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Biomedical subjects

A Alberti

Publications and source records attributed to A Alberti.

At least 379 records · Page 21Linked to original sources

An antibody which precipitates Dane particles in acute hepatitis type B: relation to receptor sites which bind polymerized human serum albumin on virus particles.

An antibody, which is distinct from the HBsAg- reacts with antigenic sites on Dane particles- HBcAg and HBeAg, was studied by radioimmunoprecipitation of radioactive intact hepatitis B virions in sera obtained early in the course of acute hepatitis type B. The antibody, previously termed anti-Dane particle (anti-DP) antibody, was reactive with Dane particles and HBsAg particles obtained from HBeAg-positive sera but not with HBsAg particles from anti-HBe containing sera. The expression on virus particles of the evoking antigen correlated with levels of binding sites for polymerized human serum albumin (pHSA) as detected by solid-phase radioimmunoassay. In acute hepatitis B sera, levels of anti-DP antibody activity showed inverse correlation with expression of pHSA receptors on circulating virus particles, although the two reactivities were not mutually exclusive. In inhibition experiments, pHSA blocked precipitation of Dane particles by anti-DP positive sera, while native human albumin and polymerized bovine albumin had no effect. The inhibition by pHSA of the anti-DP reaction appeared specific since identical concentrations of pHSA did not interfere with precipitation of virus particles by anti-HBs. Affinity chromatography studies with anti-DP insolubilized on Sepharose 4B columns showed selective binding to the gel of radioactive Dane particles; 125I-HBsAg was not reactive. The binding of Dane particles to anti-DP columns was completely inhibited when virus particles were applied to the gel in pHSA; pretreatment of the column with pHSA did not affect the reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Centrifugation, Density Gradient↗

T lymphocyte sensitization to HBcAg and T cell-mediated unresponsiveness to HBsAg in hepatitis B virus-related chronic liver disease.

Using a newly developed indirect T lymphocyte migration inhibition test, cell-mediated immunity to HBsAg and HBcAg was directly and simultaneously examined in a total of 21 patients with HBsAg-positive chronic liver disease (CLD), and in seven subjects whose sera contained anti-HBs (2 previous acute hepatitis B; 4 hepatitis B vaccine recipients and 1 chronic active hepatitis). T cell sensitization to HBcAg was invariably detected in the HBsAg-positive CLD patients tested (12/12), whereas T cell sensitization to HBsAg was not present in any of the patients (0/21). In contrast, T cell sensitization to HBsAg was present in all anti-HBs-positive subjects. These results support the hypothesis that the cellular immune response to HBcAg, rather than to HBsAg, is implicated in the pathogenesis of HBsAg-positive CLD. Moreover, the observation that the addition of T cells from patients with HBsAg-positive CLD to T cells from anti-HBs positive subjects in a ratio of 1 to 9 reversed their sensitization to HBsAg, suggests that a hyperactivity of HBsAg-specific suppressor T cell population may be responsible for persistent HBs antigenemia.

Adult↗

Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B.

Seventy consecutive HBsAg- and HBeAg-positive patients with biopsy-proven chronic hepatitis were followed prospectively with serial determinations of SGPT levels and hepatitis B virus serum markers including HBsAg, HBeAg, anti-HBe and hepatitis B virus DNA. During a period of 1 to 11 years (mean +/- S.D.: 5.0 +/- 2.3 years), 28 patients remained persistently HBeAg positive, most with continuing biochemical and histologic activity, while 41 cases seroconverted to anti-HBe. One patient became HBeAg and anti-HBe negative. After seroconversion, 87.8% of the cases showed sustained normalization of SGPT, and clearance of hepatitis B virus DNA from serum and histologic improvement was documented in 79% of the cases who had a control liver biopsy, while 15.8% developed cirrhosis. In two patients (4.9%), the disease remained active despite seroconversion, and both cases had evidence of continuing hepatitis B virus replication. Finally, reactivation of liver damage and of hepatitis B virus replication was observed in three additional patients (7.3%) who had transiently normalized SGPT after seroconversion. All 70 patients were analyzed for hepatitis delta virus markers, and only two persistently HBeAg-positive cases were found positive for antibody to hepatitis delta virus in serum, one also having hepatitis delta antigen in the liver. These findings indicate that, in chronic hepatitis type B, termination of virus replication is associated in most patients with biochemical and histologic regression of inflammatory activity. After anti-HBe seroconversion has occurred, virus replication and liver disease may persist or reactivate in a small proportion of patients thus giving origin to the well-recognized group of anti-HBe positive, hepatitis B virus DNA-positive chronic hepatitis type B.

