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Biomedical subjects

D Bailey

Publications and source records attributed to D Bailey.

At least 37 records · Page 2Linked to original sources
PubMed1994

Inhibition of cholesteryl ester transfer protein in normocholesterolemic and hypercholesterolemic hamsters: effects on HDL subspecies, quantity, and apolipoprotein distribution.

The effects of cholesteryl ester transfer protein (CETP) inhibition on the serum lipoprotein profile in both normocholesterolemic and hypercholesterolemic hamsters has been determined following subcutaneous injection of 12.5 mg/kg of the CETP neutralizing monoclonal antibody, TP2. Inhibition of CETP activity was greater than 60% and resulted in a 30-40% increase in high density lipoprotein (HDL) in both normal and hypercholesterolemic animals. These HDL effects were observed 1 day post-injection, were maximal by 4 days, and returned to control values by 14 days. Inhibition of CETP activity resulted in a decrease in both low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol concomitant with HDL increase, and in hypercholesterolemic animals resulted in increased total serum cholesterol. In addition to the quantitative differences in LDL and HDL, there were significant increases in the size of the HDL, a shift to smaller LDL particles, and changes in apolipoprotein (apo) composition as evaluated by FPLC and Western blot analysis. Large apoA-I-poor and apoE-containing HDL became prevalent in hypercholesterolemic hamsters after CETP inhibition. In addition, the size of the CETP-containing HDL particles increased with inhibition of transfer activity. While these effects were apparent in normocholesterolemic animals, the changes in apolipoprotein distribution and HDL subspecies as detected on native gels were more significant in the hypercholesterolemic animals. The changes in the HDL profile and apolipoprotein distribution after CETP inhibition in hamsters were similar to those reported in CETP-deficient Japanese subjects, suggesting the utility of the hypercholesterolemic hamster as an in vivo model for the understanding of the lipoprotein changes associated with CETP inhibition.

Animals↗
PubMed1994

Cell cycle dependent regulation of the protein kinase TTK.

TTK is a novel protein kinase detectable in all proliferating human cells and tissues. Expression of the TTK gene is markedly reduced or absent in resting cells and in tissues with a low proliferative index. In view of the apparent association between TTK gene expression and cell proliferation, we examined the regulation of this protein kinase during transit of the cell cycle. We found very low levels of TTK mRNA and protein in starved cells. When cells are induced to enter the cell cycle, levels of TTK mRNA, protein and kinase activity increase at the G1/S phase of the cell cycle and peak in G2/M. TTK mRNA levels, as well as kinase activity, drop sharply in early G1, whereas protein levels are largely maintained. TTK may play a role in cell cycle control.

Cell Cycle↗
PubMed1993

Mutations of the p53 gene do not occur in testis cancer.

To characterize the role of p53 in the development of testis cancer, we looked for mutations in the coding sequences of the p53 gene. DNA was obtained both from familial and sporadic testis cancer specimens, as well as from peripheral blood from members of a testis cancer kindred. Mutations in the p53 gene were screened using a combination of constant denaturant gel electrophoresis and single-strand conformational polymorphism analysis, 2 screening methods that can detect single base changes. Abnormalities detected by these methods were confirmed by sequencing of the corresponding cloned polymerase chain reaction products. All conserved regions of the p53 coding sequences were examined, encompassing all previously reported sites of mutations. No mutations were found in any of 22 germ cell cancers of the testis or in the germline DNA of 17 members of the testis cancer family. This is in striking contrast to most other human cancers, in which mutations of p53 are the most commonly described molecular event associated with tumorigenesis. We conclude that dysfunction of tumor suppressor gene or genes other than p53 may prove to play an important role in the development of germ cell cancers of the testis.

Genes, p53↗
PubMed1993

X-ray-crystallographic studies of complexes of pepstatin A and a statine-containing human renin inhibitor with endothiapepsin.

