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H P Fortmeyer

Publications and source records attributed to H P Fortmeyer.

At least 19 recordsLinked to original sources
PubMed1999

Chronic selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in rats.

OBJECTIVE/METHODS: In order to investigate whether selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in the rat hindlimb, rats were selectively bred to establish two strains, one with a pronounced hypertriglyceridemia (HT) and the other with normal plasma levels of triglycerides (LT). RESULTS: Carotid arteries and aortae removed from 3, 6, 9 and 12 month old LT- and HT-rats exhibited a normal morphology. However, marked morphological differences were observed between vessels from 18-20 month old HT- and LT-rats. The endothelium-dependent vasodilator acetylcholine (2 to 50 micrograms/kg), administered into the iliac artery, elicited a concentration-dependent increase in hindlimb blood flow which was not different in 3, 6 and 9 month old LT- or HT-rats but was impaired in 12 and 18-20 month old HT-rats. In contrast the endothelium-independent vasodilator sodium nitroprusside enhanced blood flow in both strains to a similar extent. Neither administration of the nitric oxide (NO) synthase (NOS) substrate, L-arginine, nor the NOS inhibitor NGnitro-L-arginine, affected the responsiveness to endothelium-dependent vasodilators in 12 month old HT-rats. These attenuated responses could not be attributed to a decrease in endothelial NOS expression as Western blot analysis revealed identical levels of this enzyme in the aortae and carotid arteries from LT- and HT-rats. Determination of superoxide anion (O2-) formation however, demonstrated a markedly elevated production of O2- in aortae from HT-rats. CONCLUSION: We conclude that chronic selective hypertriglyceridemia, an independent risk factor in the development and progression of atherosclerosis, leads to an endothelial dysfunction which is associated with an increased vascular O2- production and a subsequent decrease in bioavailable NO.

Acetylcholine↗
PubMed1996

Effect of Graves' intrathyroidal lymphocytes. Effect of Graves' disease intrathyroidal lymphocytes (ITL) on xenotransplants of human thyroid tissue in athymic nude mice.

It has been suggested that ITL are of importance in the pathogenesis of human autoimmune thyroid disease. Aim of our study was to investigate function and morphology of xenotransplanted human thyroid tissue in nude mice following systemic application of lymphocyte preparations from patients with Graves' disease (GD) and non-toxic nodular goiter (NTG). ITL obtained from 13 patients with GD and peripheral blood lymphocytes (PBL) from 12 patients with NTG were injected into nude mice bearing 8 weeks old xenografts of normal human thyroid tissue. ITL- and PBL-subsets were analyzed by flow cytometer (FACScan) before engraftment. Two days after injection the thyroid transplants were examined histologically (HE) as well as immunohistologically by staining with: CD3, CD31, CD45R, HLA class II, ICAM-1, VCAM-1, IgG, IgM and Ki67. Flow cytometry showed a significant higher number of the lymphocyte-subsets CD3, DR+ and CD4 in GD-ITL as compared to the subsets in NTG-ITL. After injection of GD-ITL to the nude mice also a significant higher number of CD3+ human lymphocytes was found in the transplants. GD-lymphocytes stimulated thyroid tissue function significantly more pronounced than NTG-lymphocytes (histomorphological evaluation). In addition, a significant increase of HLA-class II, ICAM-1-, VCAM-1-, CD45-expression and number of Ig presenting plasma cells were observed only after injection of GD-ITL. Our data demonstrate, for the first time in vivo (nude mouse model), that GD-lymphocytes of both peripheral and intrathyroidal origin selectively migrate into human thyroid transplants ("homing"). They survive there for at least two days and induce significant functional as well as histological changes, like expression of gene products and IgG synthesis. These results suggest an important role of ITL in the pathogenetic mechanisms and clinical course of GD.

Animals↗
PubMed1996

[Spontaneous Hashimoto-like thyroiditis in cats].

A breeding line of domestic cats spontaneously developing symptoms of hypothyroidism between the 40th and 60th day of life (fur changes, loss of appetite, growth retardation), elevated levels of antibodies against microsomal structures and thyroglobulin, and lymphocytic thyroid infiltration has been recently established at our facility. Aim of our studies was to examine the effect of high iodine ingestion or prophylactic thyroid hormone therapy on functional and morphological characteristics of this Hashimoto-like thyroiditis in cat. From birth to day 80 of life cats were treated with iodine (n = 9; 0.1 mg/l) or thyroxin (n = 13; 2.0 micrograms/ kg/d) respectively. Untreated animals served as controls (n = 12). Cat-serum was tested for thyroid function (TT3, TT4). After 8 weeks the thyroid tissue was submitted to routine histological processing (H&E) and the inflammatory activity was scored. Additionally immunohistological staining was performed for MIB-1, IgG, IgM and MHCII expression. Both untreated hypothyroid (UHC) as well as iodine-treated (IC) cats revealed a significantly higher degree of thyroid inflammation and higher tissue levels of IgM as the thyroxin-substituted animals (TC). Epithelial proliferation decreased significantly in the IC and TC groups as compared to the untreated controls. No significant differences regarding IgG production and HLAII expression were detectable. Early thyroid hormone therapy significantly decreases both incidence and activity of autoimmune thyroiditis in cats as measured by inflammatory infiltration, IgM production and epithelial proliferation. Animals with excess iodide intake, however, show an aggravation of the autoimmune inflammatory activity.

