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Biomedical subjects

M Romano

Publications and source records attributed to M Romano.

At least 307 records · Page 17Linked to original sources
PubMed1990

Interaction of endotoxic lipid A and lipid X with purified human platelet protein kinase C.

Lipid A, the toxic principle of endotoxic lipopolysaccharide, and its precursor, Lipid X, interact with human platelets and modulate protein kinase C therein (Grabarek, J., Timmons, S., and Hawiger, J. (1988) J. Clin. Invest. 82, 964-971). We have now purified protein kinase C from human platelets and studied its interaction with endotoxic Lipids A and X. Protein kinase C-dependent phosphorylation of histone III-S was increased 15 times in the presence of Lipid A and 300 microM Ca2+. The Ca2+ requirement for such activation was lower when 4 beta-phorbol 12-myristate 13-acetate (PMA) or 1,2-diolein were added. Lipid A also induced autophosphorylation of protein kinase C, and its activation was enhanced by phosphatidylserine without reducing the Ca2+ requirement. Kinetic analysis of protein kinase C activation induced by Lipid A, in regard to ATP as a substrate, demonstrated that Lipid A increased the rate of the reaction (Vmax) without modifying the affinity of the enzyme (Km) for the substrate. Lipid X inhibited the activation of the enzyme induced by Lipid A. Lipid X also inhibited protein kinase C activation by phosphatidylserine, 1,2-diolein, and PMA. However, 10 times more of Lipid X was required for 50% inhibition (IC50) when PMA was used as an activator of protein kinase C in the presence of phosphatidylserine than when Lipid A and 1,2-diolein were used. These results support the hypothesis that endotoxic Lipid A and Lipid X exert their biological effect in platelets through direct interactions with protein kinase C.

Blood Platelets↗
PubMed1990

Progressive pneumoperitoneum in the management of giant incisional hernias: a study of 41 patients.

Forty-one patients (17 men and 24 women) were treated with progressive pneumoperitoneum before repair of giant incisional hernias. The pneumoperitoneum was induced using nitrous oxide gas and a laparoscopic insufflator, and was topped up every other day for a mean of 5.5 days with a total injection of 23.2 litres of nitrous oxide. The pneumoperitoneum was well tolerated in 30 patients, caused a mild temporary pain in 10 patients and a sharp pain in one patient; no serious side-effects occurred. All the patients underwent surgery to repair their hernias, 40 patients were available for follow-up for a mean of 25.3 months, only two hernias recurred both within 4 months of the operation.

Abdomen↗
PubMed1990

Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture.

The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells. (3) The protection by sucralfate in vitro does not seem to depend on its stimulatory effect on endogenous prostaglandin synthesis.

Aluminum Hydroxide↗
PubMed1990

Plasma and brain kinetics of large neutral amino acids and of striatum monoamines in rats given aspartame.

Two doses (250 and 1000 mg/kg body weight) of aspartame were administered orally to male rats, and plasma and brain phenylalanine and tyrosine kinetic profiles were studied. In both plasma and brain the maximum increase in phenylalanine and tyrosine levels was reached 60 min after treatment. The changes in brain levels of phenylalanine or tyrosine 0, 60, 120 or 180 min after treatment with 1000 mg AMP/kg were directly correlated with the ratio of the plasma concentration of phenylalanine or tyrosine to the overall plasma concentration of the other large neutral amino acids. The time course of monoamine and metabolite concentrations, in the corpora striatum of the brain, was studied after an oral dose of 500 mg phenylalanine/kg. No significant modifications of monoamine levels were found at any of the times studied, up to 5 hr after dosing.

Animals↗
PubMed1990

Hemoglobin from the antarctic fish Notothenia coriiceps neglecta. Amino acid sequence of the beta chain.

