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Biomedical subjects

R Rota

Publications and source records attributed to R Rota.

18 recordsLinked to original sources

Risk factors for development of de novo neoplasia after liver transplantation.

Liver transplant recipients are at greater risk for de novo neoplasia, especially lymphoma and nonmelanoma skin cancer; however, risk factors for this complication have not been well studied. Clinical and pathological records of 137 consecutive liver transplant recipients who had survived for at least 1 year were reviewed to register de novo neoplasia. Ten variables were analyzed for their association with the development of de novo malignancies by means of a log-rank test and stepwise selection in a multivariate analysis using the Cox proportional hazard model. Thirty de novo neoplasias appeared in 22 of 137 transplant recipients between 12 and 104 months after orthotopic liver transplantation (OLT; median follow-up, 69 months): 14 patients had 21 skin cancers, 6 patients had solid-organ cancer, and 3 patients developed a lymphoproliferative disease. Probabilities of de novo neoplasia were 13% at 5 years post-OLT and 26% at 8 years post-OLT. The only associated risk factor for any neoplasia was age. Age and hepatocarcinoma were independent risk factors associated with skin cancer. That hepatocarcinoma in the explanted liver is an independent risk factor for skin cancer suggests there is individual susceptibility to both neoplasias.

Adolescent↗

Is the increase in childhood asthma coming to an end? Findings from three surveys of schoolchildren in Rome, Italy.

Time trends in the prevalence of asthma, family history of asthma and atopy in Roman schoolchildren were assessed. The study population consisted of all children (aged 6-14 yrs) attending two primary schools in Rome, situated in urban areas that differed markedly in socioeconomic conditions and environmental pollution. Three questionnaire-based surveys were conducted in 1974, 1992 and 1998 in 2,259, 1,229 and 1,139 children. The prevalence of asthma in males and females increased significantly during 1974-1992 and remained stable from 1992-1998. In age groups born in the subsequent 4-yr periods it increased almost linearly, for children born from 1962-1965 to 1982-1985 (4.4%-12.5%), and remained remarkably stable in children born after 1985. Because the prevalence of asthma had a steeper trend in males than in females (approximately 0.55% x yr(-1) versus 0.25% x yr(-1)), the male:female asthma ratio increased (1:38 in 1974; 1:84 in 1992 and 1:62 in 1998). No single environmental factor, including area of residence, seemed to influence the prevalence of asthma. Family history of asthma and atopy also increased steadily (0.72% x yr(-1) and 0.30% x yr(-1) respectively) more than doubling during the 24-yr study period. The strong relationship between asthma and a family history of atopy not only persisted but also strengthened over time (23.3% of asthmatic children belonged to families with atopic illnesses in 1974 but 44.2% in 1998). The environmental factors that might explain the almost three-fold rise in childhood asthma between 1974 and 1992 remain unknown but the genetic background of the disease has presumably remained unchanged since the early 1970s. The fact that the prevalence of asthma increased no further during the past 6 yrs suggests that the progressive induction of asthma symptoms in genetically predisposed subjects is a self-limiting process that has probably come to an end in the authors' study area.

Adolescent↗

Wild-type p53 gene transfer inhibits invasion and reduces matrix metalloproteinase-2 levels in p53-mutated human melanoma cells.

The tumor suppressor gene p53 has inhibitory effects on cell growth and angiogenesis and induces apoptosis when overexpressed in melanoma and in a variety of tumor cells by adenovirus-mediated gene transfer. The invasive ability of tumor cells, facilitating local infiltration and metastasis, is related to matrix metalloproteinase levels. In melanoma, matrix metalloproteinase-2 and matrix metalloproteinase-9 have a prominent role in this process. The aim of this study was to evaluate whether wild-type p53 overexpression, obtained by a recombinant adenovirus vector (AdCMV.p53), affects cell invasiveness through modulation of matrix metalloproteinase-2 and matrix metalloproteinase-9. Two human melanoma cell lines were used in this study: the SK-MEL-110, carrying a mutated p53 gene, and the SK-MEL-147, carrying the wild-type p53 gene. SK-MEL-110 cells infected with AdCMV.p53 exhibited decreased invasion capability from day 1 after infection, compared with cells not infected or infected with the control vector AdCMV.Null. This reduced invasiveness was associated with decreased matrix metalloproteinase-2 levels in conditioned media whereas no changes were detected in matrix metalloproteinase-9 secreted levels. No modulation in matrix metalloproteinase-2 mRNA levels was detectable, however, after wild-type p53 gene transfer. Furthermore, protein expression of secreted tissue inhibitor of metalloproteinase-2 was not altered by AdCMV.p53 treatment. In contrast, in SK-MEL-147 cells, AdCMV.p53 did not affect cell invasiveness and levels of secreted matrix metalloproteinase-2. Gene transfer of wild-type p53 inhibited proliferation of both cell lines, showing that also SK-MEL-147 cells respond to wild-type p53 overexpression. This novel mechanism of action of wild-type p53 gene transfer may contribute to its antitumor effect by downregulating cell invasion and matrix metalloproteinase-2 secreted levels in mutated p53 human melanoma cell lines.

