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Biomedical subjects

C Addison

Publications and source records attributed to C Addison.

At least 19 recordsLinked to original sources
PubMed2001

The use of ambulatory blood pressure monitoring in managing hypertension according to different treatment guidelines.

OBJECTIVE: To investigate the use of ambulatory blood pressure monitoring (ABPM) in identifying and managing a group of patients referred to a tertiary centre for the assessment of their blood pressure and to illustrate the importance of introducing standardised ABPM treatment guidelines. PATIENTS AND METHODS: We examined 2000 sequential ABP recordings, 1557 were first time referrals from General Practitioners, Consultants and other hospitals. All patients were referred with suspected hypertension, resistant hypertension, white coat hypertension and for investigations of secondary hypertension. Fully trained nurse specialists fitted the monitors in the hypertension clinic and recordings were performed for 24 h. The data was then analysed and stratified according to treatment guidelines and categorised according to different definitions. RESULTS: The group of first time referrals (n = 1557) showed an even sex distribution of 789 men and 768 women, mean age 53 +/- 13.8 (12-88 years). Of this group 542 patients (35%) exhibited a white coat effect (WCE), 526 (34%) had a daytime ABP < or =139/89 mm Hg. Of these 81 (15%) had a high clinic blood pressure (ie, white coat hypertension (WCH)) according to our definition. Thirty-five of these patients were not on treatment but may have had it initiated on the basis of their clinic pressures. According to the British Hypertension Society (BHS) guidelines on clinic readings 772 (45%) of our patients would be classified as hypertensive or inadequately treated, 509 (33%) borderline and 326 (21%) as normal. Using daytime ABP levels according to O'Brien: 1031 (67%) would be defined as abnormal, 192 (12%) as borderline and 334 (21%) as normal. CONCLUSION: These results illustrates how patient management may differ markedly when treating in accordance either with the BHS guidelines for clinic readings or the suggested levels for ABP. More patients had abnormal blood pressure levels according to ABPM, even though it is superior in detecting WCE and WCH. Clear guidelines for ABPM treatment levels need to be established.

Adolescent↗
PubMed2000

Clinical features, anthropometric characteristics, and racial influences on the 'white-coat effect' in a single-centre cohort of 1553 consecutive subjects undergoing routine ambulatory blood pressure monitoring.

BACKGROUND: Patients with high office blood pressures but relatively normal readings during daytime ambulatory monitoring have been the subject of much investigation and debate. This clinical finding in part depends on an alerting reaction to the circumstances of the clinical measurement, often described as the 'white-coat effect' (WCE). Little is known of the characteristics of patients that are associated with the white coat effect in a large population of routinely referred patients. OBJECTIVE: To relate the size of the WCE (defined as the difference between office and ambulatory daytime readings) to clinical features that may influence this phenomenon. METHODS: We categorized 1553 consecutive subjects (51.3% men, aged 17-88 years), who had been referred to a single centre for the assessment of suspected hypertension prospectively into three groups: those aged <40, 40-59, and >/=60 years. RESULTS: WCE on systolic blood pressure (SBP) increased significantly with advancing age and was correlated positively to body mass index (BMI), age and treatment. We found significant correlations to sex (higher in women) and race. WCE on diastolic blood pressure (DBP) decreased slightly with advancing age and was correlated positively to BMI and significantly to race and sex. We found no correlation to age or treatment. Caucasians had a greater WCE than did non-Caucasians (P<0. 001 for SBP and DBP) and hypertensives had greater WCE than did normotensives (P<0.0001 for SBP and DBP). Multiple linear regression analysis showed that age and BMI are the most important factors influencing WCE on SBP and DBP. CONCLUSIONS: Factors such as race, age and BMI may exert important influences on the size of WCE possibly via effects on sympathetic nervous system activity.

Adult↗
PubMed1999

Genomic studies of the Lucké tumor herpesvirus (RaHV-1).

