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Biomedical subjects

L Jarvis

Publications and source records attributed to L Jarvis.

At least 19 recordsLinked to original sources
PubMed2001

HTLV antibody screening using mini-pools.

At the present time, the UK blood transfusion services do not screen blood donations for anti-HTLV. This presentation describes a pilot study to ascertain the feasibility of HTLV antibody screening using mini-pools and also provides an estimate of HTLV prevalence within our donor population in Scotland and Northern Ireland. The Abbott/Murex HTLV I/II GE80/81 ELISA was selected for the trial. Thirty confirmed HTLV positive library samples were tested at various dilutions and five were shown to be nonreactive at a dilution of 1:100. Residues of mini-pools (of up to 95 individual donations) prepared for HCV NAT testing were tested with the Abbott/Murex GE80/81 assay. Of 6666 mini-pools (equivalent to 570 609 donations) tested, six were repeatedly reactive. All six mini-pools were confirmed HTLV antibody positive by line immunoassay. Four were confirmed to be HTLV-I positive, one HTLV-II positive and one HTLV positive (unable to type). Dilutions (1:100) of the five HTLV "nonreactive" positive samples were included in each test plate and used to determine a grey-zone cut-off. Using this grey-zone system an additional six (0.09%) mini-pool samples gave repeatedly reactive grey-zone results, none of which were confirmed. The minimum Scottish/Irish HTLV donor prevalence was shown to be 1:95 000.

Blood Donors↗
PubMed2000

Inhibition of angiogenesis by a mouse sprouty protein.

Sprouty negatively modulates branching morphogenesis in the Drosophila tracheal system. To address the role of mammalian Sprouty homologues in angiogenesis, another form of branching morphogenesis, a recombinant adenovirus engineered to express murine Sprouty-4 selectively in endothelial cells, was injected into the sinus venosus of embryonic day 9.0 cultured mouse embryos. Sprouty-4 expression inhibited branching and sprouting of small vessels, resulting in abnormal embryonic development. In vitro, Sprouty-4 inhibited fibroblast growth factor and vascular endothelial cell growth factor-mediated cell proliferation and migration and prevented basic fibroblast growth factor and vascular endothelial cell growth factor-induced MAPK phosphorylation in endothelial cells, indicating inhibition of tyrosine kinase-mediated signaling pathways. The ability of constitutively activated mutant Ras(L61) to rescue Sprouty-4 inhibition of MAPK phosphorylation suggests that Sprouty inhibits receptor tyrosine kinase signaling upstream of Ras. Thus, Sprouty may regulate angiogenesis in normal and disease processes by modulating signaling by endothelial tyrosine kinases.

Animals↗
PubMed2000

Community-level determinants of child growth in an Indonesian tea plantation.

OBJECTIVES: The paper presents the results of an ecological-economic approach to identifying community-level factors that influence the physical growth of young children. DESIGN: A cross-sectional design was used to obtain both the anthropometry and the ecological-economic data. SETTING: The sites were 24 communities located in a tea plantation near Bandung, West Java, Indonesia. SUBJECTS: 415 children between the ages of 6 and 18 months. METHODS: Epidemiological and ethnographic methods were used to measure community infrastructure and services related to child growth. Anthropometry was used to measure child growth. Econometric methods, including probit and ordinary least squares regression, were used to analyze the effect of community-level factors on child growth. RESULTS: Community vaccination programs, child care services, environmental sanitation and latrines were associated with better child growth. We concluded that community-level goods and services substantially contributed to health in early childhood.

Agriculture↗
PubMed2000

Clinical teaching by community nurses in the Australian context.

A study was conducted to explore factors that impact on the clinical teaching role of community nurses involved in the education of pre-registration nursing students. Respondents were community nurses working in the Western Sydney Area Health Service in New South Wales, Australia. A self-report questionnaire was developed to collect data. Results indicate that community nurses are interested in clinical teaching, that it is an important part of their role and that they perceive themselves to be effective clinical teachers, with the majority indicating motivation to continue developing their clinical teaching skills. Aspects of clinical teaching important to community nurses included facilitating the transition of education from theory to practice, sharing expertise, knowledge and skills and maintaining high standards of nursing practice. There was little support for the view that community nurses experienced difficulty in managing the dual teaching and practice role. Approximately a third of participants reported that being with a student on a one-to-one basis could be stressful. Strategies to assist community nurses in their clinical teaching role were identified.

Attitude of Health Personnel↗
PubMed1999

Use of bovine viral diarrhoea virus as an internal control for amplification of hepatitis C virus.