1. Notothenia coriiceps neglecta is a cold-adapted notothenioid teleost, widely distributed in the Antarctic waters. 2. In comparison with fishes from temperate waters, the blood of this teleost contains a reduced number of erythrocytes and concentration of hemoglobin; the erythrocytes contain two hemoglobins, Hb1 and Hb2, respectively accounting for approximately 90, and 5% of the total. 3. The two components differ by the alpha chain; the amino acid sequence of the beta chain in common to the two hemoglobins has been established, thus completing the elucidation of the primary structure of the major component Hb 1.

Amino Acid Sequence↗
PubMed1990

Effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients.

This study was undertaken to evaluate the effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Sixteen cirrhotics were randomly assigned to metoclopramide (10 mg i.v.) or saline. Metoclopramide significantly decreased transmural variceal pressure (15.7% decrease, p less than 0.05 vs. basal value). In order to evaluate if the metoclopramide-induced drop in transmural variceal pressure was due to an effect on portal haemodynamics, we also measured, by means of real time and pulsed Doppler ultrasonography, portal vein diameter, mean velocity of portal flow, and portal venous flow. No significant change was observed before and after metoclopramide. In conclusion, metoclopramide, which increases lower oesophageal sphincter pressure, significantly decreases transmural variceal pressure in cirrhotic patients. However, it does not have any effect on portal haemodynamics.

Double-Blind Method↗
PubMed1990

Platelet-derived mitogenic activity and bone marrow fibrosis in myeloproliferative disorders.

Mitogenic activity, measured as 3H-thymidine incorporation by NIH 3T3 cells, following stimulation with platelet-rich-plasma-derived serum (PRS), platelet-poor-plasma-derived serum and platelet extract was studied in 14 patients with myeloproliferative disorders (MPD) and 7 normal subjects. Reduced mitogenic activity was found in PRS and platelet extract of patients with MPD, as compared to controls. The average levels of platelet-derived growth factor (PDGF) equivalents were as follows: 16.3 +/- 7.2 pg/10(6) platelets in controls, 6.2 +/- 2.2 pg/10(6) (p less than 0.05) platelets in patients with polycythaemia vera, 1.8 +/- 0.4 pg/10(6) (p less than 0.01) platelets in patients with idiopathic myelofibrosis and 4.0 +/- 0.8 pg/10(6) (p less than 0.05) platelets in patients with essential thrombocythaemia (Dunnett test). A reduction of intraplatelet levels of beta-thromboglobulin, although not statistically significant, was found in the same patients. No apparent relation was found between the amount of PDGF equivalents and the degree of bone marrow fibrosis.

Adult↗
PubMed1990

Familial clustering of hepatitis C virus infection and chronic liver disease.

The present study was undertaken to assess the prevalence of HCV antibodies (anti-HCV) and of chronic liver disease in relatives of anti-HCV positive subjects suffering from chronic active liver disease. We studied 122 subjects from 24 families. Each family had at least one positive anti-HCV component with histologically proven chronic liver disease. Anti-HCV was found in 32% of subjects; 82% of these were suffering from chronic liver disease diagnosed on the basis of physical examination and biochemical parameters. Prevalence of anti-HCV was higher in spouses, parents, and siblings of the index case as compared to the offspring. In conclusion, the transmission of HCV infection and of HCV-related chronic liver disease is contributed to by factors associated with the familial environment.

Adolescent↗
PubMed1990

[HR/QT ratio during ergometric test: influence of ischemia and beta blocking therapy].

