11 results on '"Emch S"'
Search Results
2. How an inhibitor of the HIV-I protease modulates proteasome activity.
- Author
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Schmidtke, G, Holzhütter, H G, Bogyo, M, Kairies, N, Groll, M, de Giuli, R, Emch, S, and Groettrup, M
- Abstract
The human immunodeficiency virus, type I protease inhibitor Ritonavir has been used successfully in AIDS therapy for 4 years. Clinical observations suggested that Ritonavir may exert a direct effect on the immune system unrelated to inhibition of the human immunodeficiency virus, type I protease. In fact, Ritonavir inhibited the major histocompatibility complex class I restricted presentation of several viral antigens at therapeutically relevant concentrations (5 microM). In search of a molecular target we found that Ritonavir inhibited the chymotrypsin-like activity of the proteasome whereas the tryptic activity was enhanced. In this study we kinetically analyzed how Ritonavir modulates proteasome activity and what consequences this has on cellular functions of the proteasome. Ritonavir is a reversible effector of proteasome activity that protected the subunits MB-1 (X) and/or LMP7 from covalent active site modification with the vinyl sulfone inhibitor(125)I-NLVS, suggesting that they are the prime targets for competitive inhibition by Ritonavir. At low concentrations of Ritonavir (5 microM) cells were more sensitive to canavanine but proliferated normally whereas at higher concentrations (50 microM) protein degradation was affected, and the cell cycle was arrested in the G(1)/S phase. Ritonavir thus modulates antigen processing at concentrations at which vital cellular functions of the proteasome are not yet severely impeded. Proteasome modulators may hence qualify as therapeutics for the control of the cytotoxic immune response.
- Published
- 1999
3. Brucella canis discospondylitis in 33 dogs.
- Author
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Long C, Burgers E, Copple C, Stainback L, Packer RA, Kopf K, Schmidt J, Emch S, and Windsor R
- Abstract
Objective: To describe the clinical and imaging findings of 33 dogs with Brucella canis discospondylitis (BDS)., Animals: 33 client owned dogs from four veterinary specialty hospitals within Colorado and Arizona with at least one positive B. canis test and spinal diagnostic imaging., Procedures: Retrospective review of signalment, physical and neurological examination findings, laboratory results, B. canis serology, and diagnostic imaging of 33 dogs with BDS. All imaging was reviewed by a board-certified veterinary neurologist. Radiographs were reviewed by a board-certified veterinary radiologist blinded to MRI and CT findings., Results: 31/33 (94%) dogs were <5 years old (median = 2.5 years, mean = 2.9 years, range 0.5-10 years). 21/29 (72%) dogs had signs of nonspecific pain, spinal pain, or lameness for >3 months (median = 6 months, mean = 8.2 months, range 5 days-4 years). Fever was seen in only 4/28 (14%) dogs. Multifocal lesions were evident on radiographs in 21/29 (72%) dogs and MRI in 12/18 (67%) dogs. Smooth, round, central end-plate lysis, defined as "hole punch" lesions, were identified radiographically in 25/29 (86%) dogs. Vertebral physitis or spondylitis without discitis was evident on MRI in 7/18 (39%) dogs., Clinical Relevance: Dogs with BDS typically present at a young age with a long duration of clinical signs. Identification of radiographic "hole punch" lesions and MRI evidence of vertebral physitis, spondylitis, and paravertebral inflammation without discitis should increase suspicion for BDS. BDS may be increasing in frequency in the southwestern United States, and dogs with signs of chronic spinal pain and/or lameness should be screened for B. canis ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Long, Burgers, Copple, Stainback, Packer, Kopf, Schmidt, Emch and Windsor.)
- Published
- 2022
- Full Text
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4. Associations Between Financial Strain and Emotional Well-Being With Physiological Responses to Acute Mental Stress.