BACKGROUND AND OBJECTIVES: Screening for hepatitis C virus (HCV) by polymerase chain reaction (PCR) will be mandatory for screening blood and plasma donors in Europe and elsewhere. This study describes an internally controlled, highly sensitive PCR method designed for screening blood donations in pools. MATERIAL AND METHODS: RNA extracted from bovine viral diarrhoea virus (BVDV) was used as an internal control to monitor the efficiency of extraction, reverse transcription and amplification steps in HCV PCR. RESULTS: Sensitivity of PCR for single molecules of HCV in the presence of 33 genome equivalents of BVDV RNA was achieved by reducing the efficiency of BVDV amplification. BVDV could be recovered at high efficiency from large volume pools (2-5 ml) by ultracentrifugation and by the NucliSens extraction method. CONCLUSION: Detection of BVDV validates the extraction, reverse transcription and amplification methods used for HCV detection in plasma pools and provides valuable quality assurance for negative results.

Animals↗
PubMed1998

High prevalence of hepatitis G virus infection in multiply transfused children with thalassaemia.

We investigated the prevalence of hepatitis G virus (HGV) RNA in relation to the frequency of blood transfusions in thalassaemic children and in volunteer blood donors in Thailand. Furthermore, we studied the frequency of coinfection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) as well as a possible relationship to the alanine aminotransferase (ALT) status of the blood samples, taken at random from thalassaemic children who have received multiple blood transfusions and from volunteer blood donors. The results show detectable HGV-RNA in 32.6% of transfusion patients and in 5% of blood donors. The prevalence of HGV-RNA peaked between the 11th and 50th transfusion. The relationship between HGV infection and ALT status was not statistically relevant.

Adolescent↗
PubMed1996

A combined management protocol for patients with coagulation disorders infected with hepatitis C virus.

The case notes of 394 adults with bleeding disorders registered at our centre together with those of the 72 patients who had died since 1971 were reviewed. 36/72 deceased patients had evidence of HCV infection. Liver decompensation was present at time of death in six. 274 (70%) of the currently registered patients had received factor concentrate or cryoprecipitate and 174 of these were screened for HCV infection. 76% of tested patients were RIBA positive. 87% of RIBA-positive patients were RT-PCR positive. 50 RIBA-positive patients, including nine who were HIV infected, have undergone percutaneous liver biopsy following appropriate factor infusion with no complication. The biopsy was assessed using a Histological Activity Index (HAI) ranging from 0 to 13. Patients with HAI > or = 6 were offered treatment with interferon. Patients with HAI < 6 were followed up with a view to re-biopsy in 2-3 years to assess progression. The median HAI was 4.5 (range 0-10) with HAI > or = 6 in 13 cases (27%). HAI was not correlated with duration of infection. haemophilia severity. RT-PCR status. HIV status or HCV genotype. Liver biopsy, a safe procedure in our hands, is an important investigation in HCV-infected patients to assess suitability for interferon therapy.

Adult↗
PubMed1995

Direct association of Grb2 with the p85 subunit of phosphatidylinositol 3-kinase.

Phosphatidylinositol 3-kinase (PI 3-kinase) has been shown to play a key role in growth factor signaling pathways, although its signaling mechanism has not been fully elucidated. Using the yeast interaction trap system, we have identified Grb2 as a PI 3-kinase interacting protein. Our experiments demonstrate that p85, the regulatory subunit of PI 3-kinase, interacts with Grb2 in vivo, and this interaction is independent of growth factor stimulation. The direct association between Grb2 and p85 was reconstituted in vitro with glutathione S-transferase fusion proteins. Domain analyses and peptide competition indicate that the association is mediated by the SH3 domains of Grb2 and the proline-rich motifs of p85 and that only one SH3 domain is required for minimal binding. The interaction does not displace the catalytic subunit of PI 3-kinase but is exclusive of Sos. Signaling through PI 3-kinase, therefore, may involve the ubiquitous adapter Grb2, which serves as a convergence point for multiple pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors.

