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Biomedical subjects

D Beebe

Publications and source records attributed to D Beebe.

14 recordsLinked to original sources
PubMed2002

Microfluidic technology for assisted reproduction.

The physical tools used in assisted reproduction have changed little over several decades. Microfluidics is an emerging technology that allows a fresh examination of the way assisted reproduction is performed. Here we review our work to develop microfluidic devices to perform the functions required in assisted reproduction. These functions include loading/unloading, culture, chemical manipulation, and mechanical manipulation of embryos and oocytes. Basic microfluidic theory and microfluidic device design and operation are discussed. Results are presented for mechanical removal of cumulus cells and for embryo culture. Results suggest that microfluidic systems will lead to improved efficiencies in assisted reproduction.

Animals↗
PubMed2000

Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.

Diabetic hyperglycaemia causes a variety of pathological changes in small vessels, arteries and peripheral nerves. Vascular endothelial cells are an important target of hyperglycaemic damage, but the mechanisms underlying this damage are not fully understood. Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase C isoforms; increased formation of glucose-derived advanced glycation end-products; and increased glucose flux through the aldose reductase pathway. The relevance of each of these pathways is supported by animal studies in which pathway-specific inhibitors prevent various hyperglycaemia-induced abnormalities. Hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells. Here we show that this increase in reactive oxygen species is prevented by an inhibitor of electron transport chain complex II, by an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase. Normalizing levels of mitochondrial reactive oxygen species with each of these agents prevents glucose-induced activation of protein kinase C, formation of advanced glycation end-products, sorbitol accumulation and NFkappaB activation.

Animals↗
PubMed2000

The expression pattern of a novel Deltex homologue during chicken embryogenesis.

We isolated a partial cDNA encoding a novel chicken homologue of human Deltex (DTX1), a member of the Notch signaling pathway. The cDtx2 sequence showed higher homology to KIAA0937 protein (92% identical) than to DTX1 (68% identical). cDtx2 is expressed widely in the epiblast at stage 4. Later in development it is expressed in many neural and sensory structures, such as neural tube, migrating neural crest cells, epidermal placodes, cranial ganglia, and the optic and otic vesicles.

Amino Acid Sequence↗
PubMed2000

The SCARFACE gene is required for cotyledon and leaf vein patterning.

Mechanisms controlling vein patterning are poorly understood. We describe a recessive Arabidopsis mutant, scarface (sfc), which maps to chromosome 5. sfc mutants have vein pattern defects in cotyledons, leaves, sepals and petals. In contrast to the wild type, in which these organs all have linear veins that are continuous with at least one other vein, in sfc mutants these organs' secondary and tertiary veins are largely replaced by small segments of discontinuous veins, which we call vascular islands. Patterning defects are manifest in cotyledon provascular tissue, suggesting that the patterning defect occurs early in organogenesis. sfc mutants have exaggerated responses to exogenous auxin. Analysis of monopteros (mp(T370)) sfc-1 double mutants suggested that SFC has partially overlapping functions with MP in patterning of both primary and secondary veins.

Arabidopsis↗
PubMed1997

Combined liver-total bowel transplantation has no immunologic advantage over total bowel transplantation alone. A prospective study in a porcine model.

BACKGROUND: Rejection remains a major obstacle to successful bowel transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early bowel rejection after combined liver-total (small- and large-) bowel transplants vs total bowel transplants alone. METHODS: We assessed the incidence of early post-transplant rejection, graft-vs-host disease, and infection after combined liver-total bowel transplants (group 1, n = 10) and total bowel transplants alone (group 2, n = 9) in outbred Yorkshire Landrace pigs. Liver and bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe). RESULTS: Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P < .001). Death rates owing to (irreversible) rejection at days 7, 14, and 21 were 0% in groups 1 and 2 (P = .48). Grading of bowel rejection episodes, based on the results of daily biopsy specimens, was not significantly different between the groups whether on individual days or overall. In group 1, the incidence of liver rejection episodes was as high as 66% (day 14 and at autopsy). At autopsy, generalized graft-vs-host disease (skin, native intestine, and native liver) was noted in 55% of group 1 and 43% of group 2 pigs (P = .55). Graft-vs-host disease was noted concurrently with rejection episodes of the liver or bowel grafts. CONCLUSIONS: Simultaneous liver grafting did not further reduce the incidence of early bowel rejection or graft-vs-host disease when compared with total bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-bowel syndrome and normal liver function.

