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排序方式: 共有796条查询结果,搜索用时 15 毫秒
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Tomasz Trojanowski Jerzy P ceszyński Krzysztof Turowski Stanisław Kamiński Igor Gościński Marian Reinfus Tadeusz Krzyszkowski Marek Pyrich Adam Bielawski Czesława Leszczyk Barbara Bendarzewska Andrzej Staszczak Halina Koźniewska 《Journal of neuro-oncology》1988,6(3):285-291
A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6 000 rads after possibly radical removal of tumors. CCNU administration in the dosis of 100 mg/sq m of body surface every 6–8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61±7 weeks, while in those receiving additional chemotherapy was 56±4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality.
Address for offprints: T Trojanowski, Department of Neurosurgery, Medical School, Jaczewskiego 8, 20-950 Lublin, Poland 相似文献
5.
Liu JQ; Bai XF; Shi FD; Xiao BG; Li HL; Levi M; Mustafa M; Wahren B; Link H 《International immunology》1998,10(8):1139-1148
Induction of mucosal tolerance by inhalation of soluble peptides with
defined T cell epitopes is receiving much attention as a means of
specifically down-regulating pathogenic T cell reactivities in autoimmune
and allergic disorders. Experimental autoimmune encephalomyelitis (EAE)
induced in the Lewis rat by immunization with myelin basic protein (MBP)
and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the
MBP amino acid sequences 68-86 and 87-99. To further define the principles
of nasal tolerance induction, we generated three different MBP peptides
(MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and
evaluated whether their nasal administration on day -11, -10, -9, -8 and -7
prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection
to Lewis rat EAE. Protection was achieved with the encephalitogenic
peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP
110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete
protection to gp-MBP-induced EAE. In contrast, nasal administration of a
mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even
at lower dosage compared to that being used for individual peptides. Rats
tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses
to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays.
Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive
IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node
cells compared to rats receiving MBP 110-128 nasally, while similar low
levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA
expressing cells were observed in the two groups. Nasal administration of
MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord
homogenate-induced EAE, and passive transfer of spleen mononuclear cells
from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE.
Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse
ongoing EAE induced with gp-MBP, although higher doses are required
compared to the dosage needed for prevention. In conclusion, nasal
administration of encephalitogenic MBP peptides can induce antigen-specific
T cell tolerance and confer incomplete protection to gp-MBP-induced EAE,
and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms
are proposed to be responsible for tolerance development after nasal
peptide administration.
相似文献
6.
Primitive Neuroectodermal Tumors of the Central Nervous System 总被引:2,自引:0,他引:2
Lucy Balian Rorke M.D. John Q. Trojanowski M.D. Ph.D. Virginia MY Lee Ph.D. Robert A. Zimmerman M.D. Leslie N. Sutton M.D. Jaclyn A. Biegel Ph.D. Joel W. Goldwein M.D. Roger J. Packer M.D. 《Brain pathology (Zurich, Switzerland)》1997,7(2):765-784
Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers. 相似文献
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers. 相似文献
7.
Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases 总被引:5,自引:2,他引:5
Huang JQ; Trasler JM; Igdoura S; Michaud J; Hanal N; Gravel RA 《Human molecular genetics》1997,6(11):1879-1885
Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative
diseases resulting from the inability to catabolize GM2 ganglioside by
beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit
(Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B
(beta beta homodimer) is also defective in Sandhoff disease. We previously
developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs)
mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff)
mice succumb to a profound neurodegenerative disease by 4-6 months of age.
Here we find that neuron death in Hexb-/- mice is associated with apoptosis
occurring throughout the CNS, while Hexa-/- mice were minimally involved at
the same age. Studies of autopsy samples of brain and spinal cord from
human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances,
in keeping with the severe expression of both diseases. We suggest that
neuron death is caused by unscheduled apoptosis, implicating accumulated
GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
相似文献
8.
