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Biomedical subjects

P Young

Publications and source records attributed to P Young.

At least 163 records · Page 9Linked to original sources
PubMed1996

A progress report on accelerated residency programs in family practice.

BACKGROUND: In 1991 the American Board of Family Practice (ABFP) approved 12 programs to participate in an experiment in medical education. Selected students in 12 medical schools are able to complete their first year of family practice residency while completing their fourth year of school. This paper reports on the progress of the programs and residents participating in this project. METHOD: Data from the ABFP in-training examination and certification examination were compiled for all trainees and graduates through 1994. Performances were compared with national norms and the performances of traditional residents in the same programs. The program directors were surveyed to assess their experiences, program effectiveness, benefits, liabilities, and implementation problems. RESULTS: Accelerated residents performed better than their peers and national norms on the ABFP in-training and certification examinations. The directors rated the clinical performance of accelerated residents as equal to or better than the clinical performance of traditional residents by the end of the program. Advantages of accelerated residency included improvements in recruiting, image, and morale. Problems occurred in order and prescription writing and acceptance of the accelerated residents by nurses, other residents, and physicians in other disciplines. CONCLUSION: Early entry into residency training of bright, highly motivated, and mature students appears to offer benefits for trainees and programs alike.

Educational Measurement↗
PubMed1996

Human keratinocytes lack the components to produce leukotriene B4.

The cellular origin of leukotriene B4 (LTB4), a potent pro-inflammatory molecule present in psoriatic lesions, has yet to be determined. In the present study, cultured human keratinocytes were evaluated for their ability to produce LTB4. Keratinocytes stimulated under a variety of conditions did not produce detectable amounts of LTB4, as measured by enzyme immunoassay and liquid chromatographic techniques. Prostaglandin E2 and 15-hydroxyeicosatetraenoic acid were the only eicosanoids detected. The capacity of keratinocytes to synthesize 5-lipoxygenase (5-LO) products, or lack thereof, was further evaluated by preparing subcellular fractions and examining them for the presence of 5-LO activity and the proteins responsible for LTB4 production. Using Western blot analysis, we detected no bands that migrated with the 78-kDa 5-LO enzyme. Subcellular fractions were also examined for the presence of the 5-LO-activating protein (FLAP). This protein, which is essential to 5-LO activity, could not be detected in any keratinocyte preparation examined. Consistent with the absence of proteins, the mRNAs for 5-LO and FLAP were undetectable by reverse transcriptase polymerase chain reactions analysis. These results demonstrate that human keratinocytes lack the crucial proteins necessary for LTB4 production.

5-Lipoxygenase-Activating Proteins↗
PubMed1996

Raising airway resistance in laryngectomees increases tissue oxygen saturation.

The physiological airflow resistance from the anterior nares to the upper trachea has recently been documented. This resistance is thought to be important in preventing alveolar collapse and in maintaining the optimum lung ventilation: perfusion ratio. This resistance is lost in laryngectomees who may have a subsequent decline in lung function and arterial oxygen saturation. A stoma filter with a resistance approximating to that of the normal upper airway has been developed and laryngectomees who wear this device demonstrate a rapid increase in tissue oxygen saturation (median increase: 1.4 kPa, P = 0.0087) without significantly altering tissue carbon dioxide saturation. This finding will have a major impact on the future rehabilitation of laryngectomees and those with a temporary tracheostomy.

Airway Resistance↗
PubMed1996

Role of mesenchymal-epithelial interactions in normal bladder development.

PURPOSE: To assess the role of cell-cell interactions in the development of bladder smooth muscle. MATERIAL AND METHODS: Bladders from 14-day rat fetuses (prior to smooth muscle differentiation) were isolated and digested with trypsin to separate the mesenchyme and epithelium. Three types of specimens were prepared for grafting under the renal capsule of syngeneic adult hosts: a) intact bladder (BL) which had been isolated from fetuses of timed pregnant rats by surgical methods alone; b) bladder mesenchyme (BLM) alone (urothelium removed following trypsinization); and c) isolated BLM recombined with bladder urothelium (BLM + BLE). After 2 weeks of in vivo growth the grafts were assessed by immunocytochemical techniques for the expression of smooth muscle cells markers (actin, myosin, vinculin, laminin and desmin). The same experiments were repeated in vitro. In the final experiment, the induction of bladder smooth muscle was elicited in situ across species lines. Fourteen-day rat BLM was grafted onto the proximal ureter of an athymic nude mouse after ipsilateral nephrectomy. RESULTS: Grafts of intact BL and BLM + BLE recombinants expressed smooth muscle differentiation. In contrast, grafts of BLM alone remained devoid of smooth muscle. This was also true for the in vitro studies in which, after 5 days of growth, BLM + BLE recombinants (n = 12) showed clear evidence of smooth muscle differentiation. In contrast, cultures of BLM alone (n = 12) exhibited poor growth without smooth muscle differentiation. In the final experiment testing the induction of smooth muscle across species, after 1 month in vivo growth the urothelium of the cut end of the ureter had invaded the grafted BLM. The BLM grafts (n = 3) had increased 30 times in size, and immunocytochemical staining showed clear expression of smooth muscle markers in the grafted BLM in proximity to the urothelium. CONCLUSION: We have shown that the differentiation of smooth muscle in the rat bladder is dependent upon an inductive interaction with the epithelium.

