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Biomedical subjects

A Alberti

Publications and source records attributed to A Alberti.

At least 253 records · Page 14Linked to original sources
PubMed1990

Fine specificity of human antibody response to the PreS1 domain of hepatitis B virus.

The preS1 domain of hepatitis B virus envelope proteins contains a site of attachment to the hepatocyte membrane that has been shown to evoke virus-neutralizing antibodies. Using synthetic peptides, we have examined kinetics and specificity of the anti-body response to preS1 during acute and chronic HBV infection. Antibodies against two continuous B cell epitopes, p (21-32) and p (32-47), which overlap with the virus receptor for hepatocytes, were detected in 17 (28%) and 28 (47%) patients, respectively, of 60 patients who were tested during acute hepatitis B. Serial testing demonstrated these anti-preS1 specificities in more than 50% of patients who became virus free. By contrast, five patients with chronic evolution of hepatitis B and 61 of 66 patients with an established chronic HBV infection were negative, independent of serological profile and liver disease activity. Fifteen (22.7%) patients with chronic hepatitis B were positive for antibody to the C-terminus p (94-117) preS1 sequence that, unlike the acute-phase anti-(21-32) and anti-(32-47) reactivities, did not behave as a virus-precipitating antibody. Acute-phase sera were found to also contain virus-precipitating antibodies directed against conformational preS1 epitopes. These results indicate that the preS1 site, which contains the binding activity for the hepatocyte membrane, elicits an early antibody response during acute hepatitis B. A defect in such antibody repertoire may participate in the chronicity process as a result of continuing reinfection of hepatocytes by circulating virions.

Acute Disease↗
PubMed1990

A double-blind comparison of bisoprolol and captopril for treatment of essential hypertension in the elderly.

The aim of the study was to compare the antihypertensive efficacy and safety of a new beta blocker with high beta 1 selectivity, bisoprolol, with captopril in 28 elderly patients, aged over 65 years, with mild-to-moderate essential hypertension (WHO classes I and II). After a placebo run-in period of 4 weeks, the patients were randomly allocated to receive bisoprolol (5 mg od) or captopril (25 mg bid) (double-dummy technique) for 6 weeks, according to a crossover double-blind design, with a 4-week washout period between the two active treatments. The doses were doubled after 2 weeks if the supine blood pressure was greater than 160/95 mmHg. In basal conditions and after 2, 4, and 6 weeks of each treatment, the blood pressure and heart rate were assessed both in the supine and erect positions. At the same time, the side effects and quality of life were investigated by a checklist and a self-assessment questionnaire. Standard laboratory tests and a resting ECG tracing were performed before and after each active treatment. The data from 24 patients (4 dropouts) showed a significant antihypertensive effect of both treatments (p less than 0.01) with a reduction of diastolic blood pressure to values less than or equal to 95 mmHg in 75% (18/24) of the patients treated with bisoprolol and in 83.3% (20/24) of those treated with captopril, without significant differences between the two drugs. Bisoprolol also produces a marked but symptom-free reduction of heart rate compared with captopril (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

Recombinant human interferon alfa-2a in community-acquired non-A, non-B chronic active hepatitis. Preliminary results of a randomized, controlled trial.

A randomized, controlled trial was undertaken to evaluate the response to recombinant interferon alfa-2a in patients with hepatitis B surface antigen negative chronic active hepatitis of unknown aetiology (community-acquired non-A, non-B hepatitis). Thirty patients were treated with thrice weekly interferon in a dose of 6 million units for 1 month, followed by 3 million units for 3 months and 1 million units maintenance therapy for 8 months. Patients who relapsed were returned to the previously effective dose. A control group of 30 patients received no treatment and were followed up for 12 months. Overall, 21/30 (70%) of treated patients had a complete response, with normalization of serum aminotransferase levels, and a further three (10%) had a partial response (a decrease to less than 50% of baseline levels). No significant changes were observed in the control patients. Five (24%) of the 21 complete responders relapsed during months 2-4 and 8/21 (38%) relapsed during maintenance therapy. Three (23%) of these 13 patients had a return to normal serum aminotransferase levels when the dose was increased and 7/13 (54%) demonstrated a significant decrease. In a retrospective analysis of patients' sera for antibody to hepatitis C virus, 23/26 patients testing positive were treatment responders compared to 1/4 antibody negative patients. Our results suggest that interferon alfa-2a is an effective treatment for community-acquired non-A, non-B hepatitis, but reactivation during treatment occurred in 62% of patients. We recommend use of a higher dose of interferon for at least 1 year with long-term follow up in order to exclude early or late reactivation after treatment withdrawal.

