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Biomedical subjects

M Ferro

Publications and source records attributed to M Ferro.

At least 91 records · Page 5Linked to original sources

Dominantly inherited ataxias in Portugal.

We analysed the clinical features of 82 patients with dominantly inherited ataxia in a cohort survey. All patients fulfilled the diagnostic criteria for Machado-Joseph disease. The mean age of onset of symptoms was 39.8 (+/- 12.5) years and the duration of the disease was 9.2 (+/- 6.7) years. Ataxia, peripheral neuropathy, and fasciculation scores correlated with age of onset and duration of disease. Upper motor neuron scores failed to correlate with age of onset. In a follow-up study we analysed the clinical data of 46 patients two years after the first examination. A paired t-test was used to compare differences between observations. The results are in agreement with those of the cross-section in time, suggesting a deterioration of the symptoms with the evolution of the disease. We conclude that dynamic definition of the disease according to age of onset and duration of symptoms is preferable to subdivision into classical types.

Adult↗

Nebulin and titin expression in Duchenne muscular dystrophy appears normal.

Monoclonal antibodies which recognize different epitopes on either titin or nebulin show normal staining patterns on frozen sections of three muscle biopsies of Duchenne muscular dystrophy (DMD). Gel electrophoresis and immunoblotting performed on two of these muscle biopsies show the normal pattern of titin and nebulin polypeptides. Since the donor of one of these biopsies has a large deletion of the 5'-region of the DMD gene, our results argue against the recent proposal that nebulin is the gene mutated in DMD.

Antibodies, Monoclonal↗

Biochemical properties of carcinogen-metabolizing enzymes in cultured hepatoma cells.

We have previously demonstrated the inducibility of both cytochrome P-448- and P-450-dependent monooxygenases in the differentiated rat hepatoma cell line MH1C1. Further experiments with these cells on the expression of different forms of cytochrome P-450, inducible not only by phenobarbital (PB) and 3-methylcholanthrene (MC), but also by metyrapone (MP), ethanol (E), and beta-naphthoflavone (BNF) are reported here. The effects of the in vitro addition of the inhibitors alpha-naphthoflavone and beta-naphthoflavone on the aryl hydroxylase activity (AHH) and the influence of protein synthesis on the induction of cytochrome P-450 were also assessed. Cultures were exposed to the inducers PB, MC, BNF, and MP during the last 6 days of culture and to E for 10 days. The inhibition of protein synthesis was obtained by adding cycloheximide (CY) to the cultured cells during the last 24 hr. The exposure of MH1C1 cells to various concentrations of MP resulted in a dose-dependent increase in AHH activity. The treatment of MH1C1 cells with different concentrations of ethanol produced a significant dose-dependent increase of monooxygenases. AHH activity, induced by the various treatments, was inhibited in a dose-dependent way by alpha-naphthoflavone and beta-naphthoflavone. Cy reduced the concentration of cytochrome P-450 and the AHH activity induced by the various treatments, thus indicating an implication of the protein synthesis in the mechanism(s) of induction.

Animals↗

Modifications of the vein wall after microsurgical end-to-side artero-venous anastomosis.

The repercussions on the venous wall of the creation of 20 artero-venous anastomoses (AVA) between the femoral artery and vein of the rat have been evaluated. The rats were killed 7, 15, 30, and 90 days after AVA, and AVAs were examined by optical microscopy and by scanning electronic microscopy. Deposits of whitish material that nearly completely occluded the venous lumen were seen, especially in the group studied longer than 90 days. These venous wall lesions, which resemble arteriosclerotic lesions, must be attributed to the new hemodynamic situation created by the AVA. The implications of such findings for the long-term validity of venous graft in vascular microsurgery and the long-term patency of the AVA in hemodialyzed children are discussed.

Animals↗

New data on kinetics of lipid peroxidation in experimental hepatomas and preneoplastic nodules.

