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1.
J Minim Invasive Gynecol ; 29(9): 1110-1118, 2022 09.
Article in English | MEDLINE | ID: mdl-35750193

ABSTRACT

STUDY OBJECTIVE: To evaluate patient characteristics that affect access to minimally invasive gynecologic surgery (MIGS) subspecialty care and identify changes during the coronavirus disease 2019 pandemic. DESIGN: Retrospective cohort study of patients referred to MIGS from 2014 to 2016 (historic cohort) compared with those referred to MIGS in 2020 (pandemic cohort). Primary outcome was the interval between referral and first appointment. SETTING: Single-institution academic MIGS division. PATIENTS: Historic cohort (n = 1082) and pandemic cohort (n = 770). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Demographics and socioeconomic variables (race, ethnicity, language, insurance, employment, and socioeconomic factors by census tract) and distance from hospital were compared between historic and pandemic cohorts with respect to referral interval using the chi-square, Fisher exact tests, and logistic regression. After adjusting for referral indication, being unemployed and living in an area with less population density, less education, and higher percentage of poverty were associated with a referral interval >30 days in the historic cohort. In the pandemic cohort, only unemployment persisted as a covariate associated with prolonged referral interval and new associated variables were primary language other than English (odds ratio, 3.20; 95% confidence interval [CI], 1.60-6.40) and "other" race (odds ratio, 2.22; 95% CI, 1.34-3.68). The odds of waiting >30 days increased by 6% with the addition of 1 demographic risk factor (95% CI, 1.01-1.10) and by 17% for 3 risk factors (95% CI, 1.03-1.34) in the historic cohort whereas no significant intersectionality was identified in the pandemic cohort. Average referral intervals were significantly shorter during the pandemic (31 vs 50 days, p <.01). Telemedicine appointments had a significantly shorter referral interval than in-person appointments (27 vs 47 days, p <.01). Of patients using telemedicine, a greater proportion were non-Hispanic, English speaking, employed, privately insured, and lived further from the hospital (p <.05). CONCLUSION: Time from referral to first appointment at a tertiary-care MIGS practice during the coronavirus disease 2019 pandemic was shorter than that before the pandemic, likely owing to the adoption of telemedicine. Differences in socioeconomic and demographic factors suggest that telemedicine improved access to care and decreased access disparities for many populations, but not for non-English-speaking patients.


Subject(s)
COVID-19 , COVID-19/epidemiology , Female , Gynecologic Surgical Procedures , Humans , Minimally Invasive Surgical Procedures , Pandemics , Retrospective Studies
3.
Proc Biol Sci ; 282(1809): 20141725, 2015 06 22.
Article in English | MEDLINE | ID: mdl-26041354

ABSTRACT

Dynamic symbioses may critically mediate impacts of climate change on diverse organisms, with repercussions for ecosystem persistence in some cases. On coral reefs, increases in heat-tolerant symbionts after thermal bleaching can reduce coral susceptibility to future stress. However, the relevance of this adaptive response is equivocal owing to conflicting reports of symbiont stability and change. We help reconcile this conflict by showing that change in symbiont community composition (symbiont shuffling) in Orbicella faveolata depends on the disturbance severity and recovery environment. The proportion of heat-tolerant symbionts dramatically increased following severe experimental bleaching, especially in a warmer recovery environment, but tended to decrease if bleaching was less severe. These patterns can be explained by variation in symbiont performance in the changing microenvironments created by differentially bleached host tissues. Furthermore, higher proportions of heat-tolerant symbionts linearly increased bleaching resistance but reduced photochemical efficiency, suggesting that any change in community structure oppositely impacts performance and stress tolerance. Therefore, even minor symbiont shuffling can adaptively benefit corals, although fitness effects of resulting trade-offs are difficult to predict. This work helps elucidate causes and consequences of dynamism in symbiosis, which is critical to predicting responses of multi-partner symbioses such as O. faveolata to environmental change.