Ranid herpesvirus 1 (RaHV-1) is the etiological agent of the Lucké renal adenocarcinoma of the North American leopard frog Rana pipiens. Construction of cosmid libraries containing RaHV-1 DNA inserts allowed the derivation of a BamHI map for the viral genome. Summation of fragment sizes indicates that the genome is 217 kbp in size, a value in accordance with the most recent published estimate (220 kbp) obtained by field-inversion gel electrophoresis. The DNA sequence of the 39,757-bp insert in 1 cosmid (cos54) was determined and was predicted to contain 21 complete and 3 partial genes. In all, 12 genes have distant counterparts in a fish herpesvirus (ictalurid herpesvirus 1) and are present in 2 blocks, 1 of which is relatively inverted. This indicates that RaHV-1 belongs to the fish virus lineage of the herpesvirus family rather than to the lineage populated by mammalian and avian viruses. The remaining 12 genes in cos54 lack counterparts in any other herpesvirus. One of these encodes a putative DNA (cytosine-5) methyltransferase. This raises the possibility that biological processes induced in the host by RaHV-1 might involve methylation of cellular DNA by the viral enzyme.

Adenocarcinoma↗
PubMed1998

Efficient adenovirus-mediated gene expression in malignant human plasma cells: relative lymphoid cell resistance.

Although adenoviruses offer several potential advantages as gene transfer vectors, some hematopoietic cells, particularly lymphoid cells, are considered relatively resistant to adenovirus-mediated gene transfer. To examine the role of adenovirus-mediated gene transfer in the lymphoid malignancy multiple myeloma (MM), we used E1- and E3-deleted adenoviral vectors to infect myeloma and lymphoma cell lines and subsequently primary bone marrow plasma cells and lymphocytes from patients with MM. Adenoviral vectors expressing LacZ or luciferase (AdCA18) reporter genes were used initially. Subsequently, we studied adenoviral vectors expressing genes of potential value in therapeutic immunomodulation, i.e., CD80 (AdB7-1) and interleukin-2 (AdIL-2). A human plasma cell line (OCI-My5) infected with LacZ or AdB7-1 vectors expressed the corresponding gene product in 95% and 85% of exposed cells, respectively. Time course experiments indicated that maximum expression of adenoviral transgenes in plasma cells was reached 3 days after infection. IL-2 was detected in the supernatant of AdIL-2-infected plasma cells, was functional, and could be detected for at least 30 days after infection. In contrast, three lymphoma cell lines (OCI-Ly2, OCI-Ly13.2, and OCI-Ly17) were significantly less sensitive to adenovirus infection, with relatively low efficiencies of gene transfer even using high adenoviral titers: Surface CD80 expression (13-25% of infected cells) and positive LacZ staining (0-5% of infected cells). Indeed, expression of luciferase was 96-168 times higher in AdCA18-infected OCI-My5 cells than in the OCI-Ly2 lymphoma cell line. Similar patterns were observed in primary plasma cells and lymphocytes from 19 MM patient bone marrow samples. After infection with AdB7-1, increased levels of CD80 expression on CD38 bright bone marrow plasma cells were observed in 84% of patients, with a 33% average increase in the number of plasma cells expressing CD80. In contrast, although increased CD80 expression was also detected on AdB7-1-infected CD19+ B lymphocytes from 63% of the MM patients, an average of only 14% of the infected lymphocytes demonstrated increased expression of CD80. Circulating T lymphocytes could not be transduced with AdB7-1. The relative resistance of B and T lymphocytes to adenovirus-mediated gene transfer warrants further investigation. Adenoviral vectors can efficiently infect malignant plasma cells and may be useful vehicles for therapeutic gene transfer.

Adenoviridae↗
PubMed1997

Intramarrow cytokine gene transfer by adenoviral vectors in dogs.

