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Biomedical subjects

K Lucas

Publications and source records attributed to K Lucas.

At least 19 recordsLinked to original sources
PubMed2001

Development of thymic and splenic dendritic cell populations from different hemopoietic precursors.

The antigen-presenting dendritic cells (DCs) found in mouse lymphoid tissues are heterogeneous. Several types of DCs have been identified on the basis of the expression of different surface molecules, including CD4, CD8alpha, and DEC-205. Previous studies by the authors showed that the mouse intrathymic lymphoid-restricted precursors (lin(-)c-kit(+)Thy-1(low)CD4(low)) can produce DCs in the thymus and spleen upon intravenous transfer, suggesting a lymphoid origin of these DCs. In the current study, the potential for DC production by the newly identified bone marrow (BM) common lymphoid precursors (CLPs), common myeloid precursors (CMPs), and committed granulocyte and macrophage precursors was examined. It was found that both the lymphoid and the myeloid precursors had the potential to produce DCs. All the different DC populations identified in mouse thymus and spleen could be produced by all these precursor populations. However, CLPs produced predominantly the CD4(-)CD8alpha(+) DCs, whereas CMPs produced similar numbers of CD4(-)CD8alpha(+) and CD4(+)CD8alpha(-) DCs, although at different peak times. On a per cell basis, the CLPs were more potent than the CMPs at DC production, but this may have been compensated for by an excess of CMPs over CLPs in BM. Overall, this study shows that the expression of CD8alpha does not delineate the hemopoietic precursor origin of DCs, and the nature of the early precursors may bias but does not dictate the phenotype of the DC product.

Animals↗
PubMed2001

Development of dendritic cells in culture from human and murine thymic precursor cells.

The earliest T-precursor population in the adult murine thymus can give rise to dendritic cells (DC) in culture if stimulated with a cocktail of cytokines that includes interleukin (IL)-3, but not with cytokine mixes based on granulocyte-macrophage colony stimulating factor (GM-CSF), normally used to generate myeloid-derived DC. This and other evidence led to the proposal that two different lineages of DC exist, one lymphoid-related and the other myeloid-related. To determine whether this selective response to cytokines was restricted to murine DC, early human thymic T-precursors were isolated and their capacity to generate DC in response to various cytokines directly compared to their murine counterparts. In contrast to cultures of murine thymic precursors, CD34+CD1a- lineage marker negative (Lin-) precursor cells from the human thymus proliferated and generated DC with both the IL-3-containing cytokine mix lacking GM-CSF and with GM-CSF based cytokine mixes. These CD34+CD1a-Lin- human precursor cells also gave rise to NK cells under appropriate culture conditions, but produced no granulocyte, monocyte, eosinophil, megakaryocyte or erythroid cells in standard soft-agar colony-forming cell assays. Thus, although apparently lymphoid-restricted, the human thymic DC precursors responded to the myeloid factor GM-CSF as well as to the cytokines selective for murine lymphoid-related DC.

Animals↗
PubMed2000

Altogether now? Professional differences in the priorities of primary care groups.

BACKGROUND: Little is known about the similarities or differences with which Primary Care Group (PCG) Board members view the relative importance of the three functions with which they are charged, or how representative these views are of local primary care teams in general. This project explores the priorities of medical and nursing PCG Board members in relation to those of local General Practitioners (GPs) and practice nurses they represent. METHODS: Postal questionnaires were sent to GPs (n=236) and practice nurses (n= 137); structured telephone interviews were carried out with PCG Board members (n=61) in East Sussex, Brighton and Hove. RESULTS: There are large differences between the views of GPs and those of their nursing colleagues on how PCG Board members should determine priorities in their work. There are also marked differences in the priorities of PCG Boards (of whom the majority are GPs) and non-Board member GPs. Whereas around two-thirds of PCG Board members believe that improving health generally and reducing inequalities in particular are the most important tasks before them, this view is not shared by most GPs in the same localities, who are generally more concerned about commissioning services. There is some doubt among GPs generally about the suitability of PCG Board members as a vehicle for the tasks they have been set, and this doubt is also found among PCG Board members themselves. CONCLUSIONS: The priorities of PCG Board members of different disciplines need to be aligned in order that they have a clear focus on the tasks before them. PCG Boards must also have priorities that are consistent with the local practitioners who elected them. Effective systems of communication will need to be developed between PCG Board members, Health Authorities and individual Primary Care Groups. Local flexibility is essential to the success of Primary Care Groups, but tackling inequalities in health must always be at the forefront of their role.

