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Biomedical subjects

H J Alter

Publications and source records attributed to H J Alter.

At least 19 recordsLinked to original sources
PubMed1992

Failure to detect vertical transmission of hepatitis C virus.

OBJECTIVE: To search for transmission of hepatitis C virus (HCV) from infected mothers to their infants. DESIGN: Prospective clinical, serologic, and molecular biologic follow-up (at least 3 months) of the infants of mothers with anti-HCV antibody. SETTING: A county hospital providing primary and referral care in high-risk obstetrics (perinatology). PATIENTS: Twenty-three mothers with anti-HCV antibody and their 24 infants. METHODS: An enzyme-linked immunosorbent assay (EIA) and a four-antigen recombinant immunoblot assay (RIBA) were used to test for anti-HCV antibody; serum HCV RNA was measured in two independent laboratories by reverse transcription and polymerase chain reaction (PCR) using nested primers in the 5'-noncoding region. Infant samples were tested for HCV RNA by PCR at delivery and after 3 to 6 months of follow-up. Each sample was tested at least four times in two independent laboratories. RESULTS: Twenty-nine of 648 mothers (4.5%; 95% Cl, 3.0% to 6.4%) had anti-HCV antibody; these women had 30 babies. Twenty-three mothers and their 24 babies were followed at least 3 months (mean follow-up, 52 weeks). Of the 23 mothers, 21 (91%; Cl, 72% to 99%) had a reactive RIBA; one woman had an indeterminate RIBA and was positive for HCV RNA by PCR. In 16 of 23 mothers (70%; Cl, 47% to 87%), PCR yielded a positive result in both laboratories. The mean maternal alanine aminotransferase (ALT) level was 1.6 times the normal value. All the babies had anti-HCV antibody in cord-blood samples, but antibody disappeared or diminished in strength in interval samples, and no infant had evidence of active production of anti-HCV antibody. Only 1 of 24 (4%; Cl, 0.1% to 21%) cord-blood samples was HCV RNA positive, and none of 24 (0%; Cl, 0% to 14%) follow-up samples was positive for HCV RNA by PCR in either laboratory. Four mothers and one baby had antibody to HIV. CONCLUSIONS: Infant anti-HCV antibody is most likely acquired passively in utero, and vertical transmission of HCV is uncommon.

Female↗
PubMed1992

High frequency of antibodies to Mycoplasma penetrans in HIV-infected patients.

Mycoplasma penetrans, a novel mycoplasma isolated from HIV-1-infected patients with AIDS, has pathogenic properties associated with in-vivo virulence. Enzyme-linked immunosorbent assay and western blotting detected a more than 100 times higher frequency of antibodies to the mycoplasma in serum from HIV-1-infected patients with AIDS (40%) than from HIV-negative controls (0.3%). Serum from 20% of HIV-1-infected, symptom-free individuals also had M penetrans specific antibodies. The antibodies' major immunoreactivity was directed against P35 and P38, the two main lipid-associated membrane protein antigens of the organism. Patients attending sexually transmitted disease clinics had a low frequency of antibody (0.9%). None of 178 HIV-negative patients with different non-AIDS diseases, many associated with immune dysfunction and/or low white cell counts, tested positive for the antibodies. M penetrans, apparently not a commensal and not a simple opportunist, is uniquely associated with HIV-1 infection and AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1992

Lack of protective immunity against reinfection with hepatitis C virus.

Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.

Acute Disease↗
PubMed1992

Interaction of immune sera with synthetic peptides corresponding to the structural protein region of hepatitis C virus.

Comparison of the deduced amino acid sequence from the structural region of the Hutchinson strain of hepatitis C virus (HCV-H) with four other HCV isolates clearly divides the five isolates into two groups based on sequence homology. The first group includes HCV-H, HCV-1, and HC-J1, while the second includes HCV-J1 and HC-J4. Among the five isolates the first 190 residues (putative nucleocapsid) are highly conserved whereas residues 196-513 exhibit significant diversity and include a hypervariable region encompassing residues 386-404. A series of overlapping decapeptides were synthesized by solid-phase pin technology according to sequence from HCV-H (amino acids 1-513), HC-J4 (amino acids 181-513), and regions from the three other isolates which exhibited sequence variation. A modified ELISA was used to measure immunoreactivity of sera from clinical posttransfusion cases and experimentally infected chimpanzees. Comparison of pre- and postinfection samples revealed 16 clusters of immunoreactive peptides within the structural region, none of which was found in the hypervariable region. Only one cluster (amino acids 73-89) was recognized by all human and chimpanzee sera. Clear variation in the immune response was observed between individuals, although no obvious difference in reactivity between acute and chronic cases was observed. Within individual profiles, the reactivity to each peptide cluster and the total number of reactive clusters increased over time.