Subject(s)
Anthozoa/parasitology , Climate Change , Dinoflagellida/physiology , Heat-Shock Response , Symbiosis , Animals , Coral Reefs , Florida , Species Specificity
4.
JSLS ; 27(2)2023.
Article in English | MEDLINE | ID: mdl-37522106

ABSTRACT

Background and Objectives: Robotic gynecologic surgery has outpaced data showing risks and benefits related to cost, quality outcomes, and patient safety. We aimed to assess how credentialing standards and perceptions of safe use of robotic gynecologic surgery have changed over time. Methods: An anonymous, online survey was distributed in 2013 and in 2021 to attending surgeons and trainees in accredited obstetrics and gynecology residency programs. Results: There were 367 respondents; 265 in 2013 and 102 in 2021. There was a significant increase in robotic platform use from 2013 to 2021. Percentage of respondents who ever having performed a robotic case increased from 48% to 79% and those who performed > 50 cases increased from 25% to 59%. In 2021, a greater percentage of attending physicians reported having formalized protocol for obtaining robotic credentials (93% vs 70%, p = 0.03) and maintaining credentialing (90% vs 27%, p < 0.01). At both time points, most attendings reported requiring proctoring for 1 - 5 cases before independent use. Opinions on the number of cases needed for surgical independence changed from 2013 to 2021. There was an increase in respondents who believed > 20 cases were required (from 58% to 93% of trainees and 29% to 70% of attendings). In 2021, trainees were less likely to report their attendings lacked the skills to safely perform robotic surgery (25% to 6%, p < 0.01). Discussion: Greater experience with robotic platforms and expansion of credentialing processes over time correlated with improved confidence in surgeon skills. Further work is needed to evaluate if current credentialing procedures are sufficient.


Subject(s)
Internship and Residency , Robotic Surgical Procedures , Female , Humans , Patient Safety , Gynecologic Surgical Procedures/methods , Credentialing
5.
Front Pain Res (Lausanne) ; 4: 1217035, 2023.
Article in English | MEDLINE | ID: mdl-37790121

ABSTRACT

Introduction: Vestibulodynia (VBD) is the most common cause of sexual pain in the United States, affecting up to 15% of reproductive-aged women during their lifetime with limited treatment options. The purpose of this study was to describe ideal physical characteristics of a vulvar film designed for insertional sexual pain in sexually active women with VBD. Methods: Twenty women were recruited to participant in one of six, semi-structured 60-minute focus group discussions regarding treatment options for VBD. Heterosexual women, aged 18-51 years old with a diagnosis of vulvodynia, vestibulodynia or insertional dyspareunia fit the inclusion criteria. Those who reported no episodes of vaginal intercourse in the prior 18 months were excluded. A new vulvar film technology loaded with 50 mg of 5% lidocaine was introduced to the group. Participants took part in focus groups on a rolling basis depending on availability. Focus group discussions were audio-recorded and transcribed verbatim. Two study investigators coded the transcripts using inductive coding and merged their respective projects to resolve disagreements. We analyzed data related to each code to develop code clusters and higher-level primary topics regarding device preferences. Data related to each of these primary topics was analyzed to assess the range of participant attitudes and preferences and to identify patterns within each primary topic. Results: One hundred and sixteen women were recruited, and twenty women were enrolled. The mean age for the participants was 33.3 years. Most women were educated with at least some college (93%), White (78.6%), married (75%), and had income greater than $100,000 (50%). Analysis of the focus group discussions identified five common topics addressed by participants: desired loaded medication, film size, film shape, film flexibility, and ease and accuracy of use. Concerns across topics included comfort, sexual spontaneity, and efficacy. Interest in loading the device with other acceptable medications or combination with lidocaine was independently noted in 2/6 (33%) of the focus groups. Discussion: Mucoadhesive vulvar thin films may be an acceptable drug delivery system for insertional sexual pain for women with VBD.

