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Biomedical subjects

R Monaco

Publications and source records attributed to R Monaco.

At least 19 recordsLinked to original sources

Zurek-Kibble mechanism for the spontaneous vortex formation in Nb-Al/Al(ox)/Nb Josephson tunnel junctions: new theory and experiment.

New scaling behavior has been both predicted and observed in the spontaneous production of fluxons in quenched Nb-Al/Al(ox)/Nb annular Josephson tunnel junctions (JTJs) as a function of the quench time, tau(Q). The probability f(1) to trap a single defect during the normal-metal-superconductor phase transition clearly follows an allometric dependence on tau(Q) with a scaling exponent sigma = 0.5, as predicted from the Zurek-Kibble mechanism for realistic JTJs formed by strongly coupled superconductors. This definitive experiment replaces one reported by us earlier, in which an idealized model was used that predicted sigma = 0.25, commensurate with the then much poorer data. Our experiment remains the only condensed matter experiment to date to have measured a scaling exponent with any reliability.

Journal Article↗

Female adnexal tumor of probable wolffian origin: clinicopathological, immunohistochemical and cytofluorimetric analyses of a 22-year-old virgin. case report.

The term female adnexal tumor of probable Wolffian origin "FATWO" designs this tumor wich arises by the rare persisting remnants of the mesonephric duct (Wolffian duct). About 40 cases have been reported in literature. Few cases of recurrence have been reported, FATWO usually shows no signs of hormonal activity. We report a case of the youngest patient affected by FATWO in October 2002. At laparotomy the left adnexa were deformed by a well-capsulated mass, totally removed and sent to the pathologist with a specimen of peritoneal fluid and of the omentum. The histological examination showed a prevalent tubular structure with focal retiform area, without intraluminal mucines. Immunohistochemical findings of the case reported are similar to those described by other authors, except for inhibin which has not been detected by us. The cytofluorimetry showed the low presence of aneuploid cells, with a very low prolifing component (< 1%).

Adnexal Diseases↗

Zurek-Kibble domain structures: the dynamics of spontaneous vortex formation in annular Josephson tunnel junctions.

Phase transitions create a domain structure with defects, which has been argued by Zurek and Kibble (ZK) to depend in a characteristic way on the quench rate. We present an experiment to measure the ZK scaling exponent sigma. Using long symmetric Josephson tunnel junctions, for which the predicted index is sigma=0.25, we find sigma=0.27+/-0.05. Further, we agree with the ZK prediction for the overall normalization.

Journal Article↗

Urinary calcium excretion in the monitoring of bone metastases from prostatic carcinoma.

BACKGROUND: One of the greatest problems in treating advanced prostate carcinoma is monitoring the therapeutic response of bone metastases. As these metastases are mainly osteosclerotic and lead to a markedly increased bone calcium requirement that may give rise to an imbalance in calcium homeostasis, the authors investigated whether changes in calcium balance may be useful for evaluating the response of bone metastases to treatment. METHODS: The study involved 268 prostate carcinoma patients: 142 in Stage A-C2 (International Union Against Cancer [UICC] staging system, 1998) and 126 with bone metastases who had failed to respond to hormone therapy and were receiving chemotherapy. Prostate-specific antigen (PSA), calcium and phosphate metabolism, and the main bone formation and resorption markers were all assayed before and after chemotherapy. RESULTS: Of the 126 patients on chemotherapy, 109 were evaluable for response: according to standard criteria, 25 (23%) had improved, 43 (39.5%) were unchanged, and 41 (37.5%) had worsened. All of the improved and 16 unchanged patients had decreased PSA and bone marker levels and an increased urinary calcium/creatinine ratio (UCa/Cr); the worsened patients had increased PSA and bone marker levels, and their UCa/Cr decreased after only six treatment cycles. PSA and UCa/Cr were the biochemical markers whose changes showed the best agreement with treatment response. CONCLUSION: The UCa/Cr ratio was the most useful marker of clinical response, mainly because it allowed an early decision to continue or to stop chemotherapy. Furthermore, UCa/Cr and PSA together identified a percentage of patients classified as unchanged on the basis of standard criteria but whose condition had actually improved.

