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Biomedical subjects

D Buck

Publications and source records attributed to D Buck.

At least 73 records · Page 4Linked to original sources
PubMed1996

Initial biocompatibility studies of a novel degradable polymeric bone substitute that hardens in situ.

Clinical management of osseous defects often requires bone grafts. The standard for treatment is autogenous bone harvested from sites such as either the iliac crest or the outer table of the calvaria. In addition to the problem of donor site morbidity and the limited supply of graft material, there is the additional operating time associated with harvesting procedures. A synthetic, bone graft substitute that can match the clinical performance of autogenous bone could alleviate these deficiencies. Therefore, a polymeric bone substitute was developed that consists of a four-armed star polymer of poly(dioxanone-co-glycolide) endcapped at each termini with a biocompatible lysine-based diisocyanate crosslinker. The polymer can be mixed with inorganic fillers such as either hydroxyapatite or tricalcium phosphate to form either injectable or moldable putty. The addition of a catalyst (for example, diethylaminoethanol and water) to the polymer produces a crosslinking reaction causing the combination to harden. This reaction is nontoxic, normo-thermic and can be performed in situ. During the course of the polymerization, carbon dioxide is liberated, producing an interconnected porous network within the implant, suitable for bone ingrowth. This paper will describe a preliminary biocompatibility assay of the bone substitute.

Animals↗
PubMed1996

Economic and other views of addiction: implications for the choice of alcohol, tobacco and drug policies.

It is the aim of this paper to provide an overview of developments in implicit and explicit economic views of addiction, to contrast these perceptions with the views of other disciplines and discuss the implications for policy. Addictive behaviours have received considerable attention from disciplines other than economics. The nature of addiction and the contribution of psychological, physiological and social factors have been strongly debated within the addictions field for many years. The views of economists are becoming increasingly important because economic studies of consumption, and tax revenue in the case of licit drugs, are one factor when framing policy. It is therefore crucial to know how economists have treated addiction. Have they neglected it and what are the implication if they have? This paper attempts to answer this question by reviewing and discussing the literature in depth and drawing out the implications for policy.

Journal Article↗
PubMed1996

Reducing the burden of coronary heart disease: health promotion, its effectiveness and cost.

Coronary heart disease (CHD) is one of five key areas identified in the Health of the Nation white paper produced by the Department of Health in 1992. The main CHD targets are to reduce death rates from CHD by at least 40% in people below 65 and 30% in those between 65 and 74 by the year 2000, respectively. Improvements in treatment and rehabilitation are expected to contribute to reducing the burden of CHD; however, in the long term, prevention is believed to hold the greatest potential. CHD health promotion therefore has a big role to play in securing the Health of the Nation targets. In contrast to treatment interventions, however, little is known about the effectiveness or cost-effectiveness of health promotion. The purpose of this article is two-fold. Its main aim is to illustrate the potential of health promotion in reducing the health burden of CHD to the turn of the century and beyond for a representative health purchaser. This is achieved with the use of an epidemiological model, Prevent, developed in the Netherlands to simulate the health outcomes associated with health promotion and prevention. A subsidiary aim is to present tentative information about the relative costs associated with different health promotion options.

Adult↗
PubMed1996

Patients' experiences of and satisfaction with care for their epilepsy.

PURPOSE: To determine condition-specific satisfaction with care, we studied patients' experience of general practitioner (primary physician) and hospital clinic care for their epilepsy and their views about the provision of information concerning the management of their condition. METHODS: A postal questionnaire was sent to an unselected, community-based population of patients with epilepsy. In addition to clinical and demographic details and previously validated scales of psychosocial well-being, the instrument contained a series of questions about patients' experiences and views of the care they received for epilepsy from both general practice and the hospital services. RESULTS: Doctors' interpersonal skills were the most influential factors affecting both patient satisfaction overall and the likelihood that doctors might discuss with patients certain clinical and social issues surrounding the management of the patient's condition. A sizable proportion of patients reported that they received insufficient information about epilepsy, both from hospital doctors and general practitioners. CONCLUSIONS: Patients with epilepsy place great importance on having a doctor who is approachable, communicative, and knowledgeable and on receiving adequate information about their condition. Clinicians may need to be made more aware of the importance of accessibility and sensitivity to the nonclinical needs of their patients. Such easily implemented changes in the delivery of care would improve services in the United Kingdom for people with epilepsy.

Adolescent↗
PubMed1996

[Self-management by psychiatrically experienced persons].

