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1.
Space Sci Rev ; 216(1): 12, 2020.
Article in English | MEDLINE | ID: mdl-32025061

ABSTRACT

The OSIRIS-REx Camera Suite (OCAMS) onboard the OSIRIS-REx spacecraft is used to study the shape and surface of the mission's target, asteroid (101955) Bennu, in support of the selection of a sampling site. We present calibration methods and results for the three OCAMS cameras-MapCam, PolyCam, and SamCam-using data from pre-flight and in-flight calibration campaigns. Pre-flight calibrations established a baseline for a variety of camera properties, including bias and dark behavior, flat fields, stray light, and radiometric calibration. In-flight activities updated these calibrations where possible, allowing us to confidently measure Bennu's surface. Accurate calibration is critical not only for establishing a global understanding of Bennu, but also for enabling analyses of potential sampling locations and for providing scientific context for the returned sample.

2.
Vet Immunol Immunopathol ; 214: 109890, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31378218

ABSTRACT

Bovine mastitis is a significant cause of economic losses in the dairy industry. Staphylococcus aureus is one of the most common contagious mastitis pathogens, whereas Staphylococcus chromogenes increasingly became a significant cause of subclinical mastitis in dairy cows. Current mastitis control measures are not effective on all mastitis pathogens. There is no effective vaccine to control Staphylococcal mastitis in dairy cows. The objective of this study was to evaluate the immune responses and protection in dairy cows vaccinated with S. aureus surface proteins (SASP) or S. chromogenes surface proteins (SCSP). We divided eighteen Holstein dairy cows randomly into three groups of 6 animals each. We vaccinated group 1 and 2 animals with SASP and SCSP with Emulsigen-D adjuvant, respectively. We injected control (group 3) animals with PBS (pH 7.2) in Emulsigen®-D. We vaccinated animals three times at 28 and 14 days before drying off, and at dry off. Two weeks after the third vaccination, we challenged each animal by dipping all teats in S. aureus culture suspension once daily for 14 consecutive days. We evaluated milk or mammary secretion and serum antibody titers during vaccination and challenge periods. We evaluated milk samples for the number of bacteria shedding and somatic cell counts (SCC). Out of six cows vaccinated with SASP, one cow was removed from the study due to injury, two were infected clinically, another two were infected subclinically, and the remaining cow was not infected. No SCSP vaccinated cows developed clinical or subclinical mastitis. Out of six control cows, two developed clinical mastitis whereas four were infected subclinically. The SCSP vaccine cross-protected against S. aureus mastitis and reduced number of S. aureus shedding in milk. We concluded that the SCSP is a promising vaccine to control Staphylococcal mastitis in dairy cows.


Subject(s)
Mastitis, Bovine/prevention & control , Membrane Proteins/immunology , Staphylococcal Infections/veterinary , Staphylococcal Vaccines/immunology , Staphylococcus aureus/immunology , Animals , Bacterial Shedding , Cattle , Cell Count , Dairying , Female , Membrane Proteins/administration & dosage , Milk/microbiology , Staphylococcal Infections/immunology , Staphylococcal Infections/prevention & control , Vaccination
3.
J Appl Toxicol ; 34(8): 857-61, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23723039

ABSTRACT

Petrolatum is widely used in cosmetics, topical pharmaceuticals and also as a vehicle in dermal toxicity studies. New Zealand white rabbits treated with white petrolatum (vehicle control) in a 2-week dermal irritation study exhibited moderate to severe erythema starting on Day 7 that subsided towards the end of the study. Histological examination of abraded and non-abraded petrolatum-treated skin obtained at termination (Day 15) revealed mild acanthosis, hyperkeratosis, dermal edema with mixed inflammatory cells in the dermis. Macroscopic and microscopic features noted in rabbits were consistent with dermal irritation to petrolatum. Wistar-Han rats, CD1 mice, C57/Bl/6J mice and Göttingen minipigs treated topically with white petrolatum did not exhibit clinical or histologic evidence of dermal irritation. Therapeutic agents developed for topical application are generally tested in rabbits during some point in development. Interpretation of skin irritation data from a single species can impact risk assessment for humans and on product labeling.


