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Biomedical subjects

M Romano

Publications and source records attributed to M Romano.

At least 397 records · Page 22Linked to original sources
PubMed1985

The immunological activity of plant toxins used in the preparation of immunotoxins--II. The immunodepressive activity of gelonin.

The immunological activity of Gelonin, a 30,000 dalton plant protein possessing close similarity to Ricin chain A as a protein synthesis inhibitor which may be of interest for the preparation of antibody-toxin conjugates, was studied in mice. At in vitro concentrations not affecting baseline radioactivity uptake, this substance reduced mitogen responses with the following order of sensitivity PHA less than ConA less than LPS. In microgram/ml concentrations it also markedly reduced macrophage-dependent cytotoxicity while not affecting NK activity. Macrophagic (but not NK) cytotoxicity and mitogen responses were similarly depressed after in vivo treatment. When given before (but not after) stimulus, Gelonin also reduced the primary responses to a T-dependent and, although to a lower degree, to a T-independent antigen, and decreased resistance to allogeneic tumor grafts and L. monocytogenes challenges. The immunopharmacological activity of this and similar substances should be considered in the design of antibody-toxin conjugates and in the evaluation of their therapeutic activity.

Animals↗
PubMed1985

In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds.

N-acetylcysteine (NAC) was administered to rats in various combinations with an enzyme inducer (Aroclor 1254) and with depletors of reduced glutathione (GSH), i.e., diethyl maleate (DEM) and buthionine sulfoximine (BSO). NAC increased intracellular glutathione levels in erythrocytes and in liver and lung cells, and replenished its stores following depletion. It did not affect the concentrations nor the spectral properties of cytochromes P-450 in hepatic and pulmonary microsomes, whereas it stimulated, especially in Aroclor-pre-treated animals, cytosolic enzyme activities involved in NADP reduction (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), in glutathione reduction (GSSG-reductase) and in the reductive detoxication of xenobiotics by-passing formation of reactive oxygen species (DT-diaphorase). In vivo treatment with the drug enhanced detoxication by liver and lung S-12 fractions of direct-acting mutagens (ICR 191, epichlorohydrin, 4-nitroquinolino-N-oxide and dichromate) and counteracted opposite effects triggered by administration of GSH depletors. The metabolic activation of procarcinogens (aflatoxin B1, 2-aminofluorene, cyclophosphamide, benzo[a]pyrene, a tryptophan pyrolysate product and cigarette smoke condensate) was inhibited by NAC in uninduced rats, while it was further stimulated in Aroclor-pre-treated animals. Additional assays, performed also with other enzyme inducers (phenobarbital and 3-methylcholanthrene) suggested that the effect of NAC on the metabolic activation of procarcinogens depends on the balance between an increased production of mutagenic metabolites (prevailing in induced animals) and their binding by intracellular thiols (prevailing under normal conditions). Thus, due to its dual role as a nucleophile and as a SH donor, NAC appears to exert protective effects by modulating glutathione metabolism and the biotransformation of mutagenic/carcinogenic compounds. This may have clinical relevance, since NAC is administered to individuals, such as cigarette smokers, who are more heavily exposed to GSH depletors and to carcinogenic agents.

Acetylcysteine↗
PubMed1985

Perinatal development of cytochrome P-450, cytochrome C reductase, aryl hydrocarbon hydroxylase, styrene monooxygenase, and styrene epoxide hydrolase in rabbit liver microsomes and nuclei.

The development of cytochrome P-450, cytochrome C reductase, aryl hydrocarbon hydroxylase, styrene monooxygenase, and styrene epoxide hydrolase was studied in fresh rabbit liver nuclear and microsomal preparations. Enzymatic activities were determined in rabbit fetus at 21 and 30 days of gestation and in rabbits at 1, 5, 11, 22, 44, and 60 days of age. In extrauterine life, nuclear cytochrome P-450, aryl hydrocarbon hydroxylase, and styrene epoxide hydrolase were found to develop later than their microsomal counterparts, whereas nuclear cytochrome C reductase developed earlier than its microsomal counterpart. The behavior of styrene monooxygenase was more complex. The only activities detectable before birth were styrene epoxide hydrolase, styrene monooxygenase, and cytochrome C reductase in both nuclei and microsomes. The microsomes-to-nuclei epoxide hydrolase activity ratio was almost ten times the microsomes-to-nuclei styrene monooxygenase ratio, indicating a dissociation in the development of the two enzymes in rabbits. Nuclear metabolic activity was high at all ages, suggesting possible toxicological relevance.

Animals↗
PubMed1985

Cadralazine, a new vasodilator, in addition to a beta-blocker for long-term treatment of hypertension.