The aim of this study was to analyze the HR/QT relation during exercise in a group of patients with effort angina (Group B) in comparison with the same relation obtained in a group of normal subjects (Group A) comparable for age and sex. The regression analysis was carried out separately during effort in upright position and during rest in clinostatic position to avoid influences on QT by the patient's posture. During effort in patients of the Group B the regression shows a lower value of the slope and of the intercept (p less than 0.001) than those obtained in the subjects of the Group A. A similar behaviour is shown also from the regressions obtained during rest in the same groups. Thus at the highest HRs we observed a longer QT in the Group B. Moreover QT of ischemic patients in the presence of ECG signs of ischemia (ST less than or equal to 1 mm) resulted significantly longer (p less than 0.01) either during effort and at rest, respect to that obtained in Group A at comparable HRs. The analysis of the regression HR/QT after administration of atenolol 100 mg per os in a subgroup of patients of Group B clearly shows a less prolonged QT at the highest HRs where ECG ischemia frequently appears. This fact is demonstrated by the presence of a higher slope (p less than 0.05) respect to that obtained in the same group without therapy. In conclusion, myocardial transient ischemia provokes a longer QT in patients with ischemic heart disease in comparison with normal subjects. Acute therapy with atenolol per os is able to condition the regression HR/QT showing a relative shortening of QT at the highest HRs respect to that carried out in the same patients in absence of therapy.

Adrenergic beta-Antagonists↗
PubMed1990

Mitral valve repair: results and the decision-making process in reconstruction. Report of 275 cases.

From January 1975 to June 1988, 275 patients underwent mitral valve repair for mitral regurgitation, pure (148 patients) or associated with mitral stenosis (127 patients). Patients with pure mitral stenosis were excluded from this study. The cause of mitral regurgitation was rheumatic in 180 patients (aged 28.6 +/- 1.2 years, mean +/- standard error of the mean) and degenerative in 84 patients (aged 54.7 +/- 1.5 years). Fifty-nine percent of the patients were in New York Heart Association classes III and IV before the operation. Intraoperative assessment of the mitral valve led us to identify four major mechanisms of mitral regurgitation: (1) restriction of leaflet motion by fibrosis (group I, 63 patients); (2) enhancement of leaflet motion by leaflet and chordal extension and prolapse (group II, 139 patients), (3) combination of both (group III, 64 patients); and (4) isolated dilatation of the anulus (group IV, 10 patients). One hundred sixty-one patients had isolated mitral disease and 114 had associated aortic or tricuspid valve disease, or both. The hospital mortality rate was 4.0%. Follow-up was 96% complete and totaled 1247.47 patient-years. At 13 years' follow-up, the survival rate was 93.0% +/- 6.8% in group I, 90.0% +/- 6.0% in group II, and 96.6% +/- 4.6% in group III. Freedom from reoperation was 78.1% +/- 21.0%, 83.2% +/- 18.9%, and 79.6% +/- 16.2%, respectively. Freedom from embolism was 94.7% for the whole series. In patients with isolated mitral valve repair, the cumulative morbidity was significantly higher in groups I (6.3 +/- 2.0%/pt-yr) and III 6.3% +/- 1.7%/pt-yr) than in group II (2.5% +/- 0.9%/pt-yr, p less than 0.05). Multivariate analysis identified age and associated tricuspid valve disease as significant predictors of reoperation (p less than 0.01 for both factors). These results suggest that conservative surgery should be used with caution in group I and III patients. In contrast, indications for mitral valve repair should be extended in group II patients. This observation has important clinical implications since, in Western countries, valve prolapse tends to be a major cause of mitral regurgitation.

Actuarial Analysis↗
PubMed1989

Effects of selective inhibitors on cyclic nucleotide phosphodiesterases of rabbit aorta.