6.
Lupus Sci Med ; 9(1)2022 11.
Article in English | MEDLINE | ID: mdl-36418076

ABSTRACT

OBJECTIVE: SLE primarily affects women of childbearing age, who have an increased risk of pregnancy complications, especially in the setting of active disease. Contraception counselling is particularly important given the teratogenicity of some medications used for SLE treatment. Our study describes the frequency of contraception counselling provided by multiple subspecialties to women with SLE and investigates associations between teratogenic medication use and receiving contraception counselling. METHODS: This was a cross-sectional retrospective study of women (aged 15-46 years) diagnosed with SLE who were seen in various outpatient clinics at a large tertiary academic medical centre over a 2-year period. Demographic data were retrieved via the university-affiliated central data repository, and additional data, including documentation of contraception counselling, were obtained via manual chart abstraction. Univariable associations between variables and contraception counselling were assessed to produce unadjusted ORs and 95% CIs. Multivariable models were generated to evaluate independent associations between variables and contraception counselling. RESULTS: Data from 478 women (52% African American, 25% Caucasian) with SLE were included. Rheumatology was the subspecialty to document contraception counselling most frequently (57%). Nearly 80% of women received counselling from at least one subspecialty, 44% from at least two. Factors associated with having lower odds of receiving contraception counselling were older age and Caucasian race. Women on teratogenic medications (methotrexate, mycophenolate mofetil/mycophenolic acid, cyclophosphamide) had higher odds of receiving contraception counselling from at least one subspecialty (OR 2.01; 95% CI 1.23 to 3.26), from two or more subspecialties (OR 2.18; 95% CI 1.50 to 3.17), and from rheumatology (OR 1.86; 95% CI 1.27 to 2.73). CONCLUSIONS: In this study, women with SLE on teratogenic medications had higher odds of receiving contraception counselling from rheumatology and from at least two subspecialties. Multidisciplinary approaches to enhance contraception counselling should be encouraged.


Subject(s)
Lupus Erythematosus, Systemic , Teratogens , Pregnancy , Female , Humans , Retrospective Studies , Cross-Sectional Studies , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Counseling , Contraception/adverse effects , Academic Medical Centers
7.
Contraception ; 105: 46-50, 2022 01.
Article in English | MEDLINE | ID: mdl-34492256

ABSTRACT

OBJECTIVES: (1) Describe contraception use in women with systemic lupus erythematosus (SLE); (2) characterize the types of contraception used by this population; (3) determine factors affecting the documentation of contraception use; (4) identify if contraception counseling was received in this population at risk for adverse pregnancy outcomes. STUDY DESIGN: This cross-sectional study analyzed data from clinic visits from 2016 - 2018 among 453 women of reproductive age who have SLE. Documentation of contraception use, contraception method, contraception counseling, and other medication use were abstracted from the medical record and analyzed with percentage based statistics, chi-squared test, t-test, and logistic regression. RESULTS: Of the 453 women included in the analysis, 71% had a method of contraception documented within 2 years of the study period. Only 37% were using highly effective contraception. 78% had documentation of contraception counseling. Half (50%) were using teratogenic medications; patients on teratogenic medications had higher odds of having a contraceptive method documented (OR 1.56, 95% CI 1.04 - 2.36) however 24% did not have any contraception documented. 28% of patients were using contraception for which they had a possible or absolute contraindication. CONCLUSIONS: Given a substantial proportion of women with SLE did not have any contraception or contraceptive counseling documented, these findings suggest the need to improve universal reproductive health counseling in patients with SLE. IMPLICATIONS: There is room to improve reproductive health care in patients with SLE through provider training to help optimize pregnancy outcomes in this high-risk population.


Subject(s)
Contraceptive Agents , Lupus Erythematosus, Systemic , Contraception , Counseling , Cross-Sectional Studies , Family Planning Services , Female , Humans , Pregnancy
8.
Psychosom Med ; 73(9): 817-25, 2011.
Article in English | MEDLINE | ID: mdl-22048839

ABSTRACT

OBJECTIVES: Treatments of female sexual dysfunction have been largely unsuccessful because they do not address the psychological factors that underlie female sexuality. Negative self-evaluative processes interfere with the ability to attend and register physiological changes (interoceptive awareness). This study explores the effect of mindfulness meditation training on interoceptive awareness and the three categories of known barriers to healthy sexual functioning: attention, self-judgment, and clinical symptoms. METHODS: Forty-four college students (30 women) participated in either a 12-week course containing a "meditation laboratory" or an active control course with similar content or laboratory format. Interoceptive awareness was measured by reaction time in rating physiological response to sexual stimuli. Psychological barriers were assessed with self-reported measures of mindfulness and psychological well-being. RESULTS: Women who participated in the meditation training became significantly faster at registering their physiological responses (interoceptive awareness) to sexual stimuli compared with active controls (F(1,28) = 5.45, p = .03, η(p)(2) = 0.15). Female meditators also improved their scores on attention (t = 4.42, df = 11, p = .001), self-judgment, (t = 3.1, df = 11, p = .01), and symptoms of anxiety (t = -3.17, df = 11, p = .009) and depression (t = -2.13, df = 11, p < .05). Improvements in interoceptive awareness were correlated with improvements in the psychological barriers to healthy sexual functioning (r = -0.44 for attention, r = -0.42 for self-judgment, and r = 0.49 for anxiety; all p < .05). CONCLUSIONS: Mindfulness-based improvements in interoceptive awareness highlight the potential of mindfulness training as a treatment of female sexual dysfunction.


