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Biomedical subjects

M Ruggiero

Publications and source records attributed to M Ruggiero.

At least 127 records · Page 7Linked to original sources

Association between vitamin D receptor gene polymorphism and nephrolithiasis.

AIMS: To study the distribution of vitamin D receptor (VDR) gene alleles in hypercalciuric and nonhypercalciuric nephrolithiasis patients, hypothesizing that distinct biochemical parameters would be associated with different VDR genotypes. METHODS: 12 hypercalciuric, 15 normocalciuric nephrolithiasis patients, and 150 healthy subjects were recruited. The individual genetic pattern for VDR was evaluated by DNA extraction followed by polymerase chain reaction amplification of the VDR gene and digestion with the restriction enzyme BsmI. RESULTS: In the hypercalciuric group, Bb patients represented 50% (6/12); bb patients 33% (4/12), and BB cases were 16% (2/12). The VDR frequency distribution was not statistically different in hypercalciuric patients and controls (Bb 72%; bb 16%; BB 12%). In the nonhypercalciuric group, the prevalence of the bb genotype (7/15; 47%) was thrice the percentage of control subjects, while the percentage of BB patients was similar to that of the control group (2/15; 13%). Patients with the bb haplotype exhibited a higher daily urinary calcium excretion. Among hypercalciuric patients, after a calcium-restricted diet, bb patients showed a 39% reduction in daily urinary calcium excretion in comparison with a nonsignificant 13% reduction observed in BB subjects (p = 0.004). CONCLUSIONS: The effects of VDR gene polymorphism on calcium metabolism contribute to the understanding of the pathogenesis of urinary calculi.

Adult↗

Effects of gemcitabine in normal and transformed human lung cell cultures: cytotoxicity and increase in radiation sensitivity.

AIMS AND BACKGROUND: Several anticancer drugs increase cell sensitivity to irradiation. Gemcitabine (2', 2' difluorodeoxycytidine) decreases the cellular dNTP pools and thus significantly increases the sensitivity to the DNA damaging effects of low-dose radiation. In this study we have investigated whether gemcitabine may play a role as radiosensitizer also in lung adenocarcinoma treatment. METHODS & STUDY DESIGN: We studied this nucleoside analogue in normal and transformed human cell lines (fetal lung and lung adenocarcinoma). After drug treatment, cell lines were irradiated with different doses. Cell damage following drug treatment and/or irradiation was assessed by measuring intracellular ATP level and by the colony forming assay. RESULTS: The two cell lines significantly differed in their sensitivity to the toxic effects of the drug; the normal cell line was much more resistant than its transformed counterpart. This difference was observed in both assays, although it was more evident in the colony forming assay. A low radiation dose (50-100 cGy) did not cause any significant damage to transformed cells; normal cells were more resistant and doses up to 500 cGy caused little damage. However, when transformed cells were pretreated for three hours with gemcitabine, even a nontoxic concentration of the drug (1-10 nM) caused a marked sensitization of the cells to irradiation (50-100 cGy). The radiosensitizing effect of gemcitabine could be observed also in normal cells, although these cells were more resistant to the damaging effects of both anticancer treatments. CONCLUSIONS: This study demonstrates that gemcitabine, a chemotherapeutic agent already used in the clinic, could be proposed as a radiosensitizer for radiation therapy of lung adenocarcinoma, having a clearly potentiating effect on lowdose radiation.

Adenocarcinoma↗

Distribution and characteristics of synoviocytes in the rabbit knee joint: a scanning/transmission electron microscopic study.

The distribution and the characteristics of A and B synoviocytes were investigated using scanning and transmission electron microscopy in the study of the three types of synovial membranes (fibrous, areolar, adipose) of the rabbit knee joint. The scanning electron microscope showed that the B-synoviocytes had dendritic processes and were separated by wide spaces in the fibrous synovium. The areolar synovium was covered by numerous B-synoviocytes of fibroblastoid-shape. The B-synoviocytes of the adipose synovium were characterized by short cytoplasmic processes. The transmission electron microscope revealed that the B-cells showed signs of intense synthetic activity such as the presence of an evident rough endoplasmic reticulum, the Golgi apparatus and many peripheric vesicles. Our study also revealed that cells with morphological and ultrastructural characteristics of macrophages, the so-called A-synoviocytes, were present in the areolar membrane. We concluded that B-synoviocytes can show variable shape under normal conditions: in particular, dendritic morphology seems to be a normal characteristic of the synoviocytes of the fibrous membrane. Moreover, our results demonstrate that A and B synoviocytes are ultrastructurally and morphologically distinct cells and that each type has different functions.

Animals↗

Cardiac magnetic resonance imaging: technique and anatomy.

Recent advances achieved in Magnetic Resonance Imaging equipment and procedures allow a thorough study of the heart, yielding anatomic, functional and angiographic information. Spin-echo sequences are specific for heart morphology while gradient-echo sequences are fundamental to the functional study. Fast sequences reduce the examination times with the possibility of single breath-hold images. Coronary arteries can be directly visualized and cardiac perfusion can be assessed. Velocity encoded images allow flow quantification and with myocardial tagging, cardiac mechanics is accurately defined.

