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Biomedical subjects

F Rosina

Publications and source records attributed to F Rosina.

At least 55 records · Page 3Linked to original sources

Expression of the c-myc protooncogene product in cells infected with the hepatitis delta virus.

The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.

Amino Acid Sequence↗

Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alpha 2b.

Eighty patients with chronic hepatitis C who completed a previously reported randomized controlled trial on the efficacy of interferon-alpha 2b were followed up for at least 36 mo after therapy discontinuation. Seventeen patients (21.2%) maintained normal ALT values throughout the follow-up; 63 (78.8%) either did not normalize the levels of ALT or relapsed during the follow-up. A significantly greater proportion of patients treated with 3 million units of interferon three times a week subcutaneously for 48 wk were long-term responders compared with patients treated for 24 wk. Sex, age, hepatitis C virus antibody status, source of infection and pretreatment levels of ALT were not predictive of long-term response. Cirrhosis was found to be an unfavorable predictive factor. After 3 yr of follow-up, clearance of viremia was observed in 58.9% of the 17 long-term responders but in none of the non-responders (p = 0.002). E2-NS1 antibody tested negative in 88.2% of long-term responders and in 14.3% of nonresponders (p = 0.001). Fifty-nine percent of long-term responders tested negative for C100-NS4 antibody compared with 14.3% of nonresponders (p = 0.031). No significant change was observed in other antibodies. Four long-term responders underwent liver biopsy 2 yr after discontinuation of therapy. All four patients had normal liver histology compared with baseline assessment of chronic active hepatitis in three and chronic persistent hepatitis in the other. Three of the four were negative for serum hepatitis C virus RNA.

Adult↗

[Combined treatment of colorectal polyps with diathermy and the Nd-YAG laser. Our experience].

Among colorectal polyps, those of the sessile and villous type are said to bear a high frequency cancer degeneration. While surgery is considered the cure, alternative choices are to be offered in the presence of contraindications or lack of an informed consent. We analyzed the results of the "combined therapy" that requires the use of the ND-YAG laser following the ablation of the lesion with diathermic snare. We used an EV laser 132 with double wavelength to allow the ablation of flat lesions and minimize the risk of perforation. We included 12 patients with sessile colorectal polyps. In 9/12 complete eradication was obtained over a follow-up 11 months; of the remaining 3, 2 dropped out, 1 did not respond. Owing to the small series, the relationship between the successful eradication and the size of the polyp cannot be evaluated. We conclude that the treatment of sessile colorectal polyps with this combined approach may be a promising one.

Aged↗

Rabbit-derived anti-HD antibodies for HDAg immunoblotting.

We studied the sensitivity and specificity of two rabbit-derived antibodies (W2 and W3) raised against two synthetic peptides of the HDAg: the C-terminus of the p24 protein (W2) and the C-terminus of the p27 protein (W3) (Chiron Co., Emeryville, CA, U.S.A.). The results were compared with those obtained with a human polyclonal anti-HD (W1). We have tested W2 and W3 against blotted serum samples from 25 patients (20 HBsAg positive anti-HD positive, three HBsAg positive anti-HD negative and two HBsAg negative anti-HD negative) and liver extracts from five HBsAg seropositive patients, two anti-HD positive and three anti-HD negative. In serum samples W3 sporadically reacted with a p31 protein present in both anti-HD positive and negative sera; W2 identified the p24 protein in 7/10 W1 positive samples but in none of 10 W1 negative; the p27 protein was captured by W2 only in one highly viremic serum. In every sample of liver extract W3 recognized a 48-kDa band. W1 and W2 stained 5 bands at 45, 27, 24, 16 and 12 kDa. The p45, p27 and p24 proteins were peculiar of HDV-infected livers; p16 and p12 were also detected in HDV free livers. W2 identified an additional 54-kDa protein in 4/5 liver extracts. For diagnostic purposes human polyclonal anti-HD represents the most sensitive probe for HDAg immunoblotting, with a specificity similar to that of rabbit-derived antibodies. The affinity of W2 and W3 antibodies for serum and liver HDAg appears to be lower than for HDAg recombinant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serological diagnosis of hepatitis B and delta virus (HBV/HDV) coinfection.