Adolescent↗

Differential distribution of hepatitis B core and E antigens in hepatocytes: analysis by monoclonal antibodies.

Current knowledge on the expression of HBeAg in hepatocytes is incomplete because of difficulties in obtaining monospecific antisera devoid of anti-HBc reactivity. In this study, we have examined by immunofluorescence the expression of HBcAg and HBeAg in cryostat liver sections from 25 chronic carriers of HBsAg using monoclonal antibodies. Although virtually all liver biopsies displayed concordance for HBeAg and HBcAg expression, the pattern of fluorescence differed markedly. Thus, monoclonal anti-HBc gave nuclear staining in all 13 reactive biopsies, while cytoplasmic staining was observed in only two of these. In contrast, monoclonal anti-HBe showed cytoplasmic reactivity coexisting with nuclear reactivity in 10 of 13 reactive biopsies. Hepatitis B virus DNA polymerase activity in the serum appeared to correlate better with the presence of HBcAg in hepatocytes rather than HBeAg. These results provide further evidence that HBeAg is expressed both in the nuclei and in the cytoplasm of infected hepatocytes. The observation that the number of cells expressing HBeAg exceeds those expressing HBcAg in carriers with active virus replication would suggest that assembly of core particles occurs in only a proportion of infected hepatocytes expressing HBeAg.

Antibodies, Monoclonal↗

Long-term follow-up of anti-HBe-positive chronic active hepatitis B.

Twenty-eight patients with chronic active hepatitis without cirrhosis who were positive for hepatitis B surface antigen and antibody to hepatitis B e antigen were followed for 1 to 15 years (mean 6.6 years) and underwent follow-up biopsy. At presentation, 12 of the 28 patients (43%) had hepatitis B virus DNA in serum, 10 (36%) had serologic evidence of hepatitis delta virus infection and 6 (21%) had no serologic markers of either hepatitis B virus replication or hepatitis delta virus infection. During follow-up, 15 (54%) patients developed active cirrhosis, including eight patients with hepatitis delta virus infection and five with hepatitis B virus DNA in serum. In seven (47%) of the 15 patients, cirrhosis developed within the first 2 years; all seven patients had bridging necrosis in the first liver biopsy, and five of these were infected with hepatitis delta virus. The remaining 13 (46%) patients did not develop cirrhosis during follow-up and showed either unchanged features of chronic active hepatitis (seven cases) or histologic improvement to chronic persistent hepatitis (five cases) or to normal liver (one case). In conclusion, the prognosis of anti-HBe-positive patients with chronic hepatitis B is poor, as 54% of the cases developed cirrhosis during a mean histologic follow-up period of 4.5 years, mainly in association with hepatitis delta virus infection or continuing hepatitis B virus replication.

Adolescent↗

Chronic lymphocytic leukemia (CLL) in younger adults: a retrospective study of 133 cases.

