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941.
Abnormal expression of “self” antigens on tumors compared with normal cells provides opportunities and challenges for development of cancer vaccines. We review recent work in pre-clinical transgenic mouse models and in clinical trials that has elucidated multiple regulatory mechanisms that interfere with the induction of effective immunity. We discuss these as being either part of the normal function of the immune system or being driven by the tumor microenvironment. Collectively this work shows that it is possible to design vaccines based on tumor-associated antigens and elicit effective immunity against abnormal expression of these antigens on tumors without causing autoimmunity. 相似文献
942.
943.
Levene A P & Goldin R D(2010) Histopathology 56 , 426–429 Physiological hepatic nuclear vacuolation—how long does it persist? Aims: Nuclear vacuolationglycogenation is a characteristic histological feature of non‐alcoholic fatty liver disease (NAFLD) that can help distinguish it from alcohol‐induced liver disease. There are, however, other associations of nuclear vacuolation of which the commonest is as a normal feature of childhood. The aim of this study was to identify how long this physiological nuclear vacuolation persists. Methods and results: Liver biopsy specimens from 872 patients with chronic hepatitis B virus infection (a condition known not to be associated with nuclear vacuolation) were studied to assess the frequency of nuclear vacuolation at different ages. All the patients studied had a body mass index of <25 kg/m2 and an alcohol intake of <15 units/week, as well as no other risk factors for liver disease. It was found that the frequency of nuclear vacuolation, in the absence of NAFLD, fell from 13% at age 20–24 years to 4% in the early 30s and to 0% at age 60–64 years. Conclusions: Physiological hepatic nuclear vacuolation is common in the 20s and persists into the 30s. This knowledge can help in the assessment of liver biopsy specimens in which nuclear vacuolation is a feature. 相似文献
944.
Amy S. DeSantis Emma K. Adam Kathryn A. Mendelsohn Leah D. Doane 《International journal of behavioral medicine》2010,17(1):74-78
Background
Hypothalamic–pituitary–adrenal (HPA) axis functioning has implications for physical and mental health. One important indicator of HPA axis functioning, the salivary cortisol awakening response (CAR), is sensitive to whether participants provide their samples at the requested times after waking. 相似文献945.
Jun Ren Lakshmi Pulakat Adam Whaley-Connell James R. Sowers 《Journal of molecular medicine (Berlin, Germany)》2010,88(10):993-1001
The metabolic syndrome is a constellation of metabolic disorders including obesity, hypertension, and insulin resistance,
components which are risk factors for the development of diabetes, hypertension, cardiovascular, and renal disease. Pathophysiological
abnormalities that contribute to the development of the metabolic syndrome include impaired mitochondrial oxidative phosphorylation
and mitochondrial biogenesis, dampened insulin metabolic signaling, endothelial dysfunction, and associated myocardial functional
abnormalities. Recent evidence suggests that impaired myocardial mitochondrial biogenesis, fatty acid metabolism, and antioxidant
defense mechanisms lead to diminished cardiac substrate flexibility, decreased cardiac energetic efficiency, and diastolic
dysfunction. In addition, enhanced activation of the renin–angiotensin–aldosterone system and associated increases in oxidative
stress can lead to mitochondrial apoptosis and degradation, altered bioenergetics, and accumulation of lipids in the heart.
In addition to impairments in metabolic signaling and oxidative stress, genetic and environmental factors, aging, and hyperglycemia
all contribute to reduced mitochondrial biogenesis and mitochondrial dysfunction. These mitochondrial abnormalities can predispose
a metabolic cardiomyopathy characterized by diastolic dysfunction. Mitochondrial dysfunction and resulting lipid accumulation
in skeletal muscle, liver, and pancreas also impede insulin metabolic signaling and glucose metabolism, ultimately leading
to a further increase in mitochondrial dysfunction. Interventions to improve mitochondrial function have been shown to correct
insulin metabolic signaling and other metabolic and cardiovascular abnormalities. This review explores mechanisms of mitochondrial
dysfunction with a focus on impaired oxidative phosphorylation and mitochondrial biogenesis in the pathophysiology of metabolic
heart disease. 相似文献
946.
Wendy J. Herbert Adam G. Davidson John A. Buford 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2010,203(2):271-283
The pontomedullary reticular formation (PMRF) of the monkey produces motor outputs to both upper limbs. EMG effects evoked
from stimulus-triggered averaging (StimulusTA) were compared with effects from stimulus trains to determine whether both stimulation
methods produced comparable results. Flexor and extensor muscles of scapulothoracic, shoulder, elbow, and wrist joints were
studied bilaterally in two male M. fascicularis monkeys trained to perform a bilateral reaching task. The frequency of facilitation versus suppression responses evoked in
the muscles was compared between methods. Stimulus trains were more efficient (94% of PMRF sites) in producing responses than
StimulusTA (55%), and stimulus trains evoked responses from more muscles per site than from StimulusTA. Facilitation (72%)
was more common from stimulus trains than StimulusTA (39%). In the overall results, a bilateral reciprocal activation pattern
of ipsilateral flexor and contralateral extensor facilitation was evident for StimulusTA and stimulus trains. When the comparison
was restricted to cases where both methods produced a response in a given muscle from the same site, agreement was very high,
at 80%. For the remaining 20%, discrepancies were accounted for mainly by facilitation from stimulus trains when StimulusTA
produced suppression, which was in agreement with the under-representation of suppression in the stimulus train data as a
whole. To the extent that the stimulus train method may favor transmission through polysynaptic pathways, these results suggest
that polysynaptic pathways from the PMRF more often produce facilitation in muscles that would typically demonstrate suppression
with StimulusTA. 相似文献
947.
