male and female Anderson-Fabry patients when compared with the corresponding Austrian population.

Adrenal Cortex Hormones↗

PubMed2004

Neointimal proliferation within carotid stents is more pronounced in diabetic patients with initial poor glycaemic state.

AIMS/HYPOTHESIS: We studied the influence of initial hyperglycaemia on neointimal proliferation within carotid Wallstents. METHODS: A total of 112 patients were followed by duplex sonography after carotid stenting for 24 months. Patients were assigned to three groups: non-diabetic subjects (group A) and diabetic patients, who were assigned according to their baseline HbA(1)c values, to group B1(HbA(1)c 6.5%). RESULTS: At baseline the groups did not differ with respect to other vascular risk factors and residual stenosis on angiograms. The maximal thickness of the layer between the stent and the perfused lumen was measured at the duplex follow-ups. At 3 months the typical ultrasonic structure of the neointima was clearly discernible. From this point on, group B2 differed significantly ( p<0.001) compared with B1 and A with respect to the maximal thickness of neointima and the time course of its ingrowth: group A vs B1 vs B2 was 0.51+/-0.39 vs 0.52+/-0.33 vs 0.56+/-0.35 at 3 months, 0.91+/-0.27 vs 0.90+/-0.38 vs 1.14+/-0.48 at 6 months, 1.02+/-0.24 vs 0.97+/-0.34 vs 1.21+/-0.44 at 12 months and 1.09+/-0.23 vs 1.10+/-0.31 vs 1.23+/-0.37 at 24 months. CONCLUSION/INTERPRETATION: Initial hyperglycaemia seems to be a predictor of more pronounced neointimal proliferation after carotid stenting independent of diabetes. As intimal hyperplasia is known to be responsible for stent restenosis, strict optimisation of the hyperglycaemic state should be aimed at before elective carotid artery stenting.

Aged↗

PubMed2003

Use of the oral glucose tolerance test to define remission in acromegaly.

An oral glucose tolerance test (OGTT) was used to assess growth hormone (GH) secretion in patients with acromegaly prior to (n = 26) and after (n = 71) transsphenoidal adenomectomy as well as in 196 controls. In controls, suppressed concentrations of GH showed a negative relationship both with body mass index (BMI) and with age. Having calculated the reference intervals for suppressed GH concentrations to be expected for any given age and BMI, we compared these individually predicted ranges to GH concentrations actually observed in patients with acromegaly during OGTT. Preoperatively, concentrations exceeded the normal range in all patients. Postoperatively, glucose-suppressed concentrations of GH were less than 2.0 ng/mL in 56 (79%) patients and less than 1.0 ng/mL in 44 (62%). However, only 37 of 71 (52%) patients had glucose-suppressed GH concentrations within the calculated reference intervals (defined by the 95th percentile of normal). Comparing these data with the patient's concentrations of insulin-like growth factor-1 (IGF-1; normal range first established and corrected for age and sex in 494 healthy individuals), congruency of both parameters was found in 59 (77%) patients with an unexplained discrepancy between GH and IGF-1 in the remaining in 16 (23%) patients. Our results confirm that concentrations of IGF-1 must be corrected for sex and age, whereas glucose-suppressed concentrations of GH depend on age and BMI. "Across-the-board" cut-off-values are clearly inadequate and should not be used. Rather, serum GH measurements obtained during an OGTT must be interpreted individually by comparison to control values taking into account both age and BMI.

Acromegaly↗

PubMed2003

Adrenocortical tumors: prevalence of impaired glucose tolerance and of "Paradoxical Rise" of cortisol during an oral glucose tolerance test.

Glucose tolerance and the behaviour of cortisol during an oral glucose tolerance test (OGTT) was investigated in 126 patients with adrenal "incidentalomas" (age: > 45 years) and in 129 age-matched controls. Impaired glucose tolerance (IGT) was found to be more common (p < 0.02) among patients with adrenal incidentalomas. Subdividing these patients by their body weight it was found that 29% (controls: 25%) of those with normal body weight (BMI 20 - 25 kg/m2) had IGT/DM. In overweight (BMI 25 - 30 kg/m2) and obese patients (BMI 30 - 40 kg/m2) the share of IGT/DM was 32% (controls: 19%) and 66% (controls 42%), respectively. The prevalence of a "paradoxical" rise in serum cortisol concentrations during the OGTT was slightly higher (p < 0.05) among patients with adrenal incidentaloma than among controls. Patients as well as controls with this abnormal behaviour of cortisol were characterized by lower basal serum cortisol concentrations (p < 0.01) but no association was seen with either the presence of IGT or with post-dexamethasone concentrations of serum cortisol. Thus both in patients with and without adrenal incidentalomas abnormal glucose tolerance is an age- and weight-dependent phenomenon unrelated to the post-prandial behaviour of serum cortisol concentrations.