51 hypertensive outpatients, whose diastolic blood pressure exceeded 100 mmHg after a 2-week period on atenolol alone (100 mg once daily) participated in this long-term study. They received, in addition to atenolol, the vasodilator cadralazine (ISF 2469; 10 to 30 mg once daily) for a standard period of 24 weeks, according to an open design. Cadralazine caused a progressive and important decrease in both systolic and diastolic blood pressure, from 173/111 mmHg (end of atenolol alone) to 154/99 mmHg (12th week, p less than 0.01/p less than 0.01; mean dose, 24.5 mg/day). At this time a diuretic was added as a third-step drug in 15/51 initial patients (29%), and final blood pressure in all patients was 150/96 mmHg (p less than 0.01/p less than 0.01), with positive results in 88% of the cases. During cadralazine treatment, heart rate was always significantly lower than before atenolol alone; the most common side effects, many of which were already present during treatment with atenolol alone, included headache, asthenia, dizziness, palpitation and flushing, and tended to disappear spontaneously as therapy progressed. Routine laboratory tests did not show important changes; sodium excretion was not reduced. In conclusion, the therapeutic efficacy of cadralazine, its low or absent salt and water retention effects, its good tolerability, and the high compliance obtained with once daily administration allowed the use of this vasodilator as a second-step drug for long-term treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1985

[Tamponade caused by localized compression of the superior vena cava and right atrium after aortic valve replacement under extracorporeal circulation].

The authors report a case of localised compression of the right atrium due to a loculated intrapericardial haematoma after open heart surgery. The patient suddenly developed signs of superior vena caval obstruction during the third postoperative week. The diagnosis was made by 2D echocardiography and superior vena cavography. The authors review the literature and discuss the main clinical features of localised cardiac tamponade, underlying the value of 2D echocardiography in the postoperative management of cardiac surgical patients.

Adult↗
PubMed1985

[Role of peri-operative treatment in the surgery of advanced valvular cardiopathies].

Between January 1981 and October 1982, 100 consecutive patients with valvular heart disease (49 p. 100 polyvalvular disease) underwent surgery. All had severe lesions; Class III or IV of the NYHA classification; cardiomegaly with an average cardio-thoracic ratio of 59 +/- 7.7 p. 100; a cardiac index of less than 2.5 1/min/m2 in 70 p. 100 of cases; pulmonary hypertension (mean PAP : 31.93 +/- 12.17 mmHg) in 89 p. 100 of cases. Half the patients were in atrial fibrillation and all had been on chronic digitalo-diuretic therapy before surgery. Thirty of the 41 patients given preoperative venous vasodilator therapy had significant reductions of their cardiothoracic ratios (63 +/- 1.5 p. 100 vs 59.1 +/- 1.6 p. 100, p less than 0.001). Conservative surgical procedures were possible in 58 cases of mitral valvuloplasty and 5 aortic valvuloplasties. Correction of functional tricuspid regurgitation (34 p. 100) was systematic. Tricuspid regurgitation masked by salt and water depletion was detected by digital palpation after clamping the pulmonary artery. In 8 cases the aortic ring had to be enlarged. The low hospital mortality (6 p. 100) and the lack of postoperative complications (assisted ventilation for less than 24 hours in 92 p. 100 of cases) compare favourably with other reported series.

Adolescent↗
PubMed1985

[Conservative surgery of the mitral valve. Immediate and late results].

A consecutive series of 130 cases of pure or predominant mitral regurgitation underwent conservative mitral valve surgery between January 1975 and January 1982. The mean age of the patients was 30 +/- 17 years; 25 patients were under 15 years of age. The most common aetiology was rheumatic fever (112/130). Fifty nine patients had associated valvular lesions requiring surgical correction. The patients were divided into 4 groups, according to the surgical technique: Group I: valvular mobilisation (35 cases); Group II: reduction of the amplitude of valvular excursion (48 cases); Group III: mixed valvular mobilisation and reduction of amplitude of excursion (45 cases); Group IV: isolated annuloplasty (2 cases). Hospital mortality was 2.3% (3 patients). Five patients (3.8%) were lost to follow-up. The mean follow-up period was 38 +/- 27 months for the 122 patients followed-up. Seven patients needed reoperation. The long term mortality was 3.1% (4 patients). Four late thromboembolic episodes were observed; they were all transient and regressive in patients with atrial fibrillation. The 7 year actuarial survival rate for the whole series, including hospital mortality, was 92% (1.0 +/- 0.5 patients/year). It was 93.7 +/- 4.9% at 7 years for isolated mitral valvuloplasty and 89.9% +/- 5.6% at 5 years for combined mitro-tricuspid procedures. The actuarial percentage of patients without thromboembolic complications was 91.2% at 7 years with a thromboembolic risk of 1.0 +/- 0.5% patients/year. Eighty eight per cent of patients were not reoperated at 7 years and the reoperation rate was 1.7 +/- 0.7% patients/year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Transposition of posterior leaflet for treatment of ruptured main chordae of the anterior mitral leaflet.