As we all-including psychiatrists-are only able to achieve true understanding of that which we have already experienced, the complete understanding of a psychosis can only be developed by the sufferers themselves. Starting in 1989 we began to organize "psychosis workshops" at the university of Hamburg in order to exchange experiences. In the meantime there are an additional of 70 "psychosis workshops" offered throughout Germany. Conversely, the "Federal Association" founded in 1992 of the same name was the result of the "Psychosis Workshop" initiated by us in 1989.

Adaptation, Psychological↗
PubMed1995

Comparative sequence analysis of the human and pufferfish Huntington's disease genes.

The Huntington's disease (HD) gene encodes a novel protein with as yet no known function. In order to identify the functionally important domains of this protein, we have cloned and sequenced the homologue of the HD gene in the pufferfish, Fugu rubripes. The Fugu HD gene spans only 23 kb of genomic DNA, compared to the 170 kb human gene, and yet all 67 exons are conserved. The first coding exon, the site of the disease-causing triplet repeat, is highly conserved. However, the glutamine repeat in Fugu consists of just four residues. We also show that gene order may be conserved over longer stretches of the two genomes. Our work describes a detailed example of sequence comparison between human and Fugu, and illustrates the power of the pufferfish genome as a model system in the analysis of human genes.

Amino Acid Sequence↗
PubMed1995

Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions.

A region of intron 22 of the factor VIII gene, which contains factor VIII-associated gene A (F8A), is repeated twice more nearer the Xq telomere. It has been proposed that intrachromosomal homologous recombination occurs between the intron 22 repeat and either of the two extragenic copies, resulting in the recurrent inversions that cause almost half of all cases of severe haemophilia A. We have precisely defined the repeated region as 9.5 kb of DNA which we have termed int22h (intron 22 homologous region). The junctions of the inversions examined were shown to represent precise exchanges between the int22h repeats, thus providing conclusive evidence for homologous recombination. The three copies of int22h were compared along 8 kb of their length, using chemical mismatch analysis, and found to be 99.9% similar. The presence of such long, almost identical inverted repeats near the Xq telomere could account for the high frequency at which the inversions occur.

Base Sequence↗
PubMed1994

Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor.

The human OX-40 cell surface antigen is a CD4+ T cell activation marker that acts as a costimulatory receptor and is a member of the nerve growth factor receptor/tumor necrosis factor (TNF) receptor family. Using a soluble form of the receptor, the extracellular region fused with human immunoglobulin Fc, we expression cloned the human OX-40 ligand cDNA from a library derived from an activated B lymphoblastoid cell line MSAB. The encoded protein is identified as gp34, a type II transmembrane antigen previously known to be expressed only by human T cell lymphotropic virus 1-infected cells. We describe gp34 as a new member of the TNF family, and find that the recombinant ligand expressed in COS cells costimulates phorbol myristate acetate, phytohemagglutinin, and anti-CD3-induced CD4+ T cell proliferation.

Amino Acid Sequence↗
PubMed1994

Quantitative light microscopy. A powerful tool to assess bone.

Quantitative light microscopy is an important tool for assessing objectively the status of histologic events. It is, therefore, extremely useful for studying the dynamics of bone. This article provides a brief description of three quantitative techniques that are applicable to histomorphometry.

Animals↗
PubMed1993

Selective expression of integrin alpha 4 beta 7 on a subset of human CD4+ memory T cells with Hallmarks of gut-trophism.

Human memory CD4+ T lymphocytes are heterogenous in expression of integrins; one subset has the unexpected phenotype beta 1 low alpha 4 high. We demonstrate that this subset is unique among CD4+ cells in expression of high levels of alpha 4 beta 7, detected by a distinctive mAb Act-1. alpha 4 beta 7 is involved in binding to both fibronectin and vascular cell adhesion molecule-1; Act-1 blocks cell binding to the former and augments binding to the latter. Act-1 expression marks a subset of memory cells that, unlike the predominant circulating memory cell, has up-regulated beta 7 rather than beta 1. Their phenotype is distinct from that described for skin-homing T cells and is fully consistent with that described for gut-homing T cells. Differential adhesion capacity of this subset is verified by selective binding to FN and vascular cell adhesion molecule-1 in a beta 1-independent fashion. Thus, alpha 4 beta 7 detected on this subset of circulating normal T cells fits the expectations for a gut-homing receptor.

Antibodies, Monoclonal↗
PubMed1993

Control of lymphocyte recirculation in man. I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition.

Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation through secondary lymphoid tissues, whereas memory/effector populations are composed of distinct subsets with differential, often tissue-selective migratory capability. In keeping with these observations, CD45RAhigh/ROlow "virgin" T cells in human peripheral blood uniformly express the peripheral lymph node homing receptor (HR) L-selectin, whereas among the CD45RAlow/ROhigh "memory/effector" subset, the expression of this HR is bimodal. To investigate the mechanisms responsible for the generation of memory/effector T cell subsets with differential homing potential, we developed a multiparameter flow cytometric technique that defines a common pathway of post-thymic T cell differentiation in secondary lymphoid tissues. Our analyses indicate that the virgin to memory T cell transition is characterized by a stepwise, unidirectional progression through distinct CD45RA+/RO+ intermediates that allow the in vivo discrimination of early, middle, and late transitional T cells. In normal peripheral blood, few T cells with a transitional phenotype are identified, but in secondary lymphoid tissues, 2 to 10% of T cells have this phenotype, including those CD45RA+ T cells that 1) are morphologically blasts, 2) are in S or G2/M phase of the cell cycle, or 3) express activation Ag. General adhesion molecules (LFA-1, LFA-3, ICAM-1) are uniformly up-regulated concordant with changes in T cell expression of CD45RA/RO in all tissues examined. Early in the transition, L-selectin is also uniformly up-regulated, but in subsequent stages, T cell expression of this HR is preferentially down-regulated in mucosal lymphoid tissues, and retained in peripheral lymph node. Differential regulation of L-selectin can also be demonstrated in vitro by the activation of virgin T cells in the presence of specific cytokines--IL-2 induces L-selectin down-regulation, whereas IL-6 and particularly TGF-beta 1 promote L-selectin up-regulation. Taken together, these findings support the hypothesis that local microenvironments within particular secondary lymphoid tissues influence HR expression at the time of CD45RA/RO conversion, and thereby contribute to the formation of CD45RAlow/ROhigh memory/effector T cell populations with tissue-selective homing behavior.

Adult↗
PubMed1993

Cloning and sequencing of the Escherichia coli panB gene, which encodes ketopantoate hydroxymethyltransferase, and overexpression of the enzyme.

The panB gene from Escherichia coli, encoding the first enzyme of the pantothenate biosynthesis pathway, ketopantoate hydroxymethyltransferase (KPHMT), has been isolated by functional complementation of a panB mutant strain with an E. coli genomic library. The gene is 792 bp long, encoding a protein of 264 amino acids with a predicted M(r) of 28,179. The identity of the gene product as ketopantoate hydroxymethyltransferase was confirmed by purification of the enzyme protein, which was overexpressed approximately 50-fold in the mutant harboring the gene on a high-copy-number plasmid. The N-terminal amino acid sequence of the purified protein was found to be identical to that predicted from the gene sequence, as was its mass, determined by electrospray mass spectrometry. Upstream of the panB gene is an incomplete open reading frame encoding a protein of 220 amino acids, which shares sequence similarity to fimbrial precursor proteins from other bacteria. Northern (RNA) analysis showed that the panB gene is likely to be cotranscribed with at least one other gene but that this is not the putative fimbrial protein, since no transcripts for this gene could be detected.

Amino Acid Sequence↗
PubMed1992

Characteristics of murine monoclonal anti-CD4. Epitope recognition, idiotype expression, and variable region gene sequence.

We have characterized a series of mouse monoclonal anti-CD4 and describe both their CD4 epitope recognition and Id expression. We also determined the V region gene sequences of these antibodies in an attempt to correlate epitope recognition and Id expression with V region sequence. All of these preparations recognize epitopes that cluster around the HIV gp120 binding site on the human CD4 molecule. However, we observed differences in epitope recognition among the anti-CD4 preparations, based on either competitive inhibition assays or functional assays, such as syncytium inhibition. Analysis of Id specificities using a polyclonal anti-Id generated against anti-Leu 3a indicated that five of the seven monoclonal anti-CD4 expressed a shared Id. Based on V region gene sequences, the V region kappa-chain (V[kappa]) from each of the seven antibodies was encoded by the V[kappa]21 gene family and expressed the J[kappa]4 gene segment. Those preparations that expressed the shared Id with anti-Leu 3a have virtually identical V[kappa] sequences, with a high degree of homology in the CDR. The VH region gene sequences of six of the seven antibodies also shared overall homology and appeared to be encoded by the J558 VH gene family. The seventh anti-CD4 VH region is encoded for by the VHGAM gene family. The majority of these antibodies used JH3 gene segment, although the JH2 and JH4 gene segments were also represented. In addition, several of these antibodies share a common sequence organization within their V-D-J joining regions that appears to involve N and P sequences to generate unique D segments. Together, these data suggest that differences in epitope recognition among the monoclonal anti-CD4 may reflect sequence variability primarily within the CDR3 region of both V[kappa] and VH. The basis for the detection of a shared Id most likely reflects the high degree of homology within the V[kappa] region sequences. In addition, these data, which are based on a limited analysis, suggest the possible restricted use of V region germ-line gene families in the secondary antibody response of BALB/c mice to specific epitopes on the human CD4 molecule.