Animals↗
PubMed1996

Change.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed1995

Using a mixture model to predict the occurrence of diabetic retinopathy.

Diabetes mellitus is a common condition which has several serious complications associated with it. In this paper a mixture model, based on one previously used to predict the onset of AIDS, is used to predict the onset of one of these complications, diabetic retinopathy, the major cause of adult blindness in the U.K. This model differs from the previous AIDS model by introducing covariates into the model and using a wider choice of mixture distributions. The fit and distributional assumptions of the model are then discussed for this example. The model is fitted to the data by maximum likelihood. It is important that the training set contains balanced numbers of individuals with and without retinopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors.

Embryonic hematopoiesis is initiated in part in the blood islands of the yolk sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a mucin-like cell surface glycoprotein that is expressed by hematopoietic progenitors and all endothelial cells of the adult and embryo, is also found on a subset of luminal hematopoietic-like cells in the yolk sac blood islands as well as on the vascular endothelium lining these early hematopoietic locations. We show here that, as in all other hematopoietic sites thus far examined, immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the vast majority of erythroid and myeloid progenitor cell colony forming activity. To examine the developmental interactions between these CD34+ hematopoietic progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using CD34 antiserum and produced cell lines by transformation with a retrovirus expressing the polyoma middle T antigen. Analysis of these cell lines for CD34, von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in Matrigel indicates that they appear to be endothelial cells, consistent with their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells on these endothelial cell lines results in up to a 60-fold increase in total hematopoietic cell number after approximately 8 days. Analysis of these expanded hematopoietic cells showed that the majority were of the monocyte/macrophage lineage. In addition, examination of the cultures showed the rapid formation of numerous cobblestone areas, a previously described morphologic entity thought to be representative of early pluripotential stem cells. Scrutiny of the ability of these endothelial cell lines to expand committed progenitor cells showed up to a sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days in culture, consistent with the notion that these embryonic endothelial cells mediate the expansion of these precursor cells. Polymerase chain reaction analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and interleukin-6 (IL-6), whereas there is a generally low or not measurable production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1, erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from these cocultures can be modified to include an erythroid population by the addition of exogenous erythropoietin. These data suggest that endothelial cell lines derived form the yolk sac provide an appropriate hematopoietic environment for the expansion and differentiation of yolk sac progenitor cells into at least the myeloid and erythroid lineages.

Animals↗
PubMed1995

Superovulatory responses to eCG in llamas (Lama glama ).

Llamas are copulation-induced single-ovulators, and multiple ovulation and embryo transfer (MOET) methods have not yet been developed for this species. Superovulatory responses to eCG given during an induced (Group A) or simulated (Group B) luteal phase were investigated using ultrasound to observe ovarian follicles and corpora lutea (CLs) and plasma progesterone was used to assess luteal function. Embryos were recovered nonsurgically. Group A (n = 19): donors were given 8 microg, im GnRH analogue (Day 0) to induce ovulation of a mature follicle, 1000 IU, im eCG (Day 7), and 250 microg PGF(2alpha) analogue (Day 9). Group B (n = 17): donors were given a subcutaneous progestagen implant (3 mg Norgestomet) at Days 0 to 7) and 1000 IU, im eCG (Day 5). When most (>65%) of the follicles in both Groups A and B had matured at 5 to 11 d post eCG, the donors were given 8 microg, im GnRH and mated once (n = 26) or twice within a 24-h interval (n = 10); embryos were recovered 6 to 9 d post ovulation. More follicles and corpora lutea were induced in Group B than in Group A, but a similar mean number of embryos were recovered (1.3 vs 1.6), and a similar proportion of donors yielded multiple embryos (35 vs 32%). The embryo recovery rate was similar for Groups A and B (39 and 37%), but it was higher (P < 0.001) with 2 (72%) rather than 1 (22%) mating, and it was negatively correlated with CL number (P < 0.05). Overall, 80% of the llamas had a precocious CL and elevated plasma progesterone concentrations when multiple follicles reached maturity. This was associated with increased subsequent superovulation and embryo recovery (P < 0.01). Peak plasma progesterone was positively correlated with the CL number (P < 0.05). From these results we conclude that superovulation may be achieved with eCG given during either an induced or a simulated luteal phase, that embryo recovery is improved following 2 matings rather than 1, and that MOET may indeed be feasible for use in the llama.

