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Biomedical subjects

A Lever

Publications and source records attributed to A Lever.

17 recordsLinked to original sources

Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society.

Several important new issues have arisen in the management of patients with hypertension. A working party of the British Hypertension Society has therefore reviewed available intervention studies on anti-hypertensive treatment and made recommendations on blood pressure thresholds for intervention, on non-pharmacological and pharmacological treatments, and on treatment goals. This report also provides guidelines on blood pressure measurement, essential investigations, referrals for specialist advice, follow up, and stopping treatment.

Aged

The promoter of the Arabidopsis thaliana plastocyanin gene contains a far upstream enhancer-like element involved in chloroplast-dependent expression.

Plastocyanin is part of the photosynthetic electron transport chain in the chloroplast and is encoded in the nucleus. Expression of the Arabidopsis thaliana plastocyanin gene is organ specific: high mRNA levels are observed in young green parts of the plant. Furthermore, expression is dependent on the presence of light and functional chloroplasts. When grown in the presence of norflurazon under white light conditions, resulting in the photo-oxidative destruction of the chloroplast, plastocyanin mRNA levels are strongly reduced. A -1579 to -9 promoter fragment confers light-regulated and chloroplast-dependent expression to the beta-glucuronidase reporter gene in transgenic tobacco plants. This suggests that regulation takes place at the level of transcription. A plastocyanin promoter deletion series ranging from -1579 to -121 which was also tested in tobacco, revealed the presence of a strong positive regulating element (PRE) in the -1579 to -705 region. Deletion of this part of the promoter resulted in a approximately 100-fold reduction of GUS expression as measured in mature leaves. Surprisingly, this enhancer-like element was capable of stimulating transcription from a position downstream of its reporter. Moreover, it could also activate a truncated CaMV 35S promoter. Deletion of this element coincides with the loss of chloroplast-dependency of reporter gene expression, as judged by norflurazon treatment of transgenic seedlings. So, the activity of the PRE itself might depend on the presence of functional chloroplasts.

Arabidopsis

Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins.

The role of the cytoplasmic domain of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins in virus replication was investigated. Deletion of residues 840 to 856 at the carboxyl terminus of gp41 reduced the efficiency of virus entry during an early step in the virus life cycle between CD4 binding and formation of the DNA provirus without affecting envelope glycoprotein synthesis, processing, or syncytium-forming ability. Deletion of residues amino terminal to residue 846 was associated with decreased stability of envelope glycoproteins made in COS-1 cells, but this phenotype was cell type dependent. The cytoplasmic domain of gp41 was not required for the incorporation of the HIV-1 envelope glycoproteins into virions. These results suggest that the carboxyl terminus of the gp41 cytoplasmic domain plays a role in HIV-1 entry other than receptor binding or membrane fusion. The cytoplasmic domain of gp41 also affects the stability of the envelope glycoprotein in some cell types.

Acquired Immunodeficiency Syndrome

Protein targeting towards the thylakoid lumen of chloroplasts: proper localization of fusion proteins is only observed in vivo.

Routeing of fusion proteins to the thylakoid lumen of the chloroplast was compared in vitro and in vivo. The Escherichia coli protein beta-lactamase was used as a passenger to study this intraorganellar sorting process. The first step, translocation of beta-lactamase into the chloroplast stroma, occurs properly both in vitro and in vivo and is dependent on the presence of a transit peptide in the protein construct. The second step, targeting towards the thylakoid lumen, is more complicated as was also observed previously when other passenger proteins were used. In vitro, the presence of a thylakoid transfer domain is not enough for routeing and proper processing. Only when the complete thylakoid lumen precursor plastocyanin was fused to beta-lactamase was the fusion protein processed adequately, but routeing was still incomplete. However, in vivo, the information present in the thylakoid transfer domain was the only requirement for proper transport towards the thylakoid lumen. These data show that in vivo, the only requirement for targeting of passenger proteins towards the thylakoid lumen is the presence of a transit peptide and a thylakoid transfer domain. Furthermore, we demonstrate that the in vitro import system does not necessarily reflect the in vivo situation with respect to intraorganellar sorting.

Amino Acid Sequence

Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector.

Human immunodeficiency virus type 1 (HIV-1) proviruses containing deletions between nucleotides 301 and 319 express viral proteins but exhibit marked attenuation in the packaging of viral RNA into virions (A. Lever, H. Gottlinger, W. Haseltine, and J. Sodroski, J. Virol. 63:4085-4087, 1989; A. Aldovini and R. A. Young, J. Virol. 64:1920-1926, 1990). Here we report that such packaging-defective proviruses can provide trans-acting viral elements required for the transfer of a HIV-1 vector to Jurkat human lymphocytes. The transferred vector was unable to encode HIV-1 genes, indicating that the long terminal repeats and the immediate flanking viral sequences are sufficient for packaging, reverse transcription, and integration. The generation of replication-competent viruses in this system was reduced to undetectable levels by providing the trans-acting viral functions on two separate expression plasmids. This defective retroviral vector provides a means of efficiently introducing desired genetic elements, in the absence of HIV-1 genes, into HIV-1 target cells.

Animals

Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions.

