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Biomedical subjects

F Hill

Publications and source records attributed to F Hill.

At least 73 records · Page 4Linked to original sources

Evolution of the primate lentiviruses: evidence from vpx and vpr.

The genomes of the four primate lentiviral groups are complex and contain several regulatory or accessory genes. Two of these genes, vpr and vpx, are found in various combinations within the four groups and encode proteins whose functions have yet to be elucidated. Comparison of the encoded protein sequences suggests that the vpx gene within the HIV-2 group arose by the duplication of an ancestral vpr gene within this group. Evolutionary distance analysis showed that both genes were well conserved when compared with viral regulatory genes, and indicated that the duplication occurred at approximately the same time as the HIV-2 group and the other primate lentivirus groups diverged from a common ancestor. Furthermore, although the SIVagm vpx proteins are homologous to the HIV-2 group vpx proteins, there are insufficient grounds from sequence analysis for classifying them as vpx proteins. Because of their similarity to the vpr proteins of other groups, we suggest reclassifying the SIVagm vpx gene as a vpr gene. This creates a simpler and more uniform picture of the genomic organization of the primate lentiviruses and allows the genomic organization of their common precursor to be defined; it probably contained five accessory genes: tat, rev, vif, nef and vpr.

Amino Acid Sequence↗

Nucleotide sequence of a Guinea-Bissau-derived human immunodeficiency virus type 2 proviral clone (HIV-2CAM2).

We report the complete nucleotide sequence of a human immunodeficiency virus type 2 (HIV-2) isolate from Guinea-Bissau (HIV-2CAM2). The genomic organization of HIV-2CAM2 is identical to that of other HIV-2 isolates but contains a stop codon in the pol gene. The deduced amino acid sequences of the viral proteins show variation of 20% in the gag, pol and vpx regions, and 25 to 45% in the tat, env and nef regions when compared to other isolates of HIV-2. This is greater than the variation observed between isolates of HIV-1.

Amino Acid Sequence↗

Polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with AIDS and AIDS-related complex.

We tried to assess the long-term safety and potential efficacy of passive immunization in AIDS-related-complex (ARC) and AIDS patients. We also wanted to establish whether hyperimmune plasma from healthy human immunodeficiency virus 1 (HIV-1)-infected individuals clears the cell-free virus from circulation. Using the polymerase chain reaction (PCR), we were able to provide conclusive evidence that hyperimmune plasma is effective and maintains long-term neutralization of viremia. Using the cell test, we found that in most patients the total antibody level was maintained; in one of the ARC patients, it actually increased 8-fold and has remained at that level for nearly 2 years. The CD4+ cell count decreased in the AIDS patients but was stable in the ARC patient. Clinically, there was an initial improvement in all patients, but five of six of the advanced/terminal AIDS patients had died by month 17. Our studies suggest that passive immunization may be safe in ARC and AIDS patients. It reduces HIV-1 viremia to levels undetectable even by PCR. To advanced/terminal patients, the benefit is of limited duration, while to ARC patients it may be long-term. Therefore, passive immunization should start early in the disease.

AIDS-Related Complex↗

Effects of passive immunization in patients with the acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome.

Infection with the human immunodeficiency virus type 1 (HIV-1) is usually followed by a vigorous immune response that temporarily protects against disease progression. After a variable asymptomatic period, acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and AIDS develop in most infected individuals. We have demonstrated that healthy HIV-1-infected individuals have neutralizing antibodies and a high titer of antiviral antibodies. In contrast, AIDS patients have undetectable levels of neutralizing antibodies, low titers of antiviral antibodies, and, frequently, HIV p24 antigenemia. These observations prompted us to attempt passive immunization in ARC and AIDS patients. Ten consistently viral-antigen-positive patients (mean, greater than 6 months) were treated, resulting in sustained clearance of p24 antigen. Patients either maintained or increased their antiviral antibody titers. The raised titers result from increased antibody synthesis by the recipients. Circulating CD4+ cell counts were unchanged after 2 months. By the third month none of these patients remained in hospital. As this treatment was of minimal toxicity, it merits wider evaluation in ARC and AIDS patients.

