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Biomedical subjects

E Galun

Publications and source records attributed to E Galun.

At least 55 records · Page 3Linked to original sources
PubMed1995

Human/mouse radiation chimera are capable of mounting a human primary humoral response.

Lubin et al recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells (PBMC) into lethally irradiated normal strains of mice, radioprotected with bone marrow (BM) from donors with severe combined immune deficiency (SCID). In the present study, we demonstrate in such human/mouse chimera a marked humoral response to recall antigen, such as tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg), as well as a significant primary response to keyhole limpet hemocyanin (KLH). Maximal anti-KLH response in human/Balb chimera was attained 2 to 4 weeks after the immunization and declined thereafter. One week after transplantation, the predominant anti-KLH subtype was IgM, while after 2 weeks, the dominance had shifted to IgG. Similar primary antibody response was also demonstrated against the human immunodeficiency virus (HIV) Nef protein. Comparison between human/Balb and human/SCID chimera showed a major difference in their ability to mount a primary response against KLH. In Balb/c recipients, more than half of the mice exhibited marked IgM titers against KLH, while there was hardly any anti-KLH IgM response in the SCID recipients. From the earliest time point onwards, when anti-KLH antibodies were found in the latter chimera, they were predominantly of the IgG type. We have previously shown that in human/Balb chimera, unlike in SCID recipients, dissemination of transplanted PBMC into the spleen and other internal organs occurs within 24 hours. Therefore, it is likely that the early seeding in the appropriate microenvironment of the lymphoid tissues, is crucial for the maintenance of virgin human B cells.

Animals↗
PubMed1995

p53 expression in patients with cirrhosis with and without hepatocellular carcinoma.

BACKGROUND: Mutated p53 acts as a dominant oncogene, whereas the wild type (wt) p53 gene product suppresses cell growth. Abnormalities in the p53 gene are reported in more than 50% of malignant tumors. Recently, an allelic loss of chromosome 17p, where the p53 gene is located, was found to be more frequent in hepatocellular carcinoma (HCC) cell lines and human tumors. In addition, in half of the cases of HCC from endemic areas for hepatitis B virus and aflatoxin, a hot spot point mutation at codon 249 was detected, as previously reported. Missense mutations in p53, mdm-2 complex formation, and other unknown mechanisms may lead to stabilization of the gene product, thus rendering it detectable by immunohistochemistry. METHODS: To assess the relationship between p53 status at a premalignant stage and in HCC, the authors studied the immunohistologic expression of p53 in HCC and in the adjacent nontumorous resected liver tissue, using monoclonal antibody to wt and mutated p53. RESULTS: Twelve of the 14 patients with liver tumors had HCC. Of the 12 patients with HCC and underlying cirrhosis, 8 (67%) had increased p53 expression in HCC cells. Eight of the 12 patients with p53-positive HCC cells had p53 overexpression in the nontumorous hepatocytes within regenerative nodules adjacent to HCC tissue. Three of 21 cirrhotic livers without a detectable tumor had increased p53 expression in the regenerative nodules. None of the 12 patients with chronic active hepatitis without cirrhosis or the 13 with a normal liver histology had increased p53 expression. CONCLUSION: p53 overexpression in some cirrhotic livers and in nontumorous livers of patients with HCC may indicate a normal p53 gene response to cellular stress or, alternatively, to an abnormally or mutated p53 gene, and could occur before the development of HCC.

Adolescent↗
PubMed1995

Hepatitis C virus viremia in SCID-->BNX mouse chimera.

Chimpanzees are currently the only nonhuman animal model for reproducible propagation of hepatitis C virus (HCV). A chimeric mouse model was used for the induction of hepatitis C viremia, using BNX (beige/nude/X-linked immunodeficient) mice preconditioned by total body irradiation and reconstituted with SCID mouse bone marrow cells. HCV-infected liver fragments from patients with HCV RNA-positive sera were transplanted under the kidney capsule of the chimeric mice. HCV-specific RNA sequences were detected by reverse transcriptase nested polymerase chain reaction (RT-PCR) in serum of approximately 50% of grafted animals. In addition, normal liver specimens were incubated with HCV serum and transplanted into chimeric mice, leading to viremia in approximately 25% of animals. Sequential histologic evaluation of the liver implants, from day 2 to week 14 after transplantation, revealed loss of lobular architecture within the implants. However, viremia persisted for 10-50 days after transplantation. These results offer a new HCV model.