H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally occurring inhibitor of aspartic proteinases, have been co-crystallized with the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6). H-189 [Pro-His-Pro-Phe-His-Sta-(statyl)-Val-Ile-His-Lys] is an analogue of human angiotensinogen. Pepstatin A [Iva(isovaleryl)-Val-Val-Sta-Ala-Sta] is a blocked pentapeptide which inhibits many aspartic proteinases. The structures of the complexes have been determined by X-ray diffraction and refined to crystallographic R-factors of 0.15 and 0.16 at resolutions of 0.18 nm (1.8 A) and 0.2 nm (2.0 A) respectively. H-189 is in an extended conformation, in which the statine residue is a dipeptide analogue of P1 and P'1 as indicated by the conformation and network of contacts and hydrogen bonds. Pepstatin A has an extended conformation to the P'2 alanine residue, but the leucyl side chain of the terminal statine residue binds back into the S'1 subsite, and an inverse gamma-turn occurs between P'1 and P'3. The hydroxy moiety of the statine at P1 in both complexes displaces the solvent molecule that hydrogen-bonds with the catalytic aspartate residues (32 and 215) in the native enzyme. Solvent molecules originally present in the native structure at the active site are displaced on inhibitor binding (12 when pepstatin A binds; 16 when H-189 binds).

Amino Acid Sequence↗
PubMed1993

Impact tolerances of the rigidly fixated maxillofacial skeleton.

A study was designed to determine how soon an athlete who undergoes rigid fixation of a facial fracture can return to full competition. The impact resistance of a rigidly fixated malar complex fracture was studied and compared with that of an intact malar complex. Twelve fresh human cadaver heads were used. A custom-designed impact device was used to deliver a blow of a specific energy to each intact malar complex. The subsequent fractures were rigidly fixated at three points using titanium miniplates and screws. A second impact of identical energy was delivered. The forces generated and the subsequent displacement of hard and soft tissues were recorded after each impact. It was concluded from this study that an impact to a rigidly fixated malar complex fracture produced less force and greater displacement of hard and soft tissues than an impact of identical energy to an intact malar complex. The potential for sustaining more severe maxillofacial injuries after an initial facial fracture should be seriously considered. The results suggest that sufficient time should be allowed for the bony healing of a facial fracture to occur, even after rigid fixation, before an athlete can resume full contact activities.

Age Factors↗
PubMed1993

A neuropsychological approach to the Bannatyne recategorization of the Wechsler Intelligence Scales in adults with learning disabilities.

An investigation was conducted of the diagnostic ability of the Bannatyne recategorization of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) into spatial, verbal-conceptual, and sequential components for adults with learning disabilities. A comparison among neuropsychological, intelligence, and achievement test data was made to evaluate the applicability of this recategorization. The Luria-Nebraska Neuropsychological Battery (LNNB), the WAIS-R, and the Wide Range Achievement Test-Revised (WRAT-R) were administered to 103 adult subjects with learning disabilities. The LNNB scales were cluster analyzed, and cluster membership was cross-tabulated against WAIS-R, WRAT-R, and demographic data. The major findings were that (a) the mean scores fit the Bannatyne pattern in two of the four clusters; and (b) the Bannatyne pattern was found in only about 20% of the total sample. It was concluded that identification of the Bannatyne pattern is of diagnostic utility, but its absence is inconclusive.

Adult↗
PubMed1993

Extensive cutaneous plasmacytomas.

An unusual case of extensive cutaneous and subcutaneous plasmacytomas is reported. Breast involvement was also a feature in this individual. The relevant literature relating to this unusual presentation of myeloma is reviewed.

Breast Neoplasms↗
PubMed1992

Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance.

The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1, and in the AUC from 23 to 65 nmol.h.l-1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (-9%) than did water (0%).

Adult↗
PubMed1992

Facilitator not teacher: a role change for tutors in open learning nursing education.

Open learning is now an established, if rapidly changing, part of post-compulsory education and training in the United Kingdom. It has also developed in significant ways within nurse education. A key role in successful open learning is that of the tutor. Differences between the activities of teaching and facilitation are defined and ways of mapping the tutor's role within these are suggested. Differences in approach can be clustered around the topics of: the locus of control; learning methodology; the learning context and media; and the curriculum. These are discussed in turn to elicit what are the key issues for tutoring in relation to each one.

Curriculum↗
PubMed1992

Decreased leukocyte adhesion with anti-CD18 monoclonal antibodies is mediated by receptor internalization.