Daily systemic administration of hematopoietic growth factors can be associated with dose-limiting systemic side effects. To overcome this, we have investigated hematopoietic cytokine gene transfer to the marrow cavity of dogs by direct intramarrow injection of adenoviral vectors. In marrow culture, replication-deficient (E1-deleted) adenoviral vectors were able to transduce marrow stromal cells, demonstrating 30-fold greater expression than from other marrow cell types. High-level (ng/ml) cytokine production from transduced stromal cells persisted for 14 days in culture. Because adenovectors could efficiently transduce marrow stromal cells in culture, we investigated if stromal cells could also be transduced in vivo following direct intramarrow vector injection. Adenovectors with genes for interleukin 6 (IL-6) and Lac Z (beta-galactosidase) were injected directly into the marrow cavity of dogs resulting in protein expression localized to within the treated marrow. To evaluate this approach further in dogs, we constructed a vector expressing biologically active canine granulocyte-macrophage colony stimulating factor (GM-CSF). 293 cells infected with ADGM-CSF demonstrated prevalent GM-CSF mRNA by Northern blot and 135 +/- 30 ng/ml of protein as measured by enzyme-linked immunosorbent assay (ELISA). In vitro bioactivity of protein expressed was confirmed by canine GM colony-forming assay (CFU-GM). In vivo high-level protein production was noted in supernatants of marrow aspirates 72 hr following direct intramarrow administration of ADGM-CSF (baseline mean +/- SEM, 27 +/- 22 ng/ml, 72-hr sample 921 +/- 461 ng/ml). A localized myeloid expansion of marrow and significant peripheral leukocytosis (neutrophilia) were noted in all ADGM-CSF-treated dogs. Peripheral blood changes lasted for up to 3 weeks in dogs following single intramarrow injection. Thus, adenoviral cytokine expression from the marrow of a single large bone (ilium) led to compartmentalized expression of growth factor and an increase of hematopoiesis sufficient to cause peripheral blood changes in a large animal model.

Adenoviridae↗
PubMed1997

The published DNA sequence of human cytomegalovirus strain AD169 lacks 929 base pairs affecting genes UL42 and UL43.

Compared with the published DNA sequence (M. S. Chee, et al. Curr. Top. Microbiol. Immunol. 154:125-170, 1990), most isolates of human cytomegalovirus strain AD169 contain an additional 929 bp after nucleotide 54612. This results in a changed reading frame for the 5'-terminal 50 codons of gene UL42 and expansion of gene UL43 (a US22 family member) from 187 (3'-truncated) to 423 (full-length) codons. The UL42 and UL43 gene products are nonessential for growth in culture.

Amino Acid Sequence↗
PubMed1997

Intradermal transgenic expression of granulocyte-macrophage colony-stimulating factor induces neutrophilia, epidermal hyperplasia, Langerhans' cell/macrophage accumulation, and dermal fibrosis.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine, is up-regulated in a number of chronic skin inflammatory diseases, particularly atopic dermatitis. However, its role in these conditions remains largely unclear. To explore its function, we have established a rat intradermal transgene model by using a replication-deficient adenoviral vector expressing GM-CSF. Intradermal GM-CSF gene transfer led to a prolonged compartmentalized expression of transgene protein in the dermis. This expression induced an unexpectedly wide spectrum of pathologies in both epidermis and dermis, including neutrophilia, epidermal hyperplasia (acanthosis), an increased number of epidermal Langerhans' cells, accumulation of MHC II-positive macrophages, as well as mild eosinophilia in the dermis at earlier stages and upper dermal fibrosis at later stages. These findings thus identify GM-CSF as a potent multifunctional cytokine at skin site that is capable of evolving numerous inflammatory processes ranging from the early acute neutrophilia to later chronic fibrotic responses, and also suggest the important role of this cytokine in the development and perpetuation of pathologic changes in chronic skin inflammatory conditions including chronic atopic dermatitis. In addition, our study presents a novel model of adult normal animals that is useful for identifying and studying key cytokines involved in inflammatory skin diseases.

Animals↗
PubMed1996

Multiple interactions control the intracellular localization of the herpes simplex virus type 1 capsid proteins.

