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Biomedical subjects

I Mora

Publications and source records attributed to I Mora.

32 records · Page 2Linked to original sources

Prolonged (6 months) treatment of chronic hepatitis B virus infection with recombinant leukocyte A interferon.

Twelve hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV-DNAp) and hepatitis B virus DNA (HBV-DNA) positive patients with chronic active hepatitis (CAH) were treated with doses of either 20 X 10(6) IU/m2 or 10 X 10(6) IU/m2 body surface of recombinant interferon (rIFN)-alpha-2A, I.M., twice a week, during a period of 6 months. No appreciable differences with respect to clinical history, liver function tests and markers of HBV replication between the two groups were apparent at the time of entry into the trial. At the third month of treatment HBV-DNAp became negative in 10 out of 12 patients (83%). After a 15-month follow-up, HBV-DNAp, HBV-DNA and HBeAg were negative in 7 out of 12 patients (38%) (responders). Furthermore, at 24 months, 2 non-responder patients became HBV-DNA and HBV-DNAp negative and one responder lost serum HBsAg. In addition, HBsAg concentration, GPT level and histological Knodell's index decreased significantly in the responder patients, while no changes were observed in non-responders. Five out of six patients who received a low rIFN dose responded to the treatment, and only 2 out of 6 with a higher dose. No unacceptable toxicity was noted in any of the 12 patients. All of them completed the course of treatment. The results suggest that long-term rIFN-alpha-2A therapy has an antiviral effect in CAH due to HBV infection and is well tolerated.

Adult↗

Liver membrane antibodies in chronic delta hepatitis.

The correlation between the presence of liver membrane antibodies (LMA) and delta superinfection in chronic hepatitis B was studied in 136 chronic hepatitis patients, 20 hepatitis B surface antigen asymptomatic carriers and 50 healthy controls, by testing for the presence of LMA, hepatitis B virus markers and anti-delta (anti-HD). Neither anti-HD nor LMA were detected in controls or in asymptomatic carriers. LMA positivity was statistically higher (p less than 0.001) in anti-HD-positive patients than in those with no anti-HD. Gamma globulin and glutamic pyruvic transaminase values were increased both in anti-HD- and LMA-positive patients with respect to those who were negative. In conclusion, a close association between the positivity to anti-HD and the presence of circulating LMA was found.

Adult↗

Inhibition of albumin binding to hepatitis B virions by monoclonal antibody to the preS2 domain of the viral envelope.

The binding of polyalbumin to hepatitis B virus (HBV)-associated envelope epitopes has been studied by means of a radioimmunoprecipitation technique. HBV particles were purified from the sera of chronic hepatitis B surface antigen (HBsAg) carriers and labelled through the endogenous HBV-DNA polymerase reaction. Human albumin, polymerized through glutaraldehyde cross-linking, was able to precipitate (100%) labelled HBV at concentrations of 31.2 and 62.5 micrograms/ml, in contrast to monomeric albumin (HSA). This event was further confirmed by immune electron microscopy. The addition of anti-HSA to the mixture HBV plus polyalbumin gave a 100% precipitation in a wide dilution range (15.6-500 micrograms/ml). The binding of polyalbumin (31.2 micrograms/ml) to virions was strongly inhibited (up to 98%) when preincubating with antibody to a glycosylation-dependent preS2 epitope on HBV. The same was accounted (up to 99%) for polyvalent IgG anti-HBs. However, antibodies to the group 'a' and subtype 'd' determinants, as well as anti-preS1 region antibodies, inhibited weakly polyalbumin binding to HBV. The binding site of the inhibitory antibody overlaps probably with neutralizing epitopes. Our findings support the hypothesis that albumin binding plays an important role in the viral life cycle.

Antibodies, Monoclonal↗

Hepatitis B surface antigen/IgM complexes: relation to receptors for polymerized human serum albumin, hepatitis B virus (HBV) DNA polymerase activity and HBV markers.

