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Biomedical subjects

A Giordano

Publications and source records attributed to A Giordano.

At least 91 records · Page 5Linked to original sources

Degradation of imazosulfuron in soil.

Imazosulfuron, 1-(2-chloroimidazo[1,2-alpha]pyridin-3-ylsulfonyl)-3- (4,6-dimethoxypyrimidin-2-yl)urea, is a new post-emergence sulfonylurea herbicide applied once per growing season, highly active at low application levels, used to control most annual and perennial broad-leaf weeds and sedges in paddy rice (75-95 g AI ha-1) and turf (500-1000 g AI ha-1), and characterised by low mammalian toxicity. The degradation of imazosulfuron in a sandy loam soil (10-15 cm depth) has been investigated under aerobic and anaerobic laboratory conditions to evaluate its likely environmental fate. Test soils were treated with imazosulfuron in acetonitrile to give a final concentration of 0.2 mg kg-1 (100 g ha-1). The treated soils were extracted with methylene chloride + acetonitrile + 1 M ammonium hydroxide (4 + 15 + 1 by volume) and analysed by HPLC. Recoveries from spiked soils ranged from 80% to 95% (RSD 0.5-2.5%; n = 3) for imazosulfuron and its metabolites 2-chloroimidazo[1,2-alpha]pyridin-3-sulfonamide (IPSN), 1-(2-chloroimidazo[1,2-alpha]pyridin-3-ylsulfonyl)-3-(4-hydroxy-6- methoxypyrimidin-2-yl)urea (HMS) and 2-amino-4,6-dimethoxypyrimidine (ADPM). The limits of quantitation ranged from 0.001 mg kg-1 to 0.005 mg kg-1. Chemical cleavage of the sulfonylurea bond to give ADPM and IPSN was the main degradation pathway in aerobic conditions, whereas a remarkable production of HMS under anaerobic conditions suggested that degradation was due to micro-organisms which had the ability to demethylate imazosulfuron. In aerobic and anaerobic conditions, imazosulfuron disappeared from the soil with a half-life of approximately 70 (90% CL 62-75; r2 = 0.98) and 4 (90% CL 3.2-4.2; r2 = 0.97) days, respectively.

Aerobiosis↗

pRb2/p130 gene overexpression induces astrocyte differentiation.

There are many data on the activity of the RB gene in neural differentiation and apoptosis, but the role of pRb2/p130 in neuronal and glial maturation has been far less investigated. To elucidate the role of pRb2/p130 in astrocyte development we overexpressed this protein in astrocytoma and normal astrocyte cultures by adenoviral-mediated gene transfer. In astrocytoma cells, p130/RB2 overexpression resulted in a significant reduction of cell growth and in an increased G(0)/G(1) cell population. We did not observe any induction of programmed cell death as determined by TUNEL reaction. Interestingly, pRb2/p130 overexpression induced astrocyte differentiation. Astrocyte cell cycle arrest and differentiation seemed to proceed through a way distinct from the p53 pathway.

Adenoviridae↗

SV40 and cell cycle perturbations in malignant mesothelioma.

Although epidemiological findings have established that exposure to asbestos fibers is the major cause of malignant mesothelioma (MM), recent studies have implicated simian virus 40 (SV40) in the etiology of some of these tumors. Cytogenetic and molecular genetic evidence suggests that multiple somatic genetic events are required for tumorigenic conversion of a mesothelial cell. As with many other types of cancer, in MM critical oncogenic events exert their action via perturbations of the cell cycle. Interactions between the retinoblastoma (Rb) family of proteins and oncoproteins encoded by SV40 lead to cell cycle alterations. Likewise, inhibition of the p53 tumor suppressor by SV40 can inactivate a crucial cell cycle checkpoint, thereby permitting cells to undergo mitosis regardless of the presence of DNA damage. Many MMs exhibit loss and/or inactivation of the tumor suppressors p16(INK4a)and p14(ARF), components of the pRb and p53 cell cycle regulatory pathways, respectively. Recent investigations have demonstrated that SV40 large T antigen, isolated from frozen biopsies of human MM specimens, binds to and inactivates various tumor suppressor gene products such as pRb and p53. In this review, we discuss how SV40-oncosuppressor interactions can lead to functional alterations of the pRb- and p53-dependent cell cycle regulatory pathways and thereby contribute to neoplastic transformation of human mesothelial cells.