Animals↗
PubMed1996

Quadruple immunosuppression in a pig model of small bowel transplantation.

Rejection remains a major obstacle to successful small bowel transplantation in humans, irrespective of the immunosuppressants. Previous large animal studies have not used quadruple immunosuppression (with high-dose intravenous cyclosporine A [CSA]) for induction, followed by triple immunosuppression for maintenance therapy. Nor have immunosuppressive doses been comparable to clinical solid organ transplants. We studied, in 78 nonrelated outbred pigs, the effect of quadruple immunosuppression (including horse anti-pig thymocyte globulin [ATG] and high-dose intravenous CSA) on the incidence and severity of rejection in the early, critical posttransplant period. Group A (n = 19) pigs were nonimmunosuppressed. Group B (n = 20) received quadruple immunosuppression: pig ATG (10 mg/kg/day x 10 days), intravenous CSA (3.0 mg/kg/day), prednisolone (2 mg/kg/day), and azathioprine (2.5 mg/kg/day); prednisolone and azathioprine were each reduced by 50% on posttransplant Days 8 and 15. Trough CSA levels were > or = 400 ng/ml for the first 7 days posttransplant, > 200 ng/ml thereafter. Recipient pigs underwent resection of large and small bowel; orthotopic transplants (proximal duodenojejunostomy, distal ileostomy) were done with systemic vein drainage. We developed a scoring system (no, mild, moderate, severe rejection) to grade the extent of both interstitial and vascular rejection: biopsies were obtained daily from the ileostomy. Rejection-free graft survival at posttransplant Days 7, 10, and 14 was 32, 26, and 16% in the nonimmunosuppressed group versus 95, 90, and 85% in the immunosuppressed group (P < 0.0001). Rejection grades were significantly better over the whole observation period in immunosuppressed pigs: interstitial rejection was not present in up to 67% of all daily biopsy specimens. Rejection was present in all specimens of nonimmunosuppressed pigs. Vascular rejection was uncommon (incidence < 10%) in both groups. Isolated vascular rejection without interstitial rejection was not found. Graft-versus-host reaction was noted in both groups in the skin only; liver and native bowel were not involved. We conclude that quadruple immunosuppression with pig ATG and high-dose intravenous CSA for induction effectively prevents moderate and severe rejection in this model. Since clinical transplant complications (rejection, lymphomas) have persisted under FK 506 treatment, our immunosuppressive regimen should be considered an alternative for bowel transplantation in humans to prevent early rejection.

Animals↗
PubMed1995

Residents' formal knowledge acquisition and preferred learning styles.

BACKGROUND: Many family practice residency programs use the Myers-Briggs Type Indicator (MBTI) in their educational programs. Our purpose was to study the relationship between learning style, as determined by MBTI personality preferences, and residents' cognitive knowledge acquisition, measured by in-service training examination (ISTE) scores during the first and third years of residency. METHODS: We evaluated 36 residents using both their first- and third-year ISTE composite scores and their MBTI scores. ISTE scores were analyzed according to the MBTI personality factors. We used the Wilcoxon Rank-Sum Test to determine the association between the improvement in residents' ISTE scores between the first- and third-year examinations and preferred learning styles. RESULTS: Significant differences were found on the composite ISTE scores for the thinking/feeling and judgment/perception scales. Feelers increased ISTE scores more than thinkers (P = .031); judgers increased ISTE scores more than perceivers (P = .04). CONCLUSIONS: Results do not support the literature or current MBTI learning theory. Intuitive residents demonstrated no advantage over sensing residents. Residents using feeling/judgment as their preferred learning style acquired more knowledge over 3 years than their thinking/perceiving counterparts, as measured by ISTE scores.

