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M L Hartoft-Nielsen

Publications and source records attributed to M L Hartoft-Nielsen.

8 recordsLinked to original sources
PubMed2005

Estimation of number of follicles, volume of colloid and inner follicular surface area in the thyroid gland of rats.

Volume is an important variable in assessing the growth and involution of the thyroid gland. The functional unit in the thyroid is the follicle, which consists of thyrocytes surrounding colloid. The size of a follicle depends on the number of cells and the amount of colloid. These are interchangeable and vary according to biological activity. Direct measurements of these variables provide information on structures involved in thyroid hormone synthesis, storage and secretion, and also on changes at the morphological and functional levels. Stereological methods are developed to obtain information on three-dimensional structures from two-dimensional sections and to achieve information on an entire organ by examining a minor part of it. Full-grown male Sprague-Dawley rats were used to develop a set of methods relying on unbiased stereological principles to determine the number of follicles, the total volume of colloid and the inner follicular surface area in the thyroid gland. The total volume of colloid was positively correlated (P < 0.021) with the number of follicles and the inner follicular surface area (P < 0.002) but not to the mean volume of colloid in each follicle. Thus under physiological conditions an increase in the total volume of colloid is associated with an increased number of follicles with a constant size distribution rather than a larger volume of colloid in each follicle. This implies that under physiological conditions there is equilibrium in the size distribution of the volume of colloid in each follicle.

Animals↗
PubMed2001

Linomide does not prevent spontaneous autoimmune thyroiditis in NOD mice.

Linomide is a potent immunomodulator and has been reported to prevent type 1 diabetes mellitus in non-obese diabetic (NOD) mice and to reduce the incidence of other autoimmune diseases in animal models. The mechanisms of action seem to involve antigen expression by down regulation of macrophage activity and to antagonise the activation of Th1 cells during the cellular immune response. With the purpose to investigate the effect of Linomide on the incidence of spontaneous autoimmune thyroiditis (AIT) in female NOD mice we administered Linomide in drinking water (100 mg/kg/day) to NOD mice from 5th to 19th week of age. The mice were sacrificed at the end of week 19. None of the mice developed diabetes during the study period. The incidence of thyroiditis was evaluated on paraffin HE-stained sections and graduated on a scale from 0 to 4. Thirty-two percent of 37 mice treated with Linomide developed thyroiditis compared to 45% of 22 controls (p=0.31, chi2 =1.00). Among the mice who developed thyroiditis no difference in the degree of thyroiditis was found. Therefore no beneficial effect of Linomide on the incidence of spontaneous AIT in NOD mice could be demonstrated.

Adjuvants, Immunologic↗
PubMed1999

[Serum thyroglobulin compared with ultrasonically detected recurrent goiter].

Thirty-nine patients were studied for 13 years following resection of non-toxic goitre in order to correlate changes in serum thyroglobulin (Tg) to relapse. Preoperative serum Tg was elevated. After operation, mean serum Tg declined to 43 micrograms/L at one year and increased to 90 micrograms/L at 10 years. Thyroid hormones showed evidence of compensated hypothyroidism at one month which normalised within one year. 13 years after resection thyroid volume was determined by ultrasonography in 30 patients. In 10 patients the thyroid volume was enlarged (> or = 28 ml). In this group delta Tg after resection was 133 micrograms/L, compared to 26 micrograms/L in the 20 patients without relapse (volume < 28 ml). Thus, repeated serum Tg determinations may provide biochemical evidence of increased growth of thyroid remnants following goitre resection.

Adult↗
PubMed1999

Models to study the pathogenesis of thyroid autoimmunity.

In vitro and in vivo models to study the pathogenesis of thyroid autoimmunity are reviewed. Animal models with experimentally induced or spontaneously developed autoimmune thyroid disease as well as transplantation models have been used extensively in these studies, but also the use of thyroid cell cultures from both humans and animals has contributed to the present state of knowledge. Cytokines may play a role in the pathogenic mechanism in thyroid autoimmunity. The major in vitro and in vivo effects of for example interleukin-1, tumour necrosis factor and gamma-interferon on differentiated thyroid cell functions are inhibitory. The advantage of using cell cultures has been the possibility of studying an influence on thyrocytes from a single agent individually, such as cytokines, hormones or growth factors. The disadvantage is that an organism is under the influence of a multitude of factors that can only be investigated in vivo in intact organisms. Both types of models have therefore been important in the understanding of thyroid autoimmunity.