Alanine Transaminase↗
PubMed1990

Chronic persistent hepatitis type B can be a progressive disease when associated with sustained virus replication.

In 44 hepatitis B virus (HBV) carriers with chronic persistent hepatitis (CPH), serial liver biopsies were available. At presentation 38 patients had HBV-DNA in their serum including 31 HBeAg positive and seven anti-HBe positive cases. The remaining six patients were anti-HBe positive and HBV-DNA negative. During a mean histologic follow-up of 4.2 years, 12 (32%) of the 38 HBV-DNA positive patients progressed to chronic active hepatitis (six cases) or to active cirrhosis (six cases), while 26 patients showed either unchanged features of CPH (21 cases), or histologic improvement to normal liver (five cases). Persistence of HBV-DNA in serum, independently of HBeAg/anti-HBe events, was significantly (p less than 0.01) associated with deterioration of liver disease, while termination of HBV replication correlated significantly (p less than 0.05) with spontaneous biochemical remission and with unchanged or improved histology. None of the six anti-HBe positive patients without serologic markers of hepatitis B virus replication showed histologic deterioration. These findings indicate that continuing HBV replication is a marker which predicts unfavourable evolution of chronic persistent hepatitis and frequent transition to chronic active hepatitis or cirrhosis.

Adolescent↗
PubMed1990

Long-term evolution of chronic hepatitis B in children with antibody to hepatitis B e antigen.

The aim of this study was to evaluate the long-term outcome of chronic hepatitis B in 27 children who had increased alanine aminotransferase activity and antibody to hepatitis B e antigen in serum from the time of their first clinical observation. Initial histologic changes were consistent with chronic active hepatitis in 13 cases (three with associated cirrhosis) and with persistent or lobular hepatitis in the remaining cases. On the basis of virologic testing, three groups of patients were identified: (1) two children had hepatitis delta antigen in the liver and anti-delta antibody in serum, and both had severe hepatitis; (2) 10 children had hepatitis B virus DNA in serum, and 60% of them had active hepatitis; (3) 15 patients had no hepatitis B virus DNA, and 33% of them had active hepatitis. During a follow-up period of 12 months to 12 years (mean +/- SD: 6.1 +/- 2.4 years), the disease remained active in both children with anti-delta antibody, but they had no major complaints. In all eight patients who could be followed in group 2, test results became negative for hepatitis B virus DNA and alanine aminotransferase activity normalized within 4 years; biochemical remission was delayed in three patients with higher hepatitis B virus DNA levels on entry, and one of these patients had a severe exacerbation of disease activity before remission. In group 3, a total of 10 patients (71%) achieved biochemical remission within 1 year, and two within 26 months; only two patients, who were transfused at birth, had long-lasting liver damage. These results indicate a trend to early remission of liver disease in children with chronic hepatitis B with antibody to hepatitis B e antigen without delta virus infection. Antiviral therapy aimed at accelerating the termination of hepatitis B virus replication may be indicated only in those with higher levels of hepatitis B virus DNA.

Adolescent↗
PubMed1990

Timing of diagnosis and lymphocyte accumulation patterns in chronic lymphocytic leukemia: analysis of their clinical significance.

In order to evaluate the clinical significance of the timing of diagnosis in chronic lymphocytic leukemia (CLL), we studied the diagnostic latency (DL), a variable related both to lymphocyte count and to lymphocyte doubling time (LDT), which points out the interval between the date of CLL diagnosis and the time at which it could have been made (lymphocyte count in peripheral blood of at least 5.0 x 10(9)/l). In two different series accounting for 221 previously untreated CLL patients the trends of the DL tended to decrease as the risk increased. In other words, the more advanced the clinical stage the shorter the DL. On the other hand, the values of lymphocyte accumulation rate (LAR), which defines the speed at which the number of lymphocytes increases over the time, were significantly lower in earlier stages of disease. Both DL and LAR had a significant impact on survival when investigated by means of univariate analysis. In a Cox's regression analysis applied to a training set of 122 patients, the combination of international clinical stages, LAR and age had the strongest value in predicting survival. The resulting model was validated in an independent subset of 99 patients (test-set cases) leading to a classification of patients into low-, intermediate-, and high-risk groups with 5-year survival rates of 89%, 31% and 8%, respectively, and with distinctively different annual mortality rates (p less than 0.001). Finally, when multivariate analysis was applied to study disease progression, LAR was the first variable to enter the regression model (p = 0.0001).

