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Biomedical subjects

M Melegari

Publications and source records attributed to M Melegari.

At least 37 records · Page 2Linked to original sources

Significance of anti-HBx antibodies in hepatitis B virus infection.

Serological responses to hepatitis B virus-X determinants have been noted in human sera, but conflicting findings concerning the correlation of anti-HBx antibodies with different stages of hepatitis B virus infection or pathological sequelae have been reported. Using an adenovirus-based eukaryotic vector, the 17 kD X protein was efficiently expressed in 293 cells. Cellular extracts containing the eukaryotic X protein have been used to screen for anti-HBx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis B virus chronic hepatitis, hepatocellular carcinoma and acute viral hepatitis. Sera from 32 of 171 (19%) chronic hepatitis B virus patients were positive for anti-HBx antibodies. Only one of thirty-two (3%) HBsAg-negative, anti-HBs/anti-HBc-positive chronic hepatitis serum was anti-HBx positive. Very few sera from primary hepatocellular carcinoma patients showed positivity for anti-HBx (8 of 149 or 5%). Anti-HBx were also detected in 8 of 48 (17%) acute viral hepatitis patients. In the four cases that were followed up weekly, anti-HBx antibodies appeared 3 to 4 wk after the onset of the clinical signs. To compare the X protein expressed in eukaryotic and prokaryotic cells as a substrate for anti-HBx antibody detection, 171 sera were screened with HBx fusion proteins expressed in Escherichia coli. The prokaryotic cell extract test seems to be more sensitive. During the chronic phase of hepatitis B virus infection, the presence of anti-HBx antibodies detected with the eukaryotic cell extract correlates with the presence of well-established markers of ongoing viral replication: serum hepatitis B virus-DNA (p less than 0.001) and intrahepatic HBcAg expression (p less than 0.001).

Biomarkers↗

Hepatitis B virus infection of peripheral blood mononuclear cells is common in acute and chronic hepatitis.

Hepatitis B virus (HBV) infection of peripheral blood mononuclear cells (PBMCs) has been observed in all stages of liver disease. Thus far all information about the physical state of HBV in mononuclear blood cells comes from Southern blot analysis and in situ hybridization. In this study we focused our attention on the presence of HBV DNA sequences in PBMCs of 30 patients with acute type B hepatitis and 6 patients with chronic active hepatitis by utilizing both Southern blot analysis and the polymerase chain reaction (PCR). Southern blot analysis showed no HBV DNA sequences in PBMCs of the acute hepatitis patients, although the sensitivity of our method enabled us to detect as little as 1 pg of cloned HBV insert. As far as the chronic hepatitis patients are concerned Southern blot analysis revealed the presence of HBV DNA sequences in 5 out of 6 patients but intermittently at successive follow-up times. On the other hand we were able to demonstrate the presence of HBV related sequences in 14 out of 30 acute hepatitis patients (5 HBeAg positive, 9 antiHBe positive) and in all 6 chronic hepatitis patients by PCR. Our results indicate that the involvement of PBMCs with HBV during acute HBV infection occurs at a very low level, often below the detection limit of the Southern blot technique.

Acute Disease↗

Detection of hepatitis B virus transcripts in patients with chronic liver disease.

Hepatitis B virus (HBV) transcription was studied by Northern blot analysis on total cellular RNA purified from liver biopsies in 70 patients with chronic liver disease (24 HBsAg positive, 15 antiHBs and/or antiHBc positive, 31 HBV negative). No transcripts were found in the HBV negative and in the antiHBs and/or antiHBc positive patients. In the others, three major RNA species were identified: i. a 3.5 kb transcript corresponding to the RNA pregenome; ii. 2.4-2.1 kb transcript corresponding to the s and preS1 gene RNA; iii. lower molecular weight species. All three forms were present simultaneously only in patients with active viral replication, with a strict relation between the presence of the 3.5 kb RNA in the liver and serum HBV-DNA. In conclusion, Northern blot analysis can easily be performed to study viral replication and it can contribute to a better understanding of the molecular processes underlying HBV infection and leading to liver disease in man.

Biopsy↗

Characterization of some parameters of non-specific immunity in dairy cattle (I).

The concentrations of serum protein and immunoglobulin, complement, lysozyme, serum bactericidal activity and blast transformation of peripheral blood lymphocytes were assessed in dairy cattle in different herds and age groups. The study aimed at defining fundamental aspects of non-specific defence under the field conditions, related to age/season/management influences. The observed differences in the expression of these parameters are discussed, with regard to their role in the immune defence of calves and their relation to colostrum uptake. The possible use of these parameters in the control of animal welfare is stressed and the possibility is put forward of predicting possible unfavourable interactions with environmental pathogens.

Animals↗

Risk factors for hepatocellular carcinoma in Italy. Male sex, hepatitis B virus, non-A non-B infection, and alcohol.