In this study three forms of cyclic nucleotide phosphodiesterase (PDE) isolated from rabbit aorta were pharmacologically characterized, and the consequence of selective inhibition of calmodulin-stimulated PDE (CaM-PDE) and cGMP specific PDE (cG-PDE) was evaluated using PDE inhibitors. The cG-PDE (F1) was selectively inhibited by M&B 22948 (IC50 = 0.5 microM) and dipyridamole (IC50 = 7 microM). The cAMP-PDE (cA-PDE, F3) was inhibited more effectively by the cA-PDE inhibitor milrinone than by other PDE inhibitors. The cA-PDE preparation appeared to contain both cG-inhibited PDE and cG-insensitive PDE based on an additive inhibition of the activity by milrinone and SQ 65442, respective inhibitors of these enzymes. Vinpocetine, 8-methoxymethyl isobutylmethylxanthine (8-MeOMeMIX) and M&B 22948 effectively inhibited CaM-PDE (F2). Vinpocetine was a more selective inhibitor of CaM-PDE than M&B 22948 or 8-MeOMeMIX. CaM-PDEs isolated from rabbit aorta and bovine brain exhibited a similar sensitivity to these inhibitors. Seventy-two percent of the cGMP-hydrolyzing activity of this rabbit aortic CaM-PDE preparation was immunoadsorbed to monoclonal antibody (ACC-1) against CaM bound to brain CaM-PDE. Vinpocetine, 8-MeOMeMIX and M&B 22948 at concentrations (30 and 100 microM) which inhibit CaM-PDE greater than 60% increased cGMP but not cAMP levels in l-norepinephrine (NE) preincubated rabbit aortic slices. At concentrations selectively inhibiting cG-PDE, dipyridamole and M&B 22948 increased cGMP levels in untreated slices but failed to increase cGMP levels significantly in NE-treated slices. By contrast, vinpocetine failed to increase cGMP significantly in untreated slices, although it increased cGMP levels in NE or KCl preincubated slices. These data indicate that, in activated (precontracted) aorta, CaM-PDE is a major enzyme, whereas in untreated aorta cG-PDE is a predominant enzyme for the hydrolysis of cGMP. This study also shows a usefulness of selective inhibitors in identifying different forms of PDE and similar drug sensitivities and immunoadsorption of aortic and brain CaM-PDEs by a monoclonal antibody.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1989

The amino acid sequence of the alpha- and beta-chains of the two hemoglobins of the Antarctic fish Notothenia coriiceps neglecta.

The blood of the Antarctic fish Notothenia coriiceps neglecta contains two hemoglobins, Hb 1 and Hb 2, which have a beta-chain in common. We have elucidated the primary structure of the beta-chain (146 residues) and of the alpha-chains (142 residues) of the two hemoglobins. The two alpha-chains differ from each other by 51 residues; in comparison with globin sequences of temperate fishes, the alpha-chain of Hb 1 is more similar to that of bluefin tuna than to the alpha-chain of Hb 2 of the same species.

Amino Acid Sequence↗
PubMed1989

Human T cell clones define S1 subunit as the most immunogenic moiety of pertussis toxin and determine its epitope map.

Human T lymphocyte clones specific for pertussis toxin (PT) were used to analyze the fine specificity of the response to PT, the basic component of new acellular vaccines against whooping cough. The majority (83%) of the clones specific for PT recognized S1, the subunit that in animal models has been shown to be highly immunogenic. To map T cell epitopes on S1, 18 S1-specific clones were tested for recognition of recombinant fragments representing NH2-terminal and COOH-terminal deletions of S1 and two recombinant S1 subunits containing amino acid substitutions. This approach led to the identification of three regions of the protein as the sequences containing T cell antigenic sites: 1-42, 181-211, and 212-235. Synthetic peptides were eventually used for a finer localization of the T cell epitopes. Two peptides, one of 13 residues (27-39) at the NH2 terminus and one of 24 residues (171-194) at the COOH terminus, stimulated proliferation of three and four clones, respectively. Both peptides are recognized in association with HLA DR1 molecules. These results stress the role of S1 in the immune response to PT and provide data useful for the development of a recombinant or synthetic antipertussis vaccine containing T cell epitopes from S1.

Amino Acid Sequence↗
PubMed1989

Natural antibacterial activity against Salmonella typhi in human cord blood.