Clinical and biological data have been evaluated, using both univariate and Cox's multivariate statistical analyses, in a series of 133 Chronic Lymphocytic Leukemia (CLL) patients with a mean age of 46.6 years (range 31-50). In univariate analyses, anemia (Hb less than 13 g/dl), peripheral blood (PB) lymphocytosis (greater than 40 x 10(9)/l) and bone marrow (BM) lymphocytosis (greater than 80 per cent) were shown to be of significant prognostic value. Multivariate analysis, through a forward stepwise procedure, showed that the most important and independent variable is the BM lymphocytosis. These results are different from those obtained in previous studies and particularly in a recent identical study performed by the same Cooperative Group on 1777 patients with a mean age of 64.2 years (Mandelli et al., 1987). No significance can be demonstrated in stratifying this series of younger patients according to different staging methods (Rai et al., 1975; Binet et al., 1981b; Mandelli et al., 1987). Therefore this population of CLL patients, with less than 50 years of age, has risk factors quite different from classical CLL. The results of the present study show that the diagnostic approach to B-CLL in younger adults must be more complete: using the common diagnostic criteria, established staging systems appear to be inadequate in this series of younger patients.

Adult↗

Chronic evolution of acute hepatitis type B: prevalence and predictive markers.

During a prospective study of acute symptomatic viral hepatitis, started in 1978, 664 consecutive adult patients, including 223 drug abusers, fulfilled the diagnostic criteria (anti-HBc IgM positivity) for acute type B hepatitis. In order to evaluate the outcome of the disease, 443 patients were followed for up to 12 months after the onset. 2.4% of the infections became chronic; the rate did not significantly differ between drug addicts and non-drug abusers, suggesting that chronic hepatitis is a rare complication of acute symptomatic hepatitis type B. Ongoing liver damage after clearance of HBsAg from serum was observed in drug abusers only (14% of the cases). Clinical, biochemical and virological features of the acute phase in patients with ongoing infection were compared with those of uncomplicated cases. Anicteric hepatitis and lower transaminase values were significantly (p less than 0.05) associated to a chronic evolution of the disease, as well as a higher prevalence of HBV-DNA, DNA polymerase and HBcAg positivity in serum. Testing HBV-DNA and DNA polymerase early in the course of the infection appeared to be of high predictive value for the subsequent outcome of the illness.

Acute Disease↗

Serum binding activity for polymerized human albumin due to antibodies detected by enzyme-linked immunosorbent assay in acute and chronic type B, A and NANB viral hepatitis.

Polymerized human serum albumin (pHSA) binding activity due to antibodies was evaluated by a sensitive and specific enzyme-linked immunosorbent assay (ELISA) in well characterized cases of acute (AVH) and chronic active (CAH) viral hepatitis. Moreover, hepatitis B virus (HBV) infection serum samples were tested for the presence of HBsAg-associated pHSA receptors detected by radioimmunoassay. Specificity of ELISA in detecting pHSA binding activity due to antibodies was assayed by testing IgG fractions from positive serum samples and purified HBsAg particles. A very high prevalence (mean = 87%) of antibody response to pHSA was detected in serum samples of patients with type B, A and post-transfusion non-A, non-B (NANB) AVH and CAH. IgM antibodies were found in 75% of type B AVH, in 77% of type A AVH and in none of the NANB cases at the onset of illness. In CAH, IgM antibodies were found in 37.5% of HBsAg-positive cases and in 44% of NANB cases. In HBV-related AVH and CAH no correlation was found between anti-pHSA antibodies and HBsAg-associated pHSA receptors or the HBeAg/anti-HBe status. The antibody response detected by ELISA showed a cross-reactivity with monomeric human albumin and heterologous polymeric and monomeric albumins. However, in HBV infection the antibody binding was significantly higher for pHSA than for monomeric human albumin or albumins from other species, thus suggesting that the antigenic sites of pHSA evoking the antibody response may differ in relation to the etiology of viral hepatitis.

Autoantibodies↗

Changes in liver membrane antigenicity and intracellular viral antigens expression in hepatitis B virus-infected hepatocytes.

