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Biomedical subjects

M Romano

Publications and source records attributed to M Romano.

At least 235 records · Page 13Linked to original sources
PubMed1995

Roles for transforming growth factor-alpha in the stomach.

The gastric mucosa maintains its integrity despite the harsh environment of an acidic luminal pH and strong mechanical stresses secondary to peristalsis of ingested contents. The mucosa has marshalled a battery of both protective and reparative mechanisms which, in general, prevent the deleterious effects of these factors that, if unchecked, may result in untoward consequences such as gastritis and peptic ulcer disease. An increasing body of evidence suggests that transforming growth factor-alpha (TGF alpha) produced by the gastric mucosa is a critical mediator of gastric mucosal homeostasis. TGF alpha inhibits acid secretion, stimulates mucosal restitution after injury (cell migration and proliferation), and augments gastric mucin levels. We review the data that support a role for this endogenously produced growth factor in both protective and reparative actions in the stomach. In addition, we discuss a possible role for overproduction of TGF alpha in the pathogenesis of Ménétrier's disease, a premalignant disorder of the stomach characterized by fundic gland hyperplasia, hypochlorhydria, increased gastric mucus, and hypoalbuminemia.

Animals↗
PubMed1994

Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect.

Hereditary eosinophil peroxidase (EPO; EC 1.11.1.7) deficiency is a rare abnormality of eosinophil granulocytes characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix. The molecular basis of the defect is not known. We report here its molecular characterization in an EPO-deficient subject and his family members. The EPO-deficient eosinophils contained EPO-related material as determined immunochemically using either monoclonal or polyclonal anti-EPO antibodies but had no spectroscopic evidence of EPO. Eosinophil precursors from the EPO-deficient subject contained normally sized EPO mRNA, which was reverse transcribed into the corresponding cDNA clones encompassing the whole gene. Sequencing of these clones disclosed two mutations, a G-->A transition causing a nonconservative replacement of an arginine residue with a histidine and an insertion causing a shift in the reading frame with the appearance of a premature stop codon. The two mutations were located on different chromosomes indicating a compound heterozygosity for the defect. Both the son and the daughter of the proband inherited the G-->A transition, and their eosinophils contained a peroxidase activity intermediate between that of control subjects and the proband, suggesting that the transition is a deficiency-causing mutation. Eosinophil precursors from the EPO-deficient subject were found to actively synthesize an EPO that was apparently normal in terms of cytochemical reaction for peroxidase and immunoreactivity with monoclonal and polyclonal anti-EPO antibodies, but spectroscopically abnormal. The cytochemical reaction for peroxidase tended to decrease or disappear in the eosinophil precursors of the EPO-deficient subject but not of a normal subject as differentiation went on, suggesting that the Arg-->His substitution causes the production of an unstable EPO that undergoes progressive degradation as the cells mature.

Amino Acid Sequence↗
PubMed1994

Stage I seminoma of the testis: long term results and toxicity with adjuvant radiotherapy.

AIMS AND BACKGROUND: Pure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento, METHODS: From 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time. RESULTS: The cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespread metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients. CONCLUSIONS: In our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.

Adult↗
PubMed1994

Molecular characterization of the functionally distinct hemoglobins of the Antarctic fish Trematomus newnesi.

Antarctic fish of the family Nototheniidae usually have a single major hemoglobin (Hb 1), often a second, minor component (Hb 2, about 5% of the total), and traces of another component (Hb C, less than 1%). These are functionally similar Bohr and Root effect hemoglobins. All species of other highly endemic fish families so far investigated also have one single major hemoglobin. The hematological features of the nototheniid Trematomus newnesi are remarkably different. It is the only Antarctic species in which Hb 1 and Hb 2 display only a very weak Bohr effect and no Root effect. Perhaps consequentially, Hb C (the only component showing regulation of oxygen binding by protons and other effectors) is not present in traces but accounts for 20-25% of the total. The primary structure of the three hemoglobins of T. newnesi and of Root effect HbC present in trace amounts in another nototheniid (Pagothenia bernacchii) is discussed in relationship with oxygen binding and in terms of molecular and stereochemical models. The hemoglobin multiplicity, the oxygen binding features of Hb 1 and Hb 2, and the presence of functionally distinct components, thus reveal that the oxygen transport of T. newnesi has unique characteristics.

Amino Acid Sequence↗
PubMed1994

Biochemical effects of acute and subacute nitrogen dioxide exposure in rat lung and bronchoalveolar lavage fluid.

