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A Giordano

Publications and source records attributed to A Giordano.

At least 127 records · Page 7Linked to original sources
PubMed2000

International conference on basic and clinical aspects of cell-cycle control.

Scientists of numerous medical and life science disciplines met in Siena, Italy to discuss the latest proceedings in basic and clinical research. General models of interconnected linear and back-feeding cell-cycle control pathways provide a basis for applied molecular research. Cell-cycle determining factors essential for the control of cellular homeostasis either become markers to determine characteristics of a disease and/or become therapeutic targets. Apart from animal and tissue culture models, molecular theories finally have to stand proof in clinical application and evaluation. Therefore, the clinical feedback to the basic scientist's bench is essential for necessary adjustments of their models to improve future approaches to research challenges. A select group of speakers provided the audience with such an interdisciplinary dialogue at the first International Conference on Basic and Clinical Aspects of Cell-Cycle Control from May 29 to 31, 2000 in Siena, Italy.

Animals↗
PubMed2000

Genetic alterations of the retinoblastoma-related gene RB2/p130 identify different pathogenetic mechanisms in and among Burkitt's lymphoma subtypes.

Alterations of cell cycle-associated genes probably contribute to the pathogenesis of Burkitt's Lymphoma (BL), in addition to c-myc translocation. Mutations disrupting the nuclear localization signal of the retinoblastoma-related gene RB2/p130 have been documented recently in BL cell lines and primary tumors. Given the importance of the RB2/p130 gene in controlling cell growth, mutations of this gene may result in uncontrolled cell proliferation. We tested the expression and genomic organization of the RB2/p130 gene in relation to the proliferative features of a series of BL samples collected from the endemic and sporadic regions, regardless of whether the samples were acquired immune deficiency syndrome (AIDS)-related. The expression of the Rb2/p130, p107, and cell proliferation-related proteins (cyclin A and B) was determined by immunohistochemistry. The structures of exons 19 through 22 of the RB2/p130 gene, encoding for the B domain and C terminus, were analyzed by polymerase chain reaction (PCR) analysis and single-strand conformation polymorphism (SSCP) technique. The direct PCR products were sequenced to identify the actual mutations. Our results suggest that BL is composed of a mixture of molecular types with distinct genetic and phenotypic patterns, probably resulting from different pathogenetic mechanisms. In endemic BL, the RB2/p130 gene is mutated in most of the cases, and the protein is restricted to the cytoplasm. In AIDS-related BL, high levels of nuclear expression of the wild-type pRb2/p130, p107, and cell proliferation-related proteins were detected. This finding is in line with the molecular mechanisms observed in virus-linked oncogenesis. Sporadic BLs were mainly characterized by the low nuclear values of the wild-type pRb2/p130 and, conversely, the high values of p107. The increased cell proliferation due to different alterations of cell growth control by Rb-related proteins may be the first step in lymphomagenesis, during which additional genetic changes, including missense mutations of c-myc, may subsequently occur.

Adolescent↗
PubMed2000

Adsorption and desorption of imazosulfuron by soil.

Understanding and quantifying the adsorption and desorption of herbicides by soil is important for predicting their fate and transport in the environment. Here we report a study concerning the adsorption and desorption, by four different soils, of imazosulfuron, 1-(2-chloroimidazo[1,2-a]pyridin-3-ylsulfonyl)-3-(4, 6-dimethoxypyrimidin-2-yl)urea, a new sulfonylurea herbicide. Both phenomena are well-described by the Freundlich equation, which shows this herbicide to be little adsorbed by each of the four soils investigated. The Freundlich adsorption constants, K(f-ads), ranged from 1.46 to 3.02. Distribution coefficients between soil and water, Kd, measured on soils of different organic matter contents and pH values showed an important effect of these two parameters on imazosulfuron retention. The Freundlich desorption data indicated that a significant amount of the imazosulfuron sorbed is not easily desorbed. The desorption process showed an evident hysteresis phenomenon, which may contribute to the persistence of imazosulfuron in soil.

Absorption↗
PubMed2000

High cyclin-dependent kinase inhibitors in Bcl-2 and Bcl-xL-expressing CD34+-proliferating haematopoietic progenitors.