Amino Acid Sequence↗
PubMed1992

Aplastic anemia and viral hepatitis. Non-A, Non-B, Non-C?

OBJECTIVE: To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection. DESIGN: Case series. SETTING: Tertiary referral centers in the United States, Japan, Italy, and Germany. PATIENTS: Twenty-eight patients with onset of aplastic anemia within 90 days after seeking medical attention for jaundice, or having serum transaminase levels 150% or more of normal (hepatitis-associated aplasia patients) and three patients who developed aplastic anemia following liver transplantation for non-A, non-B hepatitis. OUTCOME MEASURES: Presence of hepatitis C in serum, bone marrow, and liver samples, detected by the polymerase chain reaction; antibody testing; and percentage of activated peripheral cytotoxic T lymphocytes determined by immunophenotyping. RESULTS: Hepatitis ribonucleic acid was present in the serum samples of 10 (36%) patients with hepatitis-associated aplasia. However, hepatitis C virus viremia was associated with transfusions received after the onset of aplasia: seven (58%) of 12 patients with hepatitis-associated aplasia who had received 21 or more units of blood products at the time of serum sampling were viremic, compared with only three (19%) of 16 patients with hepatitis-associated aplasia who had received 20 or less units of blood products (P less than .05). Hepatitis C virus was not found in blood and bone marrow samples of three National Institutes of Health case patients tested at the time of diagnosis. None of three livers from non-A, non-B hepatitis patients who developed aplastic anemia after liver transplantation contained hepatitis C virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three- to 20-fold early in the course of hepatitis-associated aplasia. CONCLUSIONS: Our results implicate a novel, non-A, non-B, and non-C agent in both hepatitis-associated aplasia and fulminant hepatitis.

Adolescent↗
PubMed1992

IgM antibody response in acute hepatitis C viral infection.

IgM antibody against hepatitis C virus (IgM anti-HCV) was measured in serial samples from 15 transfusion recipients in whom posttransfusion chronic non-A, non-B hepatitis (NANBH) developed and three plasmapheresis donors during acute HCV infection using recombinant proteins derived from three immunodominant regions: core, NS-3, and NS-4 (c100). IgM anti-HCV core was detected in 13 of 15 posttransfusion patients. Nine of these patients had transient, acute-phase IgM anti-HCV core detected coincidentally or earlier than active IgG anti-HCV core response. The average duration of IgM anti-HCV core reactivity was 8.1 +/- 3.7 weeks. One patient lacking an IgM anti-HCV core response had detectable IgM anti-HCV NS-3 during the acute phase. Passive transfer of IgM anti-HCV was not observed in these posttransfusion cases, in contrast to the high frequency observed for IgG anti-HCV. Late IgM anti-HCV was detectable against core, c100, and NS-3 in three, two, and one posttransfusion patients, respectively. These data indicate that IgM anti-HCV core is a useful acute-phase marker in HCV infection.

Antigens, Viral↗
PubMed1992

Serological markers of posttransfusion hepatitis C viral infection.

Serological markers for hepatitis C virus (HCV) infection were measured in serial samples from 14 posttransfusion chronic non-A, non-B hepatitis patients by a semiquantitative dot blot immunoassay. The assay detected antibodies to HCV by use of recombinant proteins that represent putative HCV capsid (core), nonstructural protein 3 (NS3) (33c), and NS4 (c100) epitopes. Seroconversion to anti-HCV antibodies (anti-HCV) was detected in all patients. The average time to active antibody production detected by any of the recombinant proteins was 13.8 (range, 3.6 to 22.0) weeks posttransfusion or 4.6 (range, -4.5 to 13.4) weeks after the first biochemical marker of illness. Anti-HCV were detected earliest by the core antigen in most cases; however, the patterns of anti-HCV responses varied significantly among individuals. Overall, the addition of the core and NS3 antigens to the assay enabled the detection of the antibody response 4 to 5 weeks earlier than did the addition of the c100 antigen, the sole antigen used in current screening tests in the United States. Passively transferred antibodies were detected by at least one antigen in early posttransfusion samples from 12 patients and decayed below detectable levels for all antigens in only 2 patients. Antibodies to all three gene products were evident in the last sample from all five patients monitored for greater than 3 years from transfusion indicating the persistence of antibodies in patients with chronic illness. Our data show that the period following the onset of hepatitis during which anti-HCV are not detected by current screening assays can be greatly shortened by the detection of anti-HCV responses by a combination of core, NS3, and c100 antigens.