Adrenal Cortex Neoplasms↗

PubMed2002

Prevalence of hypergastrinemia in patients with hyper- and hypothyroidism: impact for calcitonin?

OBJECTIVES: To evaluate the prevalence of hypergastrinemia in patients with hyperthyroidism and hypothyroidism and to determine whether gastrin-induced hypercalcitonemia could explain the high prevalence of thyroid C-cell hyperplasia among patients with hyperthyroidism. METHODS: Concentrations of gastrin and of hCT were determined by commercially available radioimmunoassays. RESULTS: Elevated serum concentrations of gastrin were found in 17 of 161 (10.5%) patients with manifest hyperthyroidism (Graves' disease) and in 4 of 37 (10.8%) and 23 of 255 (9.0%) patients with manifest or subclinical hypothyroidism, respectively. Only 2 cases of hypergastrinemia of 255 subclinically hypothyroid patients (0.8%) could not be linked to thyroid autoimmune disease by either biochemical or sonographic criteria. Four patients with Graves' disease presented elevated plasma concentrations of calcitonin, but none of these patients also had an elevated serum gastrin. CONCLUSIONS: The prevalence of hypergastrinemia in autoimmune thyroid disease is about 10%. The determination of gastrin in subclinical hypothyroidism is not cost-effective in the absence of biochemical and/or sonographic markers of autoimmune thyroid disease. The determination of gastrin is of no use to predict the presence of C-cell hyperplasia commonly seen in patients with Graves' disease.

Aged↗

PubMed2000

Low-density lipoprotein cholesterol in subclinical hypothyroidism.

The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.

Age Factors↗

PubMed1998

Elevated CD69 expression on naive peripheral blood T-cells in hyperthyroid Graves' disease and autoimmune thyroiditis: discordant effect of methimazole on HLA-DR and CD69.

This study investigated T-cell activation markers HLA-DR and CD69 in both naive (CD45RA+) and memory (CD45RA-) CD4+ as well as CD8+ T cells in peripheral blood of patients with autoimmune thyroiditis (AT, N = 28) or hyperthyroid untreated Graves' disease (GDH, N = 34) using three-color flow cytometry. It was demonstrated that patients with AT, but not those with GDH, expressed increased amounts of HLA-DR antigen compared to healthy subjects (HS, N = 26) on total CD4+ (AT: 14.1%; GDH: 11.3%; HS: 10.9%) and CD8+ cells (AT: 31.9%; GDH: 23.5%; HS: 19.4%) as well as on CD45RA- CD4+ cells (AT: 11.2%; GDH: 7.7%; HS: 7.9%). In GDH (+71%) and AT (+91%) only the proportion of HLA-DR+ CD45RA+ CD8+ cells was increased vs HS. Furthermore, euthyroid GD patients on methimazole (GDE, N = 22) displayed greater HLA-DR+ expression on total and CD45RA- cells within both CD4+ (+37 and 40%, respectively) and CD8+ cells (+47 and 93%, respectively) than GDH. In addition, total and CD45RA+ CD4+ and CD8+ cells were increased vs HS. In contrast, proportions of CD69 positive T cells were increased in AT and GDH on total CD4+ (+97 and 74%, respectively) and CD8+ (+95 and 68%, respectively) cells and all subsets thereof (except for CD45RA- cells in GDH), but normalized upon thyrostatic treatment. We conclude that patients with autoimmune thyroid disease harbor an almost twofold greater proportion vs HS of (a) HLA-DR+ CD45RA+ CD8+ T cells, and of (b) CD69 on total CD4+ and CD8+ cells, and an even more marked elevation on their CD45RA+ subset in AT and untreated GD. In addition, (c) thyrostatic treatment by methimazole in GD is accompanied by a further increase in circulating HLA-DR+ CD4+ and CD8+ cells and their CD45RA- subsets, but decreased CD69 expression. These data suggest association of HLA-DR expression with ongoing autoimmunity, while increased CD69 expression relates in part also to elevated thyroid hormone concentration in GDH.