Subject(s)
Petrolatum/toxicity , Skin Diseases/pathology , Administration, Cutaneous , Animals , Cosmetics/toxicity , Disease Models, Animal , Female , Male , Mice , Mice, Inbred C57BL , Rabbits , Rats , Rats, Wistar , Risk Assessment , Skin Diseases/chemically induced , Swine , Swine, Miniature , Toxicity Tests
4.
Neuroscience ; 218: 89-99, 2012 Aug 30.
Article in English | MEDLINE | ID: mdl-22609938

ABSTRACT

The hippocampus is required for short-term memory and contains both excitatory pyramidal cells and inhibitory interneurons. These cells exhibit various forms of synaptic plasticity, the mechanism underlying learning and memory. More recently, endocannabinoids were identified to be involved in synaptic plasticity. Our goal was to describe the distribution of endocannabinoid biosynthetic enzymes within CA1 stratum radiatum interneurons and CA3/CA1 pyramidal cells. We extracted mRNA from single interneurons and pyramidal cells and used real-time quantitative polymerase chain reaction (RT-PCR) to detect the presence of 12-lipoxygenase, N-acyl-phosphatidylethanolamine-specific phospholipase D, diacylglycerol lipase α, and type I metabotropic glutamate receptors, all known to be involved in endocannabinoid production and plasticity. We observed that the expression of endocannabinoid biosynthetic enzyme mRNA does occur within interneurons and that it is coexpressed with type I metabotropic glutamate receptors, suggesting interneurons have the potential to produce endocannabinoids. We also identified that CA3 and CA1 pyramidal cells express endocannabinoid biosynthetic enzyme mRNA. Our data provide the first molecular biological evidence for putative endocannabinoid production in interneurons, suggesting their potential ability to regulate endocannabinoid-mediated processes, such as synaptic plasticity.


Subject(s)
CA1 Region, Hippocampal/enzymology , Endocannabinoids/biosynthesis , Interneurons/metabolism , Pyramidal Cells/metabolism , RNA, Messenger/analysis , Animals , CA3 Region, Hippocampal/metabolism , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
5.
Anthropol Med ; 18(3): 351-64, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22060128

ABSTRACT

Having concurrent sexual partners is a risk factor for STIs and HIV/AIDS, yet few studies have investigated the cultural meanings and functions of concurrency. A multi-method qualitative/quantitative study of sexual ideas, attitudes, and behaviors among inner-city Puerto Rican and African American emergent adults (age 18-25) in Hartford, Connecticut, USA, suggests that having concurrent partners is common in this population. Using data from 12 focus groups and 40 participants in systematic data collection techniques (e.g., pile sorts), the underlying cognitive structure of concurrency and cheating/infidelity are explored. Results suggest that participants are less tolerant of multiple partners in more committed relationships, but that very few relationships can be considered committed. Furthermore, participants see cheating as inevitable even in committed relationships. Sexual transgressions are considered the most severe form of cheating. Having an outside partner for emotional reasons or to have access to one's child were seen as more acceptable/forgivable than doing so for sexual satisfaction, social status or material goods. Multiple partnerships must be seen in the context of the inner city where resources and opportunities are scarce and young adults attempt to protect themselves from emotional injury. Documenting new and changing social constructions of infidelity is important for understanding the social context of sexual behavior in our global world and for designing culturally appropriate health interventions.


Subject(s)
Black or African American/psychology , Hispanic or Latino/psychology , Sexual Behavior/ethnology , Sexual Behavior/psychology , Adolescent , Anthropology, Medical , Cluster Analysis , Female , Focus Groups , Humans , Male , Models, Psychological , Puerto Rico , Reproductive Health , Sexual Partners , Urban Population , Young Adult
8.
Biol Direct ; 1: 27, 2006 Sep 07.
Article in English | MEDLINE | ID: mdl-16959036

