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Biomedical subjects

J H Phillips

Publications and source records attributed to J H Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1989

The recycling of a secretory granule membrane protein.

We have used N-hydroxysuccinimido-d-biotin as a reagent for labeling proteins exposed at the surface of cultured bovine adrenal chromaffin cells during Ba2+-stimulated secretion. A specific secretory granule membrane constituent, dopamine-beta-hydroxylase (DBH), has been investigated using immunoprecipitation followed by electrophoresis. Within 30 min of stimulation, exposed DBH had been cleared from the cell surface. Nevertheless, quantitation of labeled DBH using [125I] streptavidin suggested that it remained undegraded over a period of 24 h, a time during which secretory granule stores of catecholamines were being replenished. Subcellular fractionation of the cultured cells suggested that, after 3 or 4 h, the biotinylated DBH, which was still membrane-bound, was located in particulate material that also contained cytochrome b561, another major secretory granule membrane component.

Adrenal Medulla↗
PubMed1989

Comparison of compression and torque measurements of self-tapping and pretapped screws.

The choice of an internal fixation system for maxillofacial surgery is made difficult because of lack of information with respect to functional load. This study attempted to clarify some of the controversy with respect to maxillofacial use of these implants. Maximal compressive force to torque values were measured in standardized bone thicknesses of 1, 2, 3, and 4 mm. The screws tested were pretapped AO 1.5-, 2.0-, 2.7-, and 3.5-mm rescue screws and self-tapping Luhr, Champy, and AO 1.5- and 2.0-mm screws. Ten measurements were made for each screw type/bone thickness combination using a piezoelectric washer and torque screwdriver. It was apparent that for 1- and 2-mm bone thicknesses the use of self-tapping screws resulted in the highest compression values. In 3- and 4-mm bone thicknesses, pretapped screws offered the highest compression values. As expected, self-tapping screws had the highest torque values on insertion owing to torque loss in cutting the screw threads. The 2.7-mm screw offered no advantage over the 2.0-mm screws in 1- and 2-mm bone thicknesses but resulted in higher compression values in 3- and 4-mm bone thicknesses.

Animals↗
PubMed1989

Marketing strategy adjustments in the ambulatory care center industry: implications for community pharmacy.

Each stage of a product's life cycle requires marketing strategy modifications in response to changing demand levels. The purpose of this study was to investigate changes in ambulatory care center (ACC) operational characteristics indicative of product, market, and distribution channel adjustments that could have a competitive impact upon community pharmacy practice. A questionnaire was mailed to a national sample of 325 ACC managers. Evidence of new product feature additions includes increased emphasis on continued care and increased prevalence of prescription drug dispensing. Expansion into new market segments and distribution channels was demonstrated by increased participation in HMO and employer relationships. The observed adjustments in ACC marketing strategies present obvious challenges as well as less obvious opportunities for community pharmacy practice.

Ambulatory Care Facilities↗
PubMed1989

Complex facial trauma: the evolving role of rigid fixation and immediate bone graft reconstruction.

The problem of high velocity facial injuries with multiple facial fractures concerns the severity of the bony injury. Attempts at closed reduction of the large comminuted segments common to these fractures result in eventual bony collapse and soft tissue shrinkage. The solution to these problems lies in the early exposure of all fracture segments and their repair using internal fixation techniques.

Bone Plates↗
PubMed1989

Food hoarding behaviour in the golden hamster (Mesocricetus auratus): effects of body weight loss and hoard-size discrimination.

Two experiments investigated some of the factors that influence food hoarding behaviour in the golden hamster (Mesocricetus auratus). In Experiment 1, hamsters given limited access to food failed to increase the amount of food they consumed at each meal. Instead, they exhibited a significant increase in the amount of food taken to hoard during the limited access period, and this permitted hamsters who were allowed to retain their hoard to maintain body weight at levels comparable to free-feeding controls. Hamsters that were not allowed to retain hoarded food rapidly lost body weight. There was also an inverse correlation between body weight and amount of food taken to hoard in all hamsters given limited access to food, suggesting that body weight loss was one factor directly related to increased hoarding during periods of limited food accessibility. Experiment 2 investigated the effect of hoard-size discrimination on food hoarding in hamsters by artificially manipulating hoard size. The results suggested that hoarding behaviour could be influenced by artificially depleting and repleting the hoard, and this factor appears to influence hoarding in the absence of any significant changes in body weight. These results are discussed in relation to the kinds of adaptive feeding strategies that hamsters may utilize in their natural environment.