Animals↗

New trends in parathyroid scintigraphy.

The paper focusses on the recent advances in parathyroid imaging in both diagnostic and surgical fields which justify the present favourable trend towards a considerable expansion of nuclear medicine applications in this area. The main methodological advances in parathyroid scintigraphy are the rebirth of the dual-tracer (subtraction) technique with technetium-99m sestamibi, the possibility of also using 99mTc-tetrofosmin within a dual-tracer (subtraction) methodology and the more extensive use of single-photon emission tomography, which the authors believe will become the standard methodology. The indications for parathyroid scintigraphy have been affected by advances in hyperparathyroidism surgery, including wider use of unilateral neck exploration and of minimally invasive radioguided surgery. As these techniques can only be performed in hyperparathyroid patients with a single adenoma, careful pre-operative assessment is required, and parathyroid scintigraphy undoubtedly is the most accurate localisation method. To date, the majority of papers have also demonstrated the cost-effectiveness of scintigraphically guided limited neck surgery. The authors conclude that: (1) parathyroid scintigraphy can be recommended not only in persistent or recurrent hyperparathyroidism but also in hyperparathyroid patients prior to first surgery; (2) scintigraphy should always be performed by applying the most accurate technique available because reliable scintigraphy gains or reinforces the surgeon's trust, reliably guides cost-effective operative strategies and justifies the recognition of new potential diagnostic indications.

Adenoma↗

Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis.

We describe a functional and biochemical link between the myogenic activator MyoD, the deacetylase HDAC1, and the tumor suppressor pRb. Interaction of MyoD with HDAC1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression. Prodifferentiation cues, mimicked by serum removal, induce both downregulation of HDAC1 protein and pRb hypophosphorylation. Dephosphorylation of pRb promotes the formation of pRb-HDAC1 complex in differentiated myotubes. pRb-HDAC1 association coincides with disassembling of MyoD-HDAC1 complex, transcriptional activation of muscle-restricted genes, and cellular differentiation of skeletal myoblasts. A single point mutation introduced in the HDAC1 binding domain of pRb compromises its ability to disrupt MyoD-HDAC1 interaction and to promote muscle gene expression. These results suggest that reduced expression of HDAC1 accompanied by its redistribution in alternative nuclear protein complexes is critical for terminal differentiation of skeletal muscle cells.

Animals↗

Sema3a is produced by brown adipocytes and its secretion is reduced following cold acclimation.

Heat production in brown adipose tissue (BAT) and brown adipocyte recruitment depend heavily on BAT vascular and parenchymal sympathetic and sensory innervation. The expression and distribution of Sema3a, a recently discovered chemorepellent neuronal factor active on both sympathetic and sensory peripheral nerves, were studied in interscapular rat BAT. In rats maintained in thermoneutral conditions, brown adipocytes produced both active isoforms of Sema3a and showed a distinct peripheral polarized immunostaining pattern. This suggests a role for Sema3a secreted by brown adipocytes in the guidance of axons toward their correct targets. In cold-acclimated rats, where parenchymal nerve density is higher, both the expression and the immunostaining of the two active isoforms were slightly but significantly reduced and the distinct staining pattern was not observed. These data suggest that the secretion of Sema3a is inhibited in the brown adipocytes of cold-acclimated rats. Thus, Sema3a could play a role in the plastic adjustment of BAT innervation observed in different conditions of functional demand.

Acclimatization↗

Interplay between the antimetastatic nm23 and the retinoblastoma-related Rb2/p130 genes in promoting neuronal differentiation of PC12 cells.

Increasing evidence indicates that the nm23 genes, initially documented as suppressors of metastasis progression, are involved in normal development and differentiation. We have shown previously that the murine nm23 gene enhances pheochromocytoma PC12 cells responsiveness to NGF by accelerating cell growth arrest and neurite outgrowth. The present study was aimed at elucidating the mechanisms by which nm23 controls cell proliferation and promotes neuronal differentiation. We demonstrated that nm23 modulates the expression of the Rb2/p130 gene, a negative regulator of cell cycle progression also implicated in the maintenance of the differentiated state. Furthermore, we showed that nm23-H1 mutants, defective in inhibiting the invasive phenotype, downregulate Rb2/p130 expression and inhibit NGF-induced PC12 cell differentiation. In synthesis, our results provide first evidence of interplay between the nm23 and the Rb2/p130 genes in driving PC12 cells neuronal differentiation and suggest that the antimetastatic and the differentiative nm23 functions can have similar features.