Humans↗
PubMed1990

Spontaneous reactivation of hepatitis B virus infection in patients with chronic type B hepatitis.

Eighty-eight consecutive hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, heterosexual patients of Caucasian origin presenting with chronic hepatitis were followed for 1 to 15 years (mean, 5.4 years). During the study period, 45 (51%) patients cleared HBeAg and hepatitis B virus-deoxyribonucleic acid from serum and were followed for 53 +/- 29 months (mean +/- SD) after seroconversion to antibody to hepatitis B e antigen. All patients manifested biochemical improvement. During follow-up, 10 (22%) of the 45 patients experienced spontaneous reactivation of hepatitis B replication with reappearance of serum hepatitis B virus-deoxyribonucleic acid and, in 4 patients, of hepatitis B e antigen. All patients then showed biochemical exacerbation of disease. These serologic events were transient, lasting an average of 12 months, in 8 (80%) patients. All patients were asymptomatic or minimally symptomatic. Histologic findings of liver tissue from 7 patients showed progression from chronic active hepatitis to active cirrhosis in 2 (28%) patients, while in the remaining 6 cases histology remained unchanged or improved from chronic active to chronic persistent hepatitis. These data indicate that spontaneous reactivation of hepatitis B infection occurs in heterosexual patients with chronic hepatitis B and this event is usually transient and asymptomatic, although in some patients it may be the major cause of progressive hepatic damage.

Adult↗
PubMed1990

Antibodies to the RNase H domain of hepatitis B virus P protein are associated with ongoing viral replication.

Antibodies against the RNase H domain of human hepatitis B virus P protein(s) are frequent markers of acute and chronic virus infection (T. Weimer, K. Weimer, Z.-X. Tu, M.-C. Jung, G. R. Pape, and H. Will, J. Immunol. 143:3750-3756, 1989). In the present study, these antibodies were determined in serial serum samples of experimentally infected chimpanzees and naturally infected human patients with acute and chronic hepatitis B virus infection. Anti-P antibodies were found in the sera of both chimpanzees and humans early in infection shortly after the immunoglobulin M anti-HBc response; they persisted in chronic carriers with ongoing viral replication but declined and disappeared at the time of virus clearance from the sera. These data demonstrate that antibodies to the RNase H domain of the hepatitis B virus P protein are early markers of infection and a signal of ongoing virus replication. Falling titers indicate the decline or end of active virus production and may therefore be a prognostic sign of virus elimination in natural infection and after antiviral therapy.

Acute Disease↗
PubMed1989

Recognition of hepatitis B virus envelope proteins by liver-infiltrating T lymphocytes in chronic HBV infection.

The Ag specificity and cytotoxic function of human T cell clones, generated from lymphocytes infiltrating the liver of a chronic hepatitis B patient, were studied. Both class I- and class II-restricted T clones specifically proliferated to hepatitis B virus envelope proteins, but not to hepatitis B core Ag. The fine specificity of T cells was studied by using rAg having different composition in relation to HBV-envelope proteins or synthetic peptides of preS regions. The antigenic determinant recognized by T cell clones mapped to the preS2 region based on the response to r(preS1+preS2+S) and to r(preS2+S) and the failure to respond to S or preS1 alone. More precise epitope mapping was based on synthetic preS2 peptides 120-150 or 120-134, which stimulated both class I- and class II-restricted T clones, whereas preS2 153-171 or preS1 1-110 peptides did not; thus, the preS2 120-134 appears to contain both the residues binding to class I molecules and the residues binding to class II molecules. Moreover, strong and specific cytotoxic responses of these clones were observed only when HLA-matched EBV-lines, used as target cells, were previously sensitized with r(preS1+preS2+S) or preS2 peptides, which were shown to stimulate the clones. Thus, a preS2 epitope can represent a target Ag for liver-infiltrating T cells, which could kill the hepatocytes expressing the Ag plus the appropriate MHC molecule.

Adult↗
PubMed1989

HIV-1-specific B cell activation. A major constituent of spontaneous B cell activation during HIV-1 infection.