AIDS-Related Complex↗

Hospice--an update on the cost of patient care.

This follow-up survey to a study into the cost of providing Hospice in-patient care in 1984 examines in detail the cost profiles of up to 40 well established Hospices in the UK. The results are analysed in order to provide up to date financial and statistical information on the major areas of current Hospice activity.

Costs and Cost Analysis↗

Use of Karpas HIV cell test to detect antibodies to HIV-2.

Commercial enzyme-linked immunosorbent assays for HIV-1 infection often fail to detect antibodies to HIV-2. A simplified version of the HIV cell test detects antibodies to this new virus and enables typing of HIV infections. Since sera from 3 macaque monkeys infected with simian immunodeficiency virus gave weakly positive reactions, this test holds promise for discovering any further strains of HIV that may exist or evolve.

Animals↗

A novel tumour marker related to the c-myc oncogene product.

We have studied the utility of the c-myc oncogene product as tumour marker using a set of monoclonal antibodies raised against synthetic peptides constructed from sequence data of the human c-myc oncoprotein. One antibody, Myc1-9E10, raised against the C-terminal 32 amino acids, has been shown to detect specifically the 62 kDa c-myc gene product in tumour cells. Immunoblotting of sera and urine with this antibody consistently revealed a single 40 kDa band (p40). Quantitative analysis using dilution dot immunoblotting demonstrated a considerable increase in the titre of p40 in the sera of 51 patients with a wide range of advanced solid tumours when compared with 17 healthy controls and 50 patients with non-malignant diseases. Serial measurement of the p40 titre in 12 patients with resected colorectal carcinoma shows a gradual return to normal with a half-life of 7 days. Our data suggests that p40 may be a useful new marker for monitoring tumour activity.

Biomarkers, Tumor↗

Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator.

A cDNA coding for SAP-1 was isolated from a lambda gt11 human hepatoma expression library using polyclonal antibodies raised against human SAP-1. Three positive clones were isolated with inserts of approximately 0.3 Kb (S1.1), 2 Kb (S1.2) and 2.2 Kb (S-1.3). The latter 2 contained an internal EcoRI site. All three clones cross-hybridized with one another, indicating sequence homology. The nucleotide sequence of S-1.1 was determined. Colinearity was established between 19 amino acids obtained by sequencing the amino terminus of pure SAP-1 and 57 bp from the 5' end of S-1.1. The open reading frame of S-1.1 coded for 67 amino acids. One glycosylation site was found 21 residues from the amino terminus, and no stop codons were found. S-1.1 codes for a mature polypeptide chain with a calculated molecular weight of 8955 daltons, corresponding to approximately 99% of mature SAP-1.

Amino Acid Sequence↗

Primary structure of bovine brain acidic fibroblast growth factor (FGF).

The major anionic mitogenic polypeptide for endothelial cells, acidic fibroblast growth factor (FGF), has been purified to homogeneity from bovine brain and its complete primary structure established by gas-phase sequence analysis. The 140 amino acid (Mr 16,000) protein has been previously shown to be a potent growth factor for many diverse cell types of mesodermal origin, in vitro, and an angiogenic agent, in vivo. The amino acid sequence of bovine brain acidic FGF has a 53% absolute homology with that of bovine pituitary basic FGF suggesting that these endothelial cell mitogens are derived from a single ancestral gene.

Amino Acid Sequence↗

Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF.

The two major mitogenic polypeptides for endothelial cells have been purified to homogeneity. The complete primary structure of bovine pituitary basic fibroblast growth factor (FGF) and the amino-terminal amino acid sequence of bovine brain acidic FGF have been established by gas-phase sequence analyses. Homogeneous preparations of these polypeptides are potent mitogens (basic FGF, ED50 approximately equal to 60 pg/ml; acidic FGF ED50 approximately equal to 6000 pg/ml) for many diverse cell types including capillary endothelial cells, vascular smooth muscle cells, and adrenocortical and granulosa cells; in vivo, basic FGF is a powerful angiogenic agent in the chick chorioallantoic membrane assay. The available protein sequence data demonstrate the existence of significant structural homology between the two polypeptides.

Amino Acid Sequence↗