Animals↗
PubMed1994

The tomato gene for the chloroplastic Cu,Zn superoxide dismutase: regulation of expression imposed in transgenic tobacco plants by a short promoter.

The chloroplastic Cu,Zn superoxide dismutase (SOD) has an important role in the defense against damage by oxygen radicals in the chloroplasts. Here, for the first time, we report on the isolation of a genomic DNA clone from tomato that contains all the coding sequence for the chloroplastic Cu,Zn SOD as well as a 442 bp DNA fragment upstream of the translational initiation site. The latter upstream sequence has a putative TATA box and a 285 bp promoter region, 5' of the apparent transcriptional initiation and a 157 bp leader region. The coding sequence is composed of 8 exons that are interspaced by 7 introns; we termed this gene SODCp;Le:1. The 442 bp fragment was cloned into a pBI101 vector, upstream of the uidA (GUS) gene, via transcriptional fusion. Agrobacterium-mediated transformation resulted in transgenic tobacco plants. The progeny (after self-pollination) of 14 transformed plants, which expressed GUS above a threshold of 1 nmol/min per mg protein, were found to fall into two distinct groups. In the seedlings of 10 lines (group A) GUS expression was enhanced by exposure to light. In 4 lines of this group maintenance for 3 days in the dark eliminated GUS activity. The seedlings of group B expressed GUS regardless of the light/dark regime. In plants of group A, GUS expression was also developmentally regulated: high GUS activity in young leaves, low activity in mature leaves and no activity in the roots. The results suggest that this short chloroplastic Cu,Zn SOD promoter contains motifs for developmental (spatial) regulation as well as motifs responsive to light (or to oxygen radicals resulting from light-driven photosynthesis).

Amino Acid Sequence↗
PubMed1994

Prior hepatitis A virus infection enhances acute hepatitis E virus infection.

The epidemiology and clinical manifestations of hepatitis E virus (HEV) and hepatitis A virus (HAV) are similar. However, two distinct diseases develop after exposure to each one of the viruses, which are apparently unrelated clinically. It is interesting to note that all reported epidemics and single cases of acute HEV infection indicate previous exposure to HAV. This fact leads us to hypothesize that acute HEV infection is dependent on past infection by hepatitis A virus, and that the sequential infections could not solely be explained on independent outbreaks. This hypothesis, where past HAV infection serves to support acute HEV infection, may have current practical implications, and could improve our understanding of the virology and pathophysiology of the disease.

Adolescent↗
PubMed1994

Hepatitis B virus infection associated with hematopoietic tumors.

Hepatitis B virus (HBV) infection and replication have been linked to the development of hepatocellular carcinoma. Bone marrow-derived cells, as well as mesenchymal and epithelial cells, were recently shown to support HBV replication. We hypothesize that the mechanism that links HBV infection and liver tumors might also promote tumor development in tissues permissive for HBV replication. Between 1980 and 1993 we retrospectively identified 22 patients who were hepatitis B surface antigen (HBsAg) carriers and had extra-hepatic malignancies. These patients had 25 tumors, of which 22 were bone marrow derived. HBsAg was detected by immunohistochemistry in bone marrow cells of leukemia patient and of 3 of 10 lymphoma patients. In addition, in 4 of 10 patients with lymphoma, including 2 patients in which HBsAg stained bone marrow cells, HBsAg was also detected in the endothelial cells of blood vessels of the tumor tissue. These results suggest that the identification of an HBV gene product in endothelial cells might point to a role of HBV infection in the development of certain hematopoietic tumors, possibly through activation of cytokines or growth factors, which may eventually lead to bone marrow cell proliferation.

Base Sequence↗
PubMed1993

HCV RNA in patients with chronic hepatitis C treated with interferon-alpha.

