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Biomedical subjects

R Tur-Kaspa

Publications and source records attributed to R Tur-Kaspa.

At least 19 recordsLinked to original sources
PubMed1992

Estrogen suppresses hepatitis B virus expression in male athymic mice transplanted with HBV transfected Hep G-2 cells.

Hormones are known to regulate both viral and cellular genes. It has been shown previously that estrogen has an effect on liver gene transcription and mRNA stability. Sex hormones might have a role in the chronic persistence of hepatitis B virus (HBV) infection. In fact, there is a male preponderance in the incidence of chronic HBV infection, and HBsAg expression was reported to be much higher in male transgenic mice than in the females. We investigated the effect of estrogen on HBV gene expression and regulation in athymic mice bearing 2.2.15 cells, a human hepatoblastoma cell line derived from Hep G-2 transfected with HBV sequences. Both male and female mice were treated with estradiol after tumors could be observed. Episomal DNA was extracted from the tumors and hybridized with 32P-labelled HBV DNA. Southern blot and slot blot analyses demonstrated that male mice had higher expression of HBV DNA. Estrogen treatment suppressed HBV DNA expression in males, but had only a minor effect on females. HBeAg production in male mice was also inhibited by estrogen treatment. HBV RNA extracted from 2.2.15 cells showed 2-3-fold reduction following beta-estradiol treatment. Moreover, inhibition of HBV transcription by estrogen was demonstrated by an RNA pulse-labelling experiment. These data indicate that estrogen inhibits HBV expression in the in vivo model presented in this study. These results might contribute to a better understanding of the effect of sex hormones on the pathogenesis of HBV-induced liver disease.

Animals↗
PubMed1992

Hepatitis B virus precore mutants are identical in carriers from various ethnic origins and are associated with a range of liver disease severity.

Hepatitis B virus carriers in Israel are mostly HBeAg negative, of whom 5% to 10% have circulating hepatitis B virus. Recently, a hepatitis B virus variant with a stop codon in the precore region was identified, and it was suggested that specific mutations are associated with fulminant or severe chronic active hepatitis. We have analyzed serum samples from HBeAg-positive and HBeAg-negative patients by polymerase chain reaction, using primers spanning the precore/core region. Nucleotide sequence analysis (by direct sequencing) from amplified hepatitis B virus DNA demonstrated that viral genomes from all HBeAg-negative patients contain G to A mutation (nucleotide 1896), leading to the formation of a stop codon. An additional G to A mutation was identified three nucleotides downstream (nucleotide 1899). These patients are of various ethnic origins, with no unique clinical characteristics and with normal liver histology, chronic hepatitis or cirrhosis. No mutation at the precore/core region was observed in the HBeAg-positive patients. In conclusion, the precore mutations identified in hepatitis B virus carriers in Israel are identical regardless of the carrier's ethnic origin and are associated with mild-to-severe liver disease.

Adult↗
PubMed1992

Resistance of hepatitis delta virus replication to interferon-alpha treatment in transfected human cells.

Interferon-alpha (IFN-alpha) is known to inhibit both DNA and RNA viruses, including hepatitis B virus (HBV). In humans the antiviral effect, if any, of IFN-alpha on hepatitis delta virus (HDV) is complicated by the fact that HDV is spread only to patients already infected with HBV. An in vitro model system was used to assay for an antiviral effect of IFN-alpha on HDV genome replication. Hep G2 cells were transfected with a plasmid containing a trimer of HDV and treated with IFN (20 or 100 units/mL) starting 1-7 days after transfection. RNA extracted from treated and nontreated cells was assayed by both slot blot and Northern analyses. The IFN-alpha treatment as expected increased the 2'-5' oligo A synthetase RNA activity, but it did not affect HDV genome replication. Thus, in the absence of HBV, it appears that HDV is resistant to IFN-alpha.

2',5'-Oligoadenylate Synthetase↗
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

[Kaposi's sarcoma following liver transplantation].

A 54-year-old man developed Kaposi's sarcoma 2 months following orthotopic liver transplantation for hepatitis B-associated liver cirrhosis. At that time he was on combined immunosuppressive therapy (azathioprine, prednisone and cyclosporine A). The disease is very prevalent among immunosuppressed patients following renal transplantation, but is considered to be relatively rare following liver transplantation. The patient ran a relatively benign course without organ involvement and with only the skin disease. This is the first case of Kaposi's sarcoma following liver transplantation reported in Israel.