Animals↗
PubMed1999

Cytokine production in NOD mice on prophylactic insulin therapy.

We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD mice by insulin treatment as used in prophylaxis studies. The cytokines were measured by ELISA in plasma and in supernatants of spleen cells activated ex vivo by lipopolysaccharide plus phytohemagglutinin. Insulin, 0.25-0.50 IU/day, was given subcutaneously for 8 weeks starting in 4-week-old female mice. The insulin-treated and control NOD mice showed similar weight gains and, by the end of the study, both groups exhibited cell infiltration in about 25% of their islets. IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. Diabetic NOD mice, aged 28-45 weeks, had significantly elevated plasma IL-1alpha: 154+/-39 pg/ml (mean+/-SEM, p<0.0001). While ex vivo activated NOD splenocytes released similar amounts of IL-1alpha, insulin therapy increased the levels from 99+/-17 to 155+/-19 pg/10(6) cells (p<0.05). Supernatants of activated splenocytes from prediabetic NOD mice had lower levels of IL-4 (<15 pg/10(6) cells) compared with those from BALB/c mice (88+/-22 pg/10(6) cells; p<0.01), and this deficiency was partially compensated for when the NOD mice were given insulin (27+/-8; p<0.01). The levels of IFNgamma were comparable and largely unaffected by insulin treatment. Hence, insulin therapy appears to partially normalize an otherwise deficient Th2 response in NOD mice.

Animals↗
PubMed1999

Thyrotropin stimulates specifically the expression of the autoantibody binding domains of the thyroperoxidase molecule.

To get some insight on the in vitro effect of TSH on the expression of two thyroid specific antigens (thyroglobulin (Tg) and thyroid peroxidase (TPO)) on the cell surface of cultured human thyroid cells an indirect immunofluorescence-activated cell sorter (FACStar IV, Becton-Dickinson) was used. Only half of the cultures responded to TSH by increased surface expression of the thyroid specific antigen Tg. In these cells, TSH stimulation of TPO expression showed a difference in epitopes recognized by murine monoclonal antibodies. Epitopes of domain D, recognized by monoclonal antibody 1, 30, 40 and 53 which are not involved in autoimmunity, were unaffected by TSH stimulation, (n = 2-10). In contrast, TSH regulated the surface expression of the TPO epitopes recognized by monoclonal antibody 15, 18, 24 and 60, which are known to be related to the serum autoantibody binding domain of TPO, (n = 6-8; p < 0.05). This indicated that increased activity of the thyroid cells selectively stimulated the expression of autoantigenic epitopes on the cell surface and supports the concept that increased cellular activity might predispose to the autoimmune processes leading to autoimmune thyroid disease.

Animals↗
PubMed1998

Effect of intrathymic administration of mycobacterial heat shock protein 65 and peptide p277 on the development of diabetes in NOD mice: caution required in vaccination studies.

Heat shock protein 65 (hsp65) and a derived peptide, p277, are autoantigens reported in IDDM. I.p. injection of hsp65 reduced diabetes incidence in NOD mice and administration of p277 cured already diabetic mice. Also, intrathymic (i.t.) administration of whole islets or GAD65 prevented diabetes in NOD mice. The aim of this study was to evaluate whether i.t. injection of mycobacterial hsp65 or p277 can prevent diabetes in NOD mice. Three-week-old NOD female mice were injected intrathymically with 50 microg of hsp65 (n=30), 5 microg of p277 (n=30), and PBS (n=29). Diabetes incidence was observed for the following 300 days. Pancreas was then used for histological and immunohistological evaluation. No significant differences in diabetes incidence were observed among the three groups of mice. Interestingly, hsp65-treated mice developed diabetes slightly faster at 177+/-6 days compared to 202+/-8 days (p=0.015) for the p277-treated group and 197+/-7 days (p=0.033) for controls. The insulitis score and average islet size did not differ significantly among the three groups of diabetic mice. Scattered TCR-gamma/delta positive cells were found in the pancreas of all groups of mice. In contrast, a huge infiltrate of TCR-gamma/delta positive cells was detected in four out of eight (50%) p277-diabetic NOD mice. Thus, our data show an earlier onset of diabetes in hsp65-treated mice and no improvement in the incidence with either hsp65 or p277, suggesting that hsp65 acts in a different way from what was reported with GAD65. Caution is advised in future vaccination studies as hsp65 poses a potential danger.

Animals↗