Biomedical subjects
Publications and source records attributed to E Tabor.
Burn injuries of the larynx are a previously unrecognized complication of cocaine abuse. The clinical presentations and magnetic resonance imaging findings of two patients are presented. Recognition of this entity is important to avoid errors in diagnosis and in management.
Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60 microM DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution titers of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl 38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSO4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60 microM of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation.
The expression of both the Epstein-Barr virus (EBV) ORF BHRF1 and the cellular protooncogene bcl-2 was studied in EBV-transformed lymphoblastoid B cells from patients with the human genetic disorder ataxia-telangiectasia (A-T). Using the Northern blot technique, it was found that the pattern of transcription of the BHRF1 gene in A-T lymphoblastoids resembled that in EBV-transformed normal lymphoblastoid lines and Burkitt lymphoma (BL) lymphocytes. However, the 1.5-kb mature BHRF1 mRNA species present in normal lymphoblastoid cells and in BL cells was not found in the A-T lymphoblastoid cell lines. Treatment of the A-T lymphoblastoid lines with phorbol ester caused changes in the pattern of the synthesis and quantity of BHRF1-related RNA transcripts. The bcl-2 protooncogene probe did not detect bcl-2-related mRNA in the A-T lymphoblastoid lines.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A field trial of a plasma-derived hepatitis B vaccine in five rural villages in Zambia was analyzed to determine if adults in a rural African setting respond to this vaccine as well as adults in Western countries and to determine the immunogenicity of fewer than the recommended three doses; 255 residents, including 171 who were susceptible to hepatitis B, were vaccinated. Among those who received three vaccine doses, protective levels of antibody to hepatitis B surface antigen (anti-HBs) developed in 67% of adults (ages 21 to 70 years), 87% of adolescents (ages 12 to 19 years), and 100% of children (ages 0 to 11 years). The 67% of vaccinated adults who developed anti-HBs at the protective level was lower than the 96% reported among adults receiving the same vaccine at the same dose and dosage schedule in studies in Western countries. No difference was seen in the response of those receiving two doses compared with those receiving three doses among adults and adolescents, suggesting that a two-dose regimen may be acceptable in these age groups in developing countries to reduce costs and improve compliance. Use of hepatitis B vaccine in a region where prevaccination hepatitis B serologic screening was not available did not appear to increase the number of severity of adverse reactions.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Although hepatitis B virus (HBV) has been closely associated with the development of hepatocellular carcinoma (HCC), no serologic markers of HBV can be found in up to 11% of HCC patients in developing countries and up to 68% of HCC patients in industrialized countries. Despite the absence of HBV serologic markers in these HCC patients, HBV DNA sequences have been found to be integrated into HCC DNA in 13-100% of these patients, indicating a possible role of HBV in the etiology of their HCC. Although six patients with chronic non-A, non-B hepatitis virus infection who were followed have been documented to develop HCC, it is not known whether the non-A, non-B hepatitis viruses cause or contribute to the development of HCC in some HCC patients without HBV serologic markers. Ethanol, cigarette smoking, oral contraceptives, and aflatoxin also have been suggested as possible etiologies and should be studied further. Suggested etiologies that are not supported by the published data include alpha-1-antitrypsin deficiency and schistosomiasis.
The expression of fibronectin, integrin and beta-actin genes in skin fibroblasts from patients with the genetic disorder ataxia-telangiectasia (A-T) was studied. These three genes were selected because their protein products contribute to the shape and function of the fibroblast. Expression of mRNA by these genes was compared with that in fibroblasts from normal individuals and from patients with the genetic disorder, hereditary hemorrhagic telangiectasia (HHT). A-T fibroblasts were found to produce less fibronectin mRNA than normal and HHT fibroblasts. A-T fibroblasts senesce around passage level 15 while normal and HHT fibroblasts can be propagated for many more passages in vitro. However, the expression of the integrin gene in A-T fibroblasts was similar to that in normal fibroblasts, while the beta-actin gene was expressed at a higher level. The increased beta-actin mRNA levels were similar in fibroblasts of patients with the two genetic disorders, A-T and HHT, but higher than in normal fibroblasts. HHT fibroblasts differed markedly from A-T fibroblasts in having a high level of fibronectin and integrin mRNA expression. The results indicate that regulation of the fibronectin gene in A-T fibroblasts differs from that of the integrin and beta-actin genes, and that the decline in fibronectin mRNA may be linked to the shortened in vitro life-span of these cells.