Bone Neoplasms↗

Squamous papilloma of the esophagus: long-term follow up.

BACKGROUND AND AIM: Squamous papilloma of the esophagus is a rare benign tumor; less than 200 cases have been reported in the literature. The prevalence of endoscopically diagnosed squamous papilloma of the esophagus has been reported in only a very few series, and varies from 0.01 to 0.43%. Clinical relevance and possible association with other pathological conditions, namely if it is a premalignant lesion, remain a matter of debate. The etiology is controversial, although a role of human papilloma virus has been recently proposed. The aim of this study was to try to determine the prevalence, clinical relevance, possible association with other pathological conditions of the upper digestive tract, and possible etiological role of human papilloma virus on our series of squamous esophageal papillomas. METHODS: Data from a total of 7618 upper gastrointestinal endoscopies consecutively performed in 4 years were obtained. A 4-year follow up was carried out. RESULTS: Squamous esophageal papilloma was found in nine patients (0.01%). The mean size of polyps was 4 mm and the mean distance from the dental ridge was 25 cm. Only one patient had more than one polyp. Two patients had liver cirrhosis and three had peptic ulcer disease. All squamous esophageal papillomas were removed and tested for human papilloma virus with commercial available kits for in situ hybridization, but none was found positive. CONCLUSION: Squamous papilloma of the esophagus is an uncommon disease that does not appear to predispose to esophageal cancer. No association was found with human papilloma virus.

Adolescent↗

Usefulness of bone quantitative ultrasound in management of osteoporosis in men.

In order to evaluate the usefulness of QUS at the phalanx in the diagnosis of osteoporosis and in the prediction of fracture risk in males. The study consisted of 182 subjects (age 61.2 +/- 9.4 yr), of which 22 had had a previous nontraumatic bone fracture. In all subjects, bone mineral density (BMD) at the lumbar spine and femur was measured by DXA. Moreover, in the same subjects, QUS parameters, the amplitude-dependent speed of sound (AD-SOS), and the parameters characterizing the graphic trace (fast-wave amplitude, signal dynamic, and bone transmission time [BTT]) were assessed at the phalanxes using the DBM Sonic 1200 (IGEA). According to World Health Organization (WHO) criteria, all the patients were divided into two groups: 62 osteoporotic subjects and 120 nonosteoporotic subjects. All QUS parameters were significantly lower in osteoporotic than in nonosteoporotic patients. Receiver operating characteristic (ROC) analysis showed a moderate ability of AD-SOS, BTT, and ultrasound bone profile index (UBPI) in distinguishing between healthy and osteoporotic men. Among osteoporotic patients, BMD values were lower in patients with fracture than in those without fracture. AD-SOS and BTT were significantly reduced in men with fracture. Furthermore, in a regression analysis, only BTT and DXA parameters were predictive of fracture. Moreover, performing a multivariate regression analysis BTT entered before BMD at the lumbar spine and at Ward's triangle. In conclusion, our data show that QUS parameters are reduced in osteoporotic males; however, only BTT was comparable to DXA parameters in the prediction of fracture risk in men.

Absorptiometry, Photon↗

Testing the kibble-zurek scenario with annular josephson tunnel junctions

In parallel with Kibble's description of the onset of phase transitions in the early Universe, Zurek has provided a simple picture for the onset of phase transitions in condensed matter systems, supported by agreement with experiments in 3He and superconductors. We show how experiments with annular Josephson tunnel junctions can, and do, provide further support for this scenario.

Journal Article↗

Quantitative ultrasound and bone mineral density in patients with primary hyperparathyroidism before and after surgical treatment.