Amino Acid Sequence↗
PubMed1992

Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural killer leukemia cell line.

NK cells and certain CTL can recognize and lyse targets without restriction by the MHC. NK cells do not express CD3/TCR complexes and the membrane receptors participating in MHC-unrestricted cytotoxicity are largely unknown. We demonstrate that YT2C2, a human NK leukemia cell line, expresses the CD28 differentiation Ag and can spontaneously lyse both murine and human cell lines expressing B7, a B cell- activation Ag that is a ligand for CD28. The participation of CD28/B7 interactions in MHC-unrestricted cytotoxicity mediated by YT2C2 cells was demonstrated by correlation of target sensitivity with levels of B7 expression, inhibition of cytotoxicity by anti-CD28 or anti-B7 mAb, and by making both murine and human cell lines susceptible to YT2C2-mediated lysis by genetic transfection with expression vectors containing B7 cDNA. However, CD28/B7 interactions alone were insufficient to initiate cytotoxicity. mAb inhibition experiments and selection of CD54- (intercellular adhesion molecule-1) deficient B cell targets indicated that CD11a/18 (lymphocyte function-associated Ag-1) also cooperated in CD28/B7-dependent cytotoxicity. The requirement for both CD28/B7 and lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 interactions in YT2C2-mediated MHC-unrestricted cytotoxicity was confirmed by demonstrating that efficient lysis of murine L cells required cotransfection with both B7 and intercellular adhesion molecule-1. These findings support the concept that MHC-unrestricted cytotoxicity may not be due to a unique receptor, but may result from interactions between an appropriate array of "adhesion" molecules with their ligands.

Antigens, CD↗
PubMed1992

CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes.

Engagement of the CD3/T cell antigen receptor complex on small, resting T cells is insufficient to trigger cell-mediated cytotoxicity or to induce a proliferative response. In the present study, we have used genetic transfection to demonstrate that interaction of the B7-BB1 B cell activation antigen with the CD28 T cell differentiation antigen costimulates cell-mediated cytotoxicity and proliferation initiated by either anti-CD2 or anti-CD3 monoclonal antibody (mAb). Moreover, a B7-negative Burkitt's lymphoma cell line that fails to stimulate an allogeneic mixed lymphocyte response is rendered a potent stimulator after transfection with B7. The mixed leukocyte reaction proliferative response against the B7 transfectant is inhibited by either anti-CD28 or B7 mAb. We also demonstrate that freshly isolated small, resting human T cells can mediate anti-CD3 or anti-CD2 mAb-redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma transfected with human B7. These preexisting cytotoxic T lymphocytes in peripheral blood are present in both the CD4 and CD8 subsets, but are preferentially within the CD45RO+ "memory" population. While small, resting T cells apparently require costimulation by CD28/B7 interactions, this requirement is lost after T cell activation. Anti-CD3 initiates a cytotoxic response mediated by in vitro cultured T cell clones in the absence of B7 ligand. The existence of functional cytolytic T cells in the small, resting T cell population may be advantageous in facilitating rapid responses to immune challenge.

Animals↗
PubMed1992

Preoperative radiological evaluation of the liver by computerized tomographic portography in patients with hepatic tumors.

The main objective of preoperative imaging studies is to define as accurately as possible the number, size, location, and relationship of tumor masses in the liver to pertinent portal and hepatic venous vasculature. Computerized tomographic portography images hepatic veins and segmental portal vein branches and identifies the anatomical location of tumor nodules with excellent sensitivity and a low false-positive rate. The intraoperative correlation of computerized tomographic portography on 30 patients in the last 20 months at this institution shows a sensitivity of 88 per cent with a low rate of false-positivity. The ability to detect metastatic lesions in the liver by computerized tomographic portography diminishes when the lesions are noted to be less than 1 cm. The authors conclude that the preoperative interpretation of the computerized tomographic portogram provides valuable information not previously available to the surgeon operating on the liver.

Adult↗