We have previously described the isolation of primitive, slow-proliferating progenitors from normal, circulating CD34+ cells by using the fluorescent dye 5-6-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE). CFDA-SE(bright) (primitive) and CFDA-SE(dim) (differentiating) cells were isolated following cytokine stimulation on the basis of their different proliferation rates. In the present work we analysed the expression levels of a number of proteins involved with differentiation, proliferation and survival/apoptosis in CFDA-SE(bright)/CD34+/slow-proliferating cells that were previously defined as progenitors capable of differentiating into different lineages. The aim of this work was to gain a better understanding of our model system in order to define some of the important parameters that regulate differentiation in haematopoietic progenitors. GATA-1 and PU.1 RNA levels were similar in freshly isolated (d 0) CD34+ and in CFDA-SE(bright) (bright) cells, whereas they increased in CFDA-SE(dim) (dim) cells. Accordingly, Nm23 was expressed at higher levels in bright cells. Moreover, bright cells had higher p21WAF1/CIP1, p27KIP1 and p16Ink4 protein levels than dim cells. Consistently, Cdc2 and Cdk2 kinase activity was much higher in the dim than in the slower proliferating bright cells. C-myc and p53 levels were higher in bright cells than in d 0 CD34+ and dim cells, and so was Bcl-xL, which followed the trend we have previously described for Bcl-2. Thus, bright cells, despite having a higher proliferation rate than the starting d 0 CD34+ population, have strikingly elevated levels of cyclin-dependent kinase inhibitors, which are likely to also act as inhibitors of differentiation.

Antigens, CD34↗
PubMed2000

Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with echo-Doppler assessment.

Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary disease (COPD) has been loosely related to the severity of illness, being significantly reduced in the most severe cases. Pulmonary hypertension is associated with lower NO output from the lung. In this study expired NO was measured in patients with severe stable COPD with or without cor pulmonale (CP). Echocardiographic estimates of right heart function, lung function, diffusion capacity, respiratory muscle strength, and arterial blood gases were obtained in 34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was measured by chemiluminiscence to obtain fractional exhaled concentrations at peak (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO showed a negative correlation with both systolic pulmonary artery pressure (Pspa) (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but not with any measurement of lung function. When the patients were divided according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7 +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6 +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO production from the airways was significantly lower and inversely related to development of CP in patients with severe COPD. Impaired endothelial release may account for the reduced levels of expired NO.

Aged↗
PubMed2000

Latest developments in gene transfer technology: achievements, perspectives, and controversies over therapeutic applications.

Over the last decade, more than 300 phase I and phase II gene-based clinical trials have been conducted worldwide for the treatment of cancer and monogenic disorders. Lately, these trials have been extended to the treatment of AIDS and, to a lesser extent, cardiovascular diseases. There are 27 currently active gene therapy protocols for the treatment of HIV-1 infection in the USA. Preclinical studies are currently in progress to evaluate the possibility of increasing the number of gene therapy clinical trials for cardiopathies, and of beginning new gene therapy programs for neurologic illnesses, autoimmuno diseases, allergies, regeneration of tissues, and to implement procedures of allogeneic tissues or cell transplantation. In addition, gene transfer technology has allowed for the development of innovative vaccine design, known as genetic immunization. This technique has already been applied in the AIDS vaccine programs in the USA. These programs aim to confer protective immunity against HIV-1 transmission to individuals who are at risk of infection. Research programs have also been considered to develop therapeutic vaccines for patients with AIDS and generate either preventive or therapeutic vaccines against malaria, tuberculosis, hepatitis A, B and C viruses, influenza virus, La Crosse virus, and Ebola virus. The potential therapeutic applications of gene transfer technology are enormous. However, the effectiveness of gene therapy programs is still questioned. Furthermore, there is growing concern over the matter of safety of gene delivery and controversy has arisen over the proposal to begin in utero gene therapy clinical trials for the treatment of inherited genetic disorders. From this standpoint, despite the latest significant achievements reported in vector design, it is not possible to predict to what extent gene therapeutic interventions will be effective in patients, and in what time frame.