The aim of this study was to assess the pattern of ultrasound (QUS) parameters and bone mineral density at different skeletal sites in patients with primary hyperparathyroidism (PHPT) before and after surgical treatment. In 22 patients (age range 28-74 years) with PHPT we measured speed of sound (SOS), attenuation (BUA) and Stiffness at the calcaneus, amplitude-dependent speed of sound (AD-SoS) at proximal phalanges, and bone mineral density at lumbar spine (BMD-LS) and at the mid-radius (BMD-MR) and ultra-distal radius (BMD-UDR) before, 1 and 2 years after surgical operation. Twenty-two age- and sex-matched healthy subjects provided control data. Before surgery, all parameters apart from SOS were significantly lower in PHPT patients than in controls. At the end of the study period, BMD-LS increased by 7.0%, BMD-UDR by 7.4% and BMD-MR by 11.0%. The changes in ultrasound parameters after surgery were lower (0.44% for SOS, 2.2% for BUA, 3.3% for Stiffness and 2.6% for AD-SoS); however, the increase was statistically significant (p < 0.05 and p < 0.01, respectively) only for Stiffness and AD-SoS. Our results indicate that parathyroidectomy increases both axial and appendicular BMD and influences QUS parameters differently at the calcaneus and at the phalanges. The combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery.

Absorptiometry, Photon↗

Quantitative ultrasound at the phalanges in healthy Italian men.

In the last decade there has been a growing interest in quantitative ultrasound (QUS) techniques as a new method in the assessment of bone status in metabolic bone diseases. Many studies have shown that QUS parameters can predict vertebral and femoral fracture risk in patients with osteoporosis. However, most of the studies were performed in women, whereas few data are available for men. The aim of this study was to build up a normative database on a healthy Italian male population for QUS parameters at the phalanges. Amplitude-dependent speed of sound (AD-SoS) and three parameters (first wave amplitude, FWA; signal dynamic, SDy; time frame, TF) characterizing the graphic trace of the ultrasound signal were measured at the phalanges in 286 healthy subjects (age range 20-87 years). First, the QUS device was adapted to compensate for the difference in finger thickness between men and women. Preliminary data on 150 healthy subjects showed a significant difference between the traditional and adapted device, and the latter was independent of finger thickness variations. AD-SoS showed a significant (p<0.001) decrease with aging, expressed by a second-order polynomial equation. The peak value (2122 m/s) was observed in the fourth decade; thereafter it decreased to 1980 m/s at the ninth decade. Likewise, FWA and SDy were significantly (p<0.001) reduced after the fourth decade, whereas TF remained stable over time until the last decade. In conclusion, in men AD-SoS showed a negative trend with aging. The pattern with aging of parameters characterizing the graphic trace was different from the pattern for AD-SoS, suggesting the possibility of obtaining further information on phalanx bone physical properties which could be useful in the differential diagnosis of metabolic bone diseases and in the assessment of fracture risk.

Adult↗

Conformational and molecular basis for induction of apoptosis by a p53 C-terminal peptide in human cancer cells.

A p53-derived C-terminal peptide induced rapid apoptosis in breast cancer cell lines carrying endogenous p53 mutations or overexpressed wild-type (wt) p53 but was not toxic to nonmalignant human cell lines containing wt p53. Apoptosis occurred through a Fas/APO-1 signaling pathway involving increased extracellular levels of Fas/FasL in the absence of protein synthesis, as well as activation of a Fas/APO-1-specific protease, FLICE. The peptide activity was p53-dependent, and it had no effect in three tumor cell lines with null p53. Furthermore, the C-terminal peptide bound to p53 protein in cell extracts. Thus, p53-dependent, Fas/APO-1 mediated apoptosis can be induced in breast cancer cells with mutant p53 similar to the recently described Fas/APO-1 induced apoptosis by wt p53. However, mutant p53 without p53 peptide does not induce a Fas/APO-1 activation or apoptosis. Docking of the computed low energy conformations for the C-terminal peptide with those for a recently defined proline-rich regulatory region from the N-terminal domain of p53 suggests a unique low energy complex between the two peptide domains. The selective and rapid induction of apoptosis in cancer cells carrying p53 abnormalities may lead to a novel therapeutic modality.

Amino Acid Sequence↗

Intratumor heterogeneity of chromosome 1, 7, 17, and 18 aneusomies obtained by FISH and association with flow cytometric DNA index in human colorectal adenocarcinomas.

