Search PubMed⌕ Search

Biomedical subjects

G Karsenty

Publications and source records attributed to G Karsenty.

121 records · Page 7Linked to original sources
PubMed1986

Value of the 99mTc-methylene diphosphonate bone scan in renal osteodystrophy.

The value of radionuclide bone scanning in the diagnosis of renal osteodystrophy is still debated. In order to re-examine this issue, 25 uremic patients treated by intermittent hemodialysis underwent 99m-Technetium Methylene Diphosphonate (99mTc-MDP) bone scan. They were subdivided into three groups according to quantitative bone histology. Group 1 (N = 8) had pure dialysis osteomalacia, group 2 (N = 7) mixed lesions, and group 3 (N = 10) pure osteitis fibrosa. The scintigraphic studies were interpreted by means of a five point semi-quantitative scale. Using this quantification, all but one group 1 patients had decreased bone tracer uptake, and all patients of group 3 had an increased uptake (chi square test of Yates, P less than 0.001). Among patients of group 2, bone uptake was decreased in the three patients with clearly reduced mineralization front and moderate osteitis fibrosa, but it was increased in all patients with severe osteitis fibrosa and subnormal mineralization front. A quantitative analysis of regional tracer uptake into bone was performed in two patients: one of group 2 and one of group 3. The results obtained clearly corroborated the semi-quantitative findings. Thus, in hemodialysis patients with symptomatic bone disease, the 99mTc-MDP bone scan provides useful information for the differential diagnosis between dialysis-related osteomalacia and secondary hyperparathyroidism. In patients with mixed lesions, the importance of bone tracer uptake appears to depend on the extent of the mineralization front and on the intensity of osteitis fibrosa.

Adult↗
PubMed1986

[Hashimoto's thyroiditis with intra-thyroid production of a monoclonal antithyroglobulin autoantibody].

A 46-year old man had an Hashimoto's thyroiditis. The disease was particular by the voluminous goiter, associated with pressure symptoms and by the presence of a monoclonal Ig.G Kappa. Because of a possibly associated lymphoma of the thyroid, a total thyroidectomy was performed. Post-operative course showed a rapid and total disappearance of monoclonal Ig.G and antithyroglobulin autoantibodies. There was no pathological feature of thyroid malignancy. We could show that the monoclonal Ig.G bore an antithyroglobulin activity and that this monoclonal antithyroglobulin autoantibody was produced with in the thyroid. This case demonstrate that a monoclonal proliferation can arise from autoreactive B lymphocytes infiltrating the thyroid during Hashimoto's thyroiditis. Such a mechanism could explain, in some cases, the well-known association between lymphomas of the thyroid and Hashimoto's thyroiditis.

Antibodies, Monoclonal↗
PubMed1985

Phosphate fluxes in isolated enterocytes from vitamin D replete and vitamin D deficient rats--early effects of calcitriol.

In the present work we studied rapid in vitro effects of calcitriol (1,25(OH)2 vitamin D3) on the intestinal transport of inorganic phosphate (Pi). Enterocytes from vitamin D replete (D+) as well as vitamin D depleted (D-) rats were isolated mechanically from the duodeno-jejunum. In this model, Pi uptake was a temperature and Na+-dependent phenomenon. The in vitro-addition of calcitriol (1 pM) resulted in a significant enhancement of initial Pi uptake rate by enterocytes from D+ (P less than 0.01) and D- (P less than 0.05) rats. This effect which was Na+-dependent, was observed within the time of 20 min, but not before. A similar effect on Pi uptake rates of D+ or D- enterocytes could be elicited by the in vitro addition of the methyl ester of cis-vaccinic acid (MCVA) which is thought to increase membrane fluidity by modifying the lipid composition of the cell membrane. The stimulatory effect of calcitriol on Pi uptake rate was blunted in the presence of the methyl ester of transvaccinic acid (MTVA) thought to decrease membrane fluidity. Enterocyte Pi efflux rate constant (oKPi) remained unchanged in the presence of calcitriol (1 pM). In conclusion, the study demonstrates a rapid in vitro effect of calcitriol on Pi uptake by isolated enterocytes from D+ and D- rats. It suggests, but does not prove, that the hormone may act via an action independent of genomic nuclear activation.