- Author
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Steptoe A, Emch S, and Hamer M
- Subjects
- Blood Pressure, Emotions, Female, Heart Rate, Humans, Male, Mental Health, Stress, Psychological
- Abstract
Objective: This study aimed to investigate associations between financial strain and emotional well-being, health, and physiological responses to acute mental stress., Methods: Participants were 542 healthy men and women aged 53 to 76 years from the Whitehall II study divided into those who reported no (n = 316), some (n = 135), or moderate/severe (n = 91) financial strain. Emotional well-being and self-reported health were assessed at baseline and 3 years later. Laboratory mental stress testing involved assessment of blood pressure (BP), heart rate, and lipid reactivity and recovery, and plasma interleukin 6 responses to challenging behavioral tasks. Analyses adjusted for objective financial status, age, sex, socioeconomic status (SES), and marital status., Results: Financial strain was positively associated with more depressive symptoms; lower positive affect; greater loneliness; lower optimism, self-esteem, and sense of control; and poorer self-reported physical health, mental health, and sleep (all, p < .001). Longitudinally, financial strain predicted poorer outcomes 3 years later, but associations were attenuated after baseline levels were taken into account. Financial strain was associated with reduced systolic and diastolic BP reactivity to acute stress (mean systolic BP increase = 32.34 [15.2], 28.95 [13.1], and 27.26 [15.2] mm Hg in the none, some, and moderate/severe financial strain groups), but not with heart rate, interleukin 6, or lipid responses., Conclusions: Financial strain was correlated with a range of emotional and health-related outcomes independently of objective financial status. The diminished BP reactions to acute mental stress suggest that financial strain may contribute to dynamic chronic allostatic load.
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- 2020
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5. Alcohol Use in College: The Relationship Between Religion, Spirituality, and Proscriptive Attitudes Toward Alcohol.
- Author
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Kathol N and Sgoutas-Emch S
- Subjects
- Adolescent, Adult, California epidemiology, Female, Humans, Male, Spirituality, Students statistics & numerical data, Young Adult, Alcohol Drinking epidemiology, Alcohol Drinking psychology, Health Knowledge, Attitudes, Practice, Religion, Students psychology, Universities
- Abstract
Developing interventions to address the problem of college drinking requires the identification of contributing factors to drinking behavior. It is believed that religion and spirituality (R/S) play a role, but the mechanism is unclear. Using a multi-dimensional R/S measure, an alcohol behavior inventory, and a religious affiliation proscription question, this study was designed to dive deeper into this connection. This study found that religious singing/chanting and reading sacred text were the best predictors of lower alcohol consumption. Furthermore, participants who perceive their religious tradition to be proscriptive reported less alcohol consumption and higher religious/spiritual profiles.
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- 2017
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6. Girls Get Free Drinks: Undergraduates' Misunderstandings of Heterosexual Privilege.
- Author
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Nunn LM, Sgoutas-Emch S, Sumner S, and Kirkley E
- Subjects
- Adolescent, Female, Humans, Male, Young Adult, Heterosexuality, Hierarchy, Social, Sexual and Gender Minorities, Students psychology
- Abstract
Heterosexual privilege is a challenging concept to teach in undergraduate courses. Using data from self-reflection essays on the first and last days of the semester, we present students' learning and growth in their understanding of heterosexual privilege and their ability to distinguish it from cisgender privilege. The majority of students accurately identified an instance of heterosexual privilege in their lives and discussed the counterpart to privilege: the marginalization and/or disenfranchisement experienced by individuals who hold other sexual identities. This article highlights the two most common misunderstandings of heterosexual privilege that emerged in students' writing. On the first day of class, 18.2% outright denied that heterosexual privilege exists, and 17.6% conflated gender with sexuality. It reduced to 11.9% and 11.3%, respectively, on the last day of class. We saw growth in students' sophistication of perspective even for some students who demonstrated these misunderstandings at the end of the term.
- Published
- 2017
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7. Canine Butterfly Glioblastomas: A Neuroradiological Review.
- Author
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Rossmeisl JH, Clapp K, Pancotto TE, Emch S, Robertson JL, and Debinski W
- Abstract
In humans, high-grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical, winged-like appearances. This particular tumor manifestation has been coined a "butterfly" glioma (BG). While canine and human gliomas share many neuroradiological and pathological features, the BG morphology has not been previously reported in dogs. Here, we describe the magnetic resonance imaging (MRI) characteristics of BG in three dogs and review the potential differential diagnoses based on neuroimaging findings. All dogs presented for generalized seizures and interictal neurological deficits referable to multifocal or diffuse forebrain disease. MRI examinations revealed asymmetrical (2/3) or symmetrical (1/3), bihemispheric intra-axial mass lesions that predominantly affected the frontoparietal lobes that were associated with extensive perilesional edema, and involvement of the corpus callosum. The masses displayed heterogeneous T1, T2, and fluid-attenuated inversion recovery signal intensities, variable contrast enhancement (2/3), and mass effect. All tumors demonstrated classical histopathological features of glioblastoma multiforme (GBM), including glial cell pseudopalisading, serpentine necrosis, microvascular proliferation as well as invasion of the corpus callosum by neoplastic astrocytes. Although rare, GBM should be considered a differential diagnosis in dogs with an MRI evidence of asymmetric or symmetric bilateral, intra-axial cerebral mass lesions with signal characteristics compatible with glioma.