In order to assess the efficacy of interferon-alpha on hepatitis C viral RNA in patients with chronic hepatitis C, we analyzed the levels of HCV RNA in sera and liver tissues of 16 patients pre- and posttreatment using a semiquantitative polymerase chain reaction method. Fifteen of 16 patients were positive for anti-HCV antibodies by four-antigen recombinant immunoblot assay (4-RIBA). Only two patients demonstrated normalization of ALT in response to interferon; three patients showed a partial response. Only one patient from the partial responder group displayed a significant reduction of HCV RNA level posttreatment. In the nonresponder group, several patients, although their ALTs remained elevated, demonstrated significant decreases in HCV RNA levels in either serum or liver in response to interferon. Our data suggest that interferon treatment of chronic hepatitis C may not be effective in eradicating HCV infection and a reduction in ALT is infrequently associated with a decrease in HCV RNA level in either serum or liver. Cessation of treatment is frequently associated with the recrudescence of HCV replication and disease.

Adult↗
PubMed1993

The relationship between short-term antibiotic treatments and fatigue in healthy individuals.

Antibiotic treatment tends sometimes to result in sensations of fatigue and decreased physical performance. The effects of antibiotics were therefore studied in 50 healthy, male trainees, aged 18-25 years, assigned in a random, double-blind fashion to one of the following treatments: tetracycline, ampicillin, trimethoprim/sulphamethoxazole, placebo I and placebo II. Duration of treatment was five times the half-life of each agent and the placebo was matched accordingly. Muscle enzyme activity (serum glutamine oxaloacetate transaminase, lactate dehydrogenase, creatine phosphokinase), maximal aerobic capacity (VO2max), muscle strength (MS), and rating of subjective sensation of fatigue were assessed prior to and upon conclusion of treatment. Compared to pretreatment values, plasma enzymes activity was elevated in all five groups (P < 0.005). No differences in VO2max or in MS were found among the subjects treated with either one of the antibiotics or those given a placebo. A significant difference in VO2max was found between the groups treated for 1 day (antibiotic and placebo) and the groups treated for 3 days (antibiotic and placebo) (P < 0.0001). The rating of subjective sensation was not affected by any of the agents. We concluded that in healthy individuals, a short-term antibiotic treatment had no deleterious effect on aerobic capacity or on muscle strength and was not associated with subjective side effects. The time interval between the two maximal tests could, however, have affected the aerobic capacity. Physiological disturbances associated with a sensation of fatigue following a longer period of antibiotics cannot be excluded.

Adolescent↗
PubMed1993

Retinoblastoma and p53 tumor suppressor genes in human hepatoma cell lines.

We analyzed the status of retinoblastoma and p53 genes in 10 human hepatoma cell lines. Polyclonal anti-peptide antibodies generated against peptides homologous to COOH-terminal and leucine-zipper domains of the retinoblastoma protein allowed us to identify two cell lines (Hep 3B and FOCUS) with abnormal expression. The same cell lines have both lacked p53 expression. In contrast to the retinoblastoma gene, the expression of the p53 gene was abnormal in six additional cell lines. Indeed, only the Hep G2 hepatoblastoma cell line (and its derivative Hep G2/2215) appeared to have normal p53 and retinoblastoma gene expression. Our studies indicate that p53 abnormalities are common but retinoblastoma gene aberrations are rare in human hepatoma cell lines.

Amino Acid Sequence↗
PubMed1992

Improvement of plant regeneration and GUS expression in scutellar wheat calli by optimization of culture conditions and DNA-microprojectile delivery procedures.

Genetic transformation of cereals by direct DNA delivery via microprojectile bombardment has become an established procedure in recent years. But the derivation of functional transgenic plants, especially in wheat, is still problematic, mainly due to low efficiency of DNA delivery and the reduced regeneration capability of microprojectile-bombarded tissue. We focussed on these two aspects and found that the regeneration of scutellar calli of wheat can be rendered highly efficient and considerably accelerated by a liquid culture phase in screen rafts. We also found that the expression of a reporter gene following DNA delivery by microprojectile can be improved by maintaining the scutellar calli in 0.25 M mannitol before and after bombardment, by bombardment in the presence of silver thiosulfate and Ca(NO3)2 (rather than CaCl2) and by the elimination of spermidine from the DNA/microprojectile mixture. A protocol that includes all these features leads to several-fold higher transient expression of the reporter gene than have previously published procedures.