Adenoviridae↗
PubMed2000

The Rb family of cell cycle regulatory factors: clinical implications.

The retinoblastoma gene family is composed of three members: the product of the retinoblastoma gene (pRb), which is one of the most well studied tumor suppressor genes and two related proteins, pRb2/p130 and p107, which have been shown to be structurally and functionally similar to pRb. The three retinoblastoma family members show growth suppressive properties, although the growth arrest mediated by each of the three pocket regions of the proteins is not identical. This supports the idea that although the three members may complement each other, they are not fully functional or redundant. Among the three family members, the retinoblastoma-related gene product pRb2/p130 is a tumor suppressor gene and an effective candidate target for gene therapy approach. The aim of this review is to examine the role of the Rb family members in growth regulation discussing their putative prognostic and therapeutical impact in human cancer.

Animals↗
PubMed2000

The RB2/p130 gene: the latest weapon in the war against lung cancer?

Lung cancer is the second cause of death after cardiovascular diseases and is the major cause of cancer deaths in the Western world. Large scale screening trials conducted 15-20 years ago using chest X-rays and sputum cytology were able to detect stage I cancers but failed to impact on survival. This is because of the early metastatic potential of small primary tumors. It is important then to detect lung cancer at an earlier stage, studying and identifying genetic lesions that could indicate a new target(s) for gene therapy. The retinoblastoma-related gene pRb2/p130, a new tumor suppressor gene cloned in 1993, is emerging as one of the candidate markers and targets for gene therapeutic approach. Effective genetic therapy requires both a genetic material to be used therapeutically and a means to deliver it. A scope for this review is to examine some of the gene delivery systems mostly used, discussing their weaknesses and strengths, and to discuss the role of pRb2/p130 in lung cancer.

Gene Transfer Techniques↗
PubMed2000

Uncommon left hepatic duct injury during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is currently the gold standard in the treatment of symptomatic gallstones but has been shown to have a higher incidence of biliary tree lesions (0.3-1%) compared with reported traditional open approaches. Loss of three-dimensional view and of depth perception is the main limit of the laparoscopic approach, especially if particular risk factors are associated (e.g., postinflammatory fibrosis, anatomic variations). Moreover, inadequate training may justify the increase of biliary tract lesions. The authors describe a unique case of left hepatic duct clipped without section of the duct itself during an otherwise "easy" operation. At the reintervention, because of the favorable local condition, a reconstruction was possible after a small duct resection with a ductal-hepatic anastomosis over a T-tube. This was removed after 8 months because of the good patency of the biliary tree and the absence of cholestasys. A long-term follow-up is mandatory for a complete functional evaluation.

Adult↗
PubMed2000

Genomic organization, promoter analysis, and chromosomal mapping of the mouse gene encoding Cdk9.

Cdk9, previously known as PITALRE, belongs to the Cdc2 family of protein kinases. We report the isolation and characterization of the complete gene coding for the murine Cdk9 protein. The gene contains seven exons spanning over 6 kb of genomic DNA, and the exon/intron boundaries conformed to the GT/AG rule. The Cdk9 gene mapped on mouse chromosome 2, which is consistent with the known region of synteny with human chromosome 9q34.1. The length of the individual exons ranged from 82 to 850 bp, and introns ranged from 452 to 1,465 bp. The further 5' flanking region of the gene showed features of a housekeeping promoter, such as the lack of a canonical TATA box and the presence of a CCAAT box as well as several GC boxes, which are potential binding sites for numerous transcription factors. Additionally, we performed a basic analysis of the transcriptional activity of the promoter and found that the 364 bp of Cdk9 5' flanking region were able to elicit high transcriptional levels of a luciferase reporter gene in NIH3T3 cells. This study provides the molecular basis for understanding the transcriptional control of the Cdk9 gene, and could serve to facilitate the molecular genetic investigation of Cdk9 function during mouse embryonal development.

3T3 Cells↗
PubMed2000

Relationship between myocardial 123I-metaiodobenzylguanidine scintigraphic uptake and heart rate variability in patients with syndrome X.