A 13-year-old girl with mitral regurgitation resulting from rupture of multiple chordae of the anterior leaflet had repair by transposition of a part of the posterior leaflet to the free edge of the anterior mitral cusp. Postoperative clinical hemodynamic, and angiographic studies showed perfect function of the mitral valve. This technique seems to be a good solution for mitral repair in the presence of ruptured anterior mitral chordae.

Adolescent↗
PubMed1985

Properties of lipoprotein complexes isolated by affinity chromatography from human aorta.

We have isolated from the same human aortic intima-media, using a sequential extraction procedure and affinity column chromatography, different ApoLDL-containing lipoprotein complexes. The neutral lipid composition of the fractions retained by the anti-ApoLDL immunoglobulin, from saline extracts and elastase-treated samples, was similar to that of plasma low density lipoproteins. The fatty acids of phosphatidylcholine, triglycerides and cholesterol esters of all three fractions have a lower content of linoleic acid than plasma low density lipoproteins. By electron microscope the three lipoprotein fractions appeared polydisperse. All the fractions contained particles in the density range of low density plasma lipoproteins but those from elastase extracts and guanidinium-HC1 extracts contained also lipoproteins with densities below 1.019 g/ml. We found large variation in the composition of fractions from different aortas. The lipoproteins isolated from buffered saline were found associated with 2 to 4 micrograms of glycosaminoglycan (GAG) per 100 micrograms of protein. The associated GAG was made of chondroitin-6-SO4, dermatan and chondroitin-4-SO4 in a 3:2:1 ratio.

Aorta, Thoracic↗
PubMed1985

Prominent role of DT-diaphorase as a cellular mechanism reducing chromium(VI) and reverting its mutagenicity.

Rat liver postmitochondrial (S-12) fractions accounted for the bulk of the activity of whole cell homogenates in reducing chromium(VI) and accordingly in decreasing its mutagenicity. Both cytosolic (S-105) and microsomal fractions concurred to this process, which in all subcellular preparations tested was selectively induced by phenobarbital and especially by Aroclor 1254, but not by 3-methylcholanthrene. Cytosolic fractions were markedly more efficient in reducing chromium(VI) than microsomal fractions recovered from the same amount of tissue (liver or lung), although the latter preparations had a higher specific activity. The microsomal activity was exclusively NADPH dependent. A minor part of the cytosolic reduction was determined by nonenzymatic components, notably by some electron donors and chiefly by reduced glutathione, which proved to reduce chromium(VI) at physiological concentrations. However, also in cytosolic fractions, the most important contribution to chromium reduction was enzyme catalyzed, as shown by the following properties: thermolability; requirement for exogenous NADH or NADPH [supplied as such or in the form of a NADPH-generating system (S-9 mix)]; and saturation by chromium(VI). The likely involvement of DT-diaphorase in this metabolic process is supported by several findings, including its sharp pH dependence and its partial suppression by known inhibitors of this enzyme protein, such as p-chloromercuribenzoate, L-thyroxine, and dicumarol (which conversely did not counteract the metabolic deactivation of the other direct-acting mutagens 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine 2HCl and epichlorohydrin). Similarly, cytosolic reduction of chromium(VI) was partially inhibited by selective metabolic depletors of both coenzymes of DT-diaphorase, i.e., NADPH and NADH. Pretreatment of rats with enzyme inducers (phenobarbital and 3-methylcholanthrene) stimulated the activity of DT-diaphorase in liver cytosolic fractions. A dramatic stimulation (35 to 40 times over untreated controls) was produced by Aroclor 1254, which also coinduced the liver cytosolic activity of enzymes involved in the glucose 6-phosphate-dependent pathway of both nicotinamide-adenine-dinucleotide phosphate and glutathione reduction (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase). In the lung cytosol, a slight yet significant stimulation of some of these enzyme activities was determined by the daily intratracheal instillations of high doses of chromium(VI) itself for 4 weeks, a condition which has been found to enhance the pulmonary metabolism of this metal ion.

Animals↗
PubMed1984

Amino acid sequence of the carboxy-terminal end of human erythrocyte glucose-6-phosphate dehydrogenase.

Human erythrocyte glucose-6-phosphate dehydrogenase was purified to homogeneity by a simplified procedure, consisting of 2',5'-ADP-Sepharose affinity chromatography, followed by Sephadex G-100 gel filtration. The carboxy-terminal region of the protein was identified by carboxypeptidase digestion: the sequence -Lys-Leu-COOH was found instead of the reported -Gly-COOH, thus showing identity with the carboxy-terminal sequence of glucose-6-phosphate dehydrogenase from human leukocytes and platelets. In addition, the carboxyl-terminal peptide was isolated from a tryptic digest of the protein and sequenced. The sequence is: Trp-Val-Asp-Pro-His-Lys-Leu.