Attitude of Health Personnel↗
PubMed1999

Starting smoking: girls' explanations of the influence of peers.

A questionnaire survey of cigarette smoking completed in six secondary schools by 4773 pupils aged 11-16 years included five items concerning the circumstances of smoking initiation: (1) age at first cigarette; (2) source of supply; (3) location of first smoke; (4) persons present; and (5) perceived degree of coercion. Although there was a highly significant gender difference on the item concerning age at first cigarette, with the average for boys lower than that for girls, the remaining items showed no gender effects. In order to explore further the reasons for the observed higher prevalence of cigarette smoking among teenage girls compared to boys, 33 focus groups were undertaken with girls in Years 7 and 9. These qualitative data provide evidence of the social representations of different groups and of smoking and non-smoking identities. Any understanding of smoking among girls needs to take account the dynamics of girls' membership in groups of never, experimental and regular smokers in determining subsequent smoking behaviour.

Adolescent↗
PubMed1998

High-frequency electric field trapping of individual human spermatozoa.

We present a new touch-free technique for trapping, positioning and selecting human spermatozoa. This can be done in free solution (culture medium) by high-frequency electric fields. Ultramicroelectrodes fabricated by photo- and electron-beam lithography on quartz and glass substrates were used to create field cages or long field channels. If the conductivity of the external salt solution is higher than the average value of sperm cell conductivity, negative polarization and negative dielectrophoresis occur. As a result, the induced cell polarization leads to forces repelling spermatozoa from the electrodes towards the field minimum. Using four planar electrodes a field funnel can be formed in which an individual spermatozoon is retarded while swimming. The same can be done more effectively in three-dimensional cages created by an octopole electrode system. In these systems, rapidly swimming spermatozoa could be trapped for several seconds but some spermatozoa stop moving if exposed to field strengths of more than 500 V/cm at frequencies in the MHz range. However, in stripwise and interdigitated electrodes, rapidly swimming sperm cells could be very well positioned in front of a break-electrode by a combination of electric field trapping and field induced laminar fluid streaming. This technique can be applied to bring individual spermatozoa to a defined position for characterization followed by sampling with capillaries.

Animals↗
PubMed1998

The linkage between T-cell and dendritic cell development in the mouse thymus.

Thymic dendritic cells (DC) mediate negative selection at a relatively late stage of the T-cell developmental pathway. We present evidence that the development of thymic DC and of T-lineage cells is linked via a common precursor at an early stage of thymocyte development. T-lineage precursor populations from the adult mouse thymus, prior to T-cell receptor gene rearrangement, display a capacity to produce DC as well as T cells in the thymus, and are very efficient precursors of DC in culture. These lymphoid/DC precursors have little capacity to form myeloid cells, indicating that thymic DC are a lymphoid-related rather than myeloid-related lineage. In contrast to myeloid-related DC, granulocyte-macrophage colony-stimulating factor is not required for the development of these lymphoid-related DC in vivo or in vitro. DC can develop in mutant mice lacking mature T cells, provided the common precursors are present. However, in mutant mice lacking functional Ikaros transcription factors, there are deficiencies in lymphoid precursor cells, in mature lymphoid cells and in DC.

Animals↗
PubMed1997

Adolescent girls' constructions of smoking identities: implications for health promotion.

A model of social identities constructed in terms of group membership is used to explore the incidence of cigarette smoking among adolescent girls. A sharp increase in girls' smoking at about 14 years of age related both to age and to puberty is demonstrated in a discriminant function analysis. The model is successful in identifying membership in never smoked and regular smoker groups but does not identify occasional smokers. Girls' ratings of 13 identity descriptors are summarised in similar, three scale nonsmoker and smokers identities. The nonsmoker identity is rated higher on the "mature" and "sensible" scales while the smoker identity is rated higher on the "fun-loving" scale and a fourteenth descriptor, breaks rules. The descriptors loading on the "mature" scale are contested suggesting that members of both smoking and nonsmoking groups value cool, popular, grown-up and makes up own mind. Material from focus group discussions demonstrates that the particular meanings of some descriptors may vary with group membership and values. Both the prevalence analysis and the focus group material support the hypothesis that interventions are best targeted at specific groups and that the occasional smoker identity needs to be targeted specifically in interventions designed to reduce smoking among adolescent girls.