The presence and the level of hepatitis B surface antigen (HBsAg)/IgM complexes were determined in 54 chronic HBsAg carriers in relation to receptors for polymerized human serum albumin (pHSA-R) tested by specific radioimmunoassay, and to hepatitis B virus-DNA polymerase (HBV-DNAp). HBsAg/IgM complexes, correlated significantly with the HBsAg concentration but, at a similar HBsAg concentration, significant highest values of HBsAg/IgM complexes were found among HBeAg positive patients. In addition, a significant correlation was found between HBsAg/IgM complex levels, HBeAg titres and HBV-DNAp activity (r = 0.628, p less than 0.001 and r = 0.559, p less than 0.001, respectively). Moreover, a positive linear correlation was found when comparing HBsAg/IgM complexes and pHSA-R levels (r = 0.848, p less than 0.001). Patients who were positive for HBsAg/IgM complexes had a significantly higher glutamate-pyruvate transaminase (GPT) level than those who did not show any complexes. In conclusion, HBsAg/IgM complexes seemed to be indirectly related to HBV replication.

Antigen-Antibody Complex↗

Receptors for polymerized human serum albumin and other hepatitis B virus markers during acute hepatitis B--predictive value of the outcome of the disease.

Polymerized human serum albumin virus receptors (pHSA-R) HBsAg, HBeAg, antiHBc-IgM, hepatitis B virus (HBV) DNA polymerase activity and HBV-DNA were studied in 47 acute hepatitis B patients, divided into three groups: 26 HBeAg(+) initially, with favorable outcome; 4 HBeAg (+), with chronic outcome; and 17 antiHBe (+), with favorable outcome. In the basal sample only 2 and 8 patients in Group I were HBV-DNAp and HBV-DNA positive, respectively, and became negative during the follow-up. In contrast all patients in Group II remained positive to both HBV-markers. After a one-month follow-up 100% of the patients in Group II were positive for pHSA-R and HBeAg, in contrast to 25% among those with a favorable outcome in Group I (p less than 0.005). Meanwhile, only 6 out of 17 patients in Group III remained positive for pHSA-R. A significant decrease in pHSA-R and HBsAg concentrations was observed in patients from Group I (p less than 0.005 and p less than 0.05, respectively) 15 days after the onset of the disease, while concentrations of both parameters did not vary in Group II. A significant decrease in HBsAg and pHSA-R concentrations was found in patients from Group III after 15 days (p less than 0.05) and one month follow-up (p less than 0.05), respectively. As a result, pHSA-R and HBeAg are the best prognostic indicators in acute hepatitis B. A decrease in HBsAg and pHSA-R concentrations two weeks after the onset may have predictive value.

Acute Disease↗

Radioimmunoassay for detecting hepatitis B core antigen in serum from patients with chronic hepatitis B infection.

The core antigen component of hepatitis B virus (HBV), HBcAg, may be used as a marker of viral replication. We describe a radioimmunoassay for HBcAg in serum, and compare results with those by other similar methods. Samples are centrifuged over a sucrose gradient containing 2-mercaptoethanol, and the resulting pellets are resuspended in a nonionic detergent solution. After a bead coated with anti-HBcAg is incubated with this suspension, 125I-labeled anti-HBcAg is added, and is also bound by the antigen. The specificity of the method was verified by blocking with purified IgG antibodies to HBcAg. When we tested by this method for HBcAg in sera from 60 patients with chronic HBV infection, all those with circulating HBV-DNA polymerase tested positive for HBcAg. All sera from HBV-negative controls showed no detectable HBcAg. The correlation between the presence of HBcAg and HBV-DNA polymerase was significant (r = 0.715, p less than 0.001). Samples can be tested more quickly and easily with this method, and its sensitivity compares well with that of other similar methods.

Chronic Disease↗

Vaccination against hepatitis B in renal dialysis units: short or normal vaccination schedule?

Three I.M. injections of hepatitis B vaccine (Merck Sharp & Dohme) were administered, according to the recommended schedule (0, 1, 6 mos), to seronegative individuals of one renal dialysis unit (33 patients, 58 health care personnel) and, according to a shorter regimen (0, 1, 3 mos), in another unit of similar characteristics (30 patients, 53 health care personnel). Staff members and renal patients received, respectively, 20 y 40 mcg of vaccine per injection. In the early vaccination phase, the two regimens did not lead to a difference in seroconversion rates nor in anti-HBs titers. After a 9-month surveillance, lower seroconversion rates, although not significant, were observed with the accelerated regimen among staff members (84.2%) and renal patients (79.2%) as compared with 93% and 87.5%, respectively, following the normal schedule. At the same time, anti-HBs titers were significantly lower (p less than 0.001) in the staff (316 RIA U) and patients (93 U) vaccinated according to the short regimen than in their respective counterparts (4196 and 1047 U) assigned to the normal schedule. A fourth dose of vaccine given to subjects with low and no anti-HBs titers significantly increased seroconversion and anti-HBs levels, although with little success among the former non-responders.