Animals↗
PubMed1989

Growth after construction of the temporomandibular joint in children with hemifacial microsomia.

Free costochondral grafts have been used to construct the absent ascending ramus and condylar head of 22 children with hemifacial microsomia (HFM) who were less than 14 years of age. Evidence of continued growth was demonstrated in all patients. Growth was determined by measurement of cephalograms or by inference; if the patient grew extensively in height but his/her face remained symmetric, the graft was inferred to have grown. In two patients, considerable overgrowth occurred, displacing the chin to the opposite side and causing a class III malocclusion. Variations in age or type of adjunctive operations did not affect growth. There appears to be no single explanation for all findings. Because all of the grafts grew, early joint construction and correction of hemifacial microsomia are advocated.

Adolescent↗
PubMed1988

Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes.

CD16 Ag is associated with the low affinity FcR for IgG expressed on human NK cells and granulocytes. In this study, we demonstrate that NK cells specifically lyse murine anti-CD16 hybridoma cell lines, but do not lyse hybridomas against other cell surface differentiation Ag expressed on NK cells. Moreover, the CD18 structure is involved in the CD16-specific xenogeneic interaction between human effector cells and murine hybridoma target cells. Although interaction with anti-CD16 hybridomas or antibodies triggers the cytolytic mechanism of NK cells, this interaction does not induce cellular proliferation. In contrast to NK cells, CD16+ granulocytes do not lyse anti-CD16 hybridoma cell targets and do not mediate ADCC against antibody-coated human tumor cell targets. These findings indicate a fundamental difference in the antibody-dependent cellular cytotoxicity mechanisms of NK cells and granulocytes. Comparative biochemical analysis of CD16 on NK cells and granulocytes revealed significant differences in the size of the polypeptides obtained after removal of N-linked carbohydrate residues with endo-F and N-glycanase digestion.

Animals↗
PubMed1988

Constitutive expression of a phosphorylated activation antigen (Leu 23) by CD3bright human thymocytes.

Leu 23 is a human cell surface differentiation Ag expressed very early during lymphoid cell activation. Resting T lymphocytes do not express Leu 23. However, expression of Leu 23 glycoprotein can be induced on the Jurkat T leukemia cell line within a few hours after stimulation with soluble anti-CD3 mAb or Con A. After removal of the stimulus Leu 23 is expressed for greater than 30 h. A total of 20 to 30% of resting human thymocytes was unexpectedly stained by anti-Leu 23 mAb. Biochemical analysis revealed that the Leu 23 Ag expressed on thymocytes is a phosphorylated disulfide-linked dimer composed of 28- and 32-kDa subunits. Within the thymus, Leu 23 is preferentially expressed on the CD3bright, mostly CD4+ CD8- or CD4- CD8+ subpopulations. By contrast, CD3dim CD4+CD8+ thymocytes expressed only very low levels of Leu 23, and CD7+ CD3- CD4- CD8- thymocytes were Leu 23-. However, Leu 23 was induced on the CD3dim thymocytes by in vitro culture of thymocytes with anti-CD3-conjugated Sepharose. The transition from CD3dim to CD3bright within the thymus may be an important differentiation stage and influence selection of the antigenic repertoire. Therefore, the ability to detect subpopulations within the thymus that express Leu 23 Ag may help to identify thymocytes activated in vivo, possibly by the functional engagement of their CD3/TCR.

Antigens, CD↗
PubMed1988

The effects of IL-4 on human natural killer cells. A potent regulator of IL-2 activation and proliferation.

NK cells are directly activated by rIL-2 and subsequently undergo rIL-2-dependent proliferation in vitro. Herein, we report that rIL-4 is a potent regulator of human NK cells. Although rIL-4 had no effect on the cytotoxic activity of resting NK cells, it was capable of inhibiting in a concentration-dependent manner the rIL-2-induced cytolytic activation of NK cells against NK cell-resistant tumor cell targets. rIL-4 acted directly on NK cells and did not require accessory cells. rIL-4-induced inhibition of NK cell activation was specific for rIL-2 in that activation of NK cell cytolysis by IFN-alpha was not affected. These results represent the first direct evidence that rIL-2 and IFN-alpha activate NK cells by different pathways. rIL-4 also effectively blocked the rIL-2-dependent proliferation of NK cells. The results presented in this study clearly demonstrate that rIL-4 is a potent regulator of IL-2-dependent mechanisms of NK cell activation and proliferation and thus may play an important physiologic role in vivo.