Adult↗

PubMed1998

Increased CD69 and human leukocyte antigen-DR expression on T lymphocytes in insulin-dependent diabetes mellitus of long standing.

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n = 31; median age +/- SD, 28 +/- 6.9 yr) and of long standing (DML; n = 27; age, 33 +/- 10.4 yr; median duration of disease, 105 months), CD4+ and CD8+ T cells were analyzed to determine their naive and memory subsets as well as their expression of human leukocyte antigen (HLA)-DR, interleukin-2 receptor alpha-chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 +/- 8.2 yr) served as controls. No deviation was seen in either IDDM group compared to HS in CD25 expression on CD4+ or CD8+ cells or in their CD45RA+ or CD45RA- subsets. HLA-DR expression, however, was increased (P < 0.05) in total CD8+ cells and CD45RA+ cells, with CD45RA- CD8+ cells joining the prevailing pattern only in DML. Among CD4+ cells, increased expression of HLA-DR molecules was restricted to total and CD45RA- cells in DML. CD69 expression did not differ between IDDM and HS, but differed between DML (CD4+, CD8+, and CD45RA- CD4+) and DM only. In conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to memory cells (CD45RA-) among CD4+ cells in DML and is more markedly confined to naive (CD45RA+) than to memory CD8+ cells, whereas the early activation antigen CD69 is more readily expressed in DML than in DM. The observed activation of circulating T cells suggests an ongoing immune process in IDDM both at clinical manifestation and after long duration.

Adult↗

PubMed1996

Haptoglobin phenotyping by newly developed monoclonal antibodies. Demonstration of haptoglobin uptake into peripheral blood neutrophils and monocytes.

We have generated two IgG murine mAbs that recognize native human haptoglobin (Hp). These mAbs, 3A8 and 4B2, efficiently bind to the Hp complex regardless of the serum donor's phenotype. The specificity of mAb 3A8 was confirmed by immunoaffinity purification of 3A8-binding material from human serum and subsequent N-terminal amino acid sequencing of the invariant 40-kDa chain. mAb 3A8 and 4B2 were also reactive with cell-associated Hp when studied by immunocytochemistry. When human peripheral blood leukocytes were tested, 90% of the granulocytes and a lesser (and variable) fraction of monocytes displayed an intense intracytoplasmatic granular staining. This was confirmed by flow cytometric analysis of permeabilized leukocytes and by demonstrating the presence of Hp (of the expected Hp serum phenotype) in extracts of washed granulocytes by immunoblotting. Leukocytes obtained from a Hp phenotype 2-2 donor, incubated in culture medium supplemented with 10% serum from a donor possessing the Hp 1-1 phenotype, contained both Hp phenotypes when analyzed by immunoblotting after a 6-h incubation period. In addition, Hp was actively exocytosed by granulocytes following their exposure to Candida albicans. These observations suggest that exogenous Hp is concentrated within granulocytes and not synthesized de novo and is, in turn, exocytosed following neutrophil activation. Northern blotting analysis is consistent with the lack of haptoglobin gene transcription in granulocytes. These findings together with the earlier observations that Hp modulates granulocyte activity suggest that Hp levels may be enhanced locally at sites of inflammation to modulate granulocyte activity.

Amino Acid Sequence↗

PubMed1995

Tumor necrosis factor-alpha induction of major histocompatibility complex class II antigen expression is inhibited by interferon-gamma in a monocytic cell line.

Regulation of major histocompatibility complex (MHC) class II antigen expression by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. The analysis of class II gene regulation benefits greatly from the existence of mutants with defects in regulatory factors. We report the establishment of a subclone of the human monocytic cell line U937, termed C119/9, with unusual cytokine regulation of MHC class II expression. In contrast to the parental U937 cell line, only tumor necrosis factor (TNF)-alpha, and not interferon (IFN)-gamma induces the expression of MHC class II antigens on C119/9 cells, and paradoxically, this induction was inhibited almost completely by IFN-gamma. The HLA-DR induction is controlled at the transcriptional level by the first 150 bp of the class II promoter which contains all the class II consensus elements. Both HLA-DR and -DQ mRNA are induced by TNF-alpha treatment, and both are diminished upon co-treatment with TNF-alpha and IFN-gamma. This antagonism between TNF-alpha and IFN-gamma seem to be restricted to MHC class II genes. This subline of U937 cells may be useful in further studies of MHC class II regulation.