B cell activation is a well known consequence of HIV-1 infection, and seropositive subjects show high numbers of spontaneously activated Ig-secreting cells in circulation. To better define the importance of the HIV-1-specific response in this phenomenon, we first studied whether in vitro spontaneous anti-HIV-1 antibody production was accompanied by reactivation of memory B lymphocytes. Unstimulated PBL from HIV-1-infected individuals with prior history of hepatitis B and/or EBV infection did not consistently show spontaneous in vitro synthesis of anti-hepatitis B core Ag or anti-EBV antibodies; in addition, PWM-induced synthesis of anti-hepatitis B virus and anti-EBV antibodies was decreased compared to HIV-1-seronegative subjects. Moreover, in comparing the frequencies of activated HIV-1-specific B cell precursors and activated Ig-secreting precursors in limiting dilution experiments, a sizable fraction (20 to 40%) of circulating cells spontaneously secreting Ig produced antibody against HIV-1 determinants. The ratio between the two frequencies fitted in very well with the amount of Ig removed from unstimulated culture supernatants after HIV-1-specific antibody absorption with solid-phase HIV-1. These findings indicate that B cell activation during HIV-1 infection is mainly oriented toward a specific response to HIV-1 determinants; the possible relevance of this phenomenon to lymphomagenesis in AIDS patients is discussed.

Absorption↗
PubMed1989

Lymphoproliferative disease of granular lymphocytes in a patient with concomitant hepatitis B virus infection of CD4 lymphocytes.

In this report we studied a 35-year-old male who developed an abnormal expansion of granular lymphocytes (GL) which spontaneously regressed over a period of 2 years. The immunological and molecular characterizations of expanded cells showed the CD3+,CD8+,HNK-1+ phenotype, a polyclonal organization of the T-cell receptor beta-chain gene and normal natural killer activity. At the time of presentation, spot and blot hybridization techniques revealed the presence of viral hepatitis B virus (HBV) DNA sequences only in highly enriched CD4+ T cells, while proliferating GL were negative. With this as a background, we addressed the question of whether in our case the polyclonal GL proliferation represented an immunoreactive response against CD4+ infected cells. In particular, we tested the possibility that expanded GL could be cytotoxic against autologous infected CD4+ cells. At the time of the first determination, when several of the CD4+ cells harbored HBV, GL showed a minimal degree of cytotoxicity against 51Cr-labeled CD4+ cells; 2 years later, when GL became capable of lysing these targets, the appearance of the specific cytotoxicity was concomitant with the disappearance of the HBV-infected CD4+ cells and with the recovery of granular lymphocytosis. Taken together, our data suggest that in this case GL proliferation could represent an immunoreactive process against CD4+ cells.

Adult↗
PubMed1989

Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis.

To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HBeAg/anti-HBe status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HBeAg-positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum sIL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.

Acute Disease↗
PubMed1989

Identification of an attachment site for human liver plasma membranes on hepatitis B virus particles.

The surface antigen of hepatitis B virus (HBsAg) exposes three protein domains: preS1, preS2, and S. In a previous study we have shown that preS1 sequences expressed in transfected yeast cells bind specifically to plasma membranes of human liver. In this study we show that purified virus particles from a virus carrier bind also specifically to such membranes. Subviral HBsAg filaments which are rich in preS1 bind well too, while HBsAg 20-nm particles which contain small amounts of preS1 bind to a much lesser degree. The binding can be inhibited by a monoclonal antibody which recognizes a sequential epitope between amino acids 27 and 49 of the preS1 domain.

Antibodies, Monoclonal↗
PubMed1989

Hepatitis B virus DNA forms in the liver of chronically infected individuals. Relation to replication profile.

To analyze the profile of HBV-DNA forms in the liver in relation to different levels of virus replication, liver biopsies from 52 chronic HBsAg carriers were studied by Southern blot analysis. Quantitative evaluation of the major HBV-DNA molecules was carried out by densitometry in 27 patients with ongoing hepatitis B virus (HBV) replication in the liver. Significant variations in the intensity of the different bands were noted in individual cases, but statistical correlation between the amount of single stranded forms and levels of serum HBV-DNA was not observed. In contrast, the amount of linear 3.2 kb HBV-DNA appeared to have an inverse correlation with levels of circulating virions. Only the 3.2 kb form was detected in three patients negative for serum HBV-DNA. In these cases with 'inactive' state of episomic HBV genome seroconversion to anti-HBe occurred from 12 months before to 4 months after the time of liver biopsy testing. This 3.2 kb form can therefore be interpreted as a pattern of transition from the replicative to the non-replicative state of the virus.

Antigens, Viral↗