Lipid peroxidation has been found decreased in several hepatomas. The decline has been shown already at the level of preneoplastic nodules obtained after DEN treatment of rats. A substantial exception is represented by the hepatoma cell line MH1C1, deriving from a slightly deviated Morris tumor. Most of the described experiments estimated lipid peroxidation levels in terms of malonaldehyde production by the thiobarbituric acid test. It is now clear that this test does not account for several other aldehydes produced during lipid peroxidation. We now investigated by high performance liquid chromatography (HPLC) the whole range of non-polar aldehydes produced by tumor homogenates and by preneoplastic nodules both in basal conditions and after stimulation with ADP-iron or ascorbate. It was reduced in the preneoplastic nodules as well as in the DEN-induced hepatoma. The susceptibility to the prooxidant effect of ADP-iron or ascorbate was strongly decreased in all hepatomas as well as in preneoplastic nodules. It has been recently published that hepatoma cells are more susceptible than normal liver to the toxic action of aldehydes. This was attributed at least in part to the decreased activity of aldehyde dehydrogenases, as well as to their different distribution in tumor cells. A deeper study on aldehyde metabolism in hepatomas has shown that alcohol dehydrogenase and NADPH-aldehyde reductase also are markedly decreased in Yoshida hepatoma cells and the MH1C1 cell line. However, glutathione transferase, that can use hydroxynonenal as a substrate, is strongly decreased in Yoshida hepatoma cells but not in MH1C1 cells.

Alcohol Dehydrogenase↗

Adenocarcinoma of the appendix.

Three cases of adenocarcinoma of the appendix are reported. All three patients presented with acute appendicitis and the tumors were diagnosed only on histologic examination of the excised appendix. The first patient subsequently had a right hemicolectomy and was proven to have a Dukes' B tumor. The second patient probably had a Dukes' B also, but no further surgery was performed because of advanced presenile dementia. Advanced disease was found in the third patient. Analysis of 145 cases reported over the last ten years suggests that, unless the tumor is in Dukes' A stage, right hemicolectomy should be carried out if the patient is fit for radical surgery. The overall prognosis appears to be the same as that for carcinoma of the colon.

Adenocarcinoma↗

Methylglyoxal-induced DNA-protein cross-links and cytotoxicity in Chinese hamster ovary cells.

The technique of alkaline elution was applied to study the capacity of methylglyoxal to induce DNA damage and repair in Chinese hamster ovary cells. DNA cross-linking was observed after a 90-min exposure to a subtoxic dose (1.5 mM), and the cross-links were fully repaired by 24 h. The cross-linking appeared to be DNA-protein in nature, since proteinase treatment removed the effect. When the same cells were exposed to methylglyoxal in the presence of a rat liver metabolic system, both cytotoxicity and cross-linking frequency were significantly reduced.

Aldehydes↗

DNA-damaging activity of biotic and xenobiotic aldehydes in Chinese hamster ovary cells.

Alkaline elution was employed to study DNA damage in CHO-Kl cells treated with a series of biotic and xenobiotic aldehydes. DNA cross-linking was measured in terms of the reduction in the effect of methyl methanesulphonate on the kinetics of DNA elution and was observed in cells treated with formaldehyde, acetaldehyde, methylglyoxal and malonaldehyde. Propionaldehyde, valeraldehyde, hexanal and 4-hydroxynonenal produced DNA single-strand breaks, or lesions which were converted to breaks in alkali. Both types of DNA damage occurred in cells exposed to malealdehyde. These findings support the hypothesis of a carcinogenic effect of the aldehydic products (malonaldehyde, methylglyoxal, propionaldehyde, hexanal, 4-hydroxynonenal) released in biomembranes during lipid peroxidation.

Aldehydes↗

Induction of cytochrome(s) P450-dependent drug metabolism in cultured MH1C1 hepatoma cells.

A cell line derived from a Morris hepatoma, MH1C1, was examined for its in vitro expression of monooxygenases. These cells were found to contain different forms of cytochrome P450, as shown by the response to inducers, namely phenobarbital (PB), 3-methylcholanthrene (MC) and metyrapone (MP). MH1C1 cell monolayers exposed to PB or MC showed an increase in the concentration of two spectrally distinct forms of cytochrome P450. The PB and MC treatments elicited enzyme activities towards the substrates aminopyrine and benzo(a)pyrene, respectively. The cell treatment with metyrapone led to a simultaneous stimulation of aminopyrine demethylase and benzo(a)pyrene hydroxylase activities, so underlining the peculiar features of this inducer.

Animals↗

Further experiments on lipid peroxidation in transplanted and experimental hepatomas.