Journal Article↗
PubMed1995

Current trends in molecular recognition and bioseparation.

Molecular recognition guides the selective interaction of macromolecules with each other in essentially all biological processes. Perhaps the most impactful use of biomolecular recognition in separation science has been in affinity chromatography. The results of the last 26 years, since Cuatrecases, Wilchek and Anfinsen first reported the purification of staphylococcal nuclease, have validated the power of biomolecular specificity for purification. This power has stimulated an explosion of solid-phase ligand designs and affinity chromatographic applications. An ongoing case in point is the purification of recombinant proteins, which has been aided by engineering the proteins to contain Affinity-Tag sequences, such as hexa-histidine for metal-chelate separation and epitope sequence for separation by an immobilized monoclonal antibody. Tag technology can be adapted for plate assays and other solid-phase techniques. The advance of affinity chromatography also has stimulated immobilized ligand-based methods to characterize macromolecular recognition, including both chromatographic and optical biosensor methods. And, new methods such as phage display and other diversity library approaches continue to emerge to identify new recognition molecules of potential use as affinity ligands. Overall, it is tantalizing to envision a continued evolution of new affinity technologies which use the selectivity built into biomolecular recognition as a vehicle for purification, analysis, screening and other applications in separation sciences.

Chromatography, Affinity↗
PubMed1995

Insulin inhibits the phosphorylation of alpha-Gi-2 in intact hepatocytes.

Challenge of intact hepatocytes with insulin reduced the level of phosphorylated alpha-Gi-2 found under basal (resting) conditions. At maximally effective concentrations of insulin the steady-state labelling of alpha-Gi-2 was reduced by approximately 21%. Insulin achieved this in a time- and dose-dependent fashion, exhibiting an IC50 value of 109 +/- 22 pM. The increased labelling of alpha-Gi-2 seen after challenge of cells with phorbol 12-myristate 13-acetate was also attenuated by insulin. Treatment of hepatocytes with the protein phosphatase inhibitor okadaic acid increased the labelling of alpha-Gi-2 in a fashion which was insensitive to the action of insulin. It is suggested that insulin may reduce the level of phosphorylation of alpha-Gi-2 by stimulating intracellular protein phosphatase activity and that this action may offer a molecular explanation for the ability of insulin to inhibit adenylate cyclase activity in hepatocytes by increasing the level of non-phosphorylated alpha-Gi-2.

Adenylyl Cyclases↗
PubMed1995

Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins.

Human interleukin 5 (hIL5) and soluble forms of its receptor alpha subunit were expressed in Drosophila cells and purified to homogeneity, allowing a detailed structural and functional analysis. B cell proliferation confirmed that the hIL5 was biologically active. Deglycosylated hIL5 remained active, while similarly deglycosylated receptor alpha subunit lost activity. The crystal structure of the deglycosylated hIL5 was determined to 2.6-A resolution and found to be similar to that of the protein produced in Escherichia coli. Human IL5 was shown by analytical ultracentrifugation to form a 1:1 complex with the soluble domain of the hIL5 receptor alpha subunit (shIL5R alpha). Additionally, the relative abundance of ligand and receptor in the hIL5.shIL5R alpha complex was determined to be 1:1 by both titration calorimetry and SDS-polyacrylamide gel electrophoresis analysis of dissolved cocrystals of the complex. Titration microcalorimetry yielded equilibrium dissociation constants of 3.1 and 2.0 nM, respectively, for the binding of hIL5 to shIL5R alpha and to a chimeric form of the receptor containing shIL5R alpha fused to the immunoglobulin Fc domain (shIL5R alpha-Fc). Analysis of the binding thermodynamics of IL5 and its soluble receptor indicates that conformational changes are coupled to the binding reaction. Kinetic analysis using surface plasmon resonance yielded data consistent with the Kd values from calorimetry and also with the possibility of conformational isomerization in the interaction of hIL5 with the receptor alpha subunit. Using a radioligand binding assay, the affinity of hIL5 with full-length hIL5R alpha in Drosophila membranes was found to be 6 nM, in accord with the affinities measured for the soluble receptor forms. Hence, most of the binding energy of the alpha receptor is supplied by the soluble domain. Taken with other aspects of hIL5 structure and biological activity, the data obtained allow a prediction for how 1:1 stoichiometry and conformational change can lead to the formation of hIL5.receptor alpha beta complex and signal transduction.