Subject(s)
Awareness , Meditation/methods , Reaction Time , Sensation , Sexual Dysfunctions, Psychological/psychology , Sexuality/psychology , Adolescent , Anxiety/psychology , Arousal , Attention , Depression/psychology , Female , Humans , Male , Meditation/psychology , Self Concept , Sex Factors , Sexuality/physiology , Students/psychology , Women/psychology , Young Adult
9.
Nat Med ; 6(1): 41-8, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10613822

ABSTRACT

Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that limits vessel density in normal tissues and curtails tumor growth. Here, we show that the inhibition of angiogenesis in vitro and in vivo and the induction of apoptosis by thrombospondin-1 all required the sequential activation of CD36, p59fyn, caspase-3 like proteases and p38 mitogen-activated protein kinases. We also detected increased endothelial cell apoptosis in situ at the margins of tumors in mice treated with thrombospondin-1. These results indicate that thrombospondin-1, and possibly other broad-spectrum natural inhibitors of angiogenesis, act in vivo by inducing receptor-mediated apoptosis in activated microvascular endothelial cells.


Subject(s)
Apoptosis/physiology , CD36 Antigens/physiology , Endothelium, Vascular/physiology , Melanoma, Experimental/blood supply , Neovascularization, Pathologic/physiopathology , Neovascularization, Physiologic/physiology , Proto-Oncogene Proteins/physiology , Thrombospondin 1/pharmacology , Angiostatins , Animals , Apoptosis/drug effects , CD36 Antigens/genetics , Caspases/metabolism , Endothelium, Vascular/drug effects , Fibroblast Growth Factor 2/pharmacology , Humans , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Melanoma, Experimental/pathology , Melanoma, Experimental/secondary , Mice , Mice, Knockout , Microcirculation , Mitogen-Activated Protein Kinases/metabolism , Neovascularization, Pathologic/prevention & control , Neovascularization, Physiologic/drug effects , Peptide Fragments/pharmacology , Plasminogen/pharmacology , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/deficiency , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-fyn , Signal Transduction/physiology , p38 Mitogen-Activated Protein Kinases
10.
J Exp Med ; 194(9): 1289-98, 2001 Nov 05.
Article in English | MEDLINE | ID: mdl-11696594

ABSTRACT

Retinal pigment epithelial (RPE) cells employ alphavbeta5 integrin and CD36 receptors to phagocytose photoreceptor outer segment fragments (OS). We explored special properties of RPE phagocytosis to identify the contribution of CD36 to RPE phagocytosis measuring effects of CD36 antibodies on OS binding and internalization kinetics. Early, CD36 antibodies had no effect on OS binding or internalization. Both control and CD36 antibody treated RPE initiated internalization approximately 2 hours after OS challenge. Later, bivalent CD36 IgG accelerated OS engulfment while monovalent Fab fragments inhibited engulfment. Cross-linking Fab fragments restored the accelerating activity of intact IgG. Strikingly, antibodies were effective even if added to OS already bound by RPE. alphavbeta5 blocking antibody reduced OS binding equally well in the presence of CD36 antibodies but CD36 antibodies accelerated internalization of remaining bound OS. Furthermore, CD36 ligation at either apical or basal RPE surface partially substituted for soluble factors that are required for internalization but not for binding of OS at the RPE apical surface. Our results demonstrate that CD36 ligation is necessary and sufficient to activate the OS internalization mechanism of RPE. They suggest that CD36 acts as a signaling molecule in postbinding steps of RPE phagocytosis independently of the OS binding receptor alphavbeta5 integrin.