Cell Line↗
PubMed1988

The effects of recombinant interleukin 2-activated natural killer cells on autologous peripheral blood hematopoietic progenitors.

In the present study, we demonstrate that resting and rIL-2-activated NK cells had no inhibitory effects on peripheral blood-derived hematopoietic progenitor (HP) cells. Peripheral blood HP cells were similar to bone marrow progenitors in phenotype and clonogenic colony formation capabilities. Peripheral blood HP cells could be cocultured in vitro with rIL-2-activated autologous NK cells for 3 d without adverse effects on the HP cells. Acute myelogenous leukemia patients in stable remission were shown to have normal percentages of NK cells and elevated percentages of peripheral blood HP cells. NK cells from most of these patients could be activated with rIL-2 to lyse fresh uncultured tumor cells as well as autologous leukemia cells without effecting the peripheral blood HP cells. These results suggest that rIL-2-activated NK cells may be used to purge peripheral blood HP cell preparations of residual tumor cells before hematopoietic reconstitution.

Cell Separation↗
PubMed1988

Interleukin 2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu-23 activation antigen.

IL-2 potentiates both growth and cytotoxic function of T lymphocytes and NK cells. Resting peripheral blood NK cells can respond directly to rIL-2, without requirement for accessory cells or cofactors, and enhanced cytotoxicity can be measured within a few hours after exposure to this lymphokine. In this study, we describe an activation antigen, Leu-23, that is rapidly induced and phosphorylated after IL-2 stimulation of NK cells and a subset of low buoyant density T lymphocytes. Previously, it has been uncertain whether all NK cells or only a subset are responsive to IL-2. Since within 18 h after exposure to IL-2, essentially all NK cells express Leu-23, these findings indicate that all peripheral blood NK cells are responsive to stimulation by IL-2. The Leu-23 antigen is a disulfide-bonded homodimer, composed of 24-kD protein subunits with two N-linked oligosaccharides. Appearance of this glycoprotein on NK cells is IL-2 dependent and closely parallels IL-2-induced cytotoxicity against NK-resistant solid tumor cell targets.

Antigens, CD↗
PubMed1988

Structural and serological heterogeneity of gamma/delta T cell antigen receptor expression in thymus and peripheral blood.

Monoclonal antibodies (mAb) reactive against the gamma/delta T cell antigen receptor (TcR) have been used to characterize the distribution and structural properties of gamma/delta TcR-bearing lymphocytes in blood and thymus. Consistent with prior reports the TcR gamma/delta-1 and delta-1 mAb react with all gamma/delta TcR+ T lymphocytes in blood and thymus. By contrast the TCS-delta mAb was found only to react with a subset of the gamma/delta TcR-bearing T cell population. Several lines of evidence suggest that this reagent preferentially reacts with the V delta 1 gene product. Using these reagents, it was observed that gamma/delta TcR+ T lymphocytes comprise 4.6 +/- 3.5% (range 1.0-16.3%) of peripheral blood lymphocytes. However, analysis of peripheral blood from normal adult donors revealed that in 29 of 32 the TCS-delta (possibly V delta 1)-bearing cells comprised less than 30% of the total gamma/delta-TcR+ population. Biochemical analysis demonstrated that the predominant form of the gamma/delta TcR in adult peripheral blood is a disulfide-linked heterodimer, indicating preferential use of the C gamma 1 gene. The delta TcR chain from these TcR-gamma/delta-1+/TCS-delta- T cells was remarkably basic in charge, as analyzed by nonequilibrium pH gradient electrophoresis. By contrast with peripheral blood the majority of freshly isolated and interleukin 2-cultured gamma/delta TcR+ thymocytes were predominantly TcR-gamma/delta-1+/TCS-delta +, and preferentially expressed V delta 1. Moreover, both disulfide-bonded and nondisulfide-bonded gamma/delta TcR heterodimers were expressed in all thymuses examined and both forms were contained within the TCS-delta + thymic subset. Similar to recent findings in the mouse, these studies suggest a possible bias in the structural form of gamma/delta TcR based on tissue location.

Antibodies, Monoclonal↗
PubMed1988

Tail-pinch elicited eating in rats (Rattus norvegicus) and hamsters (Mesocricetus auratus).