BACKGROUND: Adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells is mediated partially by CD11/CD18 integrins. The purpose of this study was to define (1) the response of PMNs to anti-CD18 monoclonal antibody binding, and (2) the mechanism responsible for anti-CD18 monoclonal antibody-mediated decreases in PMN adhesion to endothelial cells. METHODS: Canine PMN O2- production, myeloperoxidase, and lysozyme release in response to the anti-CD18 monoclonal antibody IB4 were measured by standard assays. To examine endocytosis of CD18 receptors, PMNs incubated with IB4 and a fluorescein isothiocyanate secondary antibody were analyzed by flow cytometry. RESULTS: Treatment of PMNs with IB4 did not stimulate O2- production or degranulation but decreased adhesion of 51Cr-labeled PMNs to ex vivo canine aorta. Incubation of PMNs at 25 degrees C resulted in a decrease in fluorescence intensity that was not affected by NaN3 or vanadate but was blocked by NaF, 4 degrees C, and bafilomycin, which prevents endosomal acidification. Treatment with an antifluorescein antibody decreased the fluorescence intensity in NaF and 4 degrees C, but not in bafilomycin-treated neutrophils. CONCLUSIONS: IB4 decreases PMN-endothelial cell adhesion but does not stimulate neutrophil oxidative metabolism or degranulation. These data suggest that reduced adhesion may be the result of internalization of the CD18/IB4 complex. Anti-CD18 monoclonal antibodies may be useful in preventing PMN adhesion without the potentially deleterious effects of cell activation.

Animals↗
PubMed1991

Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets.

We have identified and biochemically characterized an antigen, 8A3, which is expressed on activated T lymphoblasts and activated platelets. Monoclonal antibodies to 8A3 were raised against the primitive lymphoid/myeloid cell line KG1a and additionally bound to the erythroleukemia-derived cell line HEL, whilst exhibiting little or no reactivity with a panel of other hematopoietic cell lines. The 8A3 antigen was expressed on poorly differentiated T-cell leukemias and on phytohemagglutinin-activated T-cells maintained in interleukin-2 (7,000 sites/cell). This antigen, though not detected on resting platelets, was expressed on thrombin-activated platelets (2,000 sites/platelet). Antibodies to 8A3 identified polypeptides of Mr 170,000 and 150,000 in lysates of surface-iodinated KG1a cells, T lymphoblasts, and activated platelets under both reducing and nonreducing conditions. However, peptide mapping and susceptibily to glycosidases indicated that the 8A3 antigen was a monomeric glycoprotein of Mr 170,000 which contained two N-linked endoglycosidase H-sensitive glycans, and that the Mr 150,000 structure was derived from it by proteolytic degradation. The 8A3 antigen was not detectably phosphorylated in KG1a cells in vivo, nor did immune complexes containing it exhibit kinase activity in vitro. Structural and serologic characteristics of the 8A3 antigen indicate that it is different from other previously described leukocyte activation antigens including transferrin receptors, interleukin-2 receptors, members of the integrin family of adhesion molecules, or "restricted" members of the leukocyte-common antigen/CD45 cluster. Furthermore, the 8A3 antigen does not appear to be related to the other previously described activation-specific platelet molecule, GMP140/PADGEM. This antibody may be useful in monitoring T-cell activation status in some clinical situations and in characterizing clinically relevant activation-associated platelet membrane alterations.

Animals↗
PubMed1991

Translocation (14;19) in acute biphenotypic leukemia.

Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation.

Adult↗
PubMed1991

A normalization technique for 3D PET data.

Prior to reconstruction, emission data from a multi-ring PET camera must be corrected (normalized) for variations in detector sensitivity. The appropriate correction coefficients are obtained by measuring the response of all coincidence lines to a calibrated source of activity (a blank scan). State-of-the-art cameras may contain up to a million such lines of response (LORs), and therefore around 400 million counts will be required to calibrate each LOR to a statistical accuracy of 5%. Alternatively, by modelling the LOR sensitivity as the product of the individual detector efficiencies and a geometrical factor, a calibration procedure has been proposed which requires the determination of only 6000 parameters from this same data set. A significant improvement in the statistical accuracy of the coefficients can therefore be expected. Recently, multi-ring scanners have been operated with the septa retracted, increasing the number of measured LORs by a factor of eight. The acquisition of the calibration data necessary to achieve adequate statistical accuracy then becomes prohibitive. We show that, by modelling the LOR sensitivity, it is possible, with certain approximations, to normalize a septa-retracted emission data set with good accuracy. The input to the model is a high statistics blank scan acquired with the septa extended, which offers a number of practical advantages.

Calibration↗
PubMed1991

A method of studying pharmacokinetics in man at picomolar drug concentrations.

