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21.
Matrix regulation of skeletal cell apoptosis II: role of Arg-Gly-Asp-containing peptides. 总被引:3,自引:0,他引:3
Robert L Perlot Irving M Shapiro Kyle Mansfield Christopher S Adams 《Journal of bone and mineral research》2002,17(1):66-76
This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells. 相似文献
22.
Ann M. Thompson Kyle R. Moore Glenn C. Thompson 《The Journal of comparative neurology》1995,351(1):104-116
The distribution of serotoninergic fibers in the guinea pig cochlear nucleus was studied with serotonin immunohistochemistry. In addition, the origin of the serotoninergic fibers was determined by combining the retrograde transport of wheat germ agglutinin-apohorseradish peroxidase (gold conjugated) with serotonin immunohistochemistry. Immunoreactivity was present in varicose and nonvaricose fibers that were unevenly distributed throughout the cochlear nucleus. The fibers were most prominent in the superficial layers of the dorsal cochlear nucleus and the anterior spherical cell area of the anteroventral cochlear nucleus. Although less prominent, serotonin-positive fibers were also present in the remaining part of the anteroventral cochlear nucleus and the posteroventral cochlear nucleus. A few positive fibers were present in the auditory nerve root and the dorsal and intermediate acoustic stiae. Double-labeled cells were found throughout the rostral- caudal extent of the serotoninergic system from the caudal linear nucleus to the nucleus raphe pallidus. However, most were confined to the dorsal (52%) and median (18%) raphe nuclei. Some serotoninergic cell groups contained retrogradely labeled cells that were not serotonin immunoreactive, indicating nonauditory afferents to cochlear nucleus containing other neurotransmitter substances. Serotonin may tonically modulate auditory processing within the cochlear nucleus as well as influence certain ascending auditory pathways. Most of the serotonin in the cochlear nucleus comes from superior raphe nuclei that also project to basal ganglia motor systems and limbic strctures. Therefore, the effect of serotonin on the cochlear nucleus may be related to level of arousal or behavioral state. © 1995 Willy-Liss, Inc. 相似文献
23.
Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease 总被引:2,自引:0,他引:2
Turk JR Henderson KK Vanvickle GD Watkins J Laughlin MH 《International journal of experimental pathology》2005,86(5):335-345
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function. 相似文献
24.
Inducible Nitric Oxide Synthase Does Not Affect Resolution of Murine Chlamydial Genital Tract Infections or Eradication of Chlamydiae in Primary Murine Cell Culture 总被引:1,自引:4,他引:1
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Kyle H. Ramsey Gurwattan S. Miranpuri Christoffer E. Poulsen Nancy B. Marthakis Laima M. Braune Gerald I. Byrne 《Infection and immunity》1998,66(2):835-838
Mice lacking inducible nitric oxide synthase (iNOS) or treated with iNOS inhibitors resolved chlamydial genital tract infections. Additionally, treatment of primary murine cell cultures with gamma interferon restricted chlamydial growth in the absence of nitric oxide. From these results, iNOS activity is unnecessary for the resolution of chlamydial genital tract infections in mice and inhibition of chlamydial growth in culture. 相似文献
25.
26.
Immunohistochemical characterization of amyloid proteins in sural nerves and clinical associations in amyloid neuropathy. 总被引:1,自引:0,他引:1
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To test whether immunohistochemical characterization of proteins in amyloid deposits in biopsied sural nerves gives reliable and useful diagnostic information using commercially available reagents, biopsy specimens of sural nerves from 38 patients with amyloid neuropathy were studied. Transthyretin (TTR) was detected in the amyloid deposits of 11 nerves, lambda light chains (LC) in 8 nerves, kappa LC in 7 nerves, and both lambda and kappa LC in 3 nerves. In 9 nerves, the amyloid deposits were too small to allow adequate immunohistochemical characterization of amyloid proteins in serial sections. Evidence that immunohistochemical characterization was correct came from: 1) evaluation of kin, 2) search for monoclonal proteins in the plasma, and 3) sequencing of the gene abnormalities in TTR+ cases. In 9 of 11 TTR+ cases, in which DNA could be obtained, sequencing of the gene showed that each of the 9 cases was heterozygous for a gene mutation; 7 had previously described mutations and 2 undescribed mutations. Therefore, in the nine sporadic cases without plasma monoclonal light chains, the immunohistochemical characterization correctly identified the protein in amyloid as transthyretin. Likewise, there was a high concordance between immunoglobulin light chains in plasma and light chains in amyloid in primary amyloidosis. Evaluation of the type, distribution, and severity of the neurologic symptoms and deficits showed: 1) the sensorimotor and autonomic neuropathy of amyloidosis characteristically affects proximal as well as distal limbs, and 2) the type of amyloidosis probably cannot be determined from the characteristics or severity of the neuropathy alone or from the location or size of amyloid deposits in nerve. 相似文献
27.