The pulmonary inflammatory response to NO2 exposure was measured by evaluating a series of biochemical and cellular parameters in rat bronchoalveolar lavage fluid. Animals were exposed to 9 mg/m3 (5 ppm) or 18 mg/m3 (10 ppm) of the gas for 24 h or 7 days. After bronchoalveolar lavage collection, a differential count of polymorphonuclear leukocytes, macrophages, and lymphocytes was done. A significant increase in polymorphonuclear leukocytes was found after 24 h of exposure, and after 7 days the number of macrophages increased significantly. After 7 days of exposure to 9 mg/m3 of NO2 (a dose that under our conditions did not induce migration of cells in the bronchoalveolar spaces) the ex vivo phorbol myristate acetate-induced superoxide anion production by resident cells was inhibited. After 24 h and 7 days of exposure to 18 mg/m3 of NO2, phorbol myristate acetate-induced superoxide anion production was lower than in the control group. The migration of polymorphonuclear leukocytes in the bronchoalveolar lavage fluid was not associated with any real increase in elastase. However, there was a dose- and time-dependent increase in alpha 1-proteinase inhibitor in response to both 9 and 18 mg/m3 of NO2. Total glutathione was significantly increased in blood by 24 h treatment with 9 or 18 mg/m3 of NO2, whereas blood oxidized glutathione was not affected. In lung tissue we observed only a significant increase of oxidized glutathione after 24 h of exposure to 9 and 18 mg/m3 of NO2. These data suggest that many biochemical and cellular parameters are altered after acute or subacute exposure to relatively high doses of NO2, especially in the first 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗
PubMed1994

Effect of transforming growth factor-alpha on gastric acid secretion in rats and monkeys.

The effect of transforming growth factor-alpha was studied in histamine-stimulated gastric acid secretion in monkeys and in pylorus-ligated rats. In monkeys, transforming growth factor-alpha given intravenously in a stepwise manner gradually reduced gastric acid secretion. A dose of 0.1 mmol/kg induced about a 50% inhibition of gastric acid output, while about 100% inhibition of the same parameter, was observed after a dose of 1 nmol/kg. Following a single administration of 1 nmol/kg intravenously in monkey, the maximum inhibitory effect on gastric acid output was reached 60 min after the administration of the drug, when a 91.8% inhibition was observed. Pretreatment values were reached 210-240 min after transforming growth factor-alpha administration. In pylorus-ligated rats, transforming growth factor-alpha, at doses of 9 and 18 nmol/kg produced an almost complete inhibition of gastric acid secretion. In this model, the ED50 was calculated to be 4.5 nmol/kg. Comparison with epidermal growth factor on the same models of gastric acid secretion showed that these two compounds have similar inhibitory potency. However, the effect of transforming growth factor-alpha on gastric acid secretion in monkeys was shorter lasting than that of epidermal growth factor.

Animals↗
PubMed1994

Noninvasive evaluation of cardiac hemodynamics during exercise in patients with chronic heart failure: effects of short-term coenzyme Q10 treatment.

In patients with chronic heart failure (CHF), the addition of coenzyme Q10 to conventional therapy reduces the hospitalization rate for worsening of heart failure and the incidence of serious cardiovascular complications. The present study was planned to assess the hemodynamic mechanisms underlying this phenomenon. Cardiac hemodynamics was evaluated continuously using an ambulatory radionuclide detector (VEST) which allows a noninvasive monitoring of left ventricular function. Six patients wit CHF (mean ejection fraction (EF): 29%) clinically documented were studied. This study was organized as a randomized double-blind, placebo controlled, cross-over trial. The enrolled patients, after a washout period, underwent the first hemodynamic evaluation with VEST. Subsequently they were randomized to receive placebo or coenzyme Q10 for 4 weeks. At the end of this period they underwent the second VEST study. The third VEST study was performed after a further 4-week period with inverted treatment. Cardiac hemodynamics were evaluated during bicycle exercise. The EF in control conditions (CC) changed from 27 +/- 11%, at rest, to 24 +/- 8%, at peak exercise. During coenzyme Q10 treatment EF showed a significant increase both at rest (33 +/- 13%, P < 0.05 vs CC) and at peak exercise (30 +/- 12%, P < 0.05 vs CC). The same trends were recorded for the stroke volume and the cardiac output. Our results demonstrate that coenzyme Q10 improves cardiac hemodynamic response to exercise in patients with CHF and suggest that noninvasive monitoring of left ventricular function allows a more reliable assessment of therapy efficacy.

Adult↗
PubMed1994

An automated system for animal exposure to nitrogen dioxide.

We have designed an automated system for controlled exposure of rodents to nitrogen dioxide (NO2). The system consists of 1) two stainless-steel exposure chambers (3.96 m3), for control and treated animals, in which temperature, humidity, and air changes are consistent with current guidelines for rodent housing; 2) a cylinder containing 1% NO2 in N2; 3) a detector connected with a personal computer system that monitors the NO2 concentration, and regulates the NO2 influx, using a closed-loop feedback; and 4) a fan system to distribute the gas uniformly within the chambers. In a typical experiment rats were exposed to 15 ppm of NO2, and changes in the differential count of polymorphonuclear leukocytes, macrophages, and lymphocytes in bronchoalveolar lavage fluid were investigated.