BACKGROUND: We have recently demonstrated a striking impairment in cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) in most patients with syndrome X. In this study we investigated the relationship between cardiac MIBG defects and cardiac autonomic activity in these patients. METHODS: MIBG myocardial scintigraphy and time-domain and frequency-domain heart rate variability (HRV) were compared in 11 syndrome X patients and 10 healthy controls. Cardiac MIBG uptake was assessed by the heart/mediastinum ratio and a cardiac MIBG uptake defect score (higher values = lower uptake). RESULTS: The heart/mediastinum ratio was lower (1.71 +/- 0.6 vs 2.19 +/- 0.3, p = 0.03) and MIBG uptake score higher (37.1 +/- 32 vs 4.0 +/- 2.5, p = 0.005) in syndrome X patients, whereas average HRV values did not differ between the two groups. However, while there were no correlations between MIBG uptake and HRV in controls, in syndrome X patients both the heart/mediastinum ratio and MIBG uptake score correlated significantly with two HRV parameters, specific for vagal activity: the square root of the mean squared differences of consecutive RR intervals (r = 0.73, p = 0.01, and r = -0.67, p = 0.02, respectively), and high frequency (r = 0.64, p = 0.03, and r = -0.74, p = 0.009, respectively). CONCLUSIONS; In patients with syndrome X, the impairment in cardiac MIBG uptake was associated with a reduction in HRV indexes mainly reflecting vagal modulation of sinus node, thus suggesting that a predominance of cardiac adrenergic activity may be present in those with abnormal cardiac MIBG scintigraphy.

3-Iodobenzylguanidine↗
PubMed2000

[Appropriateness of referral to the emergency department through a telecardiology service. "Boario Home-Care" researchers].

BACKGROUND: The use of telemedicine appears particularly promising in cardiovascular diseases; it may reduce the decisional time during an acute myocardial infarction, which is the greater part of the so-called "avoidable delay" and the inappropriate admission to the Emergency Department with the possibility of ruling out an acute pathology. The aim of our study was to show the diagnostic accuracy of a telecardiology service in the daily activity of general practitioners. METHODS: From February 1998 to February 1999, 150 general practitioners received a portable electrocardiographer (Card-Guard 7100) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for the reporting and interactive teleconsultation. RESULTS: During 1 year 3456 calls took place. At the time of the ECG recording 44% of patients were symptomatic. Chest pain was present in 669 patients (44%), dyspnea in 21%, palpitation in 18%, dizziness in 7%, and asthenia in 13%. ECG and teleconsultation solved all the problems for 2452 patients (71%) and further diagnostic tests were requested in 862 patients (25%); 142 patients (4%) were sent to the Emergency Department. Cardiological diagnosis was confirmed in 95 patients (73%), while anxiety or gastritis were presumed in 35 patients (27%). In the group of patients (n = 3314) for whom the cardiologist solved the problem without admission to the Emergency Department, there were 5 patients who were admitted to the Emergency Department for myocardial ischemia in the following 48 hours after the teleconsultation. Telecardiology service showed versus Emergency Department admission a sensitivity of 95%, a specificity of 97.5%, and a diagnostic accuracy of 92.5%. CONCLUSIONS: These data confirm a good diagnostic value to the service and a useful support to the general practitioners' activity.

Electrocardiography↗
PubMed2000

[Use of SPECT with (99m)Tc-Sestamibi in a patient affected by laryngeal carcinoma and parathyroid adenoma].

We report the case of a patient with a laryngeal carcinoma in whom asymptomatic hyperparathyroidism was also detected during the preoperative work-up. A planar (201)Thallium/(99m)Tc-pertecnetate subtraction scintigraphy was performed in order to locate the suspected parathyroid adenoma. The study showed a single area of increased (201)Thallium uptake just above the thyroid isthmus, likely due to the laryngeal tumor. The scintigraphic study was repeated using (99m)Tc-Sestamibi and (99m)Tc-pertechnetate and employing the SPECT technique. Both SPECT studies made it possible to identify correctly the parathyroid adenoma, located inferiorly and in a posterior position to the lower third of the right thyroid lobe. The laryngeal tumor and parathyroid adenoma could be excised in a single surgery session. This case is of interest due to the rarity of the coexistence of two neck tumors and the clear advantage shown by the SPECT technique with (99m)Tc-Sestamibi over the planar technique with 201Thallium.