Pulmonary marginal zone lymphoma of MALT type as a cause of localised pulmonary amyloidosis
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AIM: To describe six patients with pulmonary marginal zone lymphoma in whom amyloid deposition was identified. Marginal zone lymphoma is a recently recognised type of low grade non-Hodgkin's lymphoma. METHODS: A computerised search was performed of all patients seen at the Mayo Clinic with a diagnosis of pulmonary amyloidosis. Six patients with pulmonary amyloidosis who had biopsy confirmed extranodal marginal zone lymphoma of mucosa associated lymphoid tissue type were identified. All were women, ranging in age from 45 to 85 years. RESULTS: Five patients had amyloid deposition in conjunction with pulmonary marginal zone lymphoma at the time of the original diagnosis. One patient was referred for evaluation of localised pulmonary amyloidosis and was found to have coexisting pulmonary marginal zone lymphoma. Clinical presentation was limited to pulmonary symptoms (two of the six) or constitutional symptoms (two), or was asymptomatic (two). In all six cases, initial findings of nodular densities on screening chest roentgenograms led to further evaluation and eventual lobectomy; these findings included multiple pulmonary nodules (four), single nodule (one), and single nodule with diffuse bilateral interstitial infiltrates (one). Bone marrow was examined in five patients and was normal in all. Protein studies performed in four patients revealed no monoclonal protein. No patients had manifestations of systemic amyloidosis, such as renal, neurological, or cardiac involvement, at a median follow up of 50 months. Four of the six patients remain alive at a median of five years. CONCLUSIONS: Pulmonary marginal zone lymphoma may be found in association with localised amyloid deposition and should be considered in the differential diagnosis of localised pulmonary amyloidosis. 相似文献
28.
Immunophenotypic and genotypic characterisation of multiple myelomas with adverse prognosis characterised by immunohistological expression of the T cell related antigen CD45RO (UCHL-1).
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D M Menke H P Horny H Griesser E J Atkinson E Kaiserling R A Kyle 《Journal of clinical pathology》1998,51(6):432-437
AIMS: To investigate whether plasma cell expression of early B cell, late B cell/preplasma cell, T cell, and myelomonocytic antigens or myeloma associated lymphocytic infiltrates correlated with prognosis in bone marrow biopsy specimens of patients with multiple myeloma. METHODS: Bone marrow biopsy specimens of 23 patients with multiple myeloma were investigated for plasma cell expression and interstitial lymphocyte expression of T cell related antigen CD45RO (UCHL-1). RESULTS: Eight patients showed plasma cell expression of CD45RO and 16 showed increased tumour infiltrating CD45RO positive lymphocytes, which were correlated with poor survival by multivariate analyses (p = 0.005 and p = 0.04, respectively). B cell antigens (MB2, CD20) but no T cell specific antigens (CD3) or T cell receptor gene rearrangements were expressed by plasma cells in CD45RO positive myelomas. Of 16 patients with myeloma who had increased tumour infiltrating CD45RO positive lymphocytes, four had interstitial lymphocyte expression of B cell antigens and two had interstitial lymphocyte expression of the T cell specific antigen CD3. CONCLUSIONS: The recognition of plasma cell expression of CD45RO and increased interstitial CD45RO lymphocytes in bone marrow biopsy specimens of patients with multiple myeloma is an adverse prognostic finding not indicative of an aberrant T cell phenotype or genotype; it is consistent with B cell/pre-plasma cell antigen expression by myeloma cells and their lymphocytic precursors. 相似文献
29.
Laura Cau Michael R. Williams Anna M. Butcher Teruaki Nakatsuji Jeffrey S. Kavanaugh Joyce Y. Cheng Faiza Shafiq Kyle Higbee Tissa R. Hata Alexander R. Horswill Richard L. Gallo 《The Journal of allergy and clinical immunology》2021,147(3):955-966.e16
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30.
Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training 总被引:8,自引:0,他引:8
A Luger P A Deuster S B Kyle W T Gallucci L C Montgomery P W Gold D L Loriaux G P Chrousos 《The New England journal of medicine》1987,316(21):1309-1315
To study the effects of physical conditioning on the hypothalamic-pituitary-adrenal axis, we examined the plasma ACTH, cortisol, and lactate responses in sedentary subjects, moderately trained runners, and highly trained runners to graded levels of treadmill exercise (50, 70, and 90 percent of maximal oxygen uptake) and to intravenous ovine corticotropin-releasing hormone (1 microgram per kilogram of body weight). Basal evening concentrations of ACTH and cortisol, but not of lactate, were elevated in highly trained runners as compared with sedentary subjects and moderately trained runners. Exercise-stimulated ACTH, cortisol, and lactate responses were similar in all groups and were proportional to the exercise intensity employed. These responses, however, were attenuated in the trained subjects when plotted against applied absolute workload. Only the highly trained group had diminished responses of ACTH and cortisol to ovine corticotropin-releasing hormone, consistent with sustained hypercortisolism. We conclude that physical conditioning is associated with a reduction in pituitary-adrenal activation in response to a given workload. Alterations of the hypothalamic-pituitary-adrenal axis consistent with mild hypercortisolism and similar to findings in depression and anorexia nervosa were found only in highly trained runners. Whether these alterations represent an adaptive change to the daily stress of strenuous exercise or a marker of a specific personality profile in highly trained athletes is unknown. 相似文献