Blotting, Northern↗

PubMed1995

Modulation by high glucose of adhesion molecule expression in cultured endothelial cells.

We evaluated the influence of high ambient glucose on cellular expression of adhesion molecules, known to mediate endothelial interaction of leucocytes and monocytes. Paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were studied by fluorescence activated cell sorter analysis after exposure to 30 vs 5 mmol/l glucose. Incubation of HUVECs for 24h in 30 mmol/l glucose increased ICAM-1 (intercellular adhesion molecule-1; 116.4 +/- 16.9% of control, p < or = 0.05), but not PECAM (platelet endothelial cell adhesion molecule) expression, compared to cultures kept in 5 mmol/l glucose. Long-term exposure (13 +/- 1 days) of HUVECs to 30 mmol/l glucose increased expression of ICAM-1 to 122.5 +/- 32.2% (p < 0.002) and reduced that of PECAM to 86.9 +/- 21.3% vs the respective control culture in 5 mmol/l glucose (p < 0.02). Stimulation of confluent HUVECs, kept in 30 vs 5 mmol/l glucose for 13 +/- 1 days, with 20 U/ml interleukin-1 for 24 h (ICAM-1) and 4 h (endothelial leukocyte adhesion molecule 1) resulted in reduced ICAM-1 (84.8 +/- 27.0%, p < 0.05) and endothelial leukocyte adhesion molecule-1 (87.6 +/- 22.4%, p < 0.05) expression vs control cells, while that of PECAM (t:24 h) and vascular cell adhesion molecule-1 (t: 16 h) remained unchanged. In conclusion, it appears that differences in expression of adhesion molecules on HUVECs in response to high glucose reflects endothelial glucose toxicity, which may also induce endothelial dysfunction in diabetes.

Cell Adhesion Molecules↗

PubMed1995

Expression of MHC class II antigens on rat bone marrow cells and macrophages, and their modulation during culture with murine GM-CSF or M-CSF.

Flow cytometric analysis employing MRC OX 6 and MRC OX17 monoclonal antibodies recognizing determinants on RT1.B or RT1.D molecules, equivalent to murine I-A and I-E, respectively, was used to detect rat MHC class II antigen (Ag) expression. Approximately 5% of freshly isolated rat bone marrow cells (BMC) expressed RT1.B and over 30% displayed RT1.D molecules. The RT1.D+ cells were W3/13+, OX 7+, OX 19- and OX 22-. After one week culture of BMC with murine recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF), regardless of concentrations, 90 to 95% of the cells were scored as bone marrow-derived macrophages (BMDM phi), and over 30% expressed both RT1.B and RT1.D Ag. GM-CSF increases the percentage of BMDM phi bearing MHC class II Ag in a concentration-dependent manner. This effect seems to be specific because antibodies to interferon-gamma, tumor necrosis factor-alpha or interleukin-4 did not reduce the number of cells expressing RT1.B and RT1.D Ag. Furthermore, GM-CSF was able to trigger expression of class II molecules on rat peritoneal macrophages (M phi) and BMDM phi resulted from cultures of BMC with mouse M phi-CSF (M-CSF), and the RT1.B and RT1.D inducing effect of GM-CSF was opposed by M-CSF, and by anti-GM-CSF antibodies. The induction of MHC class II Ag synthesis by GM-CSF on rat BMDM phi was confirmed at the mRNA level by Northern blot analysis employing cDNA probes encoding the RT1.B alpha.

Animals↗

PubMed1995

Activated naive CD4+ peripheral blood T cells in autoimmune thyroid disease.

