Biomedical subjects

Vincenzo Macchia

Publications and source records attributed to Vincenzo Macchia.

10 recordsLinked to original sources

PubMed2006

Acute effects of triiodothyronine on endothelial function in human subjects.

CONTEXT: Thyroid hormone regulates several cardiovascular functions, and low T(3) levels are frequently associated with cardiovascular diseases. Whether T(3) exerts any acute and direct effect on endothelial function in humans is unknown. OBJECTIVE: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. DESIGN, SETTING, AND SUBJECTS: Ten healthy subjects (age, 24 +/- 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. INTERVENTIONS: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. MAIN OUTCOME MEASURES: We assessed changes in forearm blood flow (FBF) measured by plethysmography. RESULTS: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 +/- 0.06 and 0.23 +/- 0.04 ml/dl x min/microg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 +/- 0.77 and 3.83 +/- 0.35 ml/dl x min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-L-arginine. CONCLUSIONS: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.

Adult↗

PubMed2006

Urinary gelatinase activities (matrix metalloproteinases 2 and 9) in human bladder tumors.

The ability to degrade type IV collagen, the major component of the basement membrane, is unique to gelatinases A and B. These two matrix metalloproteinases (MMPs) are most often linked to the malignant phenotype of tumor cells, and their expression is elevated in several cases of human tumor aggressiveness and overall survival. By gelatin zymography, we verified MMP activity in the urine of patients with bladder cancer. Of these patients, 10 had well-, 8 had moderately and 7 had poorly differentiated bladder cancer. The urine of healthy volunteers with no evidence of disease was used for controls. Zymography showed five dominant gelatinolytic bands of 240, 220, 130, 92 and 72 kDa in tumor samples, whereas only traces of MMP were detected in the urine of healthy subjects. The majority of cancerous urine samples showed MMP-9 lytic activity but only a few contained MMP-2. Moreover, MMP-9 content is enhanced in the urine from patients with high-grade and advanced-stage bladder tumors. Finally, we determined the urinary levels of urinary bladder cancer (UBC), tissue polypeptide-specific antigen (TPS) and protein 22 of nuclear matrix (NMP22). The levels of TPS and NMP-22 were higher in G3 bladder cancer than in G1 and G2 neoplasias. The urinary values of these two biomarkers correlated with the increase in MMP-9 lytic activity in high-grade and advanced-stage bladder cancer.

Adenocarcinoma↗

PubMed2005

A mouse model demonstrates a multigenic origin of congenital hypothyroidism.

Congenital hypothyroidism with thyroid dysgenesis (TD) is a frequent human condition characterized by elevated levels of TSH in response to reduced thyroid hormone levels. Congenital hypothyroidism is a genetically heterogeneous disease. In the majority of cases studied, no causative mutations have been identified and very often the disease does not show a Mendelian transmission. However, in approximately 5% of cases, it can be a consequence of mutations in genes encoding the TSH receptor or the transcription factors TITF1, FOXE1, or PAX8. We report here that in mouse models, the combination of partial deficiencies in the Titf1 and Pax8 genes results in an overt TD phenotype that is absent in either of the singly deficient, heterozygous mice. The disease is characterized by a small thyroid gland, elevated levels of TSH, reduced thyroglobulin biosynthesis, and high occurrence of hemiagenesis. The observed phenotype is strain specific, and the pattern of transmission indicates that at least two other genes, in addition to Titf1 and Pax8, are necessary to generate the condition. These results show that TD can be of multigenic origin in mice and strongly suggest that a similar pathogenic mechanism may be observed in humans.

Animals↗

PubMed2005

Matrix metalloproteinase-2 and matrix metalloproteinase-9 type IV collagenases in serum of patients with pleural effusions.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are essentially involved in the turnover of the extracellular matrix (ECM). Recently, several MMPs were implicated in creating an environment that supports the initiation and maintenance of tumor growth. We verified MMP activity in the sera of patients with pleural effusions by gelatin zymography. Of these patients, 22 had malignant pleural effusion, consisting of 11 breast carcinomas and 11 lung carcinomas (7 squamous cell carcinomas and 4 adenocarcinomas), and 8 patients had benign effusions. The sera of 25 healthy subjects were used as controls. Zymography analysis showed three major gelatinolytic bands of 72, 92 and 220 kDa. The MMP-9/MMP-2 ratio was enhanced in cancer patients compared with benign diseases and healthy individuals. Furthermore, we determined the circulating levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (Ca 19-9), carbohydrate antigen 15-3 (Ca 15-3). The serum levels of Ca 15-3 were above the cut-off levels in several cancer patients. No correlation between gelatinolytic activity and high tumoral marker values was found.

Adolescent↗

PubMed2005

Analysis of glycoproteins in human colon cancers, normal tissues and in human colon carcinoma cells reactive with monoclonal antibody NCL-19-9.

The expression of sialyl Lewis(a) antigen, also known as Ca 19-9, in colon cancer, normal tissues and LS174T human colon carcinoma cells were studied. In colon adenocarcinoma and cell plasma membranes this antigen is expressed on various glycoproteins with different molecular weights ranging in size from over 200 kDa to about 100 kDa. In addition, there is very low expression in peritumoral tissues. In cytosol and culture medium this epitope is carried by a single complex-glycoprotein with a very high molecular weight resembling a mucin. In cells the rise in cAMP levels elevate the synthesis and release of the carbohydrate antigen 19-9; whereas the treatment with 1,9-dideoxyforskolin, a diterpene, which does not activate adenylate cyclase, has no effect on content of the antigen. These results suggest that cAMP is involved on the expression of glycoprotein-associated sialyl Lewis(a) antigen in LS174T cells.