ABSTRACT

BACKGROUND: DNA microarrays are a powerful technology that can provide a wealth of gene expression data for disease studies, drug development, and a wide scope of other investigations. Because of the large volume and inherent variability of DNA microarray data, many new statistical methods have been developed for evaluating the significance of the observed differences in gene expression. However, until now little attention has been given to the characterization of dispersion of DNA microarray data. RESULTS: Here we examine the expression data obtained from 682 Affymetrix GeneChips with 22 different types and we demonstrate that the Gaussian (normal) frequency distribution is characteristic for the variability of gene expression values. However, typically 5 to 15% of the samples deviate from normality. Furthermore, it is shown that the frequency distributions of the difference of expression in subsets of ordered, consecutive pairs of genes (consecutive samples) in pair-wise comparisons of replicate experiments are also normal. We describe a consecutive sampling method, which is employed to calculate the characteristic function approximating standard deviation and show that the standard deviation derived from the consecutive samples is equivalent to the standard deviation obtained from individual genes. Finally, we determine the boundaries of probability intervals and demonstrate that the coefficients defining the intervals are independent of sample characteristics, variability of data, laboratory conditions and type of chips. These coefficients are very closely correlated with Student's t-distribution. CONCLUSION: In this study we ascertained that the non-systematic variations possess Gaussian distribution, determined the probability intervals and demonstrated that the K(alpha) coefficients defining these intervals are invariant; these coefficients offer a convenient universal measure of dispersion of data. The fact that the K(alpha) distributions are so close to t-distribution and independent of conditions and type of arrays suggests that the quantitative data provided by Affymetrix technology give "true" representation of physical processes, involved in measurement of RNA abundance. REVIEWERS: This article was reviewed by Yoav Gilad (nominated by Doron Lancet), Sach Mukherjee (nominated by Sandrine Dudoit) and Amir Niknejad and Shmuel Friedland (nominated by Neil Smalheiser).

9.
Biol Direct ; 1: 18, 2006 Jun 20.
Article in English | MEDLINE | ID: mdl-16787528

ABSTRACT

BACKGROUND: Gene expression microarray technology continues to evolve and its use has expanded into all areas of biology. However, the high dimensionality of the data makes analysis a difficult challenge. Evaluating measurements and estimating the significance of the observed differences among samples remain important issues that must be addressed for each technology platform. In this work we use a consecutive sampling method to characterize the dispersion patterns of data generated from Illumina fiberoptic bead-based oligonucleotide arrays. RESULTS: To describe general properties of the dispersion we used a linear function SD = a + bY(mean), approximating the standard deviation across arrays (Y(mean) is the mean expression of a given consecutive sample). First we examined three levels of variability: 1) same cell culture, same reverse transcription, duplicate hybridizations; 2) same cell culture, reverse transcription replicates; 3) parallel cultures. Each higher level is expected to introduce a new source of variability. We observed minor differences in the constant term: the mean values are 3.5, 3.1 and 3.5, respectively. However, the mean coefficient b increased from 0.045 to 0.147 and 0.133. We compared the coefficients derived from the consecutive sampling to those obtained from the standard deviation of individual gene expressions and found them in good agreement. In the second experiment samples we detected 11 genes with systematically different expressions between the experiment samples treated with glucose oxidase and controls and corroborated the selection using the Mann-Whitney and other tests. We also compared the consecutive sampling and coincidence method to t-test: the average percentage of consistency was above 80 for the former and below 50 for the latter. CONCLUSION: Our results indicate that the consecutive sampling method and standard deviation function provide a convenient description of the overall dispersion of Illumina arrays. We observed that the constant term of the standard deviation function is at average approximately the same for duplicate hybridization as for the assays with additional sources of variability. Furthermore, among the genes affected by glucose oxidase treatment we identified 6 genes in oxidative stress pathways and 5 genes involved in DNA repair. Finally, we noted that the consecutive sampling and coincidence test provide, under given conditions, more consistent results than the t-test. REVIEWERS: This article was reviewed by Alexander Karpikov (nominated by Mark Gerstein), Jordan King and Eugene V. Koonin.