Blood Flow Velocity↗

Bone mineral density and anthropometric measures in normal and osteoporotic men.

In an ethnically homogeneous men population living in Tuscany, Italy, the relationship between age, height, body weight and bone mineral density were studied. In 50 men bone mineral density was measured by Dual Energy X ray Absorptiometry (DEXA). 13 subjects (26%) were osteoporotic. Age and bone mineral density were not related (R2 = 0.052). Bone mineral density was associated with body weight (R2 = 0.303), and height (R2 = 0.155). In osteoporotic men, mean (+/- SD) body weight was Kg. 65.8 +/- 11.2, lower than that recorded in non osteoporotic men, Kg. 77.3 +/- 10.2, (p = 0.0013). Age in osteoporotic and non-osteoporotic men did not differ (53.8 +/- 13.6 yrs and 60.9 +/- 11.8 yrs, respectively; p = 0.077). In conclusion, anthropometric factors, as predictors of bone disease, behave differently in women and men.

Adult↗

A method for separation of heparin species from biological samples by ethanol precipitation of compounds solubilized in guanidine hydrochloride.

In this paper we describe a procedure to determine glycosaminoglycan and oligosaccharide composition of biological samples such as cell cultures or tissue explants. We demonstrate that heparin species of different molecular mass can be easily fractionated by sequential ethanol precipitation in 4.0 M guanidine hydrochloride. We studied by gradient polyacrylamide gel electrophoresis fractionation of standard heparin and heparin-derived oligosaccharides by anion-exchange chromatography on DEAE-Sephacel resin eluted by increasing concentration of guanidine hydrochloride. The use of guanidine salts followed by sequential precipitation by increasing ethanol concentration allowed recovery of heparin and heparin-derived oligosaccharides.

Animals↗

Magnetic resonance (MR) evaluation of bone marrow in vertebral bodies.

Magnetic Resonance (MR) imaging was used to examine the hematopoietic bone marrow in the vertebral bodies of eight healthy subjects, and of 35 cancer patients who had been previously treated with radiation therapy. MR was instrumental in distinguishing viable hematopoietic tissue (red marrow) from adipose tissue (yellow marrow), whose presence reflected the extent of radiation-induced bone marrow injury. Different water content in proliferating hematopoietic tissue and adipose tissue enabled clear distinction of the two components even inside the same vertebral body. Three patterns of bone marrow viability were observed in irradiated patients: 1. Patients undergoing therapy at the time of MR study, and patients who had received low-intermediate dose several years before MR examination showed no alteration as compared with healthy controls (i.e. homogeneous presence of red marrow). 2. Patients who had received low-intermediate dose few years before MR, showed either partial re-colonization of yellow marrow or almost complete ablation of active red marrow with rare areas of re-colonization. 3. Patients who had received high dose, showed complete depletion of red marrow (fatty substitution) independently of the length of time elapsed since radiation therapy. Therefore, bone marrow recovery after radiation therapy was associate with two variables: received dose and length of time allowed for re-colonization by surviving hematopoietic tissue. In conclusion, our results provide evidence that MR can be purposively used to study composition and distribution of normal bone marrow, and to asses the extent of radiation-induced bone marrow injury; to monitor bone marrow recovery (or the lack of it); and in the general follow-up of treated cancer patients.

Adolescent↗

Role of three cancer "master genes" p53, bcl2 and c-myc on the apoptotic process.

We review some of the most recent developments concerning three genes involved in human cancer: p53, bcl2 and c-myc. Recent data have demonstrated that the bcl2 gene protects tumor cells from apoptosis induced by a variety of agents, including ionizing radiation, and is thus related to resistance to DNA-damaging therapeutic agents. The p53 tumor suppressor gene, however, has been related with growth arrest, apoptosis and thus with selective sensitivity to the killing effects of ionizing radiation and DNA-damaging drugs. This functional antagonism between the two genes was recently substantiated in molecular terms by demonstration of reciprocal down-regulation due to the presence of a p53-dependent transcription silencer in the untranslated region of the bcl2 gene. Growth arrest in the G1 phase of the cell cycle and induction of apoptosis are two distinct and dissectable functions of p53: bcl2 is able to antagonize the induction of apoptosis by p53, but not the growth arrest in G1. However, coexpression of bcl2 and of the oncogene c-myc efficiently antagonizes effects of p53 on G1 arrest and apoptosis, thus suggesting a cooperation between the two oncogenes. In addition, c-myc disrupts other functions of genetic control in the early G1 phase of the cell cycle including the expression of D1 cyclin. We believe that knowledge of the functional/molecular interactions between these three genes involved in human cancer is a fundamental prerequisite to improve the knowledge on prognosis and to design innovative therapeutic approaches.

Animals↗