Adult↗

Hemagglutination and immunofluorescence studies on polymerized human serum albumin binding activity in chronic hepatitis B virus infection.

The binding activity of polymerized human serum albumin was determined in 202 HBsAg carriers. The presence of polymerized human serum albumin receptor sites was tested by hemagglutination and differentiated from antihuman albumin antibodies by immunofluorescence, isolation of IgG and IgM fractions and testing of HBsAg anti-HBs immune complexes. A granular pattern with anti-HBs was specific for polymerized human serum albumin receptor sites as demonstrated with purified HBsAg. In addition, a linear pattern with fluoresceinated antihuman immunoglobulins might suggest the presence of antihuman albumin antibodies (which was generally due to an IgG antibody). However, a granular pattern with fluoresceinated antihuman immunoglobulins may indicate the presence of HBsAg anti-HBs immune complexes. A weak linear pattern was also observed simultaneously in these cases, probably due to IgM antihuman albumin antibodies or an antipolymerized human serum albumin receptor site antibody. Of 202 HBsAg-positive patients, 71 showed polymerized human serum albumin receptor sites activity. The highest percentage of polymerized human serum albumin receptor sites was found among patients showing HBeAg and hepatitis B virus DNA polymerase positivity (96%), followed by HBeAg positivity and hepatitis B virus DNA polymerase negativity (48%), and anti-HBe positivity and hepatitis B virus DNA polymerase negativity (17%). In addition, a significant correlation between polymerized human serum albumin titers and hepatitis B virus DNA polymerase was found (r = 0.573, p less than 0.01). However, at similar HBeAg titer, patients who were positive for hepatitis B virus DNA polymerase had a higher polymerized human serum albumin receptor sites titer than those who were negative for hepatitis B virus DNA polymerase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

IgG and IgM autoantiidiotype antibodies against antibody to HBsAg in chronic hepatitis B.

Antibody directed against HBsAg carries idiotypic determinants that may induce an autoantiidiotype antibody response. We describe a solid-phase radioimmunoassay which allows specific detection of either IgG or IgM antibody to antibody directed against HBsAg. Among 138 chronic hepatitis B virus carriers, IgG autoantiidiotype was detected in 98 (71%) and IgM autoantiidiotype in 10 (80%). The autoantiidiotype reaction was blocked with antibody directed against HBsAg after removal of immune complexes by polyethylene glycol precipitation. The prevalence and levels of both classes of autoantiidiotype antibodies were highest in patients with hepatitis B virus DNA or HBeAg in serum. During follow-up, patients who lost hepatitis B virus DNA and HBeAg from serum had lower titers of autoantiidiotype and were less likely to have autoantiidiotype than patients who persisted in having hepatitis B virus DNA and HBeAg in serum. Thus, the presence and titer of autoantiidiotype correlated with serologic evidence of active viral replication in chronic hepatitis B. These findings suggest that the antibody directed against HBsAg response may play a role in modulating viral replication in chronic hepatitis B.

Adult↗

Muscle stretch used as conditioning stimulus for assessing a reciprocal inhibition.

The disynaptic Ia-alpha inhibition between the tibialis anterior and the soleus muscles is now well known. This neuronal organization has been established thanks to the analysis of the Hoffmann reflex (H reflex) changes following an electrical stimulation of the antagonist muscle nerve. In some cases, anatomical constraints impede the use of this classical technique for assessing a reciprocal Ia inhibition between muscles. Furthermore, an electrical stimulus solicits the primary spindle afferents in conditions which are very different from their natural stimulus: the muscle stretch. Thus we have undertaken to analyse the changes of a soleus H reflex following a rapid stretch of the ankle dorsiflexors and therefore of their prime-mover: the tibialis anterior. The mechanical perturbations were imposed with a strong initial acceleration and a limited angular displacement thanks to an original device including electromagnet and spring. This technique, derivated from the quick release technique, was applied on relaxed muscles to avoid a co-contraction phenomenon. 45 to 50 ms after the initiation of the mechanical perturbation an early reflex response was observed on the stretched tibialis anterior. The area of this first reflex response was related to the initial acceleration of the passive dorsiflexion. Several arguments are presented in favour of the myotatic origin of this reflex component. The passive dorsiflexion used as a conditioning stimulus led to a strong and longlasting inhibition of the test soleus H reflex. The early inhibition of the soleus H reflex was observed only about 18 ms after the conditioning stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