The B cell-specific cell surface molecule CD19 plays a role in regulating immunoglobulin (Ig) receptor signaling, and cross-linking CD19 activates several signaling molecules in mature human B cells. In surface Ig-negative B cell precursors, a protein tyrosine kinase (PTK)-dependent homotypic aggregation response can be triggered by cross-linking CD19. In the current study, we examined the outcome of PTK-mediated signal transduction following CD19 cross-linking on surface Ig negative and surface Ig positive B cell lines, as well as freshly isolated surface Ig-negative B cell precursors. PTK activation resulted in the tyrosine phosphorylation of multiple protein substrates and peaked at 0.5-1 min following CD19 cross-linking in all B-lineage cells examined. One of the tyrosine-phosphorylated substrates was identified as the hematopoietic-specific protein Vav, a guanine nucleotide exchange factor that activates the Ras pathway. Evidence consistent with Ras pathway activation was also demonstrated by MEK activation and subsequent phosphorylation of a MAP kinase fusion protein. CD19 cross-linking, sequential immunoprecipitation, and Western blotting revealed that: (a) Vav becomes associated with CD19, (b) phosphatidylinositol 3-kinase (PI 3-kinase) becomes associated with CD19, and (c) PI 3-kinase becomes associated with Vav. No such physical interaction occurred following control IgG1 cross-linking or cross-linking of class I major histocompatability complex cell surface molecules. Coupled with a previous report (Tuveson, D.A., Carter, R.H., Soltoff, S.P., and Fearon, D.T. (1993) Science 260, 986-988), our data support a model in which CD19 cross-linking induces the formation of a signaling complex that leads to the activation of two pathways involving Ras and PI 3-kinase.

Antigens, CD↗
PubMed1993

Signal transduction through the CD19 receptor during discrete developmental stages of human B-cell ontogeny.

We present evidence that the CD19 receptor is functionally operative and transmits pleiotropic signals throughout the pro-B, pre-pre-B, pre-B, early B, and mature B cell stages of human B-cell ontogeny. The signaling ability of CD19 does not depend on the existence of a functional B-cell antigen receptor complex (ARC). In B-cell precursors (BCP) lacking a functional ARC, CD19 is physically and functionally associated with Src family protein tyrosine kinases (PTK). The engagement of the CD19 receptor on BCP with a high affinity anti-CD19 monoclonal antibody (mAb) or its homoconjugate rapidly activates the associated PTK and results in tyrosine phosphorylation of CD19. Moreover, this proximal PTK activation step triggers downstream stimulation of several different intracellular messenger systems. Remarkably, CD19 becomes rapidly phosphorylated on tyrosine residues upon engagement of several other surface receptors as well, suggesting that it may function as a common response element linked via tyrosine phosphorylation to multiple BCP/B-cell receptors and signaling pathways. Furthermore, in all B-lineage lymphoid cell populations, co-approximation of the receptors CD19 and CD72 (ligand for the CD5 T-cell receptor) generates a stronger signal than the engagement of either individual receptor. These convergent observations constitute a strong argument for an important regulatory function of CD19 in human BCP and prompt the hypothesis that the CD19 receptor may play an important role in cognate interactions between B- and T-lineage lymphoid compartments as well as the coordinate production of BCP at multiple stages of human B-cell ontogeny.

Antigens, CD↗
PubMed1992

The distribution of the fiber cell intrinsic membrane proteins MP20 and connexin46 in the bovine lens.

MP20 is an intrinsic membrane protein previously identified in mammalian lens fiber cells. To identify a possible role for this protein in the lens, the distribution of MP20 and connexin46 has now been examined. Western immunoblotting with an anti-peptide antibody generated to the C-terminal 8 amino acids of MP20 confirmed the presence of this protein in the lens of several different mammalian species. A monoclonal antibody 5H1 was prepared that, in Western blots of bovine lesn membranes, recognized the same component as an antibody to rat connexin46 (Cx46). The apparent molecular mass of this component decreased from 59 kDa to 55 kDa following treatment of lens membranes with alkaline phosphatase. A monoclonal antibody to connexin-related MP70 recognized a 70 kDa component in bovine lens membranes confirming the presence of these two different connexin proteins in bovine lens membranes. To localize MP20 and Cx46 in the bovine lens membrane, lens fiber cell bundles were immunofluorescently labeled with both the MP20 antibody, and the monoclonal antibody to Cx46. Cx46 was identified in large plaques on the broad faces of the lens fiber cells throughout the outer 1 mm of the lens cortex. MP20 colocalized with Cx46 only in a restricted area 0.5 mm to 1.0 mm into the lens. In other regions of the lens, MP20 appeared more diffusely distributed over the fiber cell surface, although apparently concentrated in the ball-and-socket regions at the corners of the narrow side of the inner cortical lens fiber cells. These inner cortical regions were devoid of Cx46. A difference in distribution of these two proteins was confirmed in studies of immunofluorescently labeled lens cryosections. Furthermore, immunogold electron microscopy of purified lens membranes identified MP20 in both junctional regions (with Cx46) and in single membranes. These results provide evidence for a role for MP20 in mammalian lens fiber cell junctional formation or organization.

Animals↗
PubMed1991

Strong priming of T cells adoptively transferred into scid mice.

