Search PubMed⌕ Search

Biomedical subjects

R A Phillips

Publications and source records attributed to R A Phillips.

265 records · Page 15Linked to original sources
PubMedDate not supplied

Ambulatory blood pressure monitoring and echocardiography--noninvasive techniques for evaluation of the hypertensive patient.

Clinic blood pressure measurements have only limited ability to determine which hypertensive patients are at greatest risk of cardiovascular events. Ambulatory blood pressure monitoring allows for noninvasive measurement of blood pressure throughout the 24-hour period. This may help to clarify discrepancies between blood pressure values obtained in and out of the clinic and confirm the presence of white-coat hypertension, broadly defined as an elevated clinic blood pressure but a normal ambulatory blood pressure. Ambulatory blood pressure values have been shown to have a better relationship to cardiovascular morbidity and mortality and end-organ damage than clinic blood pressure values. Further, patients with white-coat hypertension appear to be at greater risk of cardiovascular morbidity and end-organ damage than a normotensive population, although they are at less overall risk than a hypertensive population. Hypertensive heart disease is characterized by diastolic dysfunction, increased left ventricular mass, and coronary flow abnormalities. Left ventricular hypertrophy increases the risk of coronary heart disease, congestive heart failure, stroke, ventricular arrhythmias, and sudden death. A variety of invasive and noninvasive techniques are described herein that measure left ventricular mass, diastolic function, and coronary blood flow abnormalities. Most antihypertensive treatments promote regression of left ventricular hypertrophy and reversal of diastolic dysfunction, which may decrease symptoms of congestive heart failure and improve survival.

Blood Pressure↗
PubMedDate not supplied

Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma.

Through family studies and analysis of patients with congenital chromosome abnormalities, the germ-line mutation responsible for the hereditary form of the eye tumour, retinoblastoma, has been assigned to the q14 region on chromosome 13 and closely linked to an enzyme called esterase D (ESD). Knudson has proposed that as few as one somatic event in addition to the germ-line mutation is required to induce tumours in patients with the hereditary form of retinoblastoma; the non-hereditary form requires two somatic events to occur in the same cell. The somatic event(s) may involve either mutation of the remaining normal gene at 13q14 or mutation of a gene at another site in the genome. Here we have examined six retinoblastoma patients who are heterozygous for electrophoretic variants of ESD. Although the normal cells of all six patients expressed both variants, the tumour cells of four patients expressed enzyme from only one of the two ESD alleles. We tentatively conclude that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinoblastoma (RB) locus.

Cell Line↗
PubMedDate not supplied

Retrovirus transfer of a bacterial gene into mouse haematopoietic progenitor cells.

The haematopoietic system is made up of a hierarchy of cells with different developmental, functional and proliferative capacities. Although cellular diversity appears to arise from the commitment and maturation of stem cells, the molecular basis for this differentiation process is unknown. The introduction of cloned DNA sequences into haematopoietic progenitor cells would provide a novel approach for studying this differentiating in vivo system. One laboratory has reported DNA-mediated transfer of genes into mouse bone marrow cells. However, retroviruses offer a number of advantages over DNA-mediated gene transfer procedures, including high efficiency infection of a wide range of cell types in vitro and in vivo, stable and low copy integration into the host chromosome, and a defined integrated provirus structure. For these reasons recombinant DNA techniques have been utilized to construct high efficiency retrovirus vectors expressing foreign genes. We demonstrate here, using such a retrovirus vector, the transfer of a dominant selectable drug-resistance gene into defined classes of mouse haematopoietic progenitor cells. These observations should facilitate the development of molecular genetic approaches to fundamental and clinical problems in haematopoiesis.

Animals↗
PubMedDate not supplied

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma.

Inheritance of a mutation at the Rb-1 locus, which has been mapped to band q14 of human chromosome 13, results in predisposition to retinoblastoma. Cloned DNA segments homologous to arbitrary loci of human chromosome 13 and which reveal polymorphic restriction endonuclease recognition sequences, have been used to look for somatic genetic events that might occur during tumorigenesis. A comparison of constitutional and tumour genotypes from several cases indicates that tumorigenesis may result from the development of homozygosity for the mutant allele at the Rb-1 locus. The homozygosity in these cases results from mitotic nondisjunction, resulting in loss of the homologous wild-type chromosome, or from a mitotic recombination event.