- Published
- 2016
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8. Fiberoptic microneedle device facilitates volumetric infusate dispersion during convection-enhanced delivery in the brain.
- Author
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Hood RL, Andriani RT Jr, Emch S, Robertson JL, Rylander CG, and Rossmeisl JH Jr
- Subjects
- Animals, Cerebrum, Coloring Agents administration & dosage, Craniotomy, Drug Delivery Systems methods, Evans Blue administration & dosage, Evans Blue pharmacokinetics, Gadolinium administration & dosage, Gadolinium pharmacokinetics, Hyperthermia, Induced instrumentation, Infusions, Intraventricular, Liposomes, Magnetic Resonance Imaging, Male, Rats, Rats, Inbred F344, Rhodamines administration & dosage, Rhodamines pharmacokinetics, Serum Albumin administration & dosage, Serum Albumin pharmacokinetics, Coloring Agents pharmacokinetics, Convection, Drug Delivery Systems instrumentation, Hyperthermia, Induced methods, Lasers, Needles, Optical Fibers
- Abstract
Background and Objectives: A fiberoptic microneedle device (FMD) was designed and fabricated for the purpose of enhancing the volumetric dispersal of macromolecules delivered to the brain through convection-enhanced delivery (CED) by concurrent delivery of sub-lethal photothermal hyperthermia. This study's objective was to demonstrate enhanced dispersal of fluid tracer molecules through co-delivery of 1,064 nm laser energy in an in vivo rodent model., Materials and Methods: FMDs capable of co-delivering fluids and laser energy through a single light-guiding capillary tube were fabricated. FMDs were stereotactically inserted symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth of 1.5 mm. Laser irradiation (1,064 nm) at 0 (control), 100, and 200 mW was administered concurrently with CED infusions of liposomal rhodamine (LR) or gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of 0.1 µl/min for 1 hour. Line pressures were monitored during the infusions. Rodents were sacrificed immediately following infusion and their brains were harvested, frozen, and serially cryosectioned for histopathologic and volumetric analyses., Results: Analysis by ANOVA methods demonstrated that co-delivery enhanced volumetric dispersal significantly, with measured volumes of 15.8 ± 0.6 mm(3) for 100 mW compared to 10.0 ± 0.4 mm(3) for its fluid only control and 18.0 ± 0.3 mm(3) for 200 mW compared to 10.3 ± 0.7 mm(3) for its fluid only control. Brains treated with 200 mW co-delivery exhibited thermal lesions, while 100 mW co-deliveries were associated with preservation of brain cytoarchitecture., Conclusion: Both lethal and sub-lethal photothermal hyperthermia substantially increase the rate of volumetric dispersal in a 1 hour CED infusion. This suggests that the FMD co-delivery method could reduce infusion times and the number of catheter insertions into the brain during CED procedures., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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9. Mosaic variegated aneuploidy without microcephaly: implications for cytogenetic diagnosis.
- Author
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Micale MA, Schran D, Emch S, Kurczynski TW, Rahman N, and Van Dyke DL
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- Abnormalities, Multiple genetics, Child, Preschool, Chromosomes, Human, Pair 19, Cytogenetic Analysis, Female, Humans, Karyotyping, Microcephaly diagnosis, Abnormalities, Multiple diagnosis, Aneuploidy, Mosaicism, Trisomy diagnosis
- Abstract
Mosaic variegated aneuploidy (MVA) is a rare condition characterized by multiple trisomies, rarely monosomies, and a non-specific phenotype including microcephaly, growth and mental retardation, mild malformations, and an increased risk of malignancy. We describe a patient with MVA in whom trisomy 19 mosaicism was originally suspected. The patient was the product of an uncomplicated term pregnancy and delivery. Significant findings were mental retardation, obesity, mild epicanthal folds, tapering fingers, relatively small hands and feet, alternating exotropia, nasal speech limited to short phrases, and generalized hypotonia. There is no family history for birth defects, mental retardation, or consanguinity. The initial peripheral blood chromosome study showed trisomy 19 in 4 of 31 metaphase cells. Because mosaic trisomy 19 is rare, the study was extended to 100 cells, wherein two cells with trisomy 8 were identified. A second blood karyotype was obtained and found to be 47,XX,+8[3]/47,XX,+19[3]/47,XX, +18[2]/47,XX,+9[1]/46,XX[91]. Skin fibroblast chromosome studies revealed a 46,XX karyotype in 120 cells examined. There was no evidence of premature centromere separation. Mutations in the BUB1B gene that encodes a key mitotic spindle checkpoint protein have been described in MVA; however, no mutations of this gene were identified in our patient. This case illustrates the importance of considering other possibilities when confronted with an extremely rare diagnosis such as mosaic trisomy 19. In addition, it shows the importance of not simply interpreting a low percentage of multiple aneuploidies as cell culture artifact, because an additional work-up to rule out MVA may be warranted since this diagnosis is associated with an increased risk of malignancy., ((c) 2007 Wiley-Liss, Inc.)
