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Biomedical subjects

A J Zuckerman

Publications and source records attributed to A J Zuckerman.

At least 73 records · Page 4Linked to original sources

Enterically transmitted non-A, non-B hepatitis: recovery of virus-like particles from an epidemic in south Delhi and transmission studies in rhesus monkeys.

An epidemic of viral hepatitis, serologically characterized as due to non-A, non-B hepatitis, occurred in a village of South Delhi, India, in December, 1986, through January, 1987. Water contaminated with fecal matter was the apparent source of infection. Disease-associated virus-like particles were detected by immune electron microscopy in the feces of three patients within 5 days of illness. The virus-like particles were agglutinated by autologous acute-phase serum but not by convalescent serum. Rhesus monkeys inoculated with particle-containing fecal suspensions developed biochemical and morphologic features of acute, self-limited hepatitis. The findings in the present study and in earlier investigations of sporadic non-A, non-B hepatitis suggest that (i) the epidemic form and a proportion of sporadic cases of this infection in India may be related, both being enterically transmitted and associated with infection by a 27- to 32-nm virus-like particle, (ii) antibody responses to this virus occur early in disease and are transient and (iii) the rhesus monkey may prove to be a suitable model for studies of epidemic non-A, non-B hepatitis.

Adolescent↗

Viruslike particles in liver in sporadic non-A, non-B fulminant hepatitis.

In a patient who followed the typical clinical course of fulminant hepatitis attributable to "sporadic" non-A,non-B (NANB) hepatitis and who finally received treatment by orthotopic liver grafting, three, apparently separate, virus-like agents (26, 45, and 80 nm) and cytoplasmic, reticular tubular structures (CTS) were identified in collapsed and regenerating areas of liver using electron microscopy. The 80-nm particles present within vacuoles, together with the finding of intranuclear rods in association with the smaller particles (26 nm), are similar to those found in the nuclei of cells infected with several different arboviruses. The third type of particle, existing as 45-nm spheres and rods, is similar in morphology only to some form of polyoma virus, which, hitherto, has not been reported as affecting the liver. Unlike typical polyoma virus, replication of the virus "cores" (25-26 nm) was extranuclear and appeared to be occurring in vacuoles. Although analysis for serological markers against a representative panel for arboviruses, flaviviruses, phleboviruses, arenavirus, and nairovirus was negative, an insect vector was implicated in the clinical history.

Adult↗

Pre-S proteins in hepatitis B.

Two reactive sequences of the pre-S regions of hepatitis B surface antigen were synthesized chemically and used in micro-ELISAs for the assay of pre-S1 and pre-S2 antigens in serum from patients with acute and chronic hepatitis B. Pre-S1 antigen correlated well with the presence of HBV-DNA and was no longer detectable on cessation of viral replication, after natural recovery and after successful treatment with alpha-interferon. Pre-S2 proteins were also lost after treatment with alpha-interferon. The results show that the assay of pre-S1 and pre-S2 proteins in serum provides additional useful markers for assessing patients with acute and chronic hepatitis B infection and for monitoring the response to treatment with interferon.

Amino Acid Sequence↗

Toga-like virus as a cause of fulminant hepatitis attributed to sporadic non-A, non-B.

Virus-like particles (60-70 nm) with spiked surfaces budding into cell vacuoles and rod-shaped inclusions were detected in nuclei of hepatocytes from a British patient transplanted for sporadic non-A, non-B fulminant hepatitis (NANB-FHF), probably contracted in Kenya. Identical particles were seen in two successive grafts (days 2 and 10) at regrafting for recurrent FHF. Ultrastructural features resembled those of the RNA-containing arbovirus, Rift Valley fever virus, but serological markers against a representative panel for arboviruses (Togaviruses) and transmission in mice proved negative. The particles shared features with the different arboviruses seen in the hepatectomy specimen of a second patient with NANB-FHF, and in both patients an insect vector was implicated in the clinical history. The particles were identical in size to those of a third patient with NANB-FHF, who had remained in the United Kingdom. These findings, together with the recent report of isolation of an RNA-containing virus resembling the Togaviridae, in parenteral NANB, suggest that several exotic virus-like agents resembling the arboviruses may be involved in the aetiology of NANB, including in the sporadic forms of FHF in the United Kingdom.

Adolescent↗

Hepatitis A antibody in blood donors in North East Thames region: implications to prevention policies.

A total of 1786 blood donors were screened for the presence of anti-hepatitis A antibody (anti HAV). 64.5% of the donors were found to be positive. The prevalence of the antibody was found to be age-related, 55% at 18 years and 75% at 65 years. No relationship was noted between the presence of antibody, foreign travel or a specific destination. Assay of antibody levels in selected seropositive individuals gave a mean level of 5.0 IU/ml. The prevalence of infection in this selected population is important in the context of passive immunization with normal human immunoglobulin and for defining a policy of immunization with hepatitis A vaccines, which are currently undergoing clinical trials.