Aged↗

PubMed2004

Rhes is involved in striatal function.

The development and the function of central nervous system depend on thyroid hormones. In humans, the lack of thyroid hormones causes cretinism, a syndrome of severe mental deficiency. It is assumed that thyroid hormones affect the normal development and function of the brain by activating or suppressing target gene expression because several genes expressed in the brain have been shown to be under thyroid hormone control. Among these, the Rhes gene, encoding a small GTP-binding protein, is predominantly expressed in the striatal region of the brain. To clarify the role of Rhes in vivo, we disrupted the Rhes gene by homologous recombination in embryonic stem cells and generated mice homozygous for the Rhes null mutation (Rhes(-/-)). Rhes(-/-) mice were viable but weighed less than wild-type mice. Furthermore, they showed behavioral abnormalities, displaying a gender-dependent increase in anxiety levels and a clear motor coordination deficit but no learning or memory impairment. These results suggest that Rhes disruption affects selected behavioral competencies.

Age Factors↗

PubMed2004

New approaches in the diagnostic procedure of malignant pleural effusions.

The content of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (Ca 19-9), carbohydrate antigen 15-3 (Ca 15-3) and the expression of LewisY related carbohydrate antigens in benign and malignant pleural effusion were determined. These included 35 malignant pleural effusions: 13 breast cancers, 12 lung cancers (6 squamous cell carcinomas, 5 adenocarcinomas and 1 microcytoma), 2 mesotheliomas, 1 epithelioma, 1 kidney cancer, 1 hepatocarcinoma, 1 colon carcinoma, 3 lymphomas, 1 osteosarcoma and 9 benign pleural effusions. We showed that pleural fluid content of CEA, Ca 19-9 and Ca 15-3 were higher in malignant than in benign effusions. However CEA levels in squamous lung cancers were very high in both serum and pleural fluids whereas its levels were only slightly above the cut-off in breast cancers and in lung adenocarcinomas. Serum and pleural fluid Ca 15-3 values were higher in breast and in lung cancers with the highest values in the patients with breast cancer. Furthermore, the LewisY related carbohydrate antigens, evaluated by the reactivity of the cell extracts to MAb B3, were expressed only in breast cancers. These data suggest that pleural fluid content of CEA, and Ca 15-3 associated with the immunoblotting of cell extracts with MAb B3 appear to be very useful to improve the diagnosis of malignant pleural effusions.

Adult↗

PubMed2003

Role of cytokeratins, nuclear matrix proteins, Lewis antigen and epidermal growth factor receptor in human bladder tumors.

The content of urinary bladder cancer antigen (UBC), tissue polypeptide specific antigen (TPS), nuclear matrix protein 22 (NMP22), and the expression of LewisY carbohydrate antigens and of epidermal growth factor receptor (EGF-R) in bladder tumor tissues were determined. These included 14 well, 6 moderately and 11 poorly differentiated bladder cancers. Cytosol UBC and TPS were higher in the well and in the moderately differentiated bladder tumors than in the poorly differentiated bladder cancers; whereas cytosol NMP22 was higher in the poorly differentiated bladder cancers than in the well and in the moderately differentiated bladder tumors. The Lewis related carbohydrate antigens, evaluated by the reactivity of the tissues to monoclonal antibody B3, were highly expressed in poorly differentiated tumors. The EGF-R was strongly expressed in a large number of poorly differentiated bladder tumors. These data suggest that the determination of cytosol NMP22 and the immunoblotting with B3 and EGF-R antibodies might be useful to obtain more information on the differentiation of bladder tumors.

Aged↗

PubMedDate not supplied

Cyclic AMP-dependent secretion of Ca 19-9 by LS174T human colon carcinoma cells.

Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in culture medium of a human colon cancer cell (LS174T) inhibits cellular growth and stimulates Ca 19-9 expression. The raise in cAMP level was produced by dibutyryl cyclic AMP (DBcAMP) or by forskolin an agent acting at the level of cAMP generation. Both these agents in a range of concentration between 10(-3)-10(-5) M have an inhibitory effect on the growth which is dose and time dependent. The inhibition was reversible as demonstrated by complete restoration of cell growth soon after the withdrawal of the substances from the culture medium. When cAMP levels in culture medium was raised, an increase in Ca 19-9 expression was observed and it appears that cyclic nucleotides have at least two effects: the first to cause rapid release of already synthesized Ca 19-9 and second to stimulate new antigen synthesis. The findings of the present study demonstrated that LS174T cells are unable to proliferate upon sustained accumulation of intracellular cyclic AMP suggesting the use of strategies able to increase cAMP levels for therapy of colon cancer. Furthermore, the finding that cAMP may also be a regulator of Ca 19-9 synthesis and release indicates the utility of cell line LS174T as a model for studies on the mechanism of synthesis and secretion of specific tumoral markers in colon cancer.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

[Expression of Lewis carbohydrate antigen in human tumors].

In this study we show, by immunoblotting, that Mab B3, a newly isolated monoclonal antibody, reacts with a variety of glycoproteins with different molecular weights expressed in gastric, pancreatic and colorectal cancers. The reactivity pattern differed in cancers arising in different tissues, though no correlation was observed with the histopathological characteristics of the lesions analysed. MAb B3 does not react with liver, brain or kidney cancers and has a limited reactivity with lung cancers but reacts very strongly with metastatic lesions. Because of the limited reactivity of this antibody with normal tissues, MAb B3 genetically fused with toxin in the form of a recombinant immunotoxin may be useful in treating certain kinds of cancer such as metastatic lesions. However, until current trials are completed, we will not know whether this immunotoxin will be helpful in cancer treatment.

Adult↗