To better understand the clinical significance of changes in lymphocytes in thyroid disease this study analyzed the proportion of CD19+, CD3+, CD4+ and CD8+ cells among circulating lymphocytes in Graves' disease (GD, n = 34) and autoimmune hypothyroidism (AH, n = 28) vs healthy subjects (n = 15). In addition, the expression of CD25 and CD45 isoforms on CD4+ T cells as well as their modulation by methimazole in patients with GD was measured using three color flow cytometry. It was observed that, irrespective of age, both patients with GD (17.6 +/- 7.0% +/- SD) and those with AH (19.0 +/- 9.5%) had an increased percentage of the CD25+CD45RA+ (naive) subpopulation of helper cells vs healthy subjects (7.9 +/- 2.3%, p < 0.0001). In patients with AH peripheral memory cells and hence overall CD25+ cells were more frequent among helper cells (56.7 +/- 12.2%) than in healthy subjects (40.8 +/- 14.0%, p < 0.001). Patients with GD (46.2 +/- 13.4%) did not differ from normal subjects in this respect. Treatment of GD with MMI reduced the percentage of CD25+CD45RA+ cells among CD4+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells are significantly reduced in AH (23.9 +/- 4.9%) and untreated Graves' disease (23.2 +/- 6.6%) vs healthy subjects (32.2 +/- 5.9%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Circulating selectins, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in hyperthyroidism.

Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble P-selectin, and soluble L-selectin (sL-selectin), tumor necrosis factor-alpha, and interleukin-6 were measured in patients with Graves' disease (GD) (n = 33), in patients with toxic nodular goiter (n = 34), and in a group of healthy controls (n = 36). The serum levels of sICAM-1, sVCAM-1, sE-selectin, and sL-selectin were markedly elevated in patients with GD and in patients with toxic nodular goiter before treatment with methimazole (P < 0.05 for all). After 8 weeks of therapy, serum concentrations of sVCAM-1 and sE-selectin normalized, whereas serum levels of sL-selectin and sICAM-1 remained elevated. Hormone concentrations normalized after 2 weeks, clearly preceding falling levels of circulating adhesion molecules. Serum concentrations of soluble P-selectin, TNF-alpha, and interleukin-6 did not differ among patients with GD and toxic nodular goiter and healthy subjects. Serum levels of sVCAM-1 and sICAM-1 correlated with the serum concentrations of TSH receptor antibodies (n = 33; r = 0.921 and r = 0.792, respectively) and thyroid peroxidase antibodies (n = 33; r = 0.682 and r = 0.761, respectively) but not thyroglobulin antibodies. However, no correlation between serum levels of sE-selectin, sL-selectin, and soluble P-selectin or cytokines and serum levels of thyroid peroxidase antibodies, TSH receptor antibodies, or thyroglobulin antibodies, respectively, was found. In addition, no correlation between serum levels of adhesion molecules or cytokines and thyroid hormones was seen. We conclude that both the action of thyroid hormones and the autoimmune process in GD may contribute to elevated levels of soluble adhesion molecules.

Adult↗

PubMed1995

High-glucose--triggered apoptosis in cultured endothelial cells.

High ambient glucose concentration, linked to vascular complications in diabetes in vivo, modulates mRNA expression of fibronectin, collagen, tissue-type plasminogen activator, and plasminogen activator inhibitor and induces delayed replication and excess cell death in cultured vascular endothelial cells. To determine the role of high ambient glucose (30 mmol/l) in apoptosis, paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were exposed to both high (30 mmol/l) and low (5 mmol/l) concentrations of glucose for short-term (24, 48, and 72 h) and long-term (13 +/- 1 days) experiments. Incubation of HUVECs with high glucose for > 48 h increased DNA fragmentation (13.7 +/- 6.5% of total DNA, mean +/- SD) versus cultures kept in 5 mmol/l glucose (10.9 +/- 5.6%, P < 0.005), as measured by [3H]thymidine assays. Data were confirmed by apoptosis-specific fluorescence-activated cell sorter analysis of confluent HUVEC cultures, which displayed after long-term exposure to 30 mmol/l glucose a 1.5-fold higher prevalence of apoptosis than control cultures exposed to 5 mmol/l glucose (P < 0.005). In contrast, no increase in DNA fragmentation in response to 30 mmol/l glucose was seen for standardized cell lines (K 562, P 815, YT) and fibroblasts. Expression of clusterin mRNA, originally reported to be a molecular marker of apoptosis, was only slightly affected by short-term (24-h) high-glucose exposure but was significantly reduced after long-term incubation in 30 mmol/l glucose (82.2 +/- 13.8% of control) versus 5 mmol/l glucose, which questions the role of clusterin gene expression as a marker of apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis↗