Amino Acid Substitution↗

Long-latency auditory-evoked potentials in severe traumatic brain injury.

OBJECTIVE: To detect the effects of different deviant stimuli on long-latency auditory-evoked potentials (LLAEPs) in patients with severe impairment of consciousness from traumatic brain injury (TBI) and to define their prognostic value for late functional outcome. DESIGN: Correlational study on a prospective cohort. SETTING: Brain injury rehabilitation center. PATIENTS: Eleven volunteers and 21 consecutively sampled patients with severe TBI referred to the inpatient intensive rehabilitation unit of primary care in a university-based system. MAIN OUTCOME MEASURES: The LLAEPs recorded with different paradigms; and the Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS), FIMtrade mark instrument, and Neurobehavioural Rating Scale (NBHRS). RESULTS: N100-P150 complex showed high reliability. Patients with good outcomes showed N100 and P150 mean latencies similar to those of unimpaired patients and shorter than patients with unfavorable outcomes. When the deviant stimulus was the patient's name, N100 latency showed high correlations with DRS (p <.007), FIM (p <.01), and NBHRS (p <.009). P250 and P300 showed a low percentage of occurrence with passive paradigms in both patients and controls. Their scores were inversely correlated to the Glasgow Coma Scale (p <.03) and the Innsbruck Coma Scale (p <.003), but no significant correlations were found with functional and behavioral outcomes. Patients with GOS score 1-2 1 year posttrauma had significantly longer latency and lower amplitude of N100 and P150 than those with GOS score 4-5. CONCLUSIONS: LLAEPs can be recorded in patients with severe impairment of consciousness by means of passive paradigms. The use of a stimulus that is relevant for the patient can enhance the accuracy of the test and its relationship with functional outcome.

Adolescent↗

Expression of cell-cycle-associated proteins pRB2/p130 and p27kip in vulvar squamous cell carcinomas.

Squamous cell vulvar carcinoma accounts for 4% of all gynecologic malignancies. The cause of vulvar cancer is still unclear. Identification of new biologic factors involved in vulvar carcinogenesis may be useful in clarifying the natural history of this malignancy. We investigated the immunohistochemical expression of the retinoblastoma-related proteins pRB2/p130 and CKI p27kip1 in a series of 51 invasive squamous cell carcinomas of the vulva (ISCCs) and in synchronous normal vulvar skin, non-neoplastic epithelial disorders (NNED) and vulvar intraepithelial neoplasia (VIN). Normal vulvar skin staining showed positivity for both pRB2/p130 and p27kip1. Loss of pRB2/p130 occurred in 29 (57%) of 51 specimens of ISCCs, and in 1 of 7 specimens with VIN (14%; P = .04). We also observed a significant decrease of pRB2/p130 expression from NNED to neoplastic tissues (VIN and ISCCs) (P = .004). Loss of p27kip1 expression was found in 16 of 51 specimens (31%) of invasive carcinomas, in 1 (14%) of 7 specimens of VIN, and in 2 of 18 specimens of NNED (11%). pRB2/p130 and p27(kip1) did not correlate significantly with any of the clinicopathologic parameters examined. Our data indicate that loss of pRB2/p130 and p27kip1 are frequent events in invasive vulvar carcinomas compared with synchronous premalignant lesions, non-neoplastic epithelial disorders, and normal vulvar skin. The significant progressive decrease of pRB2/p130 expression from non-neoplastic epithelial alterations through intraepithelial neoplasia to invasive vulvar carcinomas suggests a role for this tumor suppressor gene in vulvar carcinogenesis.

Aged↗

Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma.