Animals↗
PubMed1985

Monoclonal human thyroid cell line GEJ expressing human thyrotropin receptors.

By using the hybridoma technology, a monoclonal human thyroid cell line was obtained by fusing fresh normal human thyroid cells with a human lymphoblastoid cell line. The resultant cell line, called GEJ, has been selected for its expression of thyrotropin (TSH) receptors and has morphological and functional characteristics of normal human thyroid cells. In the presence or absence of human TSH, the GEJ cell line accumulates iodide, produces thyroid hormones, expresses thyroid membrane antigens, and binds approximately equal to 600 molecules of TSH per cell. The binding site for TSH has all the characteristics of specific receptor (i.e., temperature and time dependencies, dissociation of bound TSH only by high amounts of TSH, and a glycoprotein nature). Scatchard analysis described a curvilinear graph with two dissociation constants (Kd = 0.12 X 10(-9) M and 1.6 X 10(-9) M) with, respectively, 1.2 X 10(3) and 7.2 X 10(3) binding sites per cell. This human thyroid cell line that expresses TSH receptors could be a useful tool for the study of human thyroid disorders.

Cell Line↗
PubMed1985

Early effects of vitamin D metabolites on phosphate fluxes in isolated rat enterocytes.

The present studies were designed to explore the possibility that, in addition to its well-known steroidlike action, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active vitamin D3 metabolite, modulates inorganic phosphate (Pi) transport across the intestinal mucosa through more rapid membrane effects. Enterocytes were mechanically isolated from the duodenojejunum of vitamin D-replete rats. In this model enterocyte Pi uptake was a temperature-dependent as well as a Na+-dependent process. In vitro addition of 1,25(OH)2D3 (1 pM) led to a significant increase in Na+-dependent initial Pi uptake velocity (iVpi) within 20 min (P less than 0.001). No effect was seen for shorter incubation times (5 and 15 min). Incubation of the cells with cycloheximide did not inhibit the hormone-mediated increase of iVpi. 25-Hydroxyvitamin D3 significantly increased iVPi (P less than 0.05) at a concentration of 1 nM but not 1 pM. Vitamin D3 at a concentration of 1 microM had no effect on iVPi. Enterocyte Pi efflux rate constant was not modified by the presence of 1,25(OH)2D3(1pM). Thus, the early in vitro effect of 1,25(OH)2D3 on Pi uptake by isolated enterocytes suggests a nongenomic action of the hormone, possibly by modifying the lipid structure of the plasma membrane.

Animals↗
PubMed1985

Clinical and histological resolution of systemic amyloidosis after renal cell carcinoma removal.

This report describes the case of a 62-year-old woman with systemic amyloidosis involving the kidneys and digestive tract, consecutive to a renal cell carcinoma. Within 3 years after tumor removal, both the nephrotic syndrome and protein loss enteropathy regressed. Histological examination showed the disappearance of the potassium permanganate-sensitive deposits within the digestive tract. This indicates that clinical remission of systemic amyloidosis may be associated with morphologic disappearance of amyloid deposits.

Amyloidosis↗
PubMed1985

Elevated metabolic clearance rate of 1 alpha,25-dihydroxyvitamin D3 in hyperthyroidism.

Metabolic clearance rate (MCR) and daily production rate (DPR) of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) were measured in 7 hyperthyroid patients and 8 control subjects after a single injection of tritiated 1,25(OH)2D3. Using a bicompartmental analysis, MCR of 1,25(OH)2D3 was found to be significantly higher in hyperthyroid than in control subjects (11.5 +/- 4.4 vs 5.9 +/- 2.4 ml/min (SD), P less than 0.01). No significant difference in plasma 1,25(OH)2D and DPR of 1,25(OH)2D3 was demonstrated. MCR was again measured 1 month after initiation of treatment in 4 hyperthyroid patients and remained elevated. In 2 of these patients, MCR was once more determined 6 months later and had declined towards normal. No correlation was found between MCR and DPR and either plasma calcium, phosphate, immunoreactive PTH, 1,25(OH)D and T3 values. In conclusion, MCR of 1,25(OH)2D3 is elevated in hyperthyroidism, but this finding is probably unrelated to the effect of thyroid hormones on bone metabolism.