Antigens, Viral↗
PubMed1979

Non-A, non-B hepatitis: ultrastructural evidence for two agents in experimentally infected chimpanzees.

Two different ultrastructural alterations were observed in liver cells of chimpanzees inoculated with plasma derived from two different patients with non-A, non-B hepatitis. During the acute phase of illness in one group of four chimpanzees, peculiar tubular structures, composed of two unit membranes with electron-opaque material in between, were observed in the cytoplasm of hepatocytes. In contrast, these structures were never detected in the liver cells of the second group of five chimpanzees that received the second inoculum, However, nuclear changes, usually associated with aggregates of 20- to 27-nanometer particles, were found in hepatocytes of the latter animals. Although these particles resembled viruses, they were not as uniform as small virus particles often appear. In five other chimpanzees inoculated with non-A, non-B hepatitis material not known to be related to the first two inocula, cytoplasmic structures were found in four, and nuclear structures were found in the remaining one. Thus, all 14 chimpanzees inoculated with transmissible non-A, non-B hepatitis agents could be classified as having either nuclear or cytoplasmic changes. These observations add support to epidemiologic data suggesting that there may be more than one agent of non-A, non-B hepatitis.

Animals↗
PubMed1979

Circulating immune complexes in non-A, non-B hepatitis. Possible masking of viral antigen.

Serial serum samples from 22 patients with transfusion-associated non-A, non-B hepatitis and 2 chimpanzees with the experimentally induced disease were tested for circulating immune complexes by Raji-cell radioimmunoassay. 13 patients (59%) and 1 chimpanzee had circulating immune complexes immediately before, coincident with, or during the return to normal of raised aminotransferase activity. 7 of the 10 patients with chronic non-A, non-B hepatitis had detectable complexes at levels which waxed and waned in parallel with changes in serum aminotransferase activity. Immune complexes may contain and mask viral antigens, and their presence may explain the failure of conventional immunological techniques to detect virus antigens.

Acute Disease↗
PubMed1979

The chronic sequelae of non-A, non-B hepatitis.

Twenty-six of 388 patients (6.7%) followed prospectively after open-heart surgery developed non-A, non-B hepatitis. Of these 26, 12 had an elevated (often fluctuating) serum alanine aminotransferase (SGPT) for greater than 1 year. Liver biopsy, done in eight of 12, showed chronic active hepatitis in six and chronic persistent hepatitis in two; one patient with chronic active hepatitis had early cirrhosis. Anicteric patients with peak SGPT greater then 300 IU/L were at greatest risk of developing chronic hepatitis. Chronic non-A, non-B hepatitis was symptomatically mild and unaccompanied by physical signs or laboratory evidence of autoimmune disease or severe chronic liver disease. In all 12 patients there was spontaneous improvement in serum transaminase over a period of 1 to 3 years, and four patients had sustained normalization of SGPT. Thus chronic active hepatitis is a common sequela of acute non-A, non-B hepatitis but may have a better prognosis than chronic active hepatitis of other causes.

Acute Disease↗
PubMed1978

Transmission of hepatitis B virus infection by transfusion of frozen-deglycerolized red blood cells.

Chimpanzees were used to determine the ability of prior freezing of red blood cells to prevent the transmission of Type B post-transfusion hepatitis. Four units of human whole blood were each inoculated with 10(6) infectious doses of hepatitis B virus. Although all units became HBsAg negative after freezing and deglycerolization, hepatitis B virus infection developed in all four chimpanzees when these units were transfused. Two of these chimpanzees had only serologic evidence of infection, including the development of HBsAg and antibody to both the hepatitis B surface and core antigens; in these animals, the incubation periods were prolonged (24 to 25 weeks). In contrast, the other two animals also had elevated serum glutamic pyruvic transaminase (peaks of 190 and 461 IU per liter) and had a more rapid onset. There was no hepatitis B virus infection in two nontransfused controls. Our results do not support the use of frozen red blood cells for the prevention of post-transfusion hepatitis.