- Published
- 2007
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10. Evidence for the existence of a non-catalytic modifier site of peptide hydrolysis by the 20 S proteasome.
- Author
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Schmidtke G, Emch S, Groettrup M, and Holzhutter HG
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- Animals, Binding Sites, Cysteine Endopeptidases metabolism, Enzyme Activation, Humans, Hydrolysis, Liver enzymology, Mice, Multienzyme Complexes metabolism, Proteasome Endopeptidase Complex, Substrate Specificity, Cysteine Endopeptidases chemistry, Multienzyme Complexes chemistry
- Abstract
The 20 S proteasome is an endoprotease complex that preferentially cleaves peptides C-terminal of hydrophobic, basic, and acidic residues. Recently, we showed that these specific activities, classified as chymotrypsin-like, trypsin-like, and peptidylglutamyl peptide-hydrolyzing (PGPH) activity, are differently affected by Ritonavir, an inhibitor of human immunodeficiency virus-1 protease. Ritonavir competitively inhibited the chymotrypsin-like activity, whereas the trypsin-like activity was enhanced. Here we demonstrate that the Ritonavir-mediated up-regulation of the trypsin-like activity is not affected by specific active site inhibitors of the chymo-trypsin-like and PGPH activity. Moreover, we show that the mutual regulation of chymotrypsin-like and PGPH activities by their substrates as described previously by a "cyclical bite-chew" model is not affected by selective inhibitors of the respective active sites. These data challenge the bite-chew model and suggest that effectors of proteasome activity can act by binding to non-catalytic sites. Accordingly, we propose a kinetic "two-site modifier" model that assumes that the substrate (or effector) may bind to an active site as well as to a second non-catalytic modifier site. This model appears to be valid as it describes the complex kinetic effects of Ritonavir very well. Since Ritonavir partially inhibits major histocompatibility complex class I restricted antigen presentation, the postulated modifier site may be required to coordinate the active centers of the proteasome for the production of class I peptide ligands.
- Published
- 2000
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11. The effects of an acute psychological stressor on cardiovascular, endocrine, and cellular immune response: a prospective study of individuals high and low in heart rate reactivity.
- Author
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Sgoutas-Emch SA, Cacioppo JT, Uchino BN, Malarkey W, Pearl D, Kiecolt-Glaser JK, and Glaser R
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- Adolescent, Adrenocorticotropic Hormone blood, Adult, Epinephrine blood, Humans, Hydrocortisone blood, Leukocyte Count, Lymphocyte Activation immunology, Male, Norepinephrine blood, Stress, Psychological immunology, T-Lymphocyte Subsets immunology, Arousal physiology, Blood Pressure physiology, Heart Rate physiology, Hormones blood, Immunity, Cellular immunology, Stress, Psychological complications
- Abstract
High and low reactors were preselected on the basis of their heart rate reactivity to a speech stressor in a prescreening session. In the main study, subjects were exposed to a mental arithmetic plus noise stressor. Cardiovascular activity was recorded during baseline and stressor, and blood was drawn prior to and following the stressor for endocrine and immune assays. Results revealed that the stressor decreased the blastogenic response to concanavalin A and increased natural killer cell numbers and cytotoxicity, absolute numbers of CD8+ T-lymphocytes, norepinephrine and epinephrine levels, heart rate, and blood pressure responses. In addition, cortisol and natural killer cell cytotoxicity responses to the stressor differentiated individuals high versus low in heart rate reactivity. These results suggest that the interactions among the autonomic nervous system, endocrine system, and immune system are not only amenable to psychophysiological analysis but that such analyses may play an important role in illuminating underlying mechanisms.
- Published
- 1994
- Full Text
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