BACKGROUND: The origin and evolution of somatic chromosome aberrations in colorectal cancer is still poorly understood. The data in the literature suggest that some specific chromosome aberrations are more common. It is not known, however, if there is a correlation of these with near-diploid and high aneuploidy previously proposed to be a characteristic of the adenoma-carcinoma sequence. METHODS: Chromosome 1, 7, 17 and 18 numerical aberrations and 1p deletions were evaluated by fluorescence in situ hybridization analysis for 20 human sporadic colorectal adenocarcinomas in 70 distinct tumor sectors and correlated with flow cytometric DNA index (DI) values. RESULTS: Aneusomy for at least one of the investigated chromosomes was observed in 60 of 70 tumor sectors corresponding to 19 of 20 adenocarcinomas (95%). Deletions at 1p, observed in 8 of 18 adenocarcinomas (44%), were intratumor homogeneous in 7 of 8 tumors. In contrast, the other aberrations were intratumor heterogeneous. Aneusomies of chromosomes 1, 7, and 17 were strongly associated with DNA high aneuploidy (DI > or = 1.4), whereas aneusomy of chromosome 18 and 1p deletions were equally common among DNA diploid and near-diploid tumors (DI < 1.4 and DI not equal to 1). CONCLUSIONS: Overall, these data suggest the existence of different aneuploidization routes correlated with specific chromosome aberrations. In addition, intratumor homogeneity of 1p deletions appears to be an indication of early occurrence or strong selection. We also suggest that tumors with monosomies and in particular monosomies-trisomies for the same chromosomes support a model of aneuploidization and chromosome instability during the colorectal tumor progression based on loss of symmetry during chromosome segregation (Giaretti: Lab Invest 71:904-910, 1994).

Adenocarcinoma↗

Bone turnover and the response to alendronate treatment in postmenopausal osteoporosis.

This study investigated whether bone turnover influences the response to alendronate in women with postmenopausal osteoporosis. One hundred postmenopausal osteoporotic women were randomized to receive either alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 50) or calcium alone (n = 50). Vertebral and radial bone density, measured by DXA, and markers of bone turnover were assessed at baseline and after 1 and 2 years. At the end of treatment, alendronate users showed an increase of 5.0% and 2.3%, respectively, at the lumbar spine and ultradistal radius; in the group treated only with calcium, bone mineral density (BMD) decreased by 1.6% at the lumbar spine and 1.3% at the ultradistal radius. The difference between the two groups was significant (P < 0.001). The patients were divided into high (HT) or low (LT) bone turnover groups, as assessed by 24-hour whole body retention (WBR%) of (99m)Tc-methylene-diphosphonate. The response to alendronate treatment was greater in HT patients compared with LT patients. In fact, at the end of the study period, BMD at the lumbar spine had increased by 7.9% in HT patients and by 3.0% in LT patients; the difference between the two groups was significant (P < 0.001). No significant difference between the two groups was found for BMD at the ultradistal radius. In conclusion, the present study demonstrates that 2-year treatment with alendronate has highly positive effects on bone mass at both the lumbar spine and ultradistal radius. The increase in bone mass, especially at the axial level, is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful in predicting the response to alendronate treatment.

Absorptiometry, Photon↗

Molecular dynamics analysis of the structures of ras-guanine nucleotide exchange protein (SOS) bound to wild-type and oncogenic ras-p21. Identification of effector domains of SOS.

The X-ray crystal structure of the ras oncogene-encoded p21 protein bound to SOS, the guanine nucleotide exchange-promoting protein, has been determined. We have undertaken to determine if there are differences between the three-dimensional structures of SOS bound to normal and oncogenic (Val 12-p21) proteins. Using molecular dynamics, we have computed the average structures for both complexes and superimposed them. We find four domains of SOS that differ markedly in structure: 631-641, 676-691, 718-729, and 994-1004. Peptides corresponding to these sequences have been synthesized and found to be powerful modulators of oncogenic p21 in cells as described in an accompanying paper. We find that the SOS segment from 809-815 makes contacts with multiple domains of ras-p21 and can facilitate correlated conformational changes in these domains.

Models, Molecular↗

Identification of a glutathione-S-transferase effector domain for inhibition of jun kinase, by molecular dynamics.