E A Clark K L Leach J Q Trojanowski V M Lee 《Laboratory investigation; a journal of technical methods and pathology》1991,64(1):35-44
Brain kinases may play important roles in normal memory as well as in the pathogenesis of neurodegenerative diseases. However, there is scant information on these enzymes in the human brain. For this reason, we characterized the immunohistochemical localization of protein kinase C (PKC) isozymes in human Alzheimer's disease (AD) and non-AD control brains. Using monoclonal antibodies to PKC alpha, PKC beta, and PKC gamma isozymes, we (a) determined the distribution of each PKC isozyme in eight different brain regions (cerebellum, hippocampus, as well as midfrontal, orbital frontal, motor, occipital, parietal, and temporal cortices) from AD and non-AD control brains and found that these patterns were generally similar to those in the rat brain; (b) showed that there were no significant differences in the normal staining intensity of the monoclonal antibodies in AD and non-AD control brain regions except in the hippocampus; (c) observed striking PKC immunoreactivity in globular and linear profiles in the periphery (corona) of AD senile plaques; and (d) demonstrated that PKC alpha immunoreactivity was enhanced in reactive astrocytes associated with senile plaques and other lesions (embolic infarcts) in both AD and non-AD control brains. The data on the normal distribution of each PKC isozyme were corroborated in quantitative studies of PKC alpha, PKC beta, and PKC gamma protein levels in human postmortem brain regions by Western blotting using our antibodies. We conclude that these three major PKC isozymes can be analyzed directly in postmortem human brain, which is an important first step in understanding the potential role that abnormal phosphorylation might play in the pathogenesis of AD. 相似文献
9.
Monoclonal antibodies to a rat nestin fusion protein recognize a 220-kDa polypeptide in subsets of fetal and adult human central nervous system neurons and in primitive neuroectodermal tumor cells. 总被引:3,自引:1,他引:3
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T. Tohyama V. M. Lee L. B. Rorke M. Marvin R. D. McKay J. Q. Trojanowski 《The American journal of pathology》1993,143(1):258-268
Nestin is the major intermediate filament protein of embryonic central nervous system (CNS) progenitor cells. To identify proteins involved in early stages of lineage commitment in the developing human CNS we generated monoclonal antibodies to a TrpE-rat nestin fusion protein. This resulted in a monoclonal antibody (designated NST11) that did not recognize authentic human nestin, but did recognize a novel neuron-specific human polypeptide expressed in a subset of embryonic and adult CNS neurons as well as in medulloblastomas. NST11 immunoreactivity was abundant in developing spinal cord motor neurons, but was extinguished in these neurons by 17 weeks gestation. NST11 also labeled Purkinje cells at 17 weeks gestation, but Purkinje cells continued to express the NST11 antigen throughout gestation as well as in the adult cerebellum, and NST11 immunoreactivity was more abundant in Purkinje cells than in any other human CNS neurons. No NST11 immunoreactivity was detected in cells of the adult human peripheral nervous system or in a variety of adult non-neural human tissues. Further, NST11 almost exclusively stained cerebellar medulloblastomas. In Western blots of immature and mature human cerebral and cerebellar extracts, NST11 did not bind human nestin, but did detect an immunoband with a molecular weight of 220 kd. A similar immunoband was detected in medulloblastoma-derived cell lines with a neuron-like phenotype. These findings suggest that the NST11 monoclonal antibody recognizes a novel protein expressed by a subpopulation of immature and mature human CNS neurons, medulloblastomas, and medulloblastoma-derived cell lines. 相似文献
10.
Properties of antigenic determinants that distinguish neurofibrillary tangles in progressive supranuclear palsy and Alzheimer's disease 总被引:3,自引:0,他引:3
M L Schmidt V M Lee H Hurtig J Q Trojanowski 《Laboratory investigation; a journal of technical methods and pathology》1988,59(4):460-466
Neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and in progressive supranuclear palsy (PSP) differ in their location and morphology, but both appear to express the same or similar epitopes. These immunologic data may signify that both types of NFTs contain the same components and arise as a result of the same mechanisms. To explore this hypothesis, we probed PSP and AD samples of brain stem, where both PSP and AD NFTs occur, using a large panel of monoclonal antibodies (MAbs). The epitopes expressed in brain stem PSP and AD NFTs were compared with those in the NFTs of AD hippocampus. NFTs in PSP hippocampus were too infrequent for comparative analysis. The MAbs were raised to neurofilament and tau proteins, or to AD paired helical filaments. All MAbs raised to tau (three) and paired helical filaments (two) recognized brain stem PSP NFTs and AD NFTs in brain stem and hippocampus. However, 12 anti-NF MAbs specific for multiphosphorylation repeat domains or other phosphate-dependent and independent epitopes did not bind PSP NFTs, but they did detect AD NFTs in hippocampus, and 5 of these MAbs also recognized brain stem AD NFTs. We conclude that some populations of AD NFTs contain antigenic determinants that are not found in PSP NFTs. This may reflect the effect of different pathologic events specific to PSP and AD, or the selective formation of NFTs in different groups of neurons in each of these disorders. 相似文献