Animals↗
PubMed1994

The association between rifamycin-SV (R-SV) related hyperbilirubinaemia and antipyrine clearance as a new test of liver function in cirrhosis.

Several clearance tests have been used to assess the residual hepatic efficiency in liver cirrhosis. However, the altered clearance values found in cirrhotic patients may reflect not only the impairment in liver function but also a derangement in the hepatic blood-flow. Therefore, this study was designed to explore the possibility that the competition between Rifamycin-SV and bilirubin at the hepatic uptake site might be used as an index for quantitative assessment of residual hepatic efficiency in 48 patients with chronic liver disease. In this test, the interference of hepatic blood flow would be negligible. Antipyrine clearance was also evaluated in the same subjects in order to explore the cytoplasmic microsomal efficiency. Rifamycin-SV intravenous load was followed by a sustained increase in bilirubinaemia which significantly related with the degree of liver function as assessed by the Child-Pugh criteria. Also, antipyrine clearance was significantly altered in cirrhotic patients compared to controls. Moreover, a positive correlation was found between the Rifamycin-SV test and Antipyrine clearance. We suggest that a combination of these tests might be of use in the quantitative assessment of liver function.

Adult↗
PubMed1994

Enhanced adrenal renin and aldosterone biosynthesis during sodium restriction in TGR (mREN2)27.

The aim of the study was to investigate the relationships between tissue renin and the steroid production in the adrenal cortex during dietary sodium restriction in the transgenic rat (TGR) (mREN2)27. Thus the effects of a 1-wk low-sodium intake (0.04% NaCl) were studied in 5-wk-old male TGR (n = 33, systolic blood pressure = 151 +/- 3 mmHg) and in 24 age- and sex-matched outbred normotensive Sprague-Dawley (SD) rats. Measurements of plasma and tissue hormones were obtained at 0, 4, and 7 days of a low-sodium diet. Sodium restriction caused sustained increases of adrenal renin activity (from 28.5 +/- 3.5 to 87.5 +/- 4.5 ng.mg protein-1.h-1 on day 7) and of adrenal renin mRNA (+63 +/- 13 and +43 +/- 7% on days 4 and 7, respectively), whereas plasma renin activity (from 3.3 +/- 0.3 to 4.4 +/- 0.6 ng.ml-1.h-1) and renal renin activity (from 0.85 +/- 0.25 to 0.7 +/- 0.4 microgram.mg protein-1.h-1) did not change. The stimulation of the adrenal renin-angiotensin system was associated with a large increase of the aldosterone synthase cytochrome P-450 mRNA (+165 +/- 35 and +184 +/- 44%, on days 4 and 7) and of plasma aldosterone levels (from 125 +/- 32 to 338 +/- 59 pg/ml, P < 0.01). In SD rats, in spite of a more consistent increase in renal and circulating renin, mineralocorticoid production did not increase significantly. These results demonstrate that the exaggerated biosynthesis of aldosterone in TGR during sodium restriction is associated with an activation of renin in the adrenal cortex but not in the kidney.

Adrenal Glands↗
PubMed1994

Gastric endoscopic features in patients with liver cirrhosis: correlation with esophageal varices, intra-variceal pressure, and liver dysfunction.

This study was aimed at evaluating the gastric endoscopic features in patients with liver cirrhosis and at assessing whether endoscopic findings correlated with the severity of portal hypertension and of the underlying liver disease. We studied 394 cirrhotic patients and 110 controls. Prevalence of a mosaic-like pattern of the gastric mucosa was significantly higher in cirrhotics than controls (80.5 vs. 0.9%; p < 0.001). Red spots of the gastric mucosa were found in 8.1% of cirrhotic patients and in none of the control subjects. Erosions and petechiae were found in 14.5 and 5.4% of the control population, but their prevalence was significantly higher in cirrhotics (28.7 and 12.7%, respectively; p < 0.05). Severity of the mosaic-like pattern as well as the presence of red spots were closely related to the size and hemorrhagic risk of esophageal varices and to the presence of fundic varices. Also, severe mosaic-like patterns were found more frequently in patients with severe impairment of liver function, as assessed by the Child-Pugh's criteria. Furthermore, the mosaic-like pattern was more severe in cirrhotic patients with a higher degree of portal hypertension as indirectly assessed by measurement of esophageal intravariceal pressure. In conclusion, (1) a mosaic-like pattern and red spots of the gastric mucosa are the only specific signs of congestive gastropathy in liver cirrhosis, and (2) the severity of the mosaic-like pattern correlates with the severity of liver dysfunction and of portal hypertension.

Adult↗