Calcium↗
PubMed1992

Relapsing hepatitis A. Review of 14 cases and literature survey.

We have reviewed our experience with 14 cases of relapsing hepatitis A (RH-A), as well as 68 cases reported in the literature. Relapse occurs in 3 to 20% of patients with acute hepatitis A, and rarely takes the form of a polyphasic disease (multiple relapses). After a stage of typical hepatitis A, remission phase ensues, with partial or complete resolution of clinical and biochemical manifestations. Relapse usually occurs after a short period (usually less than 3 weeks). Relapse is usually clinically milder than the first phase, with variable liver function abnormalities and a tendency toward more marked cholestatic features. Not uncommonly, immune manifestations occur during this phase, including purpura, nephritis, and arthralgia, with common laboratory findings of rheumatoid factor as well as false-positive reaction to HCV-EIA tests. The clinical course in relapsing hepatitis A is almost always benign, and uneventful recovery is the rule with few exceptions. Steroid treatment, first reported in the present series, resulted in marked clinical improvement. Preliminary results suggest that R-HA is associated with a continuing viremia as well as shedding of virus in stools during the relapse phase. The pathogenesis of R-HA probably involves an interaction between persistent viral infection and immune mechanisms responding to the continuing antigenic stimulation.

Adult↗
PubMed1992

Human non-hepatocytes support hepadnaviral replication and virion production.

The competence of non-hepatocytes to support hepatitis B virus (HBV) gene expression and replication was studied by transient transfection of various human cell lines with a head-to-tail dimer of HBV DNA. Independent of their neuroectodermal, mesenchymal or epithelial origin, all non-hepatocyte cell lines tested synthesized and secreted hepatitis B surface antigen (HBsAg) and hepatitis B core/e antigen (HBc/eAg). Further analyses of two of these cell lines (LS 180 and COLO 320) identified the two major HBV transcripts of 3.6 and 2.2/2.4 kb length, respectively. LS 180 cells were permissive for HBV and duck hepatitis B virus (DHBV) DNA replication and secretion of infectious virions. COLO 320 cells also supported HBV DNA replication, but did not appear to export complete viral particles. These findings provide direct evidence that both HBV and DHBV can replicate in non-hepatic tumour cell lines, one of which is shown also to produce infectious virions.

Blotting, Northern↗
PubMed1992

Hepatitis B virus X protein is not central to the viral life cycle in vitro.

The hepatitis B x (HBx) gene is the smallest open reading frame of the hepatitis B virus (HBV) genome. It is conserved among all mammalian hepadnaviruses and is expressed during viral infection. While the HBx protein (pX) has been shown to trans-activate the transcription of a wide range of viral and cellular genes and to induce liver cancer in transgenic mice, the significance of pX for the life cycle of HBV itself has not been elucidated. To assess the function of pX in viral replication and virion export, we designed an X-minus mutant by introduction of a stop codon at the beginning of the HBx gene without affecting the viral polymerase gene product. Transient transfection analyses using different cell lines revealed that this X-minus mutant directs the synthesis of wild-type levels of viral proteins, replicative intermediates, and virion export. These data suggest that the expression of the highly conserved HBx gene is not central for the life cycle of HBV in vitro but may be involved in the pathogenicity of hepadnavirus infection, including liver cancer development.

Base Sequence↗
PubMed1991

Persistence of hepatitis B viral DNA after serological recovery from hepatitis B virus infection.

Chronic hepatitis B virus infection is a major medical problem worldwide. Apart from HBsAg carriers, hepatitis B virus has also been identified in some HBsAg-individuals with or without antibodies to viral antigens. The molecular mechanisms underlying hepatitis B virus persistence in HBsAg-individuals are unresolved, however. To identify a possible genetic basis for viral persistence, we cloned the viral genome from the liver of a patient serologically immune to hepatitis B virus infection. DNA sequence analysis of the complete viral genome identified numerous mutations in all viral genes. Analysis of the biological effects of these mutations revealed three major findings: a low level of HBsAg synthesis, absence of HBeAg production and a defect terminating viral replication. These data suggest that mutations accumulating during the natural course of hepatitis B virus infection may be a mechanism underlying viral persistence in HBsAg-individuals, presumably through escape from immune surveillance.

Aged↗