Subject(s)
CD36 Antigens/immunology , Integrins/immunology , Phagocytosis/immunology , Pigment Epithelium of Eye/immunology , Receptors, Vitronectin , Rod Cell Outer Segment/immunology , Animals , Antibodies, Monoclonal/immunology , CD36 Antigens/biosynthesis , Cell Line , Humans , Kinetics , Lipoproteins, LDL/immunology , Pigment Epithelium of Eye/cytology , Rats
11.
J Exp Med ; 181(5): 1857-62, 1995 May 01.
Article in English | MEDLINE | ID: mdl-7536797

ABSTRACT

Phagocyte recognition and ingestion of intact cells undergoing apoptosis are key events in this generally important program of cell death. Insufficient phagocyte capacity for apoptotic cells can result in failure to clear dying cells before membrane integrity is lost, resulting in leakage of noxious cell contents and severe tissue damage. However, no means has been available to increase phagocytic clearance of apoptotic cells. We now report that transfection of the macrophage adhesion molecule CD36 into human Bowes melanoma cells specifically conferred greatly increased capacity to ingest apoptotic neutrophils, lymphocytes, and fibroblasts, comparable to that exhibited by macrophages. Furthermore, when CD36 was transfected into another cell type with limited capacity to take up apoptotic bodies, the monkey COS-7 cell, similar effects were observed. Therefore, CD36 gene transfer can confer "professional" capacity to ingest apoptotic cells upon "amateur" phagocytes.


Subject(s)
Antigens, CD/genetics , Apoptosis , Phagocytosis , Animals , Antigens, CD/physiology , CD36 Antigens , Cell Line , Humans , Macrophages/immunology , Transfection
12.
J Exp Med ; 173(2): 357-65, 1991 Feb 01.
Article in English | MEDLINE | ID: mdl-1988538

ABSTRACT

In previously published studies, we had demonstrated that hydrazine sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of hydrazine sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of hydrazine sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of hydrazine sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after hydrazine sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by hydrazine sulfate. Although hydrazine sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by hydrazine sulfate. We conclude that hydrazine sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the hydrazine sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.


Subject(s)
Endotoxins/toxicity , Galactosamine/administration & dosage , Hydrazines/pharmacology , Pituitary Gland/physiology , Tumor Necrosis Factor-alpha/toxicity , Animals , Blood Glucose , Corticosterone/blood , Disease Models, Animal , Drug Hypersensitivity/mortality , Drug Hypersensitivity/prevention & control , Endotoxins/antagonists & inhibitors , Female , Hypophysectomy , Immunization , Liver/drug effects , Liver/enzymology , Mice , Mice, Inbred C3H , Phosphoenolpyruvate Carboxykinase (GTP)/metabolism , Premedication , Triiodothyronine/blood
13.
J Exp Med ; 163(6): 1595-600, 1986 Jun 01.
Article in English | MEDLINE | ID: mdl-3086483

ABSTRACT

Human endothelial cells activated with IL-1 express a surface membrane-oriented procoagulant generating system characterized by increased tissue factor synthesis and decreased thrombomodulin activity. We now report that IL-1 also stimulates endothelial cell synthesis of plasminogen activator inhibitor. This array of IL-1-induced activities shifts the balance at the endothelial cell surface to a prothrombotic influence and may reflect an early response of the blood vessel wall to injury.


Subject(s)
Endothelium/drug effects , Glycoproteins/biosynthesis , Interleukin-1/pharmacology , Plasminogen Activators/antagonists & inhibitors , Plasminogen Inactivators , Cells, Cultured , Endothelium/metabolism , Feedback , Humans , Infant, Newborn , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/pharmacology , Tissue Plasminogen Activator/antagonists & inhibitors , Umbilical Veins , Urokinase-Type Plasminogen Activator/antagonists & inhibitors
14.
J Exp Med ; 187(1): 25-35, 1998 Jan 05.
Article in English | MEDLINE | ID: mdl-9419208

ABSTRACT

Human and non-human primate salivas retard the infectivity of HIV-1 in vitro and in vivo. Because thrombospondin 1 (TSP1), a high molecular weight trimeric glycoprotein, is concentrated in saliva and can inhibit the infectivity of diverse pathogens in vitro, we sought to determine the role of TSP1 in suppression of HIV infectivity. Sequence analysis revealed a TSP1 recognition motif, previously defined for the CD36 gene family of cell adhesion receptors, in conserved regions flanking the disulfide-linked cysteine residues of the V3 loop of HIV envelope glycoprotein gp120, important for HIV binding to its high affinity cellular receptor CD4. Using solid-phase in vitro binding assays, we demonstrate direct binding of radiolabeled TSP1 to immobilized recombinant gp120. Based on peptide blocking experiments, the TSP1-gp120 interaction involves CSVTCG sequences in the type 1 properdin-like repeats of TSP1, the known binding site for CD36. TSP1 and fusion proteins derived from CD36-related TSP1-binding domains were able to compete with radiolabeled soluble CD4 binding to immobilized gp120. In parallel, purified TSP1 inhibited HIV-1 infection of peripheral blood mononuclear cells and transformed T and promonocytic cell lines. Levels of TSP1 required for both viral aggregation and direct blockade of HIV-1 infection were physiologic, and affinity depletion of salivary TSP1 abrogated >70% of the inhibitory effect of whole saliva on HIV infectivity. Characterization of TSP1-gp120 binding specificity suggests a mechanism for direct blockade of HIV infectivity that might be exploited to retard HIV transmission that occurs via mucosal routes.