Adult↗
PubMed1984

Effect of carbimazole treatment on specific and non-specific immunological parameters in patients with Graves' disease.

Twenty-two patients with newly diagnosed Graves' disease (GD) were treated with carbimazole (CBZ) for 6 months. Thyroid stimulating immunoglobulins (TSI) and T cell subsets were studied prior to treatment and after 3 and 6 months of therapy. TSI were measured on human thyroid epithelial cell monolayers by the cAMP production after the addition of highly purified GD IgG. Before treatment, serum IgG from 20 out of the 22 patients (91%) stimulated cAMP production significantly compared to normal IgG. The mean index of cAMP production (GD IgG relative to normal IgG) was 2.15. After 3 months of CBZ treatment, a non-significant decrease of the mean cAMP production index was observed, whereas it was significantly decreased at the end of the 6 month course of therapy. Before treatment, total T cells (OKT3+), helper/inducer T cells (OKT4+) and suppressor/cytotoxic T cells (OKT8+) were all significantly decreased compared with controls. After 3 or 6 months of CBZ therapy, both total T cells and helper/inducer T cells returned to a normal level, while cytotoxic/suppressor T cells remained at the same low level. Taken together, these data indicate that treatment with CBZ leads to an early increase of helper/inducer T cells followed 3 months later by a decrease of the TSI level with no change in decreased suppressor/cytotoxic T cells. The disappearance of TSI following the increased helper/inducer T cell level suggests that an anti-idiotypic reaction may have occurred, and the persistent decrease of the suppressor/cytotoxic T subset that CBZ therapy does not act upon the underlying autoimmune disease.

Adult↗
PubMed1984

[Therapeutic leukapheresis in tricholeukocytic leukemia].

Therapeutic leukapheresis was performed in a patient with hairy cell leukaemia (100,000 WBC/mm3; 98 p. 100 hairy cells) without signs of hypersplenism. Twenty-five sessions were carried out in 12 weeks. A rapid and significant improvement was observed with the WBC falling to 25,000 WBC/mm3 with 70 p. 100 of hairy cells and the normalisation of the bone marrow biopsy. When these sessions were finished, splenectomy was performed in optimal conditions. This treatment would seem to be valuable in hairy cell leukaemia without severe hypersplenism. Long-term improvement may be hoped because hairy cells have a very short turnover rate.

Adult↗
PubMed1984

Complement alternative pathway activation by chronic lymphocytic leukemia cells: its role in their hepatosplenic localization.

Using affinity-purified 125I-F(ab')2 anti-human C3, we have investigated the ability of various leukemic cells to activate complement. Lymphocytes from patients with chronic lymphocytic leukemia (CLL) activated the alternative pathway, but cells from patients with other forms of leukemia or normal lymphocytes did not do so. The amount of C3 deposited on the CLL cells was significantly higher in patients with organomegaly (i.e., splenomegaly and/or hepatomegaly). Activation of complement by CLL cells as assessed by C3 deposition on the membrane occurred both in vivo and in vitro and was not related to the N-acetylneuraminic acid content of the membrane.

Acute Disease↗
PubMed1982

[Pathophysiology of Grave's disease (author's transl)].

It has been established that Grave's disease is an autoimmune condition characterized by immunization against TSH receptors. Neither the receptors nor the stimulating immunoglobulins have been identified, but there seems to be two types of antireceptor antibodies: some stimulate the production of hormones or of thyroid stimulating immunoglobulins (TSI) and are responsible for thyrotoxicosis; others stimulate cell proliferation or thyroid growth immunoglobulins (TGI) and account for the diffuse goitre. The mechanism that triggers off autoimmunization is still unknown, but the disease frequently occurs in individuals genetically predisposed, as suggested by the high incidence of some HLA B8 and DR W3 antigens.

Autoantibodies↗