We have examined the requirements for activating unprimed T cells in vivo by transferring T cells into scid mice, which lack mature B and T cells. Purified adult thymocytes and a protein antigen, keyhole limpet hemocyanin (KLH), were injected into scid mice. scid mice injected with T cells and KLH developed cellular lymph nodes containing CD4+ and CD8+ T cells. Cells recovered from the lymph nodes of injected scid mice proliferated and secreted interleukin 2 in response to KLH in vitro. The results indicate that T cells can be primed to KLH in the scid mouse in the absence of B cells.

Animals↗
PubMed1991

Duplex sonography in splenomegaly.

The aetiology of splenomegaly is seldom clear from either clinical or imaging assessment of the spleen. In the majority of cases sonographic assessment of the spleen produces a homogeneous enlargement of variable echodensity, but with very poor correlation with pathology. A study has been undertaken to assess the Doppler characteristics of the splenic artery in splenomegaly, excluding cases of portal hypertension in an attempt to provide further diagnostic information. Duplex assessment of 18 normal subjects and 10 patients with splenomegaly due to five different causes was undertaken. Analysis of waveform, peak frequency and pulsatility index were compared and failed to demonstrate any significant change. In the normal subject there is a broad systolic spectrum related to the tortuosity of the splenic artery, with persistence of forward flow throughout diastole, a reflection of the low peripheral resistance of the spleen. In splenomegaly the broad systolic spectrum is unchanged, since vessel tortuosity persists. Pathological and physiological assessment of the spleen in splenomegaly shows that a low resistance circulation persists, explaining maintenance of the diastolic flow pattern in splenomegaly. Increased blood flow to the spleen in splenomegaly occurs either as a result of an increase in vessel diameter or an increase in flow velocity, or a variable combination of the two which does not seem to be governed by specific pathology. An increase in peak frequency in some cases reflected some increase in flow velocity but provided no useful correlation. Analysis of the pulsatility index supported the above findings without adding further information.

Adolescent↗
PubMed1988

Turcot's syndrome. A review.

Turcot's syndrome represents the association between familial multiple polyposis coli and neural tumors. The syndrome is reviewed with reference to genetics, colonic and central nervous system manifestations. This evidence suggests that Turcot's syndrome represents one manifestation of the pleiotropic autosomal dominant gene responsible for familial polyposis coli and the associated extracolonic manifestations of Gardner's syndrome. A diagnosis of Turcot's syndrome should be restricted to those patients with familial polyposis coli associated with gliomas or medulloblastomas. A further case is presented that is believed to be the first report of such a case in the United Kingdom.

Adenomatous Polyposis Coli↗
PubMed1988

Reduced hypercapnic vasoreactivity in moyamoya disease.

We measured cerebral perfusion at rest and in response to CO2 in eight patients with moyamoya disease (MMD), using the 133xenon inhalation method to determine the effect of large-vessel occlusive disease on vasoreactivity. We studied three other groups for comparison, including four with bilateral internal carotid artery occlusions (BICAO), 11 with unilateral carotid occlusion (UICAO), and six with unilateral middle cerebral artery stem occlusion (UMCAO). Resting flows appeared to correlate with the severity of occlusive disease overall. Normocapnic perfusion was lowest in the group with BICAO and decreased in proportion to the degree of contralateral stenosis in the group with UICAO. Hypercapnic perfusion correlated with the apparent adequacy of angiographic collaterals. Reactivity was lowest in the MMD group (0.79%/mm Hg) whose collateral supply was limited to leptomeningeal anastomosis from the posterior cerebral artery, but highest in the patients with BICAO (2.72%/mm Hg), each of whom showed excellent posterior communicating artery flow. The clinical course of the MMD group was compatible with the syndrome of perfusion insufficiency with repeated ischemic attacks or a saltatory progression of an ischemic deficit; CT showed infarction in the borderzone territory. These results suggest that a severely reduced hypercapnic response may help to identify patients with ischemic syndromes due to perfusion failure in the borderzones, as in MMD.

Adult↗
PubMed1988

DNA ploidy in thin melanoma.

DNA ploidy in benign nevi (BN), thin non-metastasizing melanomas (TNM) and thin metastasizing melanomas (TMM) was investigated using an image analyser to determine whether characteristics such as nuclear area (NA) and nuclear integrated optical density (IOD) could be used to distinguish between these lesions. NA measurements showed significant differences between samples of nevus cells and melanoma cells and nuclear IOD differences were significant between TNM and TMM samples. Differences in NA and nuclear IOD were detected across the three groups (BN, TNM and TMM) but the large variability within samples and within groups indicate further studies would be necessary to determine the usefulness of these results in terms of the rate of correct group classification of a single sample for diagnostic purposes.

Adolescent↗