Subject(s)
CD36 Antigens/metabolism , HIV Envelope Protein gp120/chemistry , HIV Envelope Protein gp120/metabolism , HIV-1/metabolism , Saliva/metabolism , Saliva/virology , Thrombospondin 1/metabolism , Amino Acid Sequence , Animals , Binding Sites/genetics , CD36 Antigens/genetics , CD4 Antigens/metabolism , Genes, env , HIV Envelope Protein gp120/genetics , HIV Infections/prevention & control , HIV Infections/transmission , HIV Infections/virology , HIV-1/genetics , HIV-1/isolation & purification , Humans , In Vitro Techniques , Molecular Sequence Data , Peptide Mapping , Sequence Homology, Amino Acid
15.
J Exp Med ; 166(1): 235-45, 1987 Jul 01.
Article in English | MEDLINE | ID: mdl-3598461

ABSTRACT

Platelet-derived growth factor (PDGF) is a 30,000-Mr glycoprotein that is chemotactic and mitogenic for vascular smooth muscle cells (SMC). It is also a potent vasoconstrictor. In the present study, we found that the macrophage-derived polypeptide, tumor necrosis factor (TNF), releases a factor from human umbilical vein endothelial cells (EC) that is mitogenic for SMC. Postculture medium from TNF-stimulated EC induced a 90% increase in mitogenesis is compared with controls. This effect was half-maximal at a TNF dose of 114 pM, reflected a 2.5-fold increase in PDGF-specific mRNA synthesis, and peaked at 15 h of TNF stimulation. Mitogenic activity was completely abrogated by preincubation of postculture medium with antibody to platelet PDGF. Stimulation of EC with IL-1 (60-240 pM) led to the release of similar mitogenic activity. Thus, in addition to its effects on the hemostatic and adhesive properties of EC, TNF also promotes release of PDGF, which may serve to modulate proliferation of vascular SMC during wound healing, inflammation, and atherogenesis.


Subject(s)
Endothelium/metabolism , Glycoproteins/pharmacology , Muscle, Smooth, Vascular/cytology , Platelet-Derived Growth Factor/metabolism , Cell Division , Cells, Cultured , Dactinomycin/pharmacology , Endothelium/drug effects , Humans , Kinetics , Muscle, Smooth, Vascular/metabolism , Platelet-Derived Growth Factor/genetics , RNA, Messenger/biosynthesis , Tumor Necrosis Factor-alpha , Umbilical Veins
16.
J Exp Med ; 188(7): 1359-68, 1998 Oct 05.
Article in English | MEDLINE | ID: mdl-9763615

ABSTRACT

Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the alphavbeta5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the alphavbeta5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the alphavbeta5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.


Subject(s)
Antigen Presentation/immunology , Apoptosis , CD36 Antigens/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Integrins/metabolism , Phagocytosis , Receptors, Vitronectin , T-Lymphocytes, Cytotoxic/immunology , Antigens, CD , Cells, Cultured , Histocompatibility Antigens Class I/immunology , Humans , Immunoglobulins/metabolism , Macrophages/metabolism , Membrane Glycoproteins/metabolism , CD83 Antigen
17.
J Cell Biol ; 138(3): 707-17, 1997 Aug 11.
Article in English | MEDLINE | ID: mdl-9245797

ABSTRACT

Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived from it to show that this inhibition is mediated by CD36, a transmembrane glycoprotein found on microvascular endothelial cells. Both IgG antibodies against CD36 and glutathione-S-transferase-CD36 fusion proteins that contain the TSP-1 binding site blocked the ability of intact TSP-1 and its active peptides to inhibit the migration of cultured microvascular endothelial cells. In addition, antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 to solid phase CD36 and its fusion proteins, as well as to CD36-expressing cells. Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SM, oxidized (but not unoxidized) low density lipoprotein, and human collagen 1, mimicked TSP-1 by inhibiting the migration of human microvascular endothelial cells. Transfection of CD36-deficient human umbilical vein endothelial cells with a CD36 expression plasmid caused them to become sensitive to TSP-1 inhibition of their migration and tube formation. This work demonstrates that endothelial CD36, previously thought to be involved only in adhesion and scavenging activities, may be essential for the inhibition of angiogenesis by thrombospondin-1.