Adenoma↗
PubMed2000

Role of growth hormone in chronic heart failure: therapeutic implications.

Chronic heart failure is a multi-etiological cardiovascular disorder with high prevalence and poor prognosis. Medical treatment of dilated cardiomyopathy is aimed at alleviating heart failure symptoms. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and very recently, beta-blockers have been shown to have favorable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The role of GH and IGF-1 as modulators of myocardial structure and function is well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, while IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases; impaired cardiac efficiency can also be observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by hemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is due to ventricular dilation with inadequate wall thickening that leads to impaired cardiac performance; therefore, based on previous evidence we would expect beneficial effects from the use of GH in these patients. Several papers have highlighted the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small open studies, acute and chronic GH treatment has demonstrated beneficial effects in patients with heart failure due to ischemic or idiopathic cardiomyopathy. Recently, two randomized, placebo-controlled studies did not show any significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance might be an important feature of severe heart failure and explain the diverse responses to GH therapy observed in different patients. Whether GH treatment will finally find a place in the treatment of heart failure, and with which modalities, remains to be established.

Acromegaly↗
PubMed2000

[Giant Spigelian hernia associated with inguinal hernia. Repair with polypropylene prosthesis].

Spigelian or lateral ventral hernia is a rare pathology, representing about 2% of all abdominal wall hernias. This kind of hernia can be found in the area limited from the umbilicus and anterosuperior iliac spine, near the lateral edge of the rectus abdominis. The authors describe a rare case of "giant" Spigelian hernia related with homolateral direct inguinal hernia. A seventy-year-old and obese patient had a painless huge intumescence in the right side of periumbilical area, and besides--he had a homolateral direct inguinal hernia. Abdominal computerized tomography visualized a hernial gap, which diameter is larger than 7 cm, in pararectal subumbilical site and a wide herniated bowel in interaponeurotic site. This double hernial pathology has been treated in an only solution, placing an only subfascial polypropylene prosthesis, overlapping both hernial defects. The authors believe prosthetic "tension free" repair, previous suture of the defect, represents a gold standard in the treatment of Spigelian hernia. Such refined technique allows an effective repair especially when aponeurotic defect is out of size and/or is related with subsequent homolateral hernia, also allowing an early patient's rehabilitation.

Aged↗
PubMed2000

p27Kip1 expression is associated with clinical outcome in advanced epithelial ovarian cancer: multivariate analysis.

Few biological parameters have been shown to have a prognostic role in patients with advanced ovarian cancer. p27Kip1 is a cyclin-dependent kinase inhibitor, and its loss may contribute to tumor progression. We determined whether p27Kip1 protein expression in advanced ovarian cancer could be associated with prognosis. p27Kip1 status was assessed by immunohistochemical analysis of tissue sections from primary tumors of 99 patients with stages III-IV ovarian carcinoma and was analyzed in relation to clinicopathological variables, time to progression (TTP), and overall survival (OS). p27Kip1 expression was detected in 47 (47%) of the 99 patients. p27 expression did not correlate with any of the classical clinicopathological parameters. Loss of p27 protein was significantly associated with a short TTP (P = 0.0004) and decreased OS (P = 0.0302). The 5-year TTP rate in p27-positive patients was 50% versus 11% in p27-negative patients. p27-positive cases showed a 5-year OS rate of 53% compared with 43% of p27-negative cases. In multivariate analysis, p27 expression was an independent predictor of progression of disease (P = 0.0009) and survival (P = 0.0032) when considered together with stage of disease, presence of ascites, and residual tumor at surgery. Loss of p27Kip1 conferred poor prognosis independently of proliferative index, as assessed by proliferating cell nuclear antigen immunostaining. p27 immunoreactivity can be used to predict progression of disease and survival in patients with advanced epithelial ovarian cancer and therefore may represent a new prognostic marker.

Age Factors↗