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Biomedical subjects

M L Brandi

Publications and source records attributed to M L Brandi.

At least 19 recordsLinked to original sources
PubMed1992

Cytogenetics of multiple endocrine neoplasia syndrome. II. Chromosome abnormalities in an insulinoma and a glucagonoma from two subjects with MEN1.

Cytogenetic analysis of two pancreatic islet tumors, an insulinoma and a glucagonoma was ascertained in two subjects with multiple endocrine neoplasia type 1 (MEN1). The insulinoma had a modal peak at 84 chromosomes. Most cells were pseudotetraploid, and in all cells the normal chromosomes were represented in varied numbers, i.e., from 1 to 7 copies. The tumor had 5 characteristic and consistent marker chromosomes which were identified as deletions of chromosomes 1, 2, 7, 16, and 17. All metaphases had several double minute chromosomes (dmin) of variable size and possible intermediate structures between dmin and homogeneously staining chromosomal regions. The glucagonoma had a nearly equal proportion of normal metaphases and metaphases with structural and numerical abnormalities with no consistent trend.

Chromosome Aberrations↗
PubMed1992

Relaxin influences the growth of MCF-7 breast cancer cells. Mitogenic and antimitogenic action depends on peptide concentration.

BACKGROUND: The effects of relaxin (RLX) on the human breast adenocarcinoma cell line MCF-7 have been evaluated. METHODS: The cells were maintained in culture with Dulbecco's modified Eagle's medium with 1% and 10% fetal calf serum. Highly purified porcine RLX was added at concentrations ranging between 10(-11) and 10(-6) M, and, after 96-hour incubation in the presence of the peptide, cell proliferation, intracellular cyclic adenosine monophosphate (cAMP) content, percent cycling cells, and structural and ultrastructural pattern were studied. RESULTS: The results indicate that RLX is a direct modulator of MCF-7 cell proliferation, stimulating growth at low concentrations and inhibiting growth at high concentrations. Determinations of percent cycling cells and intracellular cAMP accumulation agree with the results of the growth studies. Addition of different concentrations of 8-Br-cAMP to the culture medium results in a dose-related stimulation of MCF-7 cell proliferation. Morphologic examination shows that, in the current experiments, RLX does not induce any clear-cut signs of differentiation of MCF-7 cells in terms of activation of secretion or intracellular lipid deposition. CONCLUSION: These findings indicate that RLX should be regarded as a novel agent involved in the control of growth of human breast cancer cells.

Adenocarcinoma↗
PubMed1992

Detection of P-glycoprotein on endothelial and endocrine cells of the human pancreatic islets by C 494 monoclonal antibody.

P-glycoprotein, an integral membrane protein acting as an energy-dependent efflux pump, has been detected immunocytochemically in the human pancreatic islets using C 494 monoclonal antibody. Intense P-glycoprotein immunoreactivity was found in both endothelial cells of islet blood capillaries and in endocrine cells. Strong expression of P-glycoprotein has been found in the capillary blood vessels at blood-tissue barrier sites and in numerous kinds of cells with secretory/excretory function. Therefore the present findings suggest that P-glycoprotein may play a role in controlling the composition of the extracellular fluids and the intracellular milieu of endocrine islet cells and possibly in regulating their secretory activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results.

The effects of ipriflavone on bone cells were studied in vitro on pre-osteoclastic (FLG 29.1) and osteoblast-like (Saos-2) cells grown for 48 h either separately or in co-cultures, with or without the addition of PTH. Histological, ultrastructural and histochemical (TRAP-activity demonstration) methods were used. The main results show that ipriflavone reduces replication of FLG 29.1 cells and inhibits TRAP production by these cells both in controls and in co-cultures treated with PTH. Moreover, it has a moderate stimulatory effect on proliferation of osteoblast-like cells and reduces the PTH-induced degenerative changes of Saos-2 cells. These results suggest that the inhibitory effect of ipriflavone on FLG 29.1 cells might be indirect and might be mediated by the osteoblast-like cells.

Acid Phosphatase↗
PubMed1992

Phorbol ester induced osteoclast-like differentiation of a novel human leukemic cell line (FLG 29.1).

Studies on human osteoclast formation have been hampered by lack of a defined isolated progenitor cell population. We describe here the establishment of a human leukemic cell line (designated FLG 29.1) from bone marrow of a patient with acute monoblastic leukemia. The cultured cells are predominantly undifferentiated leukemic blasts, but addition of 12-o-tetradecanoylphorbol 13-acetate (TPA; 0.1 microM) induces irreversible differentiation into adherent, non-dividing, multinucleated cells. TPA-treated cells bear surface antigens typical of fetal osteoclasts, degrade 45Ca-labeled devitalized bone particles, display tartrate-resistant acid phosphatase in both mononuclear and multinuclear cells and receptors for calcitonin. Calcitonin increases intracellular cAMP accumulation in TPA-treated cells. TPA-treated cells show some ultrastructural features of osteoclasts as evidenced by transmission EM. These results indicate that FLG 29.1 cells may represent an osteoclast committed cell population, which upon induction with TPA acquire some morphological, phenotypical, and functional features of differentiated osteoclasts.