Alanine Transaminase↗
PubMed1978

Transmissible agent in non-A, non-B hepatitis.

Plasma or serum from 4 patients with acute or chronic non-A, non-B post-transfusion hepatitis (P.T.H.) and from a blood-donor implicated in two cases of P.T.H. was inoculated into 5 chimpanzees. Biochemical and histological evidence of hepatitis developed in these 5 chimpanzees but not in a control animal. The mean incubation period in the chimpanzees was 13.4 weeks, compared with 7.7 weeks in the 4 patients with P.T.H. The peak alanine aminotransferase (A.L.T.) levels in the 5 chimpanzees were 265, 212, 219, 70, and 62 I.U./l. Histological changes ranged from mild to conspicuous hepatitis and generally correlated with the degree of A.L.T. elevation. There was no evidence of clinical disease and all animals went on to biochemical and histological recovery. There was no serological evidence of type A or type B hepatitis. Hepatitis was transmitted by serum derived from patients with chronic as well as acute hepatitis, strongly suggesting a chronic carrier state for the agent responsible for non-A, non-B hepatitis. Non-A, non-B hepatitis thus seems to be due to a transmissible agent which can persist and remain infectious for long periods.

Acute Disease↗
PubMed1978

A study of street heroin lots for the presence of the hepatitis B surface antigen.

Hepatitis B surface antigen (HBsAg) of subtype ay predominates among narcotic addicts infected with hepatitis B virus (HBV) in Europe, Australia and the United States. However, the ad subtype predominates among the non-addict carriers of HBsAg. We investigated the possibility that heroin lots were contaminated with HBV at a source of opium production, the Middle East, a geographical region where HBsAg/ay predominates in the general population. One hundred and nine lots of street heroin were assayed for HBsAg by radioimmunoassay. None of the lots tested was reproduceably HBsAg positive. These results suggest that the heroin itself is not responsible for the high incidence of HBV infection or for the predominance of HBsAg/ay in the addict population. The predominance of HBsAg/ay among addicts in Europe and Australia as well as the United States might be due to extensive needle sharing among a mobile population of drug abusers, although such worldwide dissemination of one subtype by these means is unlikely.

Hepatitis B Surface Antigens↗
PubMed1978

Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.

Adolescent↗
PubMed1977

Non-A, non-B post-transfusion hepatitis.

To clarify the role of hepatitis-A virus (H.A.V.) in the aetiology of post-transfusion hepatitis unrelated to hepatitis-B virus, we have tested and titred pre-transfusion and convalescent serum samples from 32 patients for antibody to hepatitis-A antigen (anti-HA) by quantitative immune adherence haemagglutination. 12 patients had no detectable anti-HA in either pre-transfusion or late convalescent serum; the other 20 had anti-HA in pretransfusion serum and no significant chance in titre during convalescence. This study excludes H.A.V. as the agent responsible for these cases of post-transfusion hepatitis and supports the existence of "non-A, non-B" hepatitis virus(es).

Antibodies, Viral↗
PubMed1977

Subtypes of HBsAg in eastern and south-eastern Europe.

A total of 481 serum samples was collected from asymptomatic carriers of HBSAg as well as some patients with acute and chronic hepatitis, type B. The sera were obtained mainly from blood banks in the following countries: Poland, Hungary, Romania, Bulgaria, Yugoslavia, and the European part of the Soviet Union. Asymptomatic carriers of HBsAg from Poland and Hungary showed a preponderance of adw subtype over ayw subtype (Poland -80.7% adw, Hungary -72.2% adw). Carriers from the remaining countries showed the reverse situation: Bulgaria -71.5% ayw, Yugoslavia -79.0% ayw, Romania -82.8% ayw, Soviet Union -87.5% ayw. No individuals were found among these indigenous populations to have the adr or ayr subtypes but two carriers appeared to have the unusual subtype adyw.

Bulgaria↗