10.
Soc Sci Med ; 63(8): 2010-21, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16782250

ABSTRACT

This paper employs syndemics theory to explain high rates of sexually transmitted disease among inner city African American and Puerto Rican heterosexual young adults in Hartford, CT, USA. Syndemic theory helps to elucidate the tendency for multiple co-terminus and interacting epidemics to develop under conditions of health and social disparity. Based on enhanced focus group and in-depth interview data, the paper argues that respondents employed a cultural logic of risk assessment which put them at high risk for STD infection. This cultural logic was shaped by their experiences of growing up in the inner city which included: coming of age in an impoverished family, living in a broken home, experiencing domestic violence, limited expectations of the future, limited exposure to positive role models, lack of expectation of the dependency of others, and fear of intimacy.


Subject(s)
Black or African American/psychology , Culture , Hispanic or Latino/psychology , Sexual Behavior/ethnology , Sexually Transmitted Diseases/ethnology , Social Environment , Adolescent , Adult , Anthropology, Cultural , Connecticut/epidemiology , Decision Making , Female , Focus Groups , Humans , Interviews as Topic , Male , Risk Assessment , Risk Factors , Sexually Transmitted Diseases/epidemiology
11.
Inj Prev ; 12(3): 199-201, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16751453

ABSTRACT

OBJECTIVES: To determine the completeness of external cause of injury coding (E-coding) within healthcare administrative databases in the United States and to identify factors that contribute to variations in E-code reporting across states. DESIGN: Cross sectional analysis of the 2001 Healthcare Cost and Utilization Project (HCUP), including 33 State Inpatient Databases (SID), a Nationwide Inpatient Sample (NIS), and nine State Emergency Department Databases (SEDD). To assess state reporting practices, structured telephone interviews were conducted with the data organizations that participate in HCUP. RESULTS: The percent of injury records with an injury E-code was 86% in HCUP's nationally representative database, the NIS. For the 33 states represented in the SID, completeness averaged 87%, with more than half of the states reporting E-codes on at least 90% of injuries. In the nine states also represented in the SEDD, completeness averaged 93%. Twenty two states had mandates for E-code reporting, but only eight had provisions for enforcing the mandates. These eight states had the highest rates of E-code completeness. CONCLUSIONS: E-code reporting in administrative databases is relatively complete, but there is significant variation in completeness across the states. States with mandates for the collection of E-codes and with a mechanism to enforce those mandates had the highest rates of E-code reporting. Nine statewide ED data systems demonstrate consistently high E-coding completeness.


Subject(s)
Databases, Factual , Hospitalization/statistics & numerical data , Medical Records Department, Hospital/standards , Medical Records Systems, Computerized/standards , Wounds and Injuries/classification , Cross-Sectional Studies , Forms and Records Control/standards , Humans , Medical Records Systems, Computerized/classification , United States/epidemiology , Wounds and Injuries/epidemiology , Wounds and Injuries/etiology
12.
Neuron ; 48(2): 221-7, 2005 Oct 20.
Article in English | MEDLINE | ID: mdl-16242403

ABSTRACT

The neuropeptide Pigment-Dispersing Factor (PDF) plays a critical role in mediating circadian control of behavior in Drosophila. Here we identify mutants (groom-of-PDF; gop) that display phase-advanced evening activity and poor free-running rhythmicity, phenocopying pdf mutants. In gop mutants, a spontaneous retrotransposon disrupts a coding exon of a G protein-coupled receptor, CG13758. Disruption of the receptor is accompanied by phase-advanced oscillations of the core clock protein PERIOD. Moreover, effects on circadian timing induced by perturbation of PDF neurons require gop. Yet PDF oscillations themselves remain robust in gop mutants, suggesting that GOP acts downstream of PDF. gop is expressed most strongly in the dorsal brain in regions that lie in proximity to PDF-containing nerve terminals. Taken together, these studies implicate GOP as a PDF receptor in Drosophila.