Explore the source record for details and available documents.
Skin fibroblasts from patients with hereditary hemorrhagic telangiectasia (HHT) were compared with fibroblasts from patients with the genetic disorder ataxia-telangiectasia (A-T), and with SV40-transformed A-T fibroblasts, regarding their sensitivity to the radiomimetic drug neocarzinostatin (NCS). Whereas A-T fibroblasts were found to be hypersensitive to NCS at low concentrations (as measured by the cellular survival test), as previously reported, the HHT fibroblasts were more resistant to NCS and behaved as normal fibroblasts. The SV40-transformed A-T cells also resembled normal fibroblasts in their response to NCS in the colony formation test. In the DNA synthesis test, HHT strains of fibroblasts did not fully resemble untransformed and SV40-transformed A-T cells that continued to synthesize DNA following NCS treatment, since NCS inhibited DNA synthesis in HHT fibroblasts by 5 to 15%; whereas the same treatment in normal fibroblasts reduced DNA synthesis by 40%.
The three epidemiological forms of human non-A, non-B hepatitis have been studied by experimentally infecting non-human primates. The chimpanzee (Pan troglodytes) has been widely studied as a model for the epidemiological forms referred to as "blood-transmitted" and "coagulation-factor-transmitted" non-A, non-B hepatitis. Transmission of the "enteric" epidemiological form of non-A, non-B hepatitis to chimpanzees has been reported by one laboratory but remains to be confirmed. Two marmoset (tamarin) species, Saguinus mystax and S. labiatus, have been experimentally infected with the "blood-transmitted" form; S. mystax has been infected with the "enteric" form. A preliminary report suggesting susceptibility of marmosets to the "coagulation-factor-transmitted" form needs to be confirmed. The cynomolgus monkey (Macaca fascicularis) has been infected with the "enteric" form. Although the relationship between non-A, non-B hepatitis and hepatocellular carcinoma (HCC) is unclear, HCC has been reported in one chimpanzee, nearly 7 years after experimental infection with a non-A, non-B hepatitis virus.
The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.
Explore the source record for details and available documents.
Guillain-Barré syndrome and other neurologic syndromes occur rarely as complications of viral hepatitis, although a causal association has not been established. Seven cases of serologically documented hepatitis A have been reported with Guillain-Barré syndrome; all recovered, with mild neurologic residua in four. Eight cases of serologically documented acute hepatitis B have been reported with Guillain-Barré syndrome; all recovered, with mild neurologic residua in two. In one case, immune complexes of hepatitis B surface antigen and its antibody were present in the cerebrospinal fluid. Other neurologic syndromes have also been reported in patients with serologically defined viral hepatitis, including mononeuritis, auditory neuritis, and seizures. Chronic hepatitis B and mononeuritis multiplex are found together in 31-54% of patients with periarteritis nodosa. The mechanisms for these associations are unknown, but may include direct cytotoxicity of the virus or immune-mediated damage. Vasculitis of the vasa nervorum plays an intermediate role in at least some cases.
The phenotype of pathogenicity by direct intracerebral inoculation of herpes simplex virus type 1 (HSV-1) was mapped in the viral genome. This phenotype could be rescued by cotransfection of unit length HSV-1 DNA of an avirulent strain with the BamHI fragment L (0.70-0.738 map units) cloned from a virulent strain. The virulence function was localized in the 2.0 Kb NruI-BamHI fragment in the right-hand side of BamHI-L, the same region that encodes a virus cell-fusion gene (3). Transduction of virulence was linked with the phenotype of a larger plaque size. It is concluded that a neurovirulence function resides in the BamHI-L fragment of the HSV-1 genome, closely linked to the viral gene for cell fusion.
The virulence of herpes simplex virus-1 (HSV-1) strains by the intraperitoneal (ip) route of injection in mice depends on the presence of an intact sequence in the HpaI DNA fragment P within coordinates 0.762 to 0.787. Deletion of the HpaI-P region (e.g., strain HFEM) abrogates the ability of the virus to infect mice by the ip route without affecting pathogenicity by the intracerebral (ic) route. A recombinant virus (M1C1) derived from DNA of the HSV-1 HFEM strain and the MLUIDNA fragment (coordinates 0.761 to 0.796) spanning the HpaI-P sequence of the pathogenic strain F regained pathogenicity for mice by the ip route.