The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative cell-cycle regulator normally expressed in a number of adult tissues. This protein shares many structural and functional features with the product of the retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a fundamental role in growth control. The Rb2/p130 gene product associates with specific members of the E2F family and various cyclins, displaying a growth-suppressive activity specific for the G(0)/G(1) phases. It has been reported that Rb2/p130 is involved in the pathogenesis and progression of lung cancer and mesothelioma. We previously demonstrated for the first time that reduced immunohistochemical expression of Rb2/p130 was a strong independent predictor of poor outcome in endometrial cancer. The aim of the present study was to evaluate Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions to determine whether the protein plays a significant role in endometrial carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining in 102 specimens chosen to represent a spectrum of endometrial changes, including proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in proliferative endometrium and in hyperplasia without atypia, the mean percentage of stained nuclei being 66% and 60%, respectively, but was downregulated in secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of 38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale (negative v 1% to 50% v >50% positivity), endometrial cancer displayed significantly less staining than all other endometrial samples (P <.001). Poorly differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical hyperplasia showed a significantly lower immunoreactivity than either proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our findings of a progressive decrease in Rb2/p130 expression from hyperplastic endometrium through atypical hyperplasia to poorly differentiated carcinomas suggest the involvement of this negative cell-cycle regulator in endometrial carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically useful in the often difficult distinction between hyperplastic and atypical hyperplastic endometrium. HUM PATHOL 32:360-367.

Adenocarcinoma↗

Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure.

OBJECTIVE: To clarify the relative contribution of resting haemodynamic profile and pulmonary function to exercise capacity in patients with heart failure. SETTING: Cardiology department and cardiac rehabilitation unit in a tertiary centre. DESIGN: 161 male patients (mean (SD) age 59 (9) years) with heart failure (New York Heart Association class II-IV, left ventricular ejection fraction 23 (7)%) underwent spirometry, alveolar capillary diffusing capacity (DLCO), and mouth inspiratory and expiratory pressures (MIP, MEP, respectively, in 100 patients). Right heart catheterisation and a symptom limited cardiopulmonary exercise test were performed in 137 patients within 3-4 days. RESULTS: Mean peak exercise oxygen consumption (VO(2)) was 13 (3.9) ml/kg/min. Among resting haemodynamic variables only cardiac index showed a significant correlation with peak VO(2). There were no differences in haemodynamic variables between patients with peak VO(2) </= or > 14 ml/kg/min. There was a moderate correlation (p < 0.05) between several pulmonary function variables and peak VO(2). Forced vital capacity (3.5 (0.9) v 3.2 (0.8) l, p < 0.05) and DLCO (21.6 (6.9) v 17.7 (5.5) ml/mm Hg/min, p < 0.05) were higher in patients with peak VO(2) > 14 ml/kg/min than in those with peak VO(2) </= 14 ml/kg/min. Using a stepwise regression analysis, the respiratory and haemodynamic variables which correlated significantly with peak VO(2) were DLCO, MEP, and cardiac index, with an overall R value of 0.63. CONCLUSIONS: The data confirm previous studies showing a poor correlation between resting indices of cardiac function and exercise capacity in heart failure. However, several pulmonary function variables were related to peak exercise VO(2). In particular, lung diffusing capacity and respiratory muscle function seem to affect exercise tolerance during heart failure.

Adult↗

Brain perfusion abnormalities in Alzheimer's disease: comparison between patients with focal temporal lobe dysfunction and patients with diffuse cognitive impairment.

OBJECTIVES: Patients with Alzheimer's disease (AD) showing a selective impairment of episodic and semantic memory have recently been classified as affected by focal temporal lobe dysfunction (FTLD) and considered as a distinct subgroup of patients affected by a particular form of AD. The aim was to compare the cerebral perfusion of patients with AD with FTLD and patients with AD with the more typical profile of diffuse cognitive impairment (dAD). METHODS: Ten patients with AD with FTLD, 14 patients with AD with dAD, and 12 normal controls were studied. All the 24 patients with AD underwent a complete neuropsychological assessment. SPECT examination with [(99m)Tc]-HMPAO, using a four head brain dedicated tomograph, was performed in patients and controls. Tracer uptake was quantified in 27 regions of interest (ROIs), including lateral and mesial temporal areas. Mean counts in the 27 ROIs of controls, patients with FTLD and those with dAD were compared using an ANOVA for repeated measures with Bonferroni's correction. A logistic regression analysis, followed by a receiver operating characteristic (ROC) analysis, was also applied to select SPECT patterns which significantly differentiated patients with FTLD and those with dAD. RESULTS: Two scintigraphic patterns of abnormalities, shaping a double dissociation between the FTLD and dAD groups, emerged: a bilateral mesial temporal hypoperfusion, characteristic of FTLD and a posterior parietal (and temporal parietal) hypoperfusion characteristic of patients with dAD. CONCLUSIONS: These scintigraphic findings provide further support to the hypothesis that FTLD is not a mere stage but a distinct anatomoclinical form of AD. The combination of neuropsychological tests and [(99m)Tc]-HMPAO SPECT may be very useful in identifying patients with FTLD from the wider group of patients with dAD. This issue is particularly worthwhile, as there is increasing evidence that patients with FTLD have a slower rate of cognitive decline.