Adenoviridae↗

Scoring system has better discriminative value than Helicobacter pylori testing in patients with dyspepsia in a setting with high prevalence of infection.

OBJECTIVE: To prospectively assess the accuracy of a scoring system to predict organic diseases in dyspeptic patients in an area of South Europe, and to compare it with that of Helicobacter pylori testing in patients with dyspepsia in an environment with high prevalence of H. pylori infection. METHODS: Symptoms and demographic data were recorded in 501 consecutive dyspeptic patients referred to an outpatient gastroenterology clinic. A simple scoring system was constructed from the predictive factors obtained in a multi-variate logistic regression analysis. Overall predictive accuracy was assessed with the c statistic. The model was validated using bootstrap techniques. The accuracy of clinical judgement and H. pylori testing to predict endoscopic diagnosis was also assessed. RESULTS: Organic dyspepsia (peptic ulcer, oesophagitis or malignancies) was diagnosed in 45% of the patients. The test for H. pylori was positive in 68%, and 29% of infected patients had an ulcer. The organic dyspepsia predictive model had an accuracy of 0.79, which decreased to 0.77 after validation adjustment. The predictive accuracies for clinical judgement and H. pylori testing were 0.69 and 0.61, respectively. The addition of H. pylori testing to the scoring system resulted in a minor improvement of the predictive accuracy. CONCLUSION: In an environment with a high rate of H. pylori infection and a low prevalence of peptic ulcer among infected patients, a scoring system has higher predictive accuracy for the diagnosis of organic disease than H. pylori testing. Moreover, in this setting, H. pylori testing adds a minimum value to the predictive capability of the scoring system.

Adolescent↗

3p13 region: a possible location of a tumor suppressor gene involved in uveal melanoma.

To contribute to a better understanding of the role of chromosomal rearrangements in the tumorigenesis of uveal melanoma, we present a case in which a structural aberration of chromosome 3 could indicate the specific region in which an uveal melanoma tumor suppressor gene could be located. We obtained a primary cell culture, characterized by cytogenetic study, through GTG- and CBG-banding techniques by using a mechanical dissection of a tumor sample obtained from an uveal melanoma. Cytogenetic analysis performed in the primary cell culture highlighted the presence of a structural rearrangement involving chromosomes 3 and 22. A t(3;22)(p13;p11) was observed as the only present clonal aberration. The 3p13 breakpoint involved in the aberration observed in our case could be essential in restricting the candidate region for the locus of an uveal melanoma tumor suppressor gene located on chromosome 3.

Choroid Neoplasms↗

[Edema-inducing properties of lacidipine, nitrendipine and nifedipine in the spontaneously hypertensive rat].

INTRODUCTION: Clinical studies suggest that lacidipine (LA) is better tolerated than other DHP, in terms of peripheral edema. We evaluated edema due to LA, nitrendipine (NT) and nifedipine (NF) in SHR. METHODS: Mean arterial pressure (MAP) was measured with an intra-femoral probe. Peripheral edema was determined (i) by the plasmatic distribution of 14C-albumin, (ii) by Evans blue extravasation. RESULTS: In bolus(ip), LA, NT and NF had non different effects on plasmatic *ALB, i.e. + 3.9 +/- 1.7 (delta % vs control at 60 min; mean +/- SEM, n = 18). Evans blue extravasation (hind paws muscle = EBM) was positively correlated to MAP reduction (EBM = 0.1 x delta MAP + 5.2; p < 0.025), without differences between the molecules. In chronical administration (9 days), at comparable MAP decreases (31 +/- 2 mmHg), there was less edema formation with LA (0.05 mg/kg/j) than with NT (0.5 mg/kg/j) or NF (1.4 mg/kg/j): the variations of *ALB were respectively (% vs control at 45 min after tracer injection; mean +/- SD): + 5% (n = 10) vs. 73% (n = 14; p < 0.01 vs LA) and + 34% (n = 10; p < 0.01 vs LA); no significant change of hematocrit or plasma volume was noted. CONCLUSION: Our results confirm, in SHR, that lacidipine induces a very moderate edema formation. This does not seem to be due to a renal effect, nor to an effect on peripheral resistances. It was only observed in chronical administration, which suggests that pharmacokinetic properties of lacidipine are involved.