Adult↗

Effect of gamma irradiation on the human immunodeficiency virus and human coagulation proteins.

The effect of gamma irradiation on HIV and plasma coagulation factors F VIII:C, F VIII:vWF and FIX was studied. Donor plasma was harvested from single donations, frozen and irradiated in the frozen state at target doses from 0 to 40 kGy (0-4 mRad). HIV was inoculated into human plasma and irradiated in a similar manner. A range of other viruses, not suspended in plasma, were also irradiated to establish viral inactivation. An inactivation rate of 0.164 TCID50 dose/ml/kGy was demonstrated for HIV compared to rates of 0.00173, 0.00526 and 0.00286 log10 units/ml/kGy for F VIII:C,F VIII:vWF and FIX respectively. The use of gamma irradiation to inactivate infectious agents present in human plasma may eliminate the need for any post-production viral inactivation methods and provide a means of assuring the safety of as yet untreated products such as cryoprecipitate and fresh frozen plasma.

Blood Coagulation Factors↗

Prevention of primary liver cancer by immunization.

Primary liver cancer is one of the ten most common cancers of man and approximately 80% of cases are associated etiologically with infection with hepatitis B virus (HBV), often early in life. Infection with HBV is now preventable by active immunization, so that large-scale immunization programs will prevent the initial infection and the development of persistent infection and the carrier state, the most important risk factor in hepatocarcinogenesis.

Animals↗

Significance of maternal and infant serum antibodies to hepatitis B core antigen in hepatitis B virus infection of infancy.

The significance of IgM and IgG class antibodies to hepatitis B virus (HBV) core component (anti-HBc) was investigated in a study of maternal-fetal HBV transmission. An IgM anti-HBc response was lacking in the majority (49/53) of HBV-infected infants. This antibody thus cannot be used as an indicator of transplacental infection. However, most infants who became HBsAg positive during the first 6 months of life acquire infection in the perinatal period rather than transplacentally. Passively transferred maternal IgG anti-HBc in the infant and additional IgM anti-HBc positively in the carrier mother have no modulating influence on HBV infection of infants born to HBV carrier women.

Age Factors↗

Incidence and significance of hepatitis B core antibody in a healthy blood donor population.

To determine the current incidence of hepatitis B core antibody (anti-HBc) in a healthy blood donor population, 1,893 donors were screened for anti-HBc. Forty-one (2.16%) were found to be initially positive and 35 (1.85%) repeatably positive. Sera from the repeatably positive donors were further screened for hepatitis B surface antibody (anti-HBs), and hepatitis B virus DNA (HBV DNA) by dot hybridisation. The repeatably positive donors were subsequently recalled for further investigation, and their peripheral blood lymphocytes were also screened for HBV DNA by dot hybridisation. Eighteen (51.4%) of the anti-HBc-positive donors were also anti-HBs-positive. HBV DNA was not detected in the serum or the lymphocytes of any of the anti-HBc-positive donors.

Blood Donors↗

The complete nucleotide sequence of the genome of a hepatitis B virus isolated from a naturally infected chimpanzee.

The complete nucleotide sequence of a strain of hepatitis B virus, originally isolated from a naturally infected chimpanzee, has been determined. Interesting features of the sequence include the presence of an in-phase stop codon in the 'pre-core' region of the core antigen open reading frame. The sequence shows approximately 10% nucleotide divergence from all of the other hepatitis B virus sequences previously published and the possibility that this divergence is the result of passage through chimpanzees is discussed.

Amino Acid Sequence↗

Anti-idiotypic humoral and cellular responses to antibody to hepatitis B surface antigen in hepatitis B viral infections.

In order to investigate regulatory significance of humoral and cellular responses to the idiotypic (Id) determinants on the antibody to hepatitis B surface antigen (anti-HBs), they were studied in acute hepatitis B and in chronic HBV infection. The results were compared with humoral and cellular responses of the same patients to hepatitis B surface antigen (HBsAg). In acute hepatitis B, the responses to HBsAg, were delayed until 3-4 weeks after the onset of clinical symptoms. However, the leucocyte migration inhibition (LMI) and the lymphocyte transformation (LTT) responses to affinity purified anti-HBs were found to be evolved very early in the course of acute hepatitis B, though anti-Id antibodies were absent. The majority of chronic HBV carriers showed a poor humoral and cellular response to HBsAg. Ten out of 38 chronic carriers showed anti-Id antibodies which recognized a major cross-reactive idiotype (CRI) on the anti-HBs molecule. Twenty-five out of 38 chronic carriers also showed LMI response to the Id determinants on the anti-HBs. LMI response induced by anti-HBs could be blocked by a specific Balb/c anti-Id antibody which also recognized the CRI. Thus, in both acute and chronic HBV infections, the anti-Id humoral and cellular responses correlated with poor humoral and cellular responses to HBsAg, indicating regulatory significance.

Acute Disease↗