In this paper we studied the presence of HBsAg and immunoglobulin G on the liver cell surface in patients with chronic HBV infection. For this purpose we developed a double immunofluorescence technique which allowed the contemporary detection of membrane antigens and the intracellular expression of HBV antigens (HbsAg and HBcAg) within the same hepatocyte. In 16 selected patients (10 with CAH and 6 with normal liver or NSRH) we found that the presence of membranous HBsAg is associated to the healthy carrier state of the infection and it correlates with the presence of abundant HBsAg in the cytoplasm of liver cells. On the contrary, membrane-bound IgG was found in patients with active virus replication and its presence correlates with nuclear HBcAg. On the basis of these results a modulatory effect of the cytophilic IgG on HBV cellular expression is proposed.

Cell Membrane↗

Methods for the study of pre-S proteins of hepatitis B virus and their antibodies: pathogenetic and clinical implications.

The envelope gene of hepatitis B virus (HBV) consists of a large open reading frame which codes 3 different polypeptides by the variable use of 3 contiguous regions: the pre-S1, pre-S2 and S regions. The protein coded by the entire sequence (L protein) is identified by its unique pre-S1 epitopes and has a role in virus assembly and secretion. Pre-S1 antigens are expressed preferentially on virions and are less abundant, but present, on subviral particles. The pre-S2 sequence contains a species-specific receptor for polyalbumin, which has been implicated in virus binding to hepatocytes. Methods have been recently developed to measure pre-S1 and pre-S2 levels in serum and available data indicate that these assays may be useful in prognostic assessment of acute hepatitis B and to measure virus replication in chronic infection, although further studies are certainly needed to define specificity and sensitivity compared to conventional HBV markers. Both pre-S1 and pre-S2 are highly immunogenic and elicit anti-pre-S antibodies. Methods for detection of anti-pre-S in human sera have proved difficult to be developed due to unspecific reaction of serum components with pre-S sequences and epitope variability of the immune response in humans. Anti-pre-S2 seems a marker of recovery from acute infection, while evidence of its involvement in liver damage is weak. Both anti-pre-S2 and anti-pre-S1, but we have limited information on the latter, may be involved in virus neutralization. These issues are particularly relevant for future HB vaccine development, as it is proposed that inclusion of strategic pre-S sequences could increase efficacy.

Animals↗

Recombinant DNA techniques in the study of hepatitis B virus infection.

Recombinant DNA techniques have recently contributed a great deal of informations on hepatitis B virus (HBV) infection. Serum HBV-DNA appeared as the most sensitive marker of viral replication activity both in hepatitis B e antigen (HBeAg)-positive and in anti-HBe-positive patients. In the latter group, a significant correlation between serum viral DNA positivity and liver disease activity was present. In our experience, more than 50% of anti-HBe-positive cases with chronic liver disease showed circulating HBV-DNA, while none of healthy HBsAg chronic carriers was found positive for serum HBV-DNA. In type B acute hepatitis, viral nucleic acid sequences were detectable only in a small number of uncomplicated cases, but were observed in all the patients who progressed to chronic hepatitis. HBV-DNA represents therefore an early and useful prognostic parameter in acute infection. Several epidemiological studies have established a striking correlation between HBV infection and development of hepatoma. Using molecular hybridization techniques, viral DNA has been identified in liver cancer cells. Finally, HBV-DNA has also been identified in the pancreas, kidney, skin, bile ducts and in cells of the vascular system. In addition, the presence of viral genome has been recently identified in circulating lymphocytes of patients with acute or chronic HBsAg-positive hepatitis. These findings add further informations to the understanding of viral biology and of virus-host interactions in the natural history of the infection and associated liver disease.

Carcinoma, Hepatocellular↗

Sylvatic American trypanosomiasis in Argentina. Trypanosoma cruzi infection in mammals from the Chaco forest in Santiago del Estero.