Alleles↗
PubMedDate not supplied

Expression of human adenosine deaminase in murine haematopoietic progenitor cells following retroviral transfer.

Adenosine deaminase (ADA) deficiency, an autosomal recessive inborn error of metabolism, leads to severe combined immune deficiency in man. This enzyme, although constitutively expressed in most tissues, is expressed at high level in immature T cells, and study of the pathophysiology of the disorder indicates that increased deoxyadenosine or altered methylation capacity have toxic effects on T-cell maturation. Although bone marrow transplantation can correct the immune deficiency, this therapy is associated with graft-versus-host disease and incomplete immune restoration, and so our laboratory and others have sought to develop a method of gene replacement as a possible treatment for the disease. Moreover, characterization of the complementary DNA of the human ADA gene and some of its mutants makes it possible to design gene transfer strategies. We have now subcloned a human adenosine deaminase cDNA into the retrovirus shuttle vector pZIP-SV(B), and in this way have isolated a cell line, 4.2T, which produces high titres of replication-defective retrovirus which have been used to transfer the gene for human ADA to mouse bone marrow cells. Transfer and expression of the neomycin-resistance gene (neo) and the ADA gene in murine bone marrow colony-forming units (CFU) was demonstrated by in vitro colony formation in the presence of the antibiotic G418 or 9-xylofuranosyladenine plus deoxycoformycin, respectively. Isoenzyme analysis also showed human ADA expression in the cultured mouse bone marrow.

Adenosine Deaminase↗
PubMedDate not supplied

Tumour induction by the retinoblastoma mutation is independent of N-myc expression.

Retinoblastoma (RB) tumours form in the eyes of young children when homozygosity for a mutation at the Rb-1 locus develops in a somatic retinal cell. A similar shift to homozygosity for the RB mutation has been observed in osteogenic sarcoma (OS) tumours that commonly arise as second tumours in children who survive RB. This observation suggests that the Rb-1 locus controls the expression of genes with oncogenic potential; a possible target is the oncogene N-myc, which is sometimes amplified and over-expressed in the neuroectodermal tumours neuroblastoma and RB. However, N-myc is developmentally regulated in normal murine embryogenesis, and an alternative possibility is that the expression of the gene in tumour cells reflects their embryonic origin and is unrelated to the RB mutation. We have therefore examined N-myc expression in various fetal, adult and tumour tissues, and report here that the gene is expressed in fetal but not in adult brain and retina and in near-diploid RB tumour samples at levels similar to those observed in normal fetal retina. Only RB tumours with genomic amplification of the N-myc gene exhibited increased levels of expression; and no N-myc transcripts were detected in osteogenic sarcomas initiated by mutations at the Rb-1 locus. We therefore conclude that the expression of N-myc in RB tumours probably reflects the origin of the tumour from an embryonic tissue normally expressing the gene and is not directly associated with the mutation at the RB locus.

Animals↗
PubMedDate not supplied

Postnatal development of northern fulmar chicks, Fulmarus glacialis.

The slow growth and large fat stores characteristic of many pelagic seabird chicks were generally assumed to reflect infrequent and unpredictable food provisioning by parents. Much less attention has been focused on the importance of intrinsic physiological processes in shaping patterns of development. In this study, we examined postnatal growth and changes in water content of different organs in fulmar chicks, Fulmarus glacialis, from Fair Isle, United Kingdom. After correcting for body size, mass growth rate was as high as in inshore-feeding species, which did not support the notion of an external constraint on growth imposed by the unpredictability of pelagic prey. Pectoral muscles and plumage grew more rapidly than other tissues. Pectorals also had a high water index, probably indicating slower maturation compared with leg muscles, which need to generate heat earlier on to free adults from brooding requirements. Lean dry mass of liver, kidney, and gut decreased markedly toward fledging, presumably because of high energetic costs of maintaining large metabolic machinery in older chicks and analogous to the situation in adult waders before migration. These results suggest that the general pattern of development of fulmars may be linked to changes in resource allocation as chicks grow and possibly a compromise at the tissue level between cell division and the attainment of mature function.