Subject(s)
Circadian Rhythm/physiology , Drosophila Proteins/physiology , Neurons/physiology , Neuropeptides/metabolism , Receptors, G-Protein-Coupled/physiology , Animals , Animals, Genetically Modified , Behavior, Animal , Brain/cytology , Brain/metabolism , Drosophila , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Female , Gene Expression Regulation/genetics , Immunohistochemistry/methods , In Situ Hybridization/methods , Male , Motor Activity/genetics , Mutant Proteins/physiology , Receptors, G-Protein-Coupled/genetics , Time Factors
13.
J Neurobiol ; 63(1): 15-28, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15627264

ABSTRACT

The ability to modulate olfactory sensitivity is necessary to detect chemical gradients and discriminate among a multitude of odor stimuli. Desensitization of odorant receptors has been postulated to occur when arrestins prevent the activation of downstream second messengers. A paucity of in vivo data on olfactory desensitization prompts use of Drosophila melanogaster genetics to investigate arrestins' role in regulating olfactory signaling pathways. Physiological analysis of peripheral olfactory sensitivity reveals decreased responsiveness to a host of chemically distinct odorants in flies deficient for arrestin1 (arr1), arrestin2 (arr2), or both. These phenotypes are manifest in odorant- and dose- dependent fashions. Additionally, mutants display altered adaptive properties under a prolonged exposure paradigm. Behaviorally, arr1 mutants are impaired in olfactory-based orientation towards attractive odor sources. As the olfactory deficits vary according to chemical identity and concentration, they indicate that a spectrum of arrestin activity is essential for odor processing depending upon the particular olfactory pathway involved. Arrestin mutant phenotypes are hypothesized to be a consequence of down-regulation of olfactory signaling to avoid cellular excitotoxicity. Importantly, phenotypic rescue of olfactory defects in arr1(1) mutants is achieved through transgenic expression of wild-type arr1. Taken together, these data clearly indicate that arrestins are required in a stimulus-specific manner for wild type olfactory function and add another level of complexity to peripheral odor coding mechanisms that ultimately impact olfactory behavior.


Subject(s)
Arrestins/metabolism , Odorants , Olfactory Pathways/metabolism , Phosphoproteins/metabolism , Smell/physiology , Acetates/pharmacology , Acetone/pharmacology , Animals , Animals, Genetically Modified , Arrestins/genetics , Behavior, Animal , Butanols/pharmacology , Dose-Response Relationship, Drug , Drosophila , Drosophila Proteins , Electrophysiology/methods , Kinetics , Locomotion/drug effects , Locomotion/physiology , Mutation , Olfactory Pathways/drug effects , Olfactory Receptor Neurons/drug effects , Olfactory Receptor Neurons/physiology , Phosphoproteins/genetics , Receptors, Odorant/drug effects , Receptors, Odorant/physiology , Smell/drug effects , Stimulation, Chemical , Time Factors
14.
Insect Mol Biol ; 12(6): 641-50, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14986925

ABSTRACT

Olfaction influences many insect behaviours including mate seeking and host selection. The molecular machinery underlying insect olfactory systems is a G protein-coupled receptor pathway that, in addition to activation, requires adaptation for olfactory sensitivity and discrimination. We have previously identified ARR1 (henceforth AgARR1), a sensory arrestin from the malaria vector mosquito Anopheles gambiae that has been postulated to modulate olfactory adaptation. This report describes three additional arrestin family members including ARR2 (henceforth AgARR2), which is similar to previously characterized insect sensory arrestins and is expressed at significantly higher levels in the antennae of male vs. female A. gambiae mosquitoes. This finding is consistent with the hypothesis that AgARR2 may be important for the regulation of olfactory-driven behaviours particular to male mosquitoes.


Subject(s)
Anopheles/genetics , Arrestins/genetics , Gene Expression , Phylogeny , Smell/genetics , Amino Acid Sequence , Animals , DNA Primers , Female , Gene Library , Male , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNA , Sex Factors
15.
Proc Natl Acad Sci U S A ; 99(3): 1633-8, 2002 Feb 05.
Article in English | MEDLINE | ID: mdl-11792843

ABSTRACT

Arrestins are important components for desensitization of G protein-coupled receptor cascades that mediate neurotransmission as well as olfactory and visual sensory reception. We have isolated AgArr1, an arrestin-encoding cDNA from the malaria vector mosquito, Anopheles gambiae, where olfaction is critical for vectorial capacity. Analysis of AgArr1 expression revealed an overlap between chemosensory and photoreceptor neurons. Furthermore, an examination of previously identified arrestins from Drosophila melanogaster exposed similar bimodal expression, and Drosophila arrestin mutants demonstrate impaired electrophysiological responses to olfactory stimuli. Thus, we show that arrestins in Drosophila are required for normal olfactory physiology in addition to their previously described role in visual signaling. These findings suggest that individual arrestins function in both olfactory and visual pathways in Dipteran insects; these genes may prove useful in the design of control strategies that target olfactory-dependent behaviors of insect disease vectors.