Humans↗
PubMed1991

Prevalence of HBsAg carriers in native and immigrant pregnant female populations in Israel and passive/active vaccination against HBV of newborns at risk.

Israel has no official prevention policy at present against perinatal and horizontal transmission of hepatitis B virus (HBV) infection in newborns and children at risk. The present study was designed to assess the prevalence of HBV carrier state in a population of 11,123 pregnant women at term. Among this population (mean age 29.7 +/- 5.9), 98 women (0.88%) were found to be asymptomatic HBsAg+ carriers, and 97% of these carriers were anti-HBe+. Evidence for HBV replication, as determined by serum HBV-DNA, was established in 6.6% of the HBsAg+/anti-HBe+ population. The HBsAg carrier rate was strongly influenced by religion, continent, and country of birth of the carrier mothers. The highest relative carrier rate was found among women of Moslem origin (4.3%), as compared to Jewish women (0.67%). Most carrier women were born in Israel (56.1%) to mothers who had emigrated from regions with intermediate or high endemicity of HBV, such as North Africa or the Middle East. In these groups, the HBsAg carrier rate ranged between 1.2 and 3.0%. Ninety-three percent of newborns receiving passive/active vaccination against HBV developed protective levels of anti-HBs. Finally, evidence for horizontal transmission of HBV was found in 19.3% of 83 non-vaccinated children in families of HBsAg carriers. The present study therefore establishes HBsAg prevalence rates in specific risk groups of women at term and confirms the need for an official policy on immunization against HBV in Israel. Since over 50% of women at term belong to the defined risk groups, universal active vaccination of the entire newborn population each year is suggested as the most rational and needed policy in Israel.

Adolescent↗
PubMed1990

Corticosteroids stimulate hepatitis B virus DNA, mRNA and protein production in a stable expression system.

The effect of corticosteroids (Dexamethasone) on hepatitis B virus was investigated in human hepatoblastoma cells stable transfected with recombinant HBV DNA. Dexamethasone was found to cause elevation of HBsAg, HBeAg and viral DNA production. HBV poly(A)+ RNA was significantly increased in cells treated with Dexamethasone. Furthermore, pulse labelled nuclear HBV RNA was also stimulated by Dexamethasone. These findings, suggest that corticosteroids enhance expression of viral gene products by stimulating HBV transcription.

Adrenal Cortex Hormones↗
PubMed1990

Alpha interferon suppresses hepatitis B virus enhancer activity and reduces viral gene transcription.

Interferons inhibit replication of hepatitis B virus (HBV). The mechanism for this inhibition was investigated by analyzing the effect of interferons on transcription of a chloramphenicol acetyltransferase reporter gene under control of HBV regulatory sequences and by determining the steady-state level of viral mRNAs in permanently HBV-transfected HepG2 cells. Low doses (100 U/ml) of alpha interferon (IFN-alpha) but not IFN-gamma inhibited chloramphenicol acetyltransferase expression in cultured cells transfected with plasmids containing the HBV enhancer linked to either HBV or simian virus 40 promoters. IFN-alpha also lowered expression of HBV mRNA in HBV-transfected HepG2 cells actively replicating virus, suggesting that IFN-alpha inhibits HBV replication by reducing transcription of viral genes driven by the HBV enhancer.

Chloramphenicol O-Acetyltransferase↗
PubMed1990

Non A, non B hepatitis in the aged.

In order to study the clinical picture of non A, non B hepatitis in the elderly, a retrospective study was carried out in the two main hospitals in Jerusalem. Thirty-six patients with acute viral hepatitis, older than 65, have been hospitalized between the years 1982-1988. Seventy-two percent were diagnosed as non A, non B hepatitis. All patients were symptomatic and the main symptoms were abdominal pain, fever and jaundice. Thirty percent of the patients had marked cholestasis, while the disease was uneventful in 96% of the cases. Non A, non B hepatitis is the main type of viral hepatitis in the aged and should be suspected in patients with abdominal pain, fever and cholestasis.

Aged↗
PubMed1990

Familial Budd-Chiari syndrome due to membranous obstruction of the right hepatic vein treated with transluminal angioplasty.

We report on a 30-yr-old man with Budd-Chiari syndrome due to right hepatic vein membranous obstruction. The patient's older brother also suffered from Budd-Chiari syndrome, and died after emergent portocaval shunt operation. To the best of our knowledge, familial occurrence of this syndrome has not been described before. The patient reported herein was successfully treated with transluminal angioplasty, and 12 months after the procedure, there are no signs of portal hypertension. Transluminal angioplasty has been used rarely for dilatation of isolated hepatic vein obstruction. This procedure should be considered as the treatment of choice for Budd-Chiari syndrome due to hepatic vein membranous obstruction.