Antigens, CD↗
PubMed1992

Studies in a kindred with parathyroid carcinoma.

We report a family with primary hyperparathyroidism in four patients in two generations with apparent autosomal dominant transmission. A fifth member was probably affected. Two cases had definite parathyroid carcinoma (PC), and two had parathyroid adenoma with atypical features that could represent an early stage of cancer. In each of our patients, one parathyroid gland was abnormal. Five other parathyroid glands (in two patients) were normal in histology and size. There was no evidence of neoplasia in other tissues. Constitutional karyotypes were normal in all four patients. We identified three chromosomal abnormalities (a reciprocal translocation between chromosomes 3 and 4, trisomy 7, and a pericentric inversion in chromosome 9) in cultured PC tissue from one patient. These chromosomal changes are of unclear significance. Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1). This family shows susceptibility to cancer without antecedent hyperplasia in all parathyroids. It could help identify a novel tumor susceptibility gene.

Adenoma↗
PubMed1992

Extracellular Ca2+ sensing in C-cells and parathyroid cells.

An essential function of C-cells and parathyroid cells is to monitor the extracellular Ca2+ concentration. The Ca(2+)-dependent secretion of calcitonin (CT) and parathyroid hormone is known to be mediated by corresponding changes in the intracellular Ca2+ concentration. To address the question of whether Ca2+ influx through voltage-dependent Ca2+ channels couples the extracellular to the intracellular Ca2+, we applied the patch clamp technique to C-cells of the rMTC 44-2 cell line and to parathyroid cells of the PT-r cell line. The rMTC cells displayed dihydropyridine-sensitive, voltage-dependent, high-threshold Ca2+ channels which allowed ion influx even at the resting potential of about -40 mV. Increases of the concentration of the extracellular divalent cation or adding the Ca2+ channel agonist Bay K 8644 stimulated the steady state ion influx. In contrast, PT-r cells exhibited only fast inactivating, low-threshold Ca2+ channel currents with no steady state conductivity for Ca2+ at the resting potential of around -40 mV. We conclude that dihydropyridine-sensitive Ca2+ channels allow steady state transmembranous Ca2+ influx in C-cells, thereby increasing the cytosolic Ca2+ and CT secretion. Parathyroid cells, however, lack long-lasting Ca2+ channel currents and obviously sense the extracellular Ca2+ concentration by other mechanisms.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Parathyroid tumor biology in familial multiple endocrine neoplasia type 1: a model for cancer development.

Familial multiple endocrine neoplasia type 1 (FMEN 1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. Hyperplasia appears to be the typical histopathological lesion in FMEN 1 endocrine tumors. A circulating mitogen related to basic fibroblast growth factor was active on proliferation of clonal bovine and human parathyroid endothelial cells. Moreover, the FMEN 1 mitogen modulated differentiation of human parathyroid endothelial cell in vitro. All these facts suggested that an extrinsic factor was active on parathyroid endothelial cell growth and differentiation. The FMEN 1 gene maps to chromosome 11q13, and allelic loss in this region has been shown in FMEN 1 parathyroid and pancreatic islet tumors and rarely in anterior pituitary tumors. Together these results support the theory that FMEN 1 parathyroid clonal lesions can develop in the context of generalized hyperplasia. Similarly, in uremic hyperparathyroidism, where parathyroid hyperplasia is thought to be the primary lesion, loss of constitutional heterozygosity for chromosome 11 markers coexists in parathyroid tissue with a polyclonal pattern. Future efforts of scientists working on this genetic disorder will focus on the cloning of the FMEN 1 gene and the development of a suitable bioassay system to study its function.

Chromosomes, Human, Pair 11↗
PubMed1992

Characterization of the clinical features of five families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2.

The hereditary conditions of primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2 (MEN 2) are rare clinical entities. The initial reports of two families in which the two conditions coincided have led to the identification of at least eight additional families with this clinical syndrome. In this report we describe the clinical features in five of these eight families. The salient feature in these five families is the presence of unilateral (46%) or bilateral (64%) pruritic and lichenoid skin lesions located over the upper portion of the back. Family members describe these skin lesions as intermittently intensely pruritic leading to scratching and excoriation of the upper back region. The presence of MEN 2 has been documented in 97% of family members with this skin lesion, the one exception being a child who is at risk for development of MEN 2A in whom the diagnosis has not yet been made. Of family members who have MEN 2A, 27% do not have an identifiable skin lesion, although the skin lesion developed in one patient two years after a curative thyroidectomy for medullary thyroid carcinoma (MTC). Four of the five families have members with pheochromocytoma; one with five affected members has only MTC. The finding of this clinical syndrome in geographically diverse portions of the world and the lack of overlap with MEN 2A without the skin lesion suggest it is a distinct clinical variant of MEN 2A.

Adolescent↗
PubMed1992

[Multiple endocrine neoplasms].