Adolescent↗
PubMed1997

Biology and adoptive cell therapy of Epstein-Barr virus-associated lymphoproliferative disorders in recipients of marrow allografts.

Epstein-Barr virus (EBV) is an ubiquitous herpesvirus which is carried as a latent infection of B lymphocytes and salivary gland epithelial cells in over 90% of normal adults. Latently infected EBV-transformed B cells circulate at low frequency in the blood for the life of the host. These transformed B cells stimulate a heterogeneous and complex host cell response, ultimately leading to the development and maintenance of high frequencies of HLA-restricted T cells specific for the EBV-encoded nuclear antigens EBNA2-EBNA6 and the latency membrane proteins LMP-1 and LMP-2. Responses to latent EBV-encoded proteins are hierarchical with responses to certain epitopes predominating, dependent upon the HLA genotype of the host. Profound suppression of T-cell immunity may permit the emergence of polyclonal, oligoclonal or monoclonal EBV antigen-expressing lymphoproliferative disorders or malignant B-cell lymphomas expressing these latent EBV antigens. Adoptive transfer of small numbers of peripheral blood mononuclear cells or HLA-partially matched T cells from in vitro expanded EBV-specific T-cell lines derived from a seropositive marrow donor has induced durable regressions of bulky, widely metastatic monoclonal EBV lymphomas in a high proportion of cases. This review describes the current state of knowledge and hypothesis regarding the biology and immunology of EBV infection in the normal host, the features of donor, host and virus which contribute to the development of EBV-associated lymphoproliferative diseases and the mechanisms whereby they are controlled by adoptive transfer of immune T cells.

Bone Marrow Transplantation↗
PubMed1996

Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor.

The earliest lymphoid precursor population in the adult mouse thymus had previously been shown to produce not only T cells, but also dendritic cell (DC) progeny on transfer to irradiated recipients. In this study, culture of these isolated thymic precursors with a mixture of cytokines induced them to proliferate and to differentiate to DC, but not to T lineage cells. At least 70% of the individual precursors had the capacity to form DC. The resultant DC were as effective as normal thymic DC in the functional test of T cell stimulation in mixed leukocyte cultures. The cultured DC also expressed high levels of class I and class II major histocompatibility complex, together with CD11c, DEC-205, CD80, and CD86, markers characteristic of mature DC in general. However, they did not express CD8 alpha or BP-1, markers characteristic of normal thymic DC. The optimized mixture of five to seven cytokines required for DC development from these thymic precursors did not include granulocyte/macrophage colony stimulating factor (GM-CSF), usually required for DC development in culture. The addition of anti-GM-CSF antibody or the use of precursors from GM-CSF-deficient mice did not prevent DC development. Addition of GM-CSF was without effect on DC yield when interleukin (IL) 3 and IL-7 were present, although some stimulation by GM-CSF was noted in their absence. In contrast, DC development was enhanced by addition of the Flt3/Flk2 ligand, in line with the effects of the administration of this cytokine in vivo. The results indicate that the development of a particular lineage of DC, probably those of lymphoid precursor origin, may be independent of the myeloid hormone GM-CSF.

Animals↗
PubMed1994

Catecholamine metabolites in ganglioneuroma.

With rare exception, ganglioneuroma (GN) is a benign lesion which presents as a localized mass without metastatic potential and which is chemotherapy resistant. Thus, its distinction from neuroblastoma (NB) may be important. The diagnosis of GN implies the absence of neuroblastic elements. Incomplete resection prevents complete microscopic examination and raises the possibility that focal NB was not sampled. In an attempt to determine what features other than histology distinguish these two entities, we reviewed the charts of 25 patients with GN with regard to patient age and sex, tumor location and size, and urine catecholamine metabolite levels. One patient with GN (5%) and gross total resection had elevated quantitative vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels (2.4 x upper limit of normal for age), and two others had positive spot analyses for VMA. An additional patient with a large mass, multiple biopsies of which documented GN, also had greatly elevated (approximately 5 x normal) VMA and HVA levels. However, a subsequent attempt at resection disclosed several gross foci of NB. Even excluding this patient, there was a trend for elevated values in GN patients to correlate with tumor size (P = .07 and .14 for VMA and HVA, respectively). The incidence of elevated values appears to increase as a function of tumor size, and small tumors are not likely to result in positive urinary measurements. We conclude that while elevations of VMA and HVA are consistent with a well-documented diagnosis of GN, extreme elevations (> 3 x nl) should prompt careful serial evaluation for occult NB.