Subject(s)
Anopheles/physiology , Arrestins/physiology , Drosophila melanogaster/physiology , Olfactory Pathways/physiology , Phosphoproteins/physiology , Vision, Ocular/physiology , Amino Acid Sequence , Animals , Anopheles/genetics , Arrestins/genetics , DNA Primers , Drosophila melanogaster/genetics , Embryo, Nonmammalian/physiology , Gene Expression Regulation, Developmental , Gene Library , Larva , Malaria/transmission , Molecular Sequence Data , Phosphoproteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence Homology, Amino Acid
16.
Ther Apher ; 5(2): 84-91, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11354304

ABSTRACT

Studies of the humoral effects of the Prosorba column were conducted in conjunction with the Phase 3 trial of Prosorba versus sham therapy for rheumatoid arthritis (RA). When perfused with normal human plasma in vitro, Prosorba bound predominantly IgG with a maximal capacity of approximately 462 g of Ig per Prosorba column, equal to about 1.5% of circulating IgG. Prosorba treatment did not alter the concentrations of albumin, IgG, IgM, and IgA in 3 RA patients, except for a small dilutional effect. Kinetic studies demonstrated that Prosorba removed IgG > IgM, IgA, and IgM rheumatoid factor (RF) during the initial moments of apheresis and almost exclusively IgM RF after 15 min. No net protein removal occurred at > or = 60 min. Mean values of circulating immune complexes (CICs) were not significantly decreased by 12 weekly treatments. Complement was activated by the apheresis system upstream of the Prosorba column without changing C3 or C4 levels. We conclude that the Prosorba mechanism of action in RA is not bulk removal of Ig, but might involve modification of the CIC repertoire and could include, but not be limited to, effects related to complement activation.


Subject(s)
Arthritis, Rheumatoid/therapy , Immunoglobulins/blood , Immunosorbent Techniques , Plasmapheresis , Antigen-Antibody Complex/blood , Arthritis, Rheumatoid/immunology , Complement Activation , Double-Blind Method , Humans , In Vitro Techniques
17.
J Zoo Wildl Med ; 32(2): 257-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-12790431

ABSTRACT

The clinical, gross necropsy, and histopathology findings in two unrelated desert grassland whiptail lizards (Cnemidophorus uniparens) with teratoma are described. The desert grassland whiptail is a parthenogenic lizard species with a polyploid chromosomal complement. The chromosome composition of the teratomas from these lizards was not determined.


Subject(s)
Lizards , Ovarian Neoplasms/veterinary , Teratoma/veterinary , Animals , Autopsy/veterinary , Diagnosis, Differential , Fatal Outcome , Female , Ovarian Neoplasms/pathology , Teratoma/pathology
18.
Lupus ; 9(8): 607-13, 2000.
Article in English | MEDLINE | ID: mdl-11035436

ABSTRACT

Antibodies to human myeloperoxidase and cathepsin G have been detected in the serum of some patients with systemic lupus erythematosus. Therefore, the presence of antibodies to human myeloperoxidase and cathepsin G was examined in glomerular immune deposits. Glomerular basement membrane fragments were prepared from renal tissues obtained at autopsy from 19 patients with systemic lupus erythematosus. IgG was extracted from the glomerular basement membrane fragments and tested with sensitive immunoassays for antibodies to myeloperoxidase and cathepsin G. Antibodies to cathepsin G were not detected in the extracts but antibodies to human myeloperoxidase were found in extracts of one specimen. In the extract with 6M guanidine hydrochloride these antibodies were enriched 103-fold, compared to the initial supernatant of glomeruli, which served as a serum surrogate. The recovered antibodies to myeloperoxidase accounted for 12% of the recovered IgG. These findings add autoantibodies to human myeloperoxidase to the list of antibodies that have been shown to be present in glomerular immune deposits of patients with lupus glomerulonephritis.