The multiple disorders endocrine neoplasia syndromes are autosomal inherited disorders characterized by typical associations of tumors of the endocrine glands. Three different syndromes have been recognized, the type 1, the type 2A and the type 2B. The gene of the multiple endocrine neoplasia type 1 has been localized on chromosome 11 region q13, while the MEN 2 gene maps on the pericentromeric region of chromosome 10. The few years since the original mapping of the two disease genes have seen considerable effort by several laboratories to refine the localization of the genes and obtain good flanking markers. This effort has two purposes: 1) better presymptomatic "diagnosis" and genetic counselling based on both very close and flanking markers, and 2) definition of the molecular regions containing the MEN 1 and MEN 2 loci as a necessary first step in positional cloning efforts. In most clinical situations it is possible to identify a haplotype with the mutant allele in the middle. The calculated predictive accuracy of this test is greater than 95% for the two syndromes. Therefore, genetic linkage testing can be used for informed genetic counselling in families affected by multiple endocrine neoplasia type 1 and 2.

Alleles↗
PubMed1991

Endothelin as an autocrine factor in the regulation of parathyroid cells.

Endothelin, originally purified from porcine aortic endothelial cells, is widely distributed in tissues and is recognized as a product of epithelial cells, glial cells, and neurons in addition to endothelial cells. We found evidence by mRNA content and immunoreactivity that this peptide is synthesized in rat parathyroid epithelial cells (PT-r cells) and bovine parathyroid chief cells. The peptide synthesized by PT-r cells comigrated with synthetic endothelin 1 in reverse-phase HPLC and was diluted out in radioimmunoassay in parallel with the synthetic peptide. Bovine parathyroid endothelial cells (BPE-1 cells) did not express this peptide. Preproendothelin 1 mRNA expression by PT-r cells and endothelin 1 peptide production were regulated by calcium. Shifts in extracellular calcium either from high to low concentrations or vice versa elicited similar evanescent increases in expression of mRNA with a peak at 1 h. Synthesis of the peptide seems to be controlled by mRNA expression, and peptide in the medium appears to be continuously degraded or taken up by cells because its concentration in the medium showed a time course similar to that of mRNA expression. PT-r cells also bear a single class of receptors highly specific for endothelin 1, suggesting an autocrine regulation by endothelin 1 of the parathyroid. The facile regulation of endothelin concentrations in the medium by shifts in extracellular calcium concentration and possible autocrine regulation by endothelin 1 suggest that this peptide may mediate, at least in part, effects of calcium on the parathyroid system.

Animals↗
PubMed1991

Allelic loss on chromosome 11 in hereditary and sporadic tumors related to familial multiple endocrine neoplasia type 1.

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. The gene for this disease maps to chromosome 11q12-11q13, and allelic loss in this region has been shown in both sporadic and FMEN1-related parathyroid tumors. FMEN1-related pancreatic islet tumors, and rarely in sporadic anterior pituitary tumors. We tested for allelic loss at 7 loci on chromosome 11 in 17 tumors outside the parathyroid. We found loss of heterozygosity in 2 of 2 FMEN1-related benign pancreatic islet tumors but in none of 8 informative sporadic islet tumors (P = 0.02) including 5 malignant gastrinomas. Of 3 islet tumors from patients who had some but not all features of FMEN1, one showed allelic loss for 5 of 5 informative restriction fragment length polymorphisms, and the other 2 retained heterozygosity for all informative markers. A bronchial carcinoid from an FMEN1 patient and 3 sporadic anterior pituitary tumors showed no allelic loss. These data provide new evidence that many sporadic pancreatic islet neoplasms, even when malignant, do not develop through homozygous inactivation of the MEN1 gene.

Adenoma, Islet Cell↗
PubMed1991

Effects of ipriflavone and its metabolites on a clonal osteoblastic cell line.

Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption. A direct effect of ipriflavone on bone formation is as yet unknown. Ipriflavone and four of its metabolites (I, II, III, and V) were examined for their effects on parathyroid hormone response, collagen synthesis, alkaline phosphatase activity, and cell proliferation in a clonal cell population of rat osteoblastic cells. Pretreatment of osteoblasts with high concentrations of ipriflavone for 48 h significantly inhibited the cAMP response to parathyroid hormone, producing a shift in the dose-response curve; at lower concentrations metabolites II and III potentiated the cAMP accumulation induced by low doses of parathyroid hormone. The 48 h treatment with metabolite V at the 1 nM dose significantly stimulated collagen synthesis in osteoblastic cells. Ipriflavone and metabolite I showed a biphasic stimulatory action on the alkaline phosphatase activity of osteoblasts, with a maximal effect at the 0.1 and 1 nM doses, respectively. A similar biphasic response was observed with ipriflavone and metabolite I on osteoblastic cell growth, with a maximal effect at the 0.1 nM concentration. These results suggest a direct role of ipriflavone in modulating the synthetic and growth properties of osteoblast-like cells.

Alkaline Phosphatase↗