To investigate risk factors for hepatocellular carcinoma (HCC) in Italy--a country with medium (south: 5% to 10%) to low (north: 1% to 2%) incidence of hepatitis B virus (HBV) infection--we studied 646 consecutive patients: 58 chronic active hepatitis (CAH), 428 cirrhosis, and 160 HCC, 49% from Southern and 51% from Northern Italy. Hepatitis B surface antigen (HBsAg) was positive in 41.4% of the CAH, in 23.1% of cirrhotic patients, and in 26.2% of HCC. In the latter, HBV DNA assay increased the number of subjects with active HBV infection by about 12%. Alcohol abuse was evenly distributed in all three categories of HBV markers. Males were preferentially affected. The HCC was superimposed on cirrhosis in more than 90% of patients. Our data suggest that, in our epidemiologic setting, different factors (HBV, non-A, non-B agents, alcohol) may cooperate in the development of HCC, mainly through their potential for causing cirrhosis.

Alcohol Drinking↗

Sedative, anti-inflammatory and anti-diuretic effects induced in rats by essential oils of varieties of Anthemis nobilis: a comparative study.

The pharmacological properties of essential oils obtained from two varieties of Anthemis nobilis was studied. The two varieties, named "white-headed" or double flowered and "yellow-headed", present considerable morphological differences and yield essential oils with different composition. These essential oils proved to possess interesting anti-inflammatory and sedative properties, especially that derived from the "White-headed" variety.

Animals↗

Safety and efficacy of foot-and-mouth disease vaccines containing endonuclease-inactivated virions.

Inactivation of foot-and-mouth disease virus (FMDV) by means of virion-associated endonuclease was found to be suited to the production of safe and potent vaccines, which proved to be equal or better than those containing formaldehyde or ethyleneimine in guinea-pig potency tests. First order inactivation kinetics were regularly shown, with half life values which varied according to the different temperatures used. Inactivation brought about extensive degradation of FMDV RNA, while it did not adversely influence the integrity of critical viral epitopes on FMDV VP1.

Animals↗

Antimycotic action of alkyl derivatives of 5-(benzenesulfonamide)-1,2,3,4-tetrahydro-2-thioxo-4-pyrimidinon e.

Several series of mono-, di- and trimethyl derivatives of N-(6-amino-1,2,3,4-tetrahydro-4-oxo-2-thioxo-5-pyrimidinyl)benzene sulfonamide substituted at the benzene ring (Z), were synthesized and studied spectrophotometrically. The spectral and physical data enabled the structures of the methyl derivatives obtained by methylating (Z) to be identified. When assayed biologically as antimycotics, a small percentage of the substances exhibited mild fungicide activity.

Antifungal Agents↗

Antimycotic action of some amino-N-(5-pyrimidinyl)benzenesulfonamides.

2-, 3- and 4-amino-N-(6-amino-1,4-dihydro-4-oxo-2-mercapto (or alkylthio)-5-pyrimidinyl)benzenesulfonamides were synthesized and biologically tested on different strains of Candida albicans and Candida tropicalis. Some of the 4-aminoderivatives were also tested for antibacterial properties on numerous bacterial strains. Antimycotic activity of 4-amino compounds, expressed as MIC, is around 50 micrograms/ml and higher than that of both 2-amino- and 3-aminoderivatives. In all these compounds alkyl chain length does not seem to have any notable effects on biological activity, an exception being made for some aralkyl compounds. Antibacterial activity of 4-aminoderivatives is very low for all strains tested.

Antifungal Agents↗

[Radiotherapy of Hodgkin's disease in clinical stages I and II A: relapse of the disease and salvage therapy].

The authors describe the results of 71 patients with clinical stage I A (40 patients) and II A (31 patients) primarily treated with radiotherapy alone (61 mantle fields and 10 subtotal-nodal plus spleen irradiation). All patients achieved complete remission at the end of the treatment; 31 (43.7%) patients (15 at stage I and 16 at stage II) relapsed during the follow-up, mostly for nodal or extranodal extensions (87% of relapses). In 21/31 relapsed patients chemotherapy +/- radiotherapy was utilized as salvage treatment. Three patients died for second solid tumors and 1 patient died for jatrogenic late effect (leukemia after 4 cycles of MOPP). Despite the high percent of relapses, the long term overall survival (83.4%) of these patients is quite satisfactory mostly for the efficacy of chemotherapy as salvage treatment. However the authors think that laparosplenectomy plus subtotal-nodal irradiation is the treatment of choice for patients with Hodgkin disease at stage I and II A. Chemotherapy, instead, must be primarily utilized only for patients with a worse prognosis for hilar adenopathies or "bulky" mediastinum.

Adolescent↗

[Molecular structure with potential inhibitory action on the biosynthesis of FAH4].

Molecules formed by two pharmacophoric synthons--4-H2N--C6H4--SO2NH--and 2,4-diaminopyrimidine--were prepared. These structural units, with sulphamidic and antifolic action respectively, are bound without mutual electronic interaction, as demonstrated by their experimental electronic indices. The compounds were tested for activity on several bacterial strains and their biological activity was compared with that of molecular combinations formed by 4-aminobenzensulphonamide and substituted 2,4-diaminopyrimidines, to discover whether these two pharmacophoric synthons, so bound, are synergic.

Anti-Bacterial Agents↗