Amino Acid Sequence↗
PubMed1995

Dissatisfaction, disability, and rheumatoid arthritis.

OBJECTIVES: To investigate dissatisfaction with function in patients with rheumatoid arthritis (RA), and to see if dissatisfaction can be adequately explained by level of function. METHODS: Fifty patients with RA were assessed for disease activity, psychological status, disability, expectation of future disability, and satisfaction with both global function and individual activities of daily living (ADL). RESULTS: Fifty percent of patients expressed dissatisfaction with global function, which correlated more strongly with pain (r = 0.474) and psychological status than with function (r = 0.398). Only 10% predicted improvement in global function. Seventy-two percent expressed dissatisfaction with performing at least one ADL. CONCLUSIONS: Patient dissatisfaction with both global function and individual ADL function is high and cannot adequately be explained by disability alone. Correlation with pain and psychological status implies that modifying these variables (perhaps through education programs about pain relief or relaxation) could reduce dissatisfaction.

Activities of Daily Living↗
PubMed1995

Demonstration of hypomethylation of proteins in the brain of pigs (but not in rats) associated with chronic vitamin B12 inactivation.

1. Pigs treated with nitrous oxide for periods of 1, 2 and 4 months demonstrated markedly reduced levels of methionine synthase and concomitant reduction in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, the methylation ratio, at all time intervals. 2. Both 'O' and 'N' methylations were significantly reduced in pigs after 4 months in nitrous oxide but not after shorter periods. 3. Hypomethylation correlated with the development of clinical ataxia, but was absent when the pigs were clinically normal. It also only occurred when the S-adenosylmethionine level fell. 4. Rats maintained in nitrous oxide for 4 months showed a marked reduction of methionine synthase but no reduction in the methylation ratio or in brain hypomethylation. None of the rats became clinically ataxic. 5. Using an exogenous protein as a methyl group acceptor, it was demonstrated in an in vitro assay that the methyltransferase enzymes responsible for brain 'O' and 'N' methylation were not affected per se by nitrous oxide treatment. 6. It is concluded that reduction of the methylation ratio in the brain of pigs as a consequence of methionine synthase inhibition leads to brain hypomethylation. This hypomethylation could affect critical components of nerve tissue, inducing the vacuolar myelopathic changes seen in the spinal cord of these animals, which mimic those of subacute combined degeneration in man.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1995

Resistance, humidity and temperature of the tracheal airway.

Patients after laryngectomy are subject to a high incidence of chest complaints. In attempting to reduce these a number of 'new nose' stoma filters have recently been introduced which claim to humidify and warm air, filter particulate matter and, by increasing tracheal airway resistance, to improve lung function. Our study defines the normal tracheal temperature, humidity and resistance values which were obtained from 16 patients with a normal upper respiratory tract. These parameters will allow the available filters to be evaluated objectively and may lead to the development of a more physiological 'new nose'.

Airway Resistance↗
PubMed1995

Influence of prenatal photoperiod on postnatal plasma concentrations of progesterone and prolactin in female red deer (Cervus elaphus) reared in constant equatorial photoperiod.

Prenatal photoperiod influences postnatal prolactin secretion and the timing of reproductive development in male red deer reared from birth in a constant equatorial photoperiod (12:12 light:dark). The present trial investigated whether a similar phenomenon occurs in female red deer. Female deer whose mothers had been exposed for the last 14 weeks of gestation to long (group L, 18:6 light:dark) or short day length (group S, 6:18 light:dark) were kept from birth in constant equatorial day length with food available ad libitum. Both groups showed similar live-weight gain to 90-100 weeks of age. Blood samples taken once or twice weekly were analyzed for progesterone and prolactin. Progesterone concentrations indicated that there was no difference between the groups in the timing of the first incidence of ovarian (luteal) activity, which occurred at a normal or late age for natural puberty (67 weeks or older). Only one individual per group exhibited normal repeated luteal cyclicity since there was a high incidence of irregular or abnormal luteal function. Plasma prolactin concentrations at birth were higher in group L than group S (P < 0.001). Thereafter, although the mean and peak values did not differ significantly between the groups, there was a significant difference in the pattern of secretion; deer in group L showed significant clustering of prolactin peaks (P < 0.01) at a mean age of 48 weeks, whereas deer in group S showed a random distribution of peaks. Therefore, for female red deer raised in constant equatorial photoperiod, prenatal long day lengths did not advance timing of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