Detection and assignment of mutations and minihaplotypes in human DNA using peptide mass signature genotyping (PMSG): application to the human RDS/peripherin gene 下载免费PDF全文
Telmer CA Retchless AC Kinsey AD Conley Y Rigatti B Gorin MB Jarvik JW Retchless AR 《Genome research》2003,13(8):1944-1951
Peptide mass-signature genotyping (PMSG) is a scanning genotyping method that identifies mutations and polymorphisms by translating the sequence of interest in more than one reading frame and measuring the masses of the resulting peptides by mass spectrometry. PMSG was applied to the RDS/peripherin gene of 16 individuals from a family exhibiting autosomal dominant macular degeneration. The method revealed an A-->T transversion in the 5' splice site of intron 2 that is the likely cause of the disease. It also revealed four different minihaplotypes in exon 3 that represent particular combinations of SNPs at four different locations. This study demonstrates the utility of PMSG for identifying and characterizing point mutations and local minihaplotypes that are not readily analyzed by other approaches. 相似文献
948.
Layer K Lin G Nencioni A Hu W Schmucker A Antov AN Li X Takamatsu S Chevassut T Dower NA Stang SL Beier D Buhlmann J Bronson RT Elkon KB Stone JC Van Parijs L Lim B 《Immunity》2003,19(2):243-255
A mouse strain was identified with a recessive genetic lesion, which spontaneously developed a lymphoproliferative autoimmune syndrome exhibiting features of systemic lupus erythematosus. Positional mapping of the disease-associated locus revealed a lesion in Rasgrp1 that prevented the translation of the RasGRP1 protein. T cells from these mice failed to activate Ras or proliferate vigorously following antigen encounter and showed defects in positive selection. Peripheral RasGRP1lag T cells spontaneously adopted a memory phenotype and were able to transfer disease to lymphopenic recipient mice. CD4+ T cells accumulated in the lymphoid tissues of older RasGRP1lag mice and were resistant to activation-induced cell death. RasGRP1lag B cells were functionally normal, but activated B cells were detected in older mice, as were autoantibodies directed against self-antigens. Our findings indicate that Ras signaling pathways are required to maintain T cell tolerance and to prevent autoimmune disease. 相似文献
949.
950.
Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans 总被引:4,自引:0,他引:4 下载免费PDF全文
John C. Reed Kutbuddin Doctor Ana Rojas Juan M. Zapata Christian Stehlik Loredana Fiorentino Jason Damiano Wilfried Roth Shu-ichi Matsuzawa Ruchi Newman Shinichi Takayama Hiroyuki Marusawa Famming Xu Guy Salvesen RIKEN GER Group GSL Members Adam Godzik 《Genome research》2003,13(6B):1376-1388
Apoptosis (programmed cell death) plays important roles in many facets of normal mammalian physiology. Host-pathogen interactions have provided evolutionary pressure for apoptosis as a defense mechanism against viruses and microbes, sometimes linking apoptosis mechanisms with inflammatory responses through NFκB induction. Proteins involved in apoptosis and NFκB induction commonly contain evolutionarily conserved domains that can serve as signatures for identification by bioinformatics methods. Using a combination of public (NCBI) and private (RIKEN) databases, we compared the repertoire of apoptosis and NFκB-inducing genes in humans and mice from cDNA/EST/genomic data, focusing on the following domain families: (1) Caspase proteases; (2) Caspase recruitment domains (CARD); (3) Death Domains (DD); (4) Death Effector Domains (DED); (5) BIR domains of Inhibitor of Apoptosis Proteins (IAPs); (6) Bcl-2 homology (BH) domains of Bcl-2 family proteins; (7) Tumor Necrosis Factor (TNF)-family ligands; (8) TNF receptors (TNFR); (9) TIR domains; (10) PAAD (PYRIN; PYD, DAPIN); (11) nucleotide-binding NACHT domains; (12) TRAFs; (13) Hsp70-binding BAG domains; (14) endonuclease-associated CIDE domains; and (15) miscellaneous additional proteins. After excluding redundancy due to alternative splice forms, sequencing errors, and other considerations, we identified cDNAs derived from a total of 227 human genes among these domain families. Orthologous murine genes were found for 219 (96%); in addition, several unique murine genes were found, which appear not to have human orthologs. This mismatch may be due to the still fragmentary information about the mouse genome or genuine differences between mouse and human repertoires of apoptotic genes. With this caveat, we discuss similarities and differences in human and murine genes from these domain families. 相似文献