Subject(s)
Autoantibodies/analysis , Cathepsins/immunology , Kidney/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Peroxidase/immunology , Autopsy , Basement Membrane/immunology , Basement Membrane/pathology , Cathepsin G , Humans , Immunoglobulin G/analysis , Kidney/pathology , Kidney Glomerulus/immunology , Kidney Glomerulus/pathology , Serine Endopeptidases
19.
Clin Immunol ; 93(2): 93-106, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10527685

ABSTRACT

Functional inactivation of leukocyte adhesion molecules has been used to intervene in the development of tissue injury in experimental models of postperfusion infarction as well as autoimmune inflammation. We investigated the use of humanized monoclonal antibodies (mAb) against CD18 in the treatment of five patients with vasculitic tissue injury sufficient to threaten infarction or gangrene. The treatment was monitored in three ways: (i) whole-body gamma camera scintiscanning of autologous indium-labeled PMN, (ii) an index of the therapeutic inhibition of adhesion derived from comparison pre, during, and post mAb treatment of the ability of patients' PMN to be aggregated after activation by fMLP, and (iii) flow cytometric analysis of PMN CD18 expression. Four of five patients given anti-CD18 at 20 mg/day for up to 3 weeks showed prompt clinical improvement, with healing of the ulceration and restoration of limb function within 4 weeks, which was sustained. The fifth patient, who was not doing well clinically, decided to withdraw from all active treatment: at autopsy there was no evidence of the underlying vasculitis evident pretreatment. Our findings suggest that anti-adhesion molecule treatment might be an effective immediate treatment in severe vasculitis especially when tissue viability is threatened by progressive infarction and/or development of gangrene.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Autoimmune Diseases/pathology , Autoimmune Diseases/therapy , CD18 Antigens/immunology , Aged , Autoimmune Diseases/immunology , CD18 Antigens/analysis , Cell Adhesion/immunology , Churg-Strauss Syndrome/therapy , Fatal Outcome , Female , Humans , Immunization, Passive , Inflammation/therapy , Male , Middle Aged , Sjogren's Syndrome/therapy , Skin Ulcer/immunology , Skin Ulcer/therapy , Treatment Outcome , Vasculitis, Leukocytoclastic, Cutaneous/immunology , Vasculitis, Leukocytoclastic, Cutaneous/pathology , Vasculitis, Leukocytoclastic, Cutaneous/therapy
20.
Science ; 283(5408): 1742-5, 1999 Mar 12.
Article in English | MEDLINE | ID: mdl-10073941

ABSTRACT

Segregation Distorter (SD) in Drosophila melanogaster is a naturally occurring meiotic drive system in which the SD chromosome is transmitted from SD/SD+ males in vast excess over its homolog owing to the induced dysfunction of SD+-bearing spermatids. The Sd locus is the key distorting gene responsible for this phenotype. A genomic fragment from the Sd region conferred full distorting activity when introduced into the appropriate genetic background by germline transformation. The only functional product encoded by this fragment is a truncated version of the RanGAP nuclear transport protein. These results demonstrate that this mutant RanGAP is the functional Sd product.


Subject(s)
Carrier Proteins/genetics , Drosophila Proteins , Drosophila melanogaster/genetics , GTPase-Activating Proteins , Genes, Insect , Meiosis , Nuclear Proteins/genetics , Animals , Carrier Proteins/chemistry , Carrier Proteins/physiology , Cell Nucleus/metabolism , Crosses, Genetic , DNA, Complementary , Drosophila melanogaster/physiology , Female , Gene Duplication , Gene Expression , Male , Nuclear Proteins/chemistry , Nuclear Proteins/physiology , RNA, Messenger/genetics , Spermatids/physiology , Sulfotransferases/chemistry , Sulfotransferases/genetics , Transcription, Genetic , Transformation, Genetic
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