1. We describe a new method that enables the tissue kinetics of picomolar concentrations of drugs to be measured in man. The method is based on the administration of a drug, labelled with a short-lived positron-emitting radioisotope, such as carbon-11 (t1/2 = 20.4 min, beta + = 99.8%) or fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%), which is then detected in vivo by an array of 10 large uncollimated sodium iodide scintillation detectors, arranged as five opposing pairs, with each pair collecting data over one major organ or region of the body. 2. To illustrate the scope of the new method we report the results of administering [O-methyl-11C]-diprenorphine, an established radioligand for central opiate (mu, kappa, and delta) receptors and L-6-[18F]-fluoro-DOPA, a marker for dopaminergic neurons. 3. Only 2-10 muCi (74-370 kBq) of radioactivity are used and, as a consequence of the high specific activities with which carbon-11 and fluorine-18 labelled compounds can be prepared, the method requires less than a nanomole of drug to be administered. In many cases, this amount of drug might be considered low enough to avoid any adverse biological effect. Furthermore repeat studies are possible in many without delivering unacceptable radiation burdens. 4. The high sensitivity realised for both radioactivity and mass suggests a mean for determining the human biodistribution of a new drug at a very early stage in its development. This has potential benefit to drug discovery programmes and to ensuing drug therapies.

Blood-Brain Barrier↗
PubMed1991

Increased flow-induced ATP release from isolated vascular endothelial cells but not smooth muscle cells.

1. Freshly harvested smooth muscle cells and endothelial cells isolated from the rabbit aorta were perfused (0.5 ml min-1) and stimulated twice by an increase of flow rate (3.0 ml min-1) in order to compare their ability to release adenosine 5'-triphosphate (ATP). 2. In smooth muscle cells, the basal release of ATP (0.0265 +/- 0.0033 pmol ml-1 per 10(6) cells) was not increased during periods of increased flow (P = 0.2). 3. In endothelial cells, the concentration of ATP in the perfusate during periods of low flow (0.0335 +/- 0.0038 pmol ml-1 per 10(6) cells) was significantly increased by 14 times and 5 times during the first and second periods of increased flow, respectively. 4. The release of ATP by endothelial cells did not appear to be caused by the lysis of cells during the period of increased flow because it can be reproduced several times and because there was no difference between lactate dehydrogenase activity in perfused cells and that in non-perfused cells. 5. These results show that, of the two major cell types of the vascular wall, only endothelial cells react to shear stress by releasing ATP.

Adenosine Triphosphate↗
PubMed1991

A personal experience.

David Bailey, who is 14 years old, has a left transverse total forearm deficiency and bilateral longitudinal femur partial deficiencies. The latter fall into Torode and Gillespie's Group I, with marked femoral shortening. A wedge osteotomy was performed for his gross right coxa vara, which was successful, but an intractable fixed flexion deformity of the right knee led eventually to a knee disarticulation being performed.

Abnormalities, Multiple↗
PubMed1991

Immunohistochemical staining of germ cell tumors and intratubular malignant germ cells of the testis using antibody to placental alkaline phosphatase and a monoclonal anti-seminoma antibody.

Antibody to placental alkaline phosphatase (PLAP) has been previously used in immunoperoxidase (IMP) staining studies of germ cell tumors and intratubular malignant germ cells (ITMGC) of the testis, the latter believed to be the precursor of these tumors. In this study, we compared staining by IMP using monoclonal antibody (mAb) and polyclonal antibody to PLAP with that seen using a mAb, M2A, which was previously shown to react with testicular seminomas and ITMGC. Antibody to PLAP and M2A reacted with different cellular components, as assessed by IMP staining of placenta and prepubertal testis and by Western blotting of seminoma lysates. Antibody to PLAP stained pure seminomas (seven of seven), pure embryonal carcinomas (four of four), and the seminoma (three of three) and embryonal carcinoma (six of six) components of mixed testicular germ cell tumors. M2A stained pure seminomas (26 of 26) and the seminoma component (three of three) of the mixed tumors, but failed to stain pure embryonal carcinomas (zero of four) or the embryonal carcinoma component (zero of five) of the mixed tumors. Both antibody to PLAP and M2A stained ITMGC of the testis. Since M2A stained seminomas and ITMGC but not embryonal carcinomas, seminomas would appear to be more closely related to ITMGC than embryonal carcinomas. This result has led us to speculate on the histogenesis of testicular germ cell tumors.

Alkaline Phosphatase↗