The results of experiments on the subject of lipid peroxidation in hepatomas are described. It is now clear that lipid peroxidation is strongly decreased in most highly dedifferentiated hepatomas. It seems evident that the extent of the decline is strictly related to the degree of dedifferentiation. The model of diethylnitrosamine carcinogenesis, according to the method by Solt, Medline and Farber, has been now adopted to study the stages of carcinogenesis. It was shown that a net decline in lipid peroxidation occurs as early as at the stage of reversible nodules and progresses until the development of clear hepatomas. This change is practically simultaneous with a decline in the efficiency of the enzymes of the drug metabolizing system and in the content of cytochrome P450-Glutathione content and metabolism show also important changes. In fact, a dramatic increase in gamma-glutamyl-transpeptidase takes place very early during carcinogenesis, and is responsible for large decline in total glutathione during incubation of the homogenates. Glutathione peroxidase activity, on the contrary, is decreased, whereas glutathione reductase does not show significant changes. The supernatant of highly anaplastic tumors inhibits lipid peroxidation in normal liver homogenates, suggesting the presence of substances provided with antioxidant properties. These cannot be, however, related to a higher glutathione content. Supernatants from early nodules seem to be unable to block lipid peroxidation in normal liver homogenates. Preliminary experiments done to study the aldehyde pattern produced during lipid peroxidation, both in hepatomas and in nodules, confirm the presence of very poor lipid peroxidation and possibly of different peroxidation kinetics.

Aminopyrine N-Demethylase↗

[Clinical study of a prepared reducing diet: adequacy of the vitamin-mineral contribution in comparison to the nutritional and immunity status].

The Authors studied the effectiveness and safety of a commercial hypocaloric diet on 11 obese postmenopausal women. During the experimental period 1 meal/day has been replaced with a chemically defined low calories product. Different parameters have been evaluated to assess the nutritional status 1), anthropometric: weight, skinfold thickness, arm muscle circumference; 2) biochemical total plasma proteins, transferrin, vitamins A, E, C, B12, folic acid; plasma iron, hemoglobin, MCV, RBC; 3) immune status (T lymphocytes and immunoglobulins). Moreover blood sugar, cholesterol and triglyceride levels, as well as blood pressure have been taken into account. All the possible side effects and the diet acceptance for all the patients have been scored. After 1 month all the abnormal conditions (weight, cholesterol, blood pressure) improved, while the nutritional status and immune response remained at an optimal level.

Aged↗

["In vitro" stimulation of TBArs. Production by carbon tetrachloride in MH1C1 hepatoma (author's transl)].

It is well known that lipid peroxidation is absent or extremely low in tumour tissues. So the lack of lipid peroxidation is so far considered as a peculiar characteristic of tumour cells. Studying lipid peroxidation in three different hepatomas, we have found, however, results suggesting that the lack of lipid peroxidation cannot be retained anymore as a constant attribute of hepatoma cells. In fact, we studied the TBArs production in homogenates of the following hepatomas: AH-130 Yoshida , 3924 A Morris, MH1C1 hepatomas, in comparison with normal liver. Whereas we were able to confirm that TBArs production in Yoshida tumour is extremely low, we found that Morris 3924 A hepatoma, growing subcutaneously in the rat, displays a rather consistent TBArs production. Moreover, MH1C1 hepatoma, grown in cell culture, produces more TBArs than normal liver. AH-130 Yoshida tumour is unable to metabolize CC14. Consequently, the addition of CC14 to the homogenate doesn't stimulate TBArs production, as this substances does in the case of normal liver homogenate. A good increase in TBArs production was seen, however, with MH1C1 homogenate.

Animals↗

[Relationship between pancreatic cancer and chronic pancreatitis].

The best known papers on relations between chronic pancreatitis and tumours of the pancreas are reviewed and a description given of the anatomopathological changes which gradually lead from chronic pancreatitis to cancer. It is maintained that all cases of chronic pancreatis should be considered high risks for pancreatic carcinoma.

Chronic Disease↗

[Blood pressure during exercise stress in young normal subjects with familial hypertension (author's transl)].

The behaviour of Arterial Blood Pressure was evaluated, by treadmill stress testing, in a group of young subjects (15-30 years old) with one or two hypertensive siblings. The best fit of the interpolating slope function was used in interpretating the findings of haemodynamic data (A.B.P. during exercise). These data were analyzed in the same way in three control groups: normal subjects 15-30 years old; hypertensive patients aged 30-45; normal subjects aged 30-45. We compared function's coefficients and parameters in these selected groups. The results show no different response in the A.B.P during stress between the normal subject and the group, same aged, with hypertensive siblings. Significative differences in the function's coefficients, were found in the control hypertensive patients. The stress testing doesn't seem recommending in subjects at risk because of parenteral hypertension: no early alteration in A.B.P. seems to be unmasked during exercise stress. The males of the control normal subject show higher blood pressure exercise value than females. This different response is not present in the group with parenteral hypertension: a more strick familial resemblance in A.B.P. is suggested in female population.

Adolescent↗