Noninjurious tail-pinch (TP) elicited a normal hyperphagic reaction to a milk solution in sated rats but did not increase the amount of milk solution consumed by sated hamsters. In both rats and hamsters, TP did increase the rate of eating, but did not change the amount of time spent contacting the drinking spout in rats and actually decreased the amount of time spent contacting the spout in hamsters. These results suggest that (1) the failure of hamsters to increase meal size in response to food deprivation is also generalizable to TP-induced eating, and (2) TP-induced hyperphagia may be caused by the generalized energizing effect that TP has on ongoing behavior rather than by TP stimulation enhancing the releasing properties of environmental stimuli such as the drinking spout.

Animals↗
PubMed1988

Human T-cell-receptor delta chain: genomic organization, diversity, and expression in populations of cells.

The locus of the delta chain of the human T-cell receptor has been isolated and examined. Three D (diversity) regions and two J (joining) regions are present on the 5' side of the C (constant) region. The closest V (variable) region to the constant region is V delta 2, which in the germ line is found on the 3' side of the constant region in an inverted direction. The genomic structure of the human locus closely parallels its mouse counterpart. Several cDNA sequences and a series of rearranged genomic sequences are compared which demonstrate an enormous potential diversity in the junctional region, between the variable region and the joining region. We find the predominant utilization of the PEER variable region in thymic polyclonal gamma delta cell lines and in some peripheral blood gamma delta cell lines. Thus, the delta chain may have relatively limited variable-region diversity but a large junctional-region diversity. The implications of this observation are discussed.

Amino Acid Sequence↗
PubMed1988

Fixation effects on membranous and endochondral onlay bone-graft resorption.

Difficulties arise in the prediction of maintenance of graft volume over time when bone grafts are used for facial contour reconstruction. We hypothesize that graft fixation will decrease movement and lead to decreased resorption. Fixed and nonfixed endochondral (rib) and membranous (skull) onlay bone grafts measuring 30 X 10 X 4 mm were grafted to the mandible bilaterally in 10 adult sheep. Fixation was achieved using the lag-screw technique. Volume measurements using caliper technique were made 20 weeks postoperatively. The volume of graft present at 20 weeks was significantly greater for the fixed bone grafts (p less than 0.001): fixed membranous, 85.9 percent; fixed endochondral, 76.2 percent; nonfixed membranous, 55 percent; and nonfixed endochondral, 16.6 percent. The results are explained using biomechanical theories related to the effects of strain. At present, it is suggested by this study that when onlay bone grafts are stabilized, improved results with respect to graft resorption can be expected.

Animals↗
PubMed1988

Graded exercise testing for diagnosis of coronary artery disease in elderly patients.

We tested the clinical utility and predictive value of graded exercise testing in the diagnosis of coronary artery disease in 153 patients aged 65 years or more. Based on changes of the ST segment from baseline, the test was considered positive with 1 mm of depression lasting 0.08 seconds, negative with no changes despite 85% of predicted maximal heart rate, probably positive with 1 mm of depression at rest becoming 2 mm with exercise, probably negative with no changes at maximal heart rate (within 10 beats per minute of 85% of predicted maximal), and uninterpretable with baseline electrocardiographic changes (eg, digitalis effect, left bundle branch block, left ventricular hypertrophy, etc). A test was considered inadequate when the exercise tolerance was less than or equal to 5 METs (metabolic equivalent of the task) and/or maximal heart rate was less than 100 beats per minute. The 153 patients had 163 tests. Only 33 (20%) were considered inadequate or uninterpretable, and there were no complications requiring medical intervention. Of 82 patients who had coronary angiography, 52 (63%) had 50% stenosis of at least one major epicardial artery; 44 of these patients had positive results of exercise testing. Nine patients with negative exercise tests had negative angiograms. There were eight false-negative and seven false-positive results. These results revealed a sensitivity of 85%, a specificity of 56%, and a predictive value of 86% for a positive test.

Aged↗
PubMed1987

Evidence that the T cell antigen receptor may not be involved in cytotoxicity mediated by gamma/delta and alpha/beta thymic cell lines.

After culture in IL-2, thymocytes expressing either TCR-alpha/beta or -gamma/delta acquired the ability to lyse hematopoietic and solid tumor cell targets without deliberate immunization or apparent restriction by the MHC. Moreover, TCR-alpha/beta- and TCR-gamma/delta-bearing thymic cell lines demonstrated an essentially identical spectrum of cytolysis against several tumor cell targets. Cytotoxicity was not inhibited by antibodies against CD3 or CD2 and modulation of the CD3/TCR complex also failed to affect cytotoxicity. Thus, non-MHC-restricted cytotoxicity can be mediated by thymocytes with either TCR-alpha/beta or TCR-gamma/delta, but the TCR may not be responsible for target recognition.

Antibodies↗