metallothionein and Syndrome

Topics: Gene Expression Regulation; Humans; Immunity, Cellular; Metallothionein; Syndrome; Zinc

To compare the metallothionein (MT) immunoexpression in non-syndromic and syndromic keratocystic odontogenic tumour (KOT), to correlate MT with cellular proliferation, and to evaluate the influence of inflammation in MT.. Fourteen cases of KOT were submitted to immunohistochemistry for MT and Ki-67 analysis. The lesions were grouped according to their grade of inflammation, and statistical analysis was performed.. MT was higher in non-syndromic KOT than in syndromic KOT (p<0.05). No statistical difference in Ki-67 could be identified; however, an inverse correlation was observed between MT and Ki-67 in both lesions. When analysing inflammation, non-syndromic KOT showed no differences in either MT or Ki-67.. The MT immunophenotype of syndromic KOT was different from non-syndromic KOT. MT might not be involved in the proliferation control of both KOT. MT and Ki-67 immunoexpressions proved to be unaffected by inflammation in non-syndromic KOT.

Topics: Humans; Immunohistochemistry; Ki-67 Antigen; Metallothionein; Odontogenic Cysts; Syndrome

A low-dose mitotane (MT) regimen was evaluated as a pharmacological approach for correcting the severe hypercortisolism in a young woman affected by Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD). In the first 12 week period, the MT daily dose was progressively increased from 0.5 to 4.0 g/day. This dosage was maintained for an additional 16 weeks (cumulative dose 602 g, plasma MT maximum level 12 microg/ml), and then stopped because of sustained signs of hypoadrenalism requiring prednisone replacement. Complete regression of seborrhea, acne, and plethora was observed after 8 weeks of treatment (cumulative dose 95 g). Regular menses returned after 13 weeks (cumulative dose 197 g, plasma MT 8 microg/ml). Profound decrease of both serum cortisol (from 615 to 220 nmol/l) and urinary free cortisol (UFC) values (from 1498 to 477 nmol/day) was noted after 16 weeks of treatment (cumulative dose 314 g, plasma MT 8 microg/ml). MT treatment was associated with mild gastric discomfort and reversible increase of cholesterol plasma levels. Low serum cortisol and UFC were still observed 41 weeks after MT was discontinued (plasma MT 0.2 microg/ml). Our report demonstrates that low dose MT treatment may be a safe and effective modality for a sustained correction of hypercortisolism by PPNAD in subjects with CNC waiting for surgery.

Topics: Adrenal Cortex Diseases; Adrenal Glands; Adult; Antineoplastic Agents, Hormonal; DNA; Female; Humans; Hydrocortisone; Long-Term Care; Metallothionein; Mitotane; Multiple Endocrine Neoplasia; Pigmentation Disorders; Reverse Transcriptase Polymerase Chain Reaction; Steroids; Syndrome; Tomography, X-Ray Computed

Northern blot analysis was used to investigate the effect of dexamethasone (Dex) or zinc on messenger RNA (mRNA) levels of metallothionein-IIa (MT-IIa) in fibroblasts from a patient with cortisol hyperreactive syndrome and from three normal subjects. Dex was seen to increase MT-IIa mRNA levels and brought them to a maximum after 12 h. Zinc also increased the levels of MT-IIa mRNA and brought them to a maximum at 8 h after the addition. Dex as well as zinc caused a dose-related increase in MT-IIa mRNA levels. Dex had a maximal inductive effect on MT-IIa at a concentration of 10(-6) mol/L and zinc at a concentration of 10(-4) mol/L. There was no significant difference in the levels of basal expression of the MT-IIa gene between the patient's and normal fibroblasts. But in three separate experiments induction of MT-IIa gene by Dex obtained for the patient's fibroblasts was almost twice as much as that for normal fibroblasts. On the other hand, there were no significant difference in induction by zinc between the patient's and normal fibroblasts. These data indicated that the patient's cells were hyperreactive to glucocorticoids as seen from the effect of Dex on the MT-IIa mRNA levels.

Topics: Adrenal Glands; Cycloheximide; Dexamethasone; Endocrine System Diseases; Fibroblasts; Humans; Hydrocortisone; Kinetics; Metallothionein; RNA, Messenger; Syndrome; Zinc

The lethal milk (lm) mutation in mice causes Zn deficiency in pups nursed by lm dams. To examine tissue Zn distribution and Zn transport to milk and pups, 65Zn was administered to lactating normal and lm dams. Transport of 65Zn to milk of lm dams was approximately 50% of that transported to milk of normal dams. The lower milk 65Zn resulted in significantly less 65Zn uptake by tissues of the nursing pups. The decrease in 65Zn transport to the milk was accompanied by a significant increase in 65Zn uptake and metallothionein mRNA levels in kidney of the lm dams. The elevated Zn uptake and metallothionein expression was tissue specific and could be a reflection of altered zinc transport from mammary gland to milk. Polyacrylamide gel electrophoresis and Western transfer of mammary gland proteins from lm dams showed that a 30-kDa protein bound more 65Zn in vitro compared with proteins from normal mammary gland. Normal pups nursed by dams of the lm genotype had down-regulated metallothionein expression due to Zn deficiency. The genetic defect in lm mice decreases Zn transport to milk, thus explaining the neonatal Zn deficiency seen in normal mice fostered by lm dams. The greater metallothionein expression in dams of the lm genotype could be a secondary manifestation of altered tissue zinc distribution or a primary effect on a metallothionein regulatory mechanism.

Topics: Animals; Animals, Newborn; Biological Transport; Blotting, Northern; Densitometry; Gastric Mucosa; Intestinal Mucosa; Intestines; Kidney; Lactation; Liver; Mammary Glands, Animal; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Milk; RNA, Messenger; Syndrome; Zinc; Zinc Radioisotopes