Diagnosis of acute hepatitis B virus/hepatitis delta virus (HBV/HDV) coinfection is currently based on detection of anti-HD, however this antibody may be undetectable during the acute phase of hepatitis. To evaluate the entity of misdiagnosis of HBV/HDV coinfection in acute HBsAg-anti-HBc IgM positive hepatitis we examined sera from 245 consecutive patients obtained at admission and day 30, 60, 120, 210 and 400 of their follow-up. Anti-HD was detected in the serum of 26 out of 245 patients (10.6%). In 15% of cases it was present at admission, while in 92% it was found after 30 days. The combined detection of HDV-RNA, HDAg and IgM anti-HD in acute phase sera allowed a correct etiologic diagnosis in 69% of the cases. These findings suggest that the prevalence of HBV/HDV coinfection is underestimated when anti-HD is the only marker to be detected during the acute phase of disease. A correct etiologic diagnosis can only be made by testing acute phase sera for all the available markers of HDV. However, the best cost-effective procedure is to test any patient with HBV markers at presentation for anti-HD, 30-40 days after the onset of symptoms.

Adult↗

Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in chronic hepatitis D.

Hepatitis D virus and hepatitis B virus nucleic acids were detected by Northern and Southern blot hybridization in the sera and livers of 85 chronic carriers of HBsAg and anti-hepatitis D followed up for a mean of 10 yr. We identified three subsets of patients: 13 with hepatitis D virus and hepatitis B virus viremia, 53 with serum hepatitis D virus RNA, but without hepatitis B virus DNA and 19 negative for both nucleic acids. Genomic and subgenomic forms of hepatitis D virus RNA were detected only in patients with hepatitis D virus and hepatitis B virus viremia. Histological findings and disease activity at admission were comparable in the three groups of patients, but the outcome was significantly worse in patients with active replication of both viruses; two of them died of terminal liver failure and hepatocellular carcinoma developed in two; the remaining patients had an uneventful course. These results suggest that active hepatitis B virus replication represents an important previously unrecognized determinant of severe liver damage in patients with chronic hepatitis D virus infection. Since hepatitis B virus provides the means for hepatitis D virus secretion and release from infected cells, active hepatitis B virus multiplication favoring the spread of hepatitis D virus from cell to cell may increase the pathogenetic potential of the defective agent.

Adolescent↗

A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis: a multicenter Italian study.

To determine whether long-term therapy with recombinant interferon-alpha can improve the course of chronic delta hepatitis, 61 Italian patients with this disease were randomly assigned to receive either interferon-alpha-2b three times a week (5 MU/m2 for 4 mo and then 3 MU/m2 for another 8 mo) or no treatment. At the end of the 12-mo study, all patients were followed-up for 12 additional months. Normalization or decrease of more than 50% from baseline of serum ALT levels occurred in 42% of treated patients the fourth month of therapy, 26% the twelfth month and 3% the twenty-fourth month vs. 7%, 7% and 0%, respectively, in the control group. However, relapses occurred in 7 of 8 (87.5%) responders 1 to 10 mo (mean = 3.5 mo) after cessation of therapy. Liver biopsies were carried out at baseline and during the twelfth month of treatment. Histological improvement, mostly caused by decrease of portal inflammation, was observed in 57% of treated and 36% of untreated patients. Measures of antiviral activity (serum hepatitis delta virus RNA and intrahepatic hepatitis delta antigen) showed similar levels in treated and control patients. In treated patients the percentage of patients who were negative for HDV RNA never exceeded that of baseline. Although interferon-alpha in the dosage given in this study had no antiviral effect on patients with chronic hepatitis D, it reduced hepatic inflammation as measured by ALT levels. Whether a longer duration or reinstitution of interferon-alpha therapy would achieve long-term control of ALT levels and prevent chronic liver damage is not known.

Alanine Transaminase↗

A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis.

Eighty patients with chronic non-A, non-B hepatitis completed a randomized controlled trial of the therapeutic efficacy of recombinant interferon alfa-2b. Twenty-nine received 1 million units and 26 received 3 million units of interferon subcutaneously thrice weekly for 6 months, and 25 were controls. Normalization or a significant decrease of alanine aminotransferase values was obtained in 19/29 (66%) patients treated with 1 million units, in 18/26 (69%) patients treated with 3 million units and in one control patient (4%, p less than 0.05). However, when control patients were randomized after the initial 24 weeks to receive 1 or 3 million units of interferon for 48 weeks, 12/14 (86%) patients receiving 3 million units responded to therapy versus 3/11 patients receiving 1 million units (27%, p less than 0.05). After a 1 to 6 months follow-up period post treatment, an alanine aminotransferase relapse was observed in 18/30 (60%) responders to 3 million units and in 17/22 (77%) responders to 1 million units. Cirrhotic patients responded less than patients with non-cirrhotic disease (47 vs. 78%, p less than 0.05). Only responders treated with 3 million units significantly ameliorated their histologic picture (pre-therapy Knodell's index = 8.9, post-therapy = 6.0, p less than 0.05). The data confirm that treatment with interferon is of benefit in patients with chronic non-A, non-B hepatitis.

Adult↗