We have recently found that the glutathione-S-transferase pi-isozyme (GST-pi), a cellular detoxification enzyme, potently and selectively inhibits activation of jun protein by its upstream kinase, jun kinase (JNK). This newly identified regulatory activity of GST-pi is strongly inhibited by a group of agents that inhibit its enzymatic activity. Since loss of enzymatic activity in general does not correlate with loss of regulatory activity, it is likely that inhibitor binding induces changes in the structure of one or more domains of GST that block its interaction with JNK. To identify regions of GST that change conformation on the binding of inhibitors, we have performed molecular dynamics calculations on GST-pi to compute its average structure in the presence and absence of the inhibitor, glutathione sulfonate. Superposition of the two average structures reveals that several regions change local structure depending upon whether the inhibitor is bound or not bound. Two of these regions, residues 36-50 and 194-201, are highly exposed. We have synthesized peptides corresponding to these two segments and find that the 194-201 sequence strongly inhibits the ability of GST-pi to block the in vitro phosphorylation of jun by JNK. These results suggest that this region of GST-pi is critical to its functioning as a newly discovered regulator of signal transduction.

Amino Acid Sequence↗

K-ras2 activation and genome instability increase proliferation and size of FAP adenomas.

The possible role of K-ras2 mutations and aneuploidy toward increase of proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenomas is not known. The present study addresses these issues by investigating 147 colorectal adenomas obtained from four FAP patients. The majority of adenomas had size lower than or equal to 10 mm (86%), low grade dysplasia (63%), and were preferentially located in the right colon (60%). Normal mucosa samples were obtained from 19 healthy donors. Three synchronous adenocarcinomas were also investigated. K-ras2 mutation spectrum was analysed by PCR and Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytometry (FCM) was used for evaluating degree of DNA ploidy and S-phase fraction. Overall, incidences of K-ras2 mutations, DNA aneuploidy and high S-phase values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. In particular, among the adenomas with size lower than 5 mm, K-ras2 mutation and DNA aneuploidy frequencies were only slightly above 1%. Statistically significant correlations were found between K-ras2 and size, DNA ploidy and size and K-ras2 and S-phase (p < 0.001). In particular, among the wild type K-ras2 adenomas, high S-phase values were detected in 8% of the cases versus 57% among the K-ras2 mutated adenomas (p = 0.0005). The present series of FAP adenomas indicates that K-ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size.

Adenocarcinoma↗

Intratumor distribution of 1p deletions in human colorectal adenocarcinoma is commonly homogeneous: indirect evidence of early involvement in colorectal tumorigenesis.

BACKGROUND: Cytogenetics and molecular biology studies have indicated that a large subset of human colorectal adenocarcinomas have distal 1p chromosome arm deletions. The aim of this study was to evaluate the intratumor distribution of 1p deletions under the assumption that homogeneity is an indication of early occurrence. METHODS: Seventy-nine histologically selected primary sectors (40 superficial and 39 deep) and 3 lymph node metastases obtained from 20 human sporadic adenocarcinomas were analyzed. Interphase two-color fluorescence in situ hybridization (FISH) was applied to cytocentrifuged nuclei using a centromeric probe for chromosome 1 and a telomeric probe mapping to the 1p36 band. RESULTS: Deletions at 1p were observed in 35 of 82 tumor samples corresponding to 9 of 20 adenocarcinomas analyzed (45%). Seven of the 9 adenocarcinomas with 1p deletions showed an intratumor presence of these aberrations in all the different tumor sectors. CONCLUSIONS: These data, acquired by FISH interphase cytogenetics, confirm that 1p deletions in colorectal adenocarcinoma are common and suggest that this structural chromosomal aberration occurs mainly as an early event in colorectal tumorigenesis.

Adenocarcinoma↗

Juvenile hyaline fibromatosis: a case report.

The authors present a 9-year-old girl with a juvenile hyaline fibromatosis observed before any treatment and after surgical releases. The disorder showed impressive clinical features both concerning the size of the dermal nodules and the degree of limitation of involved joints. Although the follow-up was short, we emphasize the great role surgery can play in reaching very satisfying results, both aesthetically and functionally.

Arthritis, Juvenile↗