Herpes simplex virus type 1 (HSV-1) capsid assembly takes place in the nucleus of infected cells. However, when each of the outer capsid shell proteins, VP5, VP23 and VP26, is expressed in the absence of any other HSV-1 proteins, it does not localize to the nucleus but is distributed throughout the cell. We have previously shown that the HSV-1 capsid scaffolding protein, preVP22a, can relocate VP5 into the nucleus but does not influence the distribution of VP23. We now demonstrate that the outer capsid shell protein, VP19C, is able to relocate both VP5 and VP23 separately into the nucleus. However, nuclear localization of VP26 is only observed when VP5 is present together with either VP19C or preVP22a. Thus, pair-wise interactions involving all of the abundant capsid proteins have now been identified. Electron microscope examination of insect cells coinfected with recombinant baculoviruses expressing VP19C and VP5 reveals the presence of 70 nm diameter 'capsid-like' structures, suggesting that these two proteins can form the basic capsid shell.

Amino Acid Sequence↗
PubMed1996

The cost-effectiveness of ambulatory blood pressure monitoring.

Some people's blood pressure is elevated simply by being in a clinical environment. Twenty-four hour monitoring gives a more accurate average blood pressure reading. The initial costs of ABPM are recouped in less than two years.

Blood Pressure Monitoring, Ambulatory↗
PubMed1994

Localization of the herpes simplex virus type 1 major capsid protein VP5 to the cell nucleus requires the abundant scaffolding protein VP22a.

The intracellular distributions of three herpes simplex virus type 1 (HSV-1) capsid proteins, VP23, VP5 and VP22a, were examined using vaccinia virus and plasmid expression systems. During infection of cells with HSV-1 wild-type virus, all three proteins were predominantly located in the nucleus, which is the site of capsid assembly. However, when expressed in the absence of any other HSV-1 proteins, although VP22a was found exclusively in the nucleus as expected, VP5 and VP23 were distributed throughout the cell. Thus nuclear localization is not an intrinsic property of these proteins but must be mediated by one or more HSV-1-induced proteins. Co-expression experiments demonstrated that VP5 was efficiently transported to the nucleus in the presence of VP22a, but the distribution of VP23 was unaffected by the presence of either or both of the other two proteins.

Biological Transport↗
PubMed1992

Noninfectious L-particles supply functions which can facilitate infection by HSV-1.

The tegument of herpes simplex virus contains proteins important for the efficient initiation of infection. L-particles are noninfectious virion-related particles that lack the nucleocapsid but do contain tegument and envelope. Their ability to deliver functional proteins into cells was compared to that of virions by testing the biological activities of two tegument proteins which are present in both types of particle. Results indicated that L-particles are as efficient as virions in supplying these in a fully functional state. Thus, L-particles are biologically competent and have the potential to participate in the early stages of virus infection.

Animals↗
PubMed1992

Assembly of enveloped tegument structures (L particles) can occur independently of virion maturation in herpes simplex virus type 1-infected cells.

Cells infected with a number of alphaherpesviruses produce non-infectious virion-related particles, termed L particles, in addition to infectious virions. L particles consist of the tegument and envelope components, but lack the virus capsid and DNA. Using a herpes simplex virus type 1 (HSV-1) temperature-sensitive mutant, ts1201, which fails to produce mature virions, we show that L particle production is independent of virion formation. Moreover, the quantity and protein composition of L particles generated by this mutant at the non-permissive temperature are indistinguishable from those produced in wild-type HSV-1 infections. Electron microscopy studies suggest that the processes governing the assembly of tegument and envelope components into L particles are similar to those involved in virion maturation.

Animals↗
PubMed1992

A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization.