Adult↗
PubMed1989

Detection of hepatitis A virus RNA in serum from patients with acute hepatitis.

Hepatitis A virus (HAV) RNA was extracted from the sera of patients with acute hepatitis and then detected by molecular hybridization using cloned HAV complementary DNA (cDNA). HAV RNA was detected in 20 of 85 patients with acute HAV infection, mainly during the prodromal stage, or early during the icteric phase of the disease; it was detected as long as 21 days after its initial detection. Patients with HAV RNA in the serum had a significantly higher titer of anti-HAV IgM.

Acute Disease↗
PubMed1989

Oestrogen stimulates differential transcription of human papillomavirus type 16 in SiHa cervical carcinoma cells.

Human papillomavirus (HPV) type 16 is highly associated with cervical cancer, but it seems that cofactors such as hormones affect its potential oncogenicity. We have analysed the HPV-16 gene expression in response to sex hormones and glucocorticoids in SiHa cells, a human cervical carcinoma cell line. An eightfold induction of HPV-16 transcripts was obtained in oestrogen-treated SiHa cells. Of the five HPV-16 transcripts detected in these cells only the two major ones, the 4.6 kb and the 4.1 kb mRNA species, were affected by oestrogen. Since the five transcripts span the E6 and E7 open reading frames of the HPV-16 genome, these results suggest that the expression of the various transcripts is differentially controlled, as oestrogen regulates only two of them. We have identified in the HPV-16 genome seven different regions with a high degree of similarity to the oestrogen-responsive element consensus sequence (GGTCANNNTGACC). These sequences are located throughout the entire HPV-16 genome. Progesterone or dexamethasone had no detectable stimulatory effect on the various transcripts of HPV-16 in SiHa cells, up to 24 h after treatment of the cells. Since the E6 and E7 open reading frames have been associated with the oncogenic potential of HPV-16, the effect of oestrogen on the transcription of these viral genes may be of biological relevance in the malignant transformation of HPV-16-infected cervical cells.

Base Sequence↗
PubMed1988

The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer.

The hepatitis B virus (HBV) genome contains a specific DNA binding site for the glucocorticoid receptor. Using DNase I footprinting, this binding site was localized at HBV map positions 341-370 clockwise from the EcoRI site. The DNA sequence protected in the footprint contains two tandem copies of the GRE core hexanucleotide 5'-TGTTCCT-3'. Deletion analysis and reconstruction experiments in plasmid expression vectors demonstrated that this glucocorticoid receptor binding sequence serves as a signal for augmenting glucocorticoid-dependent activity of the HBV enhancer, which is located approximately 730 nucleotides downstream in the HBV genome. Even though it does not serve as an independent enhancer element, the HBV glucocorticoid receptor domain can therefore be categorized as a functional GRE.

Base Sequence↗
PubMed1987

The effects of dexamethasone on in vitro collagen gene expression.

Glucocorticoids have been shown to be useful in the treatment of certain types of chronic liver disease both by inhibiting fibrosis and by improving liver function. We have previously demonstrated in an in vivo model of hepatic fibrogenesis that dexamethasone inhibits the synthesis of types I and IV collagen. In the present study we have evaluated the level of regulation responsible for the dexamethasone-induced changes in collagen gene expression in a defined in vitro system. Primary cultures of adult rat hepatocytes treated with and without dexamethasone under classical cell culture conditions or using defined media were evaluated for synthesis and abundance of procollagen and beta-actin mRNAs. Cells treated with dexamethasone had decreased types I and IV procollagen mRNA steady state levels due in part to diminished transcription rates of the genes. On the other hand, beta-actin mRNA levels were unaffected by dexamethasone. Transient expression experiments were performed to more precisely define the mechanism whereby dexamethasone affects type I procollagen gene transcription. The recombinant plasmid, pAZ1009, containing the mouse alpha 2(I) procollagen gene promoter linked to the chloramphenicol acetyltransferase gene, was transfected into mouse fibroblast cell lines. Cells transfected with the pAZ1009 plasmid in the presence of dexamethasone had a significant decrease in chloramphenicol acetyltransferase activity when compared to cells not exposed to dexamethasone. These data suggest that dexamethasone inhibits collagen synthesis through a direct effect on the collagen gene promoter and appears also to have a post-transcriptional effect on procollagen mRNA content.

Actins↗