Animals↗

Paraneoplastic intestinal pseudo-obstruction associated with high titres of Hu autoantibodies.

Anti-Hu autoantibodies in high titres, as revealed with immunocytochemistry and Western blot, were present in a patient with gastrointestinal pseudo-obstruction and small-cell lung cancer (SCLC) bearing the Hu antigen. Marked neuron and nerve fibre loss were found in the myenteric plexus at postmortem. These findings show that neuronopathic Hu-associated gastrointestinal pseudo-obstruction can occur as the only paraneoplastic neurological symptom in patients with SCLC.

Antibodies, Neoplasm↗

Erythrocyte Na+/Li+ countertransport and glomerular hyperfiltration in insulin-dependent diabetics.

Erythrocyte Na+/Li+ countertransport activity was investigated in 11 controls and 22 recent onset type I (insulin-dependent) diabetic patients with normal and high glomerular filtration rates. No differences in Vmax were observed in hyperfiltering compared to normofiltering patients or controls. The Na+/Li+ activity was correlated with blood glucose levels in insulin-dependent diabetics showing good glycemic control. Total cholesterol and triglyceride concentrations were similar among the three groups. In conclusion, enhanced Na+/Li+ countertransport activity is not associated, in our case, with diabetic condition per se and with early glomerular hyperfiltration and cannot be used as a marker of renal involvement in recent onset insulin-dependent diabetics.

Adult↗

Volume-dependent K+ and Cl- fluxes in rat thymocytes.

1. Hypotonic stress unmasked inward and outward K+ and Cl- movements in rat thymocytes. This KCl flux stimulation was reduced by DIOA (dihydroindenyl-oxy-alkanoic acid), but not by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonate), quinidine, DPAC 144 (5-nitro-2-(2-phenylethyl-amino)-benzoic acid), bumetanide or ouabain. 2. In isotonic media (308 +/- 5 mosmol kg-1), the cells exhibited the following DIOA-sensitive fluxes: (i) a K+ efflux of 42.7 +/- 17.1 mmol (l cells.h)-1 (mean +/- S.D., n = 7), (ii) a Cl- efflux of 68 +/- 21 mmol (l cells.h)-1 (n = 3), (iii) a Rb+ influx of 9.7 +/- 3.9 mmol (l cells.h)-1 (n = 6) and (iv) a Cl- influx of 9.4 +/- 4.1 mmol (l cells.h)-1 (n = 6). 3. Hypotonic shock (183-200 mosmol kg-1) induced a sevenfold stimulation of DIOA-sensitive K+ and Cl- effluxes and a twofold stimulation of DIOA-sensitive Rb+ and Cl- influxes (with a Rb+ to Cl- stoichiometry of 1.04 +/- 0.31; mean +/- S.D., n = 6). 4. The DIOA-sensitive membrane carrier catalysed net outward KCl extrusion (the outward/inward flux ratio was 5-7 in isotonic media and 20 in hypotonic media at 189 mosmol kg-1). Inhibition of DIOA-sensitive 36Cl- efflux by cell K+ depletion suggested coupling of outward K+ and Cl- fluxes. Conversely, inward K+ and Cl- fluxes were found to be uncoupled in NO3- media and in K(+)-free media. 5. The results clearly show that rat thymocyte membranes possess a 1:1 K(+)-Cl- co-transport system which is strongly activated by hypotonic shock and catalyses net KCl extrusion.

Animals↗

Cell volume regulation in rat thymocytes.

1. DIOA (dihydroindenyl-oxy-alkanoic acid), a potent inhibitor of the K(+)-Cl- co-transport system, fully blocked regulatory volume decrease (RVD) in swelled rat thymocytes, with an IC50 of 2.2 +/- 0.5 x 10(-5) mol l-1 (mean +/- S.D., n = 4). Conversely, RVD was resistant to quinine, quinidine, apamin, cetiedil, amiloride, bumetanide and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonate). 2. DIOA-sensitive RVD followed mono-exponential kinetics, with t1/2 (half-lifetime) of 1-3 min and maximal capacity (Cmax) of about 55% of the initial cell swelling. Cmax and the initial rate of RVD (Vo) were both linear functions of the increase in cell volume. 3. RVD was: (i) slightly increased by replacing external Cl- by NO3-, (ii) reversed by replacing external Na+ by K+ (in the presence of external Cl-) and (iii) inhibited by cell K+ depletion. All these phenomena were blocked by DIOA (86 mumol l-1). 4. Increased membrane potassium permeability by valinomycin was unable to accelerate RVD or RVD reversal. 5. In the presence of DIOA, thymocytes responded like osmometers (the relative cell volume was a linear function of the reciprocal of the relative osmolality) in a large range of osmolalities. 6. The results strongly suggest that RVD in rat thymocytes is mediated by the K(+)-Cl- co-transport system.