Sequences required for efficient packaging of human immunodeficiency virus type 1 (HIV-1) genome RNA into virus particles were identified. Deletion of 19 base pairs between the 5' long terminal repeat and the gag gene initiation codon of HIV-1 resulted in a virus markedly attenuated for replication in human T lymphocytes. The mutant virus was characterized by nearly wild-type ability to encode viral proteins and to produce virion particles. The mutant virions exhibited a significant reduction in the content of HIV-1-specific RNA. These results identify an important component of the HIV-1 packaging signal.

Base Sequence

Regeneration of humoral immunity to herpes simplex virus following T-cell-depleted allogeneic bone marrow transplantation.

We investigated the adoptive transfer of immunity to herpes simplex virus (HSV) in 61 recipients of T-cell-depleted marrow allografts. Up to 3 months after bone marrow transplantation (BMT), high titres of HSV antibody (Ab) are passively acquired from blood products. This antibody has a half-life of 40.3 days, so that determination of recipient immunity to HSV cannot be made during the early post-transplant period. By 4 months after the allograft, seronegative recipients of seronegative donors had near-background levels of HSV Ab. Seropositive recipients, whether they were excreting virus or not, had high titres of HSV Ab regardless of donor status. Surprisingly, the seronegative recipients of HSV seropositive donors remained seronegative, a result at variance with observations made in the recipients allografts from which T-cells had not been removed. Thus, T-cell depletion modifies the adoptive transfer of humoral immunity to HSV, and an immune donor alone no longer ensures continued antibody production in the recipient.

Antibodies, Viral

Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection.

The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis and can be blocked by monoclonal anti-HBc and anti-HBe. Passive immunisation of chimpanzees with monoclonal anti-HBc and anti-HBe offers no protection against HBV infection but in both cases leads to an unusually prolonged hepatitis probably by modulation of HBc and HBe antigen display on the hepatocytes. High-titre anti-HBc in the circulation of HBe antigen-positive patients probably modulates the former protein making HBe the important target antigen for cytotoxic T cells mediating liver damage in chronic carriers. These data also support the hypothesis that passive transfer of IgG anti-HBc across the placenta may be one major factor promoting development of persistent infection in neonates infected from carrier mothers.

Animals

The immune response to hepatitis B virus.

Cell-mediated immune response to nucleocapsid determinants, including HBcAg and HBeAg, are important in the clearance of HBV-infected hepatocytes. This process is modulated by interferon and humoral responses to these antigens. Antibodies to the envelope proteins contribute to protective immunity, but the relative importance of pre-S and S determinants in evoking a response and the relative contributions of these antibodies in virus neutralization remains unclear. It is known, however, that antibodies binding to the RFHBs1 epitope on the HBs sequence 124-137 are capable of protecting against further infection and are present in convalescent subjects and in recipients of the plasma-derived and recombinant hepatitis B vaccines. Detailed analysis of the specificity of the anti-HBs response in vaccinees shows it to be qualitatively similar to that seen during recovery from natural infection.

Animals

Non-adherent, low-density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology.

Dendritic cells (DC) from human peripheral blood, known to adhere transiently and to become non-adherent by 16 hr, can be separated in the low-density interface on hypertonic Metrizamide gradients. Many more low-density cells (5.8% of the mononuclear cells separated on Ficoll) were obtained from the population that was non-adherent after only 90 min. Over 95% of these low-density cells had veiled morphology. A proportion were monocytes by phenotypic and phagocytic properties. One-third of the cells (on average) were DC on the basis of lack of monocyte phenotype and of potency as stimulators in the mixed lymphocyte reaction. Including both the 16 hr and 90 min non-adherent cells, over 2% of the mononuclear cells isolated from human peripheral blood may be DC.

5'-Nucleotidase

Increased serum concentration of T4-binding globulin in patients with hypogammaglobulinaemia.

Patients with hypogammaglobulinaemia have been regularly found to have abnormal conventional thyroid function test results. The abnormality is due to an increased plasma concentration of T4-binding globulin (TBG). As the prevalence of autoimmune thyroid disease is probably increased in hypogammaglobulinaemia this further abnormality in the plasma proteins may lead to diagnostic confusion. Administration of gammaglobulin by infusion causes a rapid but transient fall in plasma concentrations of TBG and T4 which is probably due to a temporary redistribution of the plasma proteins.

Agammaglobulinemia

XYY male.

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Adult

HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection.

In a chimpanzee model of acute type B hepatitis, at the time of onset of hepatitis B virus replication and before the development of immunity to hepatitis B virus, interferon is present in the plasma. This is followed by an increase in the display of HLA class I, but not class II proteins, on the hepatocyte membrane. In chronic hepatitis B virus infection, there is a low density of HLA class I protein display on the infected hepatocyte. Administration of alpha-interferon enhances HLA display and in many cases is followed by a transaminase elevation, seroconversion of HBe antigen to antibody and disappearance of hepatitis B virus DNA from serum, changes implying clearance of infected hepatocytes. Successful response to interferon therapy may be predicted by a rapidly rising serum beta 2-microglobulin, a component of the HLA class I molecule, during the first 2 weeks of therapy, before the rise in transaminases.

Acute Disease