Subject(s)
CD36 Antigens/physiology , Endothelium, Vascular/drug effects , Membrane Glycoproteins/pharmacology , Neovascularization, Physiologic/drug effects , Amino Acid Sequence , Animals , CD36 Antigens/genetics , CD36 Antigens/immunology , CD36 Antigens/metabolism , Cattle , Cell Movement/drug effects , Cells, Cultured , Endothelium, Vascular/physiology , Humans , Ligands , Membrane Glycoproteins/metabolism , Molecular Sequence Data , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Recombinant Fusion Proteins/pharmacology , Thrombospondins , Transfection
18.
J Cell Biol ; 121(4): 945-55, 1993 May.
Article in English | MEDLINE | ID: mdl-8491785

ABSTRACT

Leukocytes form zones of close apposition when they adhere to ligand-coated surfaces. Because plasma proteins are excluded from these contact zones, we have termed them protected zones of adhesion. To determine whether platelets form similar protected zones of adhesion, gel-filtered platelets stimulated with thrombin or ADP were allowed to adhere to fibrinogen- or fibronectin-coated surfaces. The protein-coated surfaces with platelets attached were stained with either fluorochrome-conjugated goat anti-human fibrinogen or anti-human fibronectin antibodies, or with rhodamine-conjugated polyethylene glycol polymers. Fluorescence microscopy revealed that F(ab')2 anti-fibrinogen (100 kD) did not penetrate into the contact zones between stimulated platelets and the underlying fibrinogen-coated surface, while Fab antifibrinogen (50 kD) and 10 kD polyethylene glycol readily penetrated and stained the substrate beneath the platelets. Thrombin- or ADP-stimulated platelets also formed protected zones of adhesion on fibronectin-coated surfaces. F(ab')2 anti-fibronectin and 10 kD polyethylene glycol were excluded from these adhesion zones, indicating that they are much less permeable than those formed by platelets on fibrinogen-coated surfaces. The permeability properties of protected zones of adhesion formed by stimulated platelets on surfaces coated with both fibrinogen and fibronectin were similar to the zones of adhesion formed on fibronectin alone. mAb 7E3, directed against the alpha IIb beta 3 integrin blocked the formation of protected adhesion zones between thrombin-stimulated platelets and fibrinogen or fibronectin coated surfaces. mAb C13 is directed against the alpha 5 beta 1 integrin on platelets. Stimulated platelets treated with this mAb formed protected zones of adhesion on surfaces coated with fibronectin. These protected zones were impermeable to F(ab')2 antifibronectin but were permeable to 10 kD polyethylene glycol. These results show that activated platelets form protected zones of adhesion and that the size of molecules excluded from these zones depends upon the composition of the matrix proteins to which the platelets adhere. They also show that formation of protected zones of adhesion by platelets requires alpha IIb beta 3 integrins while the permeability properties of these zones of adhesion are regulated by both alpha IIb beta 3 and alpha 5 beta 1 integrins.


Subject(s)
Blood Platelets/physiology , Cell Adhesion , Fibrinogen/physiology , Fibronectins/physiology , Platelet Activation , Cell Membrane Permeability , Fibrin/metabolism , Humans , Integrins/metabolism , Macromolecular Substances
19.
Science ; 213(4514): 1326-32, 1981 Sep 18.
Article in English | MEDLINE | ID: mdl-17732556

ABSTRACT

Pesticides have not been a satisfactory solution to the control of insect pests. Pheromones show promise as a component of integrated pest management.

20.
Science ; 183(4126): 760-2, 1974 Feb 22.
Article in English | MEDLINE | ID: mdl-17790626

ABSTRACT

S-(+)-4-Methyl-3-heptanone is the principal alarm pheromone of Atta texana. The dextrorotatory form of the ketone has also been identified from Atta cephalotes. Both enantiomers have been synthesized in high optical purity; Atta texana is more responsive to the (+) enantiomer than to the (-) form. These results implicate a chiral receptor system.

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