Animals↗

[Diagnosis and treatment of esophageal ulcers in patients seropositive for the human immunodeficiency virus (HIV-positive)].

Esophageal ulcers are often found in patients with human immunodeficiency virus infection. We have retrospectively reviewed the upper endoscopies performed in these patients during the last four years. 149 examinations were realized in 73 patients. Fourteen patients with esophageal ulcers were diagnosed. A severe immunological impairment was present in all patients (CD4 24.4 +/- 31.1 cells/ul). Symptoms were non-specific, with prevailing dysphagia and odynophagia. The etiological diagnosis was reached by histological studies and cultures in 5 cases (36%), three due to Herpes virus type I, one due to Cytomegalovirus and another one to Mycobacterium tuberculosis. Patients with multiple ulcers or small ones were successfully treated with antiviral drugs, even when the etiological studies were negative. Corticosteroids were useful in single and large ulcers in which diagnostic tests were negative.

Adult↗

Erythrocyte transmembrane Na and K fluxes in pseudohypoaldosteronism.

Pseudohypoaldosteronism (PHA) is a disease characterized by hyponatremia, hypotension, and dehydratation, despite the presence of hyperreninemic hyperaldosteronism. The membrane-bound Na,K ATPase activity and the transmembrane Na and K transport systems have been studied in vitro in red blood cells of two subjects, son and mother, affected by pseudohypoaldosteronism with different degrees of clinical involvement. Both parameters were significantly altered suggesting that the refractory response to mineralocorticoids is detectable, not only in kidneys and salivary and sweat glands, but also in red blood cells. Since pseudohypoaldosteronism, in its asymptomatic form, may be much more common than expected, we suggest the use of the tests described herein as a practical approach to the early diagnosis of pseudohypoaldosteronism in the investigation of sodium wasting syndromes.

Aldosterone↗

Dissociation of hypertension and genetically enhanced cell growth capacity in skin fibroblasts of F2 hybrid spontaneously hypertensive rats/Wistar-Kyoto rats.

Skin fibroblasts from newborn spontaneously hypertensive rats (SHR) grow faster in culture than Wistar-Kyoto rat (WKY) cells. Similar results have been described for vascular smooth muscle cells from prehypertensive and adult SHR. This suggests the existence of an intrinsic abnormality in vascular and nonvascular cells of mesodermal origin affecting cell growth control in those rats. In an attempt to determine the relation between high blood pressure and this trait, we cultured skin fibroblasts from adult SHR, WKY, F1, and F2 hybrid SHR/WKY populations by explant technique. Their growth capacity was determined by culture well DNA doubling time and by [3H]thymidine incorporation. Adult SHR fibroblasts grew more quickly (doubling time [DT] = 37.2 +/- 2.3 h, n = 8) than WKY ones (DT = 53.9 +/- 3.6 h, n = 6). Female SHR were crossed with male WKY to produce an F1 and an F2 hybrid generation presenting a Mendelian distribution of blood pressure. Skin fibroblasts were cultured from 21 rats belonging to the highest and the lowest blood pressure groups. No difference was observed between the two groups in either growth (DT = 47.5 +/- 4.1 h, n = 11 v DT = 44.6 +/- 3.2 h, n = 10) or epidermal growth factor-induced [3H]thymidine incorporation. These observations suggest that the increased growth capacity observed in SHR is not a determinant of high blood pressure initiation but may be involved in early cardiovascular enlargement.

Animals↗

Design guidelines for push-pull ventilation systems through computational fluid dynamics modeling.

Open surface tanks often are used in industrial practice. When harmful substances are involved, control of worker exposure requires the use of a local ventilation system. The push-pull system, among others, involves a jet of air that is blown from one side of the tank and collected by an exhaust hood on the opposite side; this system can save up to 50% of the ventilation air. Several guidelines are available for design of such a ventilation system, mainly based on experimental results. However, their validity is confined inside a narrow operating window. In this work a mathematical model developed based on computational fluid dynamics has been used to extend the validity of the existing guidelines outside the range in which they have been validated, with particular reference to tank width and to the velocity of the air drafts.

Air Pollutants, Occupational↗