Amino Acid Sequence↗
PubMed1984

A study of dynamic membrane phenomena during the gastric secretory cycle: fusion, retrieval and recycling of membranes.

The possibility of recycling, fusion and retrieval of membranes during the gastric secretory process was studied in isolated gastric mucosae of the toad Bufo marinus. Incorporation and efflux of 14C-inulin and horseradish peroxidase (HRP) into the tissue as well as transmission and freeze-fracture electron microscopic studies during the secretory cycle were done. HRP and 14C-inulin were incorporated into the tubulovesicular membrane system during the secreting-resting transition. Upon restimulation, markers were released towards the lumen. Marker efflux preceded onset of H+ secretion. Morphological transformations in the oxyntic cell as evidenced from transmission and freeze-fracture electron microscopy preceded acid secretion coinciding with marker efflux. At this time, images that have been associated with membrane fusion were found in the apical membranes of oxyntic cells. The results are consistent with a model where membrane area increases by a fusion mechanism at the expense of the tubulovesicular system. This transformation precedes the onset of H+ secretion. Upon cessation of the stimulus or inhibition, membranes are retrieved and the tubulovesicular system reformed. Retrieved membranes could be then reutilized in the next secretory cycle.

Animals↗
PubMed1984

Influence of heart rate on exercise-induced R-wave amplitude changes in coronary patients and normal subjects.

In order to study whether different heart rates achieved at peak exercise by normal subjects and patients with coronary artery disease (CAD) affect the results of analysis of R-wave amplitude changes (delta R), we evaluated delta R at progressively increasing heart rate (HR) steps in 60 normal subjects with negative exercise tests (ET), in 130 patients with CAD, in 88 patients with true positive and 42 with false negative ET, and in 43 patients with no CAD and false positive ET. We found that the sensitivity and specificity of delta R were HR dependent, the former decreasing and the latter increasing with progressively increasing HR steps. Mean values of delta R did not discriminate among the four groups for HRs up to 150 bpm; significant differences were found between normal subjects and CAD patients, both with true positive and false negative stress tests, at HR greater than 150 bpm. False positive patients had mean delta R similar to those found in normal subjects. We hypothesize that quantitative delta R analysis could be useful in ECG diagnosis of false negative and false positive patients at HR greater than 150 bpm.

Coronary Disease↗
PubMed1984

Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy.

Earlier work showed that in a group of women suffering from partial epilepsy, there is a decrease in seizure frequency during the luteal phase of the menstrual cycle. Moreover, iv progesterone infusions decrease the discharge frequency from penicillin epileptic foci in cats, when given in doses that reach plasma concentrations as observed during pregnancy. In the present study, iv progesterone infusions, reaching plasma concentrations as during the luteal phase, were given to 7 women with partial epilepsy. The inclusion criterion was that they should have more than one epileptic discharge per 5 min on an ordinary EEG . A 6 h EEG-registration was made. Blank and progesterone solutions were infused for 2 h respectively and the progesterone infusion was followed by a 2 h EEG recording period. 4 of the 7 patients showed a significant decrease in spike frequency during the infusion. In the patients not showing this effect, the plasma progesterone binding capacity was high. The 2 patients with the most marked progesterone effect had low progesterone binding capacity and no antiepileptic treatment. Somnolence during the test might also have influenced the results in 2 of the patients.

Action Potentials↗
PubMed1984

Postural changes and isosorbide dinitrate. A polygraphic study in patients with coronary artery disease.

Sitting or orthostatic positions and trinitrine-like drugs reduce venous return. We focused on the non-invasive assessment of postural-induced cardiovascular stress and isosorbide dinitrate (IDN) induced changes in 8 male patients with coronary artery disease (CAD), using polygraphic recordings by means of a Thermistor Pulse Transducer. The pre-ejection period (PEP) is sensitive to reduced preload and to the positive inotropic state of the myocardium. In addition, the % diastole (RR interval--electromechanical systole/RR interval) has been recently demonstrated to be correlated to coronary perfusion in CAD patients. We observed that IDN in clinostatism and the sitting position reduced preload (longer PEP) with increased heart rate (HR) and did not affect % diastole. In orthostatism, while controls showed an increased HR and prolonged PEP, the HR was higher after IDN, with a fall in PEP and a significant decrease in % diastole. We ascribed this change to adrenergic stimulation by the hypotensive actions of IDN (lowered mean blood pressure) in orthostatism and with a fall in coronary perfusion. Caution should be taken in CAD patients when postural stress could occur during IDN treatment. Moreover, polygraphic studies can be useful to detect individual responses to nitrates and serial recordings could be employed to assess late responses to chronic management with IDN.

Analysis of Variance↗