Aged↗

Expression of a human polyomavirus oncoprotein and tumour suppressor proteins in medulloblastomas.

AIMS: Although the aetiology of medulloblastoma remains elusive, several lines of evidence suggest an association with the human neurotropic polyomavirus JC and its oncoprotein T antigen. The tumour forming properties of JC virus T antigen are the result, at least in part, of its ability to bind and inactivate tumour suppressor/cell cycle regulatory proteins, such as p53 and the retinoblastoma family of proteins. METHODS: To examine potential relations between these factors, immunohistochemistry was used to determine associations between the T antigen and the expression of p53 and the retinoblastoma proteins pRb, p107, and Rb2/p130 in eight medulloblastomas. RESULTS: Only the three medulloblastomas with T antigen expression also showed nuclear positivity with antibodies to p53. Although immunohistochemistry detected nuclear labelling for pRb in five of the cases, the three that were positive for T antigen showed the highest pRb labelling. The retinoblastoma related proteins p107 and Rb2/p130 were also immunopositive in most T antigen positive medulloblastomas. Double label immunohistochemistry also demonstrated p53 and pRb positivity in the same cells that were T antigen positive. CONCLUSIONS: These correlations suggest that associations between T antigen and p53 and/or T antigen and pRb occur in some of these tumours. These data provide indirect evidence that JC virus, acting through T antigen, might be involved in the formation and progression of medulloblastoma.

Adolescent↗

Spinal cord stimulation and cerebral blood flow in stroke: personal experience.

Spinal cord stimulation (SCS) can increase cerebral blood flow (CBF) and improve stroke patients. In order to better understand the haemodynamic changes underlining the clinical improvement, we have studied with transcranial Doppler (TCD), SPECT and NIRS 18 patients harbouring a stroke. SPECT Group: An increase of regional CBF during SCS was measured far from the stroke areas in 9 patients, further decrease in CBF was found in 2, no changes in 1. TCD Group: An increase of CBF velocities during SCS was found in 4 patients, no changes in 6, a decrease in 1. NIRS Group: Data consistent with and increase in CBF were obtained during SCS in the only patient undergone such a study. In 6 patients studied with different techniques, data obtained fitted only in 2 patients. In 3 patients no changes in TCD faced with changes in SPECT. In one case an improvement in TCD was evident in the left while an improvement of SPECT was shown in the right site. SCS is a valid therapeutic tool in stroke patient even if, as matter of fact, parallelism between clinical and haemodynamic changes during SCS is not demonstrated in our patients, rising the question on the role of ischemic penumbra in mediating clinical improvement.

Adult↗

Pattern of expression of cyclin T1 in human tissues.

Cyclin T1 was recently identified, together with cdk9 (previously named PITALRE), as part of the TAK multiprotein complex, a co-factor targeted by the human immunodeficiency virus Type 1 (HIV-1) protein named Tat, suggesting a role for this complex in transcription elongation. Although studies on mRNA and protein expression have shown that cyclin T1 is ubiquitous in adult human tissues, no data have yet been reported regarding the expression of this protein in different cell lineages. Using a polyclonal antiserum raised against cyclin T1, we investigated the pattern of expression of this protein in adult human tissues by immunohistochemistry. Cyclin T1 was expressed ubiquitously, although different levels of expression were found in various organs. Some specialized tissues, such as blood, lymphoid tissues, and cells of connective tissue origin, showed high cyclin T1 expression. These specific expression patterns are only partially justified by some well-known specialized functions of cyclin T1 in certain cell types, such as its involvement in peripheral blood lymphocytes and monocyte differentiation. The high expression level found in other tissues suggests new possible roles for cyclin T1 in cell types other than those of lymphoid tissue.

Adult↗