Trypanosoma cruzi infection in sylvatic mammals of the quebracho woods of the eastern part of Santiago del Estero province, Argentina, was studied from October 1984 to December 1987. 301 mammals of 20 different species were caught. T. cruzi, characterized biologically and biochemically, was isolated by xenodiagnosis from 23 of 72 (32%) Didelphis albiventris opposums, 2/36 (5.5%) Conepatus chinga skunks, and one ferret (Galictis cuja). 53 opossum refuges were located and triatomine bugs were found in 2 of them: one male Triatoma infestans, infected with T. cruzi, and 5 uninfected nymphs of T. sordida, had all fed on opossum blood. Electrophoretic zymogram patterns of the T. cruzi populations isolated from opossums and skunks were similar to isoenzyme profiles already described for populations isolated from infected humans in Argentina. The small number of triatomines found in the opossum refuges seems inadequate to account for the prevalence of T. cruzi infection recorded for these mammals, so other possible contaminative routes of infection should be investigated.

Animals↗

Transesophageal echocardiography in the evaluation of mediastinal masses.

To assess the diagnostic impact of transesophageal echocardiography in the evaluation of mediastinal masses, 30 patients with mediastinal abnormalities detected by routine chest roentgenogram underwent transthoracic and transesophageal echocardiography. Subsequently, 29 of the patients underwent computed tomography and 16 underwent magnetic resonance imaging. The location and structure of the masses as well as their relationship to the surrounding structures were assessed. Anatomic confirmation and histopathologic diagnosis of the mediastinal masses by surgical resection and biopsy was available for all patients. Transesophageal echocardiography was more accurate than transthoracic echocardiography in detecting mediastinal masses (90% versus 73%), in identifying their structure (100% versus 90%), and in evaluating their relationship to contiguous organs (89% versus 81%). No complication was observed during the examinations. Computed tomography correctly diagnosed the location, structure, and relationships in all patients but one; magnetic resonance imaging correctly evaluated the mediastinal masses in all 16 patients. Our study suggests that transesophageal echocardiography is a valuable and safe complementary method of evaluating mediastinal masses. Moreover, this technique allows the obstruction of vessels and heart cavities, valve regurgitation, and right and left ventricular function to be easily assessed.

Adult↗

The clinical value of blunting of cyclic gray level variation for the detection of acute cardiac rejection: a two-dimensional, Doppler, and videodensitometric ultrasound study.

Aims of this study were to assess (1) whether videodensitometric analysis of myocardial gray-level variation can distinguish normal from rejecting transplanted hearts in a clinical setting and (2) whether this sign, used in combination with the other conventional two-dimensional and Doppler echocardiographic findings, might improve the accuracy of ultrasound techniques. Thirty heart transplant recipients (23 men; mean age 40 years; range 20 to 54 years) were studied in 87 different situations by endomyocardial biopsy and echocardiographic evaluation. Of the 87 situations, 37 ("rejectors") showed histologic evidence of rejection of mild (n = 17) or moderate (n = 10) severity and 50 ("nonrejectors") did not show rejection processes. Cyclic variation was decreased significantly in rejectors compared with nonrejectors in both the septum (15% +/- 10% versus 25% +/- 11%; p < 0.0001) and the posterior wall (19% +/- 10% versus 25% +/- 12%; p < 0.01). When a cutoff of 20% or greater of cyclic variation in the septal wall was taken as a positivity criterion, it yielded a 70% sensitivity and 70% specificity for identifying rejection. Sensitivity of conventional two-dimensional and Doppler echocardiographic signs was 51% and increased to 89%, increased by the videodensitometric criteria (p < 0.001). Specificity was 92% and decreased to 62% with videodensitometric criteria (p < 0.001). Overall diagnostic accuracy was 75% for conventional two-dimensional echocardiographic Doppler criteria alone and remained unchanged by the addition of videodensitometric criteria. In conclusion, blunting of cyclic gray-level variation induced by rejection is detectable with videodensitometric analysis. The clinical impact of this sign appears to be limited, because the resulting increase in sensitivity is counter-balanced by a reduced specificity compared with the currently available conventional ultrasound techniques.

Acute Disease↗