Adolescent↗
PubMed1994

Ethical dilemmas and decisions concerning the do-not-resuscitate patient undergoing anesthesia.

The growing geriatric population in this country makes it increasingly difficult to deal with the number of do-not-resuscitate (DNR) orders. In part, this is due to an increase in the number of elderly undergoing anesthesia and surgery. It can also be attributed to a rise in complex legal, ethical, and moral issues these orders pose for the healthcare professional caring for the DNR patients, including anesthetists. The term "DNR" is confusing to many, including healthcare professionals. As patients progress through the perioperative period, this confusion is compounded by the fact that administration of anesthesia encompasses interventions that include intubation, ventilation, and fluid replacement. These interventions may be regarded as resuscitative efforts outside the operating room. The anesthetist must identify and sort through a maze of conflicting courses of action, which must match the patient's desires and personal rights. The topic of DNR orders is addressed as well as some of the moral and ethical dilemmas they pose for the Certified Registered Nurse Anesthetist (CRNA). Some solutions are offered to help the nurse anesthetist make those decisions that are most "right" for the patient.

Decision Making↗
PubMed1993

Spatiotemporal expression of pregnancy-specific glycoprotein gene rnCGM1 in rat placenta.

As a basis towards a better understanding of the role of the pregnancy-specific glycoprotein (PSG) family in the maintenance of pregnancy, detailed investigations are described on the expression of a recently identified rat PSG gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide primers, rnCGM1 transcripts were identified after reverse transcription, polymerase chain reaction, and hybridization with a radiolabelled, internal oligonucleotide. Transcripts were only found in significant amounts in placenta. In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.), in secondary trophoblast giant cells and in the spongiotrophoblast. Only those secondary giant cells lining the maternal decidua were positive. In contrast, primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1 transcripts were almost exclusively detectable in the spongiotrophoblast. No rnCGM1 transcripts were found in rat embryos of these two developmental stages. Rabbit antisera were generated against the amino-terminal immunoglobulin variable-like domain and against a synthetic peptide containing the last 13 carboxy-terminal amino acids of rnCGM1. Both antisera recognized a 124 kDa protein in day 18 rat placental extracts as identified by Western blot analysis. The anti-peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c. pregnant rat that is absent from the sera of non-pregnant females. Taken together, these results confirm exclusive expression of rnCGM1 in the rat trophoblast, but unlike human PSG, negligible or no expression is found in other organs, such as fetal liver or salivary glands, indicating a more specialized function of rnCGM1. Its spatiotemporal expression pattern is conducive with a potential role of PSG in protecting the fetus against the maternal immune system and/or in regulating the invasive growth of trophoblast cells.

Amino Acid Sequence↗
PubMed1991

An improved microcomputer program for finding gene- or gene family-specific oligonucleotides suitable as primers for polymerase chain reactions or as probes.

We present here an easy-to-use computer program which finds oligonucleotides suitable as primers in polymerase chain reactions (PCR) or as probes for hybridization. In contrast to other programs used for this purpose, the additional advantage of this one is the possibility of directly detecting gene- as well as gene family-specific oligonucleotides. For this purpose, up to 200 different DNA sequences, of maximally 65,000 nucleotides each, can be scanned in a single search to ensure either single or multiple gene binding of the PCR primers or probes. Specific oligonucleotides for genes carrying internal repetitions and for single genes belonging to a set of highly conserved genes can also be detected. Many parameters such as exclusion of simple sequences, which are known to be highly repeated throughout various genomes or regions of stable secondary structures in both primer-primer and primer-template, can be taken into consideration and avoided. Furthermore, the G + C content and the length of the oligonucleotides can be changed in a broad range by the user.

Animals↗