Cord blood mononuclear cells from normal human newborns possess natural antibacterial (NA) activity against Salmonella typhi, as assessed by an in vitro test. NA activity was significantly higher than that observed in PBMC from normal adult donors. Using fractionation on nylon wool and Percoll gradient or C-dependent killing with mAb, it was found that cells of the monocyte-macrophage series and CD4+ T lymphocytes were capable of exerting NA activity in newborns, in contrast with results obtained in adults, where the effector cell was a CD4+ T lymphocyte. The capability of expressing NA activity by CD4+ T lymphocytes from cord blood was also confirmed by flow cytometry sorting. Pretreatment of cord blood mononuclear cells with F(ab')2 fragments against human IgG, but not against human IgA, abrogate the NA activity. Furthermore, human IgA anti-S. typhi cannot arm CD4+ lymphocytes in cord blood. Thus it can be suggested that in newborns, the immune system still being immature, NA activity might be the expression of a mechanism of defence against infections, acting as antibody-dependent cellular cytotoxicity expressed by monocytes and CD4+ T lymphocytes armed with preexisting maternal IgG antibodies. This differs from NA activity of adults which is only mediated by CD4+ T lymphocytes armed by IgA.

Adult↗
PubMed1989

Hemoglobin from the Antarctic fish Notothenia coriiceps neglecta. 2. Amino acid sequence of the alpha chain of Hb1.

The complete amino acid sequence of the alpha chain of the main hemoglobin of the Antarctic fish Notothenia coriiceps neglecta (family Nototheniidae) has been determined. It consists of 142 residues; an acetylated seryl residue is at the amino terminal. The molecular mass is 15,519 Da. In comparison with alpha-chain sequences of non-Antarctic poikilothermic fish hemoglobins, the homology appears to be significantly lower than that existing among the latter species. A higher homology has been found with the alpha-chain sequence of the non-poikilothermic bluefin tuna.

Amino Acid Sequence↗
PubMed1989

Exercise time: a possible source of misleading results during long-term pharmacological studies by multiple stress testings in coronary artery disease.

The assessment of chronic pharmacological treatment of stable angina requires serial exercise stress testings. It is well known that exercise tolerance can be improved by the training effect of performing repeated testings. Our study investigated the values of heart rate, systolic blood pressure, rate-pressure product, and duration of exercise at 0.1 mV ST depression during exercise and the same parameters plus the maximal ST-segment depression at peak exercise, collected from three different tests. The first and second were performed at one-week intervals before, and the third (75 days after the first), was performed after a double-blind study with a drug versus placebo. We found a significant increase of exercise duration at 0.1 mV ST depression and at peak exercise, while 6 of 12 patients increased exercise duration from the second to the third test. Individual variability of exercise duration showed increasing values, ranging from 0 to 71% (first vs. third test). In contrast, the ratio of heart rate and systolic blood pressure did not differ between the tests. Our data criticized the use of mean values of exercise time for pharmacological studies; moreover, individual variability could affect results independently of drug or placebo administration. These findings should be taken into account in order to exclude misleading results.

Adrenergic beta-Antagonists↗
PubMed1989

Effects of aspartame and carbohydrate administration on human and rat plasma large neutral amino acid levels and rat brain amino acid and monoamine levels.

Thirty fasted human volunteers were given 0.83 and 8.3 mg aspartame/kg body weight alone, as part of a basal low carbohydrate meal (648 kcal, 10% carbohydrate) or as part of a high energy carbohydrate-rich meal (1290 kcal, 34% carbohydrate). Amino acid concentrations in plasma were determined before and 30, 60 and 180 min after the consumption of aspartame. Under these conditions, which mimic realistic aspartame consumption, aspartame had no significant effect on plasma concentration of any amino acid. In addition, the effect of aspartame alone or with carbohydrates on plasma and brain amino acid levels was studied in rats after acute or subacute (14 d) oral treatment. In subacute dosing experiments aspartame was included in the diet. Brain monoamine concentrations were also measured in the same animals. Plasma concentrations of large neutral amino acids were modified under acute conditions. In contrast, after subacute treatment no significant differences in plasma or brain amino acid concentrations or in brain monoamine concentrations were observed.

Amino Acids↗