Animals↗
PubMed1993

pH in human tumour xenografts: effect of intravenous administration of glucose.

pH frequency distributions of tumours grown s.c. from 30 human tumour xenograft lines in rnu/rnu rats were analysed with the use of H+ ion-sensitive semi-microelectrodes prior to and following stimulation of tumour cell glycolysis by i.v. infusion of glucose. At normoglycemia, the average pH of the tumours investigated was 6.83 (range, 6.72-7.01; n = 268). Without exception, all xenografts responded to the temporary increase in plasma glucose concentration (PGC) from 6 +/- 1 to 30 +/- 3 mM by an accumulation of acidic metabolites, as indicated by a pH reduction to an average value of 6.43 (range, 6.12-6.78; n = 292). This pH value corresponds to a ten-fold increase in H+ ion activity in tumour tissue as compared to arterial blood. Tumour pH approached minimum values at 2-4 h after the onset of glucose administration and could be maintained at acidic levels for 24 h by controlled glucose infusion. Irrespective of pH variations between tumours grown from individual xenograft lines, there was no major difference in pH response to glucose between the four main histopathological tumour entities investigated, i.e. breast, lung and gastrointestinal carcinomas, and sarcomas. In tumours from several xenograft lines, an increase in blood glucose to only 2.5-times the normal value (14 mM) was sufficient to reduce the mean pH to 6.4. Glucose-induced acidosis was tumour-specific. The pH frequency distributions in liver, kidney and skeletal muscle of tumour-bearing rnu/rnu rats were only marginally sensitive to hyperglycemia (average pH, 6.97 vs normal value of 7.14). Tumour-selective activation of pH-sensitive anti-cancer agents, e.g. alkylating drugs, acid-labile prodrugs or pH-sensitive immunoconjugates may thus be feasible in a wide variety of human cancers.

Animals↗
PubMed1988

Glucose uptake, lactate release, ketone body turnover, metabolic micromilieu, and pH distributions in human breast cancer xenografts in nude rats.

Glucose uptake, lactate release, ketone body utilization, spatial distribution of glucose, lactate, and ATP concentrations as well as tissue pH distributions were systematically investigated in s.c. and/or "tissue-isolated" human breast cancer xenografts in T-cell-deficient rnu/rnu rats. Large variations in all parameters were detected within and between tumors indicating a very nonuniform substrate turnover. Glucose was taken up by all xenografts. Glucose consumption rates increased with increasing glucose availabilities, implying that the glucose uptake is mainly determined by the efficiency of nutritive tumor blood flow. The average glucose uptake was 0.37 mumol/g/min in medullary and 0.26 mumol/g/min in squamous cell carcinomas of the breast. At wet weights below 5 g, medullary breast cancers consumed more glucose than squamous cell carcinomas (2P less than 0.05). Most tumors (97%) released lactate in an amount linearly related to glucose consumption. The lactate production of medullary (0.33 mumol/g/min) and squamous cell (0.31 mumol/g/min) breast cancers was similar. In general, the xenografts utilized ketone bodies. beta-Hydroxybutyrate was consumed by 82% and acetoacetate by 73% of the tumors, the uptake rates being linearly related to the respective availabilities. The mean uptake of beta-hydroxybutyrate was 3.48 nmol/g/min and that of acetoacetate 2.56 nmol/g/min. No significant differences were seen between medullary and squamous cell breast cancers. The beta-hydroxybutyrate/acetoacetate ratio in the tumor-venous blood rose with decreasing tumor blood flow indicating the development of hypoxia at advanced growth stages. Glucose, lactate, and ATP levels were all very heterogeneously distributed in medullary and squamous cell tumors as compared with normal tissue. No relationship was evident between the spatial distribution of concentrations of these three substrates. The xenografts were acidotic compared with pH values in normal subcutis. The mean tissue pH in medullary breast cancers was 6.81 +/- 0.25 (SD). Compared with these values, the tissue pH distribution in squamous cell breast cancers was shifted to significantly higher values. The mean pH of the latter tumors was 7.04 +/- 0.19 (2P less than 0.001). From the experimental data presented there is clear indication that the metabolism of the xenografts investigated was mainly determined by the efficiency of nutritive blood flow, i.e., by substrate availability, and not by the metabolic demand of the cancer cells.

Animals↗