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 forms heterologous complexes with the transforming proteins encoded by several different DNA tumor viruses. p53 also assembles into stable homo-oligomers. We demonstrate that the major structural determinant for the tetramerization of p53 is an alpha-helical plus basic region motif near the C-terminus of the protein. A monomeric p53 mutant adopts a conformation distinct from both 'wild-type' and 'mutant' form as defined by PAb1620 and PAb240 monoclonal antibody recognition. Nevertheless, monomeric and dimeric mutant p53 proteins retain the ability to suppress SV40 origin-directed DNA replication in vivo. Thus, p53-p53 interaction and expression of the PAb1620 epitope is not a prerequisite for such activity. We present data suggesting that suppression of replication by p53 may occur by a mechanism that is independent of detectable p53-T antigen association.

Amino Acid Sequence↗
PubMed1991

A human tumour-derived mutant p53 protein induces a p34cdc2 reversible growth arrest in fission yeast.

We have expressed wild-type and human tumour-derived mutant p53 cDNA genes in the fission yeast Schizosaccharomyces pombe. In the case of one mutant this resulted in a growth arrest of recipient yeast cells. In contrast, wild-type p53 and three other mutant proteins tested did not block outgrowth of colonies. Human and yeast cdc2 acted as functionally equivalent extragenic suppressors of the mutant-induced growth arrest allowing the establishment of viable p53 expressor strains. In cotransformation assays the mutant allele was found to be dominant over wt p53. Our results provide the first evidence of a functional relationship between p53 and p34cdc2 in an in-vivo system and suggest that the wide variety of mutant proteins present in human tumours may fall into functionally distinct subclasses.

Blotting, Northern↗
PubMed1990

Herpes simplex virus type 1 UL28 gene product is important for the formation of mature capsids.

The herpes simplex virus type 1 temperature-sensitive (ts) DNA-positive mutant ts1203 has been characterized. The ts lesion in ts1203 was located by marker rescue within the coding region of gene UL28. Nuclei of cells infected with ts1203 at the non-permissive temperature (NPT) contained large numbers of capsids with a uniform morphology. These capsids lacked DNA but had a defined internal structure. No full capsids were detected at the NPT, suggesting that ts1203 was unable to package viral DNA. In this respect ts1203 is similar to ts1201 which has a defect in gene UL26. The capsids made by ts1203 at the NPT, however, contained a more compact internal structure than those of ts1201. In addition, ts1203 capsids were dispersed throughout the nucleus whereas ts1201 capsids were frequently found clustered together in large arrays. Southern blot and sedimentation analyses of viral DNA confirmed that ts1203 had an encapsidation defect and showed that most of the mutant DNA at the NPT was of a high Mr. The effect of the ts1203 mutation could not be reversed in the absence of de novo protein synthesis by transferring mutant-infected cells from the NPT to the permissive temperature.

Blotting, Southern↗
PubMed1990

p53 interacts with p34cdc2 in mammalian cells: implications for cell cycle control and oncogenesis.

The p53 gene product has been implicated in both human and animal tumorigenesis. p53 complexes with the transforming proteins encoded by several different DNA tumour viruses. We demonstrate that human p53 is phosphorylated by the mammalian p34cdc2 kinase in vitro and coprecipitates with p34cdc2 in vivo. Our observations suggest that phosphorylation of p53 by p34cdc2 kinase may regulate the known activities of p53 in the initiation steps of DNA replication in mammalian cells.

Amino Acid Sequence↗
PubMed1990

The p53 nuclear localisation signal is structurally linked to a p34cdc2 kinase motif.

We have identified a region of human p53 protein with striking homology to a sequence motif on Simian Virus 40 T antigen which includes the nuclear localisation signal. Mutation of basic amino acid residues in this region of p53 (residues 312 to 323; SSSPQPKKKP) compromises transport of p53 protein to the nucleus. The sequence functions efficiently as a nuclear localisation signal when fused to E. coli beta galactosidase. Serine 315 within this p53 structural motif is phosphorylated in vitro by the cell cycle kinase p34cdc2. Thus in both T antigen and p53, nuclear localisation signal and p34cdc2 kinase acceptor residue map to a contiguous region of primary amino acid sequence.

Amino Acid Sequence↗