Adult↗
PubMed1987

c-myc mRNA is elevated as differentiating lens cells withdraw from the cell cycle.

Explants of the central region of lens epithelia from early chicken embryos differentiate in vitro to form lens fiber cells when cultured in the presence of chicken vitreous humor. Hybridization of a 32P-labeled v-myc viral oncogene DNA probe to RNA extracted from differentiating explants and immobilized on nitrocellulose filters indicates that levels of 2.5 kb c-myc mRNA are transiently elevated 5-10-fold in the differentiating cells. Increased levels of c-myc mRNA are observed within 30 min of the initiation of differentiation in vitro and persist for 8-9 h. Thymidine labeling of nuclei in differentiating explants indicates that entry of cells into S phase is inhibited during this period, as differentiating cells complete a final round of mitosis and withdraw from the cell cycle. Levels of c-myc mRNA are also elevated in the peripheral region of the lens epithelium, which contains cells undergoing differentiation in vivo, suggesting that the regulation of c-myc mRNA which occurs in vitro may also occur in vivo. c-myc mRNA, c-fos mRNA, and c-src mRNA showed distinct patterns of regulation associated with lens fiber formation in vivo, thus providing evidence that the regulation of c-myc mRNA is specific to this proto-oncogene. The finding that c-myc mRNA undergoes a specific, transient elevation in differentiating lens cells as they withdraw from the cell cycle contrasts with a large body of evidence linking enhanced c-myc expression with increased cell proliferation.

Animals↗
PubMed1986

Binding interaction studies of selected receptor subpopulations after partial cross-linking receptor-ligand complexes with a photoactivated heterobifunctional reagent.

Certain hormonal and nonhormonal binding systems such as the leukoagglutinin-lymphocyte model exhibit complex receptor-ligand interactions that result in nonlinear Scatchard plots. Such plots are interpreted as indicating either homogeneous negatively interacting binding sites or heterogeneous sites with different and fixed affinity. We assessed the validity of these interpretations in our system by conjugating the ligand to a photoactivated heterobifunctional agent and cross-linking the conjugate to a subset of receptors before studying the binding interactions of non-cross-linked sites. Conjugation did not qualitatively or quantitatively affect the binding properties of the ligand. Cross-linking was specific, efficient, and stable and had no effect on irrelevant surface receptors. Cross-linking of only 3% of the total receptors resulted in 50% decreased ligand binding to high affinity sites consistent with a calculated inactivation of 85% and 2% of high and low affinity sites, respectively. Such preferential inactivation of high affinity sites in an unequivocal demonstration of binding sites heterogeneity in this system and shows a clear rejection of the homogeneous cooperation model.

Agglutinins↗
PubMed1986

Control of lens cell differentiation and ion fluxes by growth factors.

The results of these studies suggest that an insulin-like growth factor, lentropin, present in the vitreous humor of the eye, is responsible for stimulating lens epithelial cells to differentiate into lens fiber cells during normal lens growth. Lentropin has been shown to stimulate embryonic lens epithelial cells to elongate, specialize for the synthesis of delta crystallin, the major protein synthesized in chicken embryo fiber cells, and to cease DNA synthesis and mitosis. Lentropin appears to decrease the permeability of the plasma membrane to potassium and, by this mechanism, may cause lens fiber cell elongation.

Animals↗
PubMed1979

C5 chemotactic fragment induces leukocyte production of tissue factor activity: a link between complement and coagulation.

Complement-activated human plasma causes generation of tissue factor in human leukocytes. This phenomenon appears to be related to the fifth component of complement (C5) as demonstrated by the use of C5 deficient-plasma and suppression of activity with antibody to C5. Isolation of the chemotactic factor from activated serum or trypsinization of purified C5 reproduces the phenomenon. These data provide evidence for a direct link between complement products and activation of the coagulation system. Because chemotactic peptides from C5 can be generated by a variety of enzymes, our findings suggest a relationship between complement, coagulation, and inflammation.

Blood Coagulation↗