Adaptation, Physiological↗
PubMedDate not supplied

Pathogenicity and persistence of Salmonella enteritidis and egg contamination in normal and infectious bursal disease virus-infected leghorn chicks.

The pathogenicity and persistence of Salmonella enteritidis (SE) phage type 8 and resulting egg contamination in normal and infectious bursal disease virus (IBDV)-infected white leghorn chicks were evaluated over 34 weeks and in some birds over a 64-week period. Four hundred 1-day-old specific-pathogen-free (SPF) straight-run white-leghorn chickens were allotted into four treatment groups: negative control, IBDV-infected, IBDV+SE-infected, and SE-infected. Chicks were infected with IBDV at 1 day of age and with SE phage type 8 at 2 days of age. SE persisted in the gut of more than 50% of the chicks of both SE-infected groups through 34 weeks postinoculation (PI), and SE could still be isolated from cloacal/rectal swabs taken at 64 weeks. IBDV+ SE-infected chicks had severe gross lesions and significantly (P < 0.001) higher mortality (32%) than the negative control (1%), IBDV-infected (10%), and SE-infected (1%) groups. Gross lesions consisting of fibrinous pericarditis, perihepatitis, peritonitis, airsacculitis, and inspissated yolk were observed only in the IBDV+SE-infected group. SE isolations from internal organs of chickens in the IBDV+SE-infected group decreased from 83% at 8 weeks to 0% at 14 weeks PI; isolations from the SE-infected group decreased from 50% at 8 weeks to 0% at 10 weeks PI. Salmonella isolations increased from 0% to 14% in both groups at 18 weeks, corresponding with the time of sexual maturity. Of the 1,050 eggs cultured from the IBDV+SE-infected group, SE was isolated from 88 shells, five albumens, and two yolks. In contrast, of 1,258 eggs from the SE-infected group, 33 shells and none of the albumens and yolks were positive for SE. All eggs that had SE-positive contents also had SE-positive shells.

Animals↗
PubMedDate not supplied

Experimental infection and transmissibility of Mycoplasma synoviae with delayed serologic response in chickens.

Fifteen mycoplasma-free chickens were contact exposed to five chickens that had been experimentally infected with one of three different strains (two field strains and one laboratory strain) of Mycoplasma synoviae (MS). Culture and polymerase chain reaction (PCR) were positive by 3 days postinoculation (PI) in the experimentally infected birds. Lateral transmission was found by 7-14 days postexposure. Positive serum plate agglutination (SPA) results were detected 3-4 wk after positive culture and/or PCR in individual birds. By 42 days PI, all the birds in the groups exposed to field strain K1858 or K3344 had become infected as determined by culture and PCR, whereas only half of the birds in the group exposed to laboratory strain WUV1853 had become infected. Because of the unanticipated lack of seroconversion to hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) in infected chickens, the study was extended. Each group was split into two groups of 10 birds each, one of which was vaccinated with a live B1/LaSota Newcastle disease (ND) vaccine virus to determine if a viral respiratory challenge might incite a stronger antibody response to the mycoplasma infection. All the birds were tested for seroconversion 14 and 21 days later. Of the birds vaccinated for ND, a slightly greater number were MS positive by SPA than the nonvaccinated birds. This effect was not present 21 days after vaccination, and there was no significant difference in the MS HI results from these groups, suggesting that the viral respiratory infection had little direct impact on seroconversion. The virulent field strain (K3344) elicited a stronger MS antibody response than the other strains. All results from the MS ELISA were negative in all groups through 9 wk. Positive results from PCR analysis correlated well with culture results, whereas serologic tests did not detect MS infection for several weeks. Monitoring programs solely dependent on seroconversion may be inadequate for diagnosis and control of mycoplasma infections.

Agglutination Tests↗