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991.
Deregulation of apoptosis is involved in prostate cancer development and progression. This study involved an immunohistochemical "profiling" of prostate tissue specimens from patients who underwent prostatectomy for localized prostate cancer, to identify apoptosis-specific alterations associated with premalignant precursor lesions. Prostate tissue was pathologically evaluated, and areas of benign acini, high-grade prostate intraepithelial neoplasia (HGPIN), and prostate cancer were identified. Immunohistochemical analysis was performed to determine the expression of p27Kip1, a key cell cycle regulator, transforming growth factor (TGF)-beta receptor II (TbetaRII), a critical signaling effector of TGF-beta; Smad4, a downstream intracellular effector of TGF-beta signaling; p53, a key apoptosis regulator; and prostate-specific antigen (PSA), a clinical marker of prostate cancer. The apoptotic index of the same cell populations was determined using the transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end labeling assay. Our findings indicate a significant reduction in p27Kip1 immunoreactivity in HGPIN (P<0.0001) and prostate cancer (P<0.0001) compared with the benign tissue. A significant down-regulation was detected in TbetaRII expression in HGPIN and prostate cancer compared with benign prostatic hyperplasia (BPH)(P<0.001). A significant decrease was also observed in Smad4 levels in HGPIN and prostate cancer compared with BPH (P<0.001). Evaluation of the incidence of apoptosis revealed a significant decrease in the apoptotic index among the epithelial cell populations in HGPIN and a further decrease in prostate carcinoma (P<0.01). This reduced apoptotic index correlated with a significant increase in p53 immunoreactivity in the prostatic carcinoma foci. Prostate cancer cells exhibited strong nuclear staining for p53 compared with adjacent HGPIN (P<0.05) and the benign lesions of the same prostate specimens (P<0.05). A significant reduction in PSA immunostaining was detected in HGPIN and prostate carcinoma foci compared with the benign glandular epithelia (P<0.001). These results further define deregulation of TGF-beta signaling effectors as a molecular basis for loss of apoptotic control contributing to the development of prostate tumors. Identification of apoptotic regulators in precursor premalignant lesions may have prognostic significance in disease progression as well as therapeutic value for targeting prostate cancer. 相似文献
992.
993.
Kawano Y Fukuda J Itoh H Takai N Nasu K Miyakawa I 《American journal of reproductive immunology (New York, N.Y. : 1989)》2004,52(2):124-128
PROBLEM: In order to investigate the role of macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein -1 (MCP-1) in human ovulation, we studied the regulation of M-CSF and MCP-1 in cultured human granulosa cells. METHOD OF STUDY: Immortalized granulosa cells (GC1a) were cultured in serum-free medium, and incubated with interleukin (IL)-1alpha, IL-1 receptor antagonist (ra) and tumor necrosis factor (TNF)-alpha. The supernatants were collected, and M-CSF and MCP-1 were measured by ELISA. RESULTS: The levels of M-CSF and MCP-1 were increased after treatment with IL-1alpha (1 nm) and TNF-alpha (1 nm) in a time-dependent manner. The levels of M-CSF and MCP-1 were significantly increased after treatment with IL-1alpha and TNF-alpha in a dose-dependent manner. However, the levels of M-CSF and MCP-1 were significantly decreased by treatment with IL-1alpha (1 nm) and/or increasing concentrations of IL-1 ra. CONCLUSIONS: Our data indicated that M-CSF and MCP-1 were regulated by IL-1alpha and TNF-alpha. It was suggested that M-CSF and MCP-1 may play an important role in human preovulatory processes. 相似文献
994.
Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha 总被引:1,自引:0,他引:1
The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice lacking p85alpha, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules. However, a detailed analysis of splenic B cell subsets in p85alpha-deficient mice has not been reported. Here we show that these mice are deficient in four major B cell subsets: transitional-1, transitional-2, follicular and marginal zone. These defects are distinct from those observed in Xid mice that express a mutant Btk unable to interact with PI3K lipid products. Moreover, mice with both genetic lesions exhibit even greater impairment in B cell development. Finally, we show that transgenic expression of the anti-apoptotic protein Bcl-2 in p85alpha-deficient mice restores the transitional B cell subsets but not the marginal zone subset, and produces a follicular population with an aberrant phenotype. These findings establish a role for PI3K-p85alpha in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals. 相似文献
995.
Angiotensin-(1–7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors 总被引:1,自引:0,他引:1
Magaldi AJ Cesar KR de Araújo M Simões e Silva AC Santos RA 《Pflügers Archiv : European journal of physiology》2003,447(2):223-230
The peptide angiotensin-(1–7) [Ang-(1–7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1–7) effect on osmotic water permeability (P
f). P
f was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1–7), arginine vasopressin (AVP) and Ang-(3–8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1–7), but not Ang-(3–8), increased P
f significantly. The effect of Ang-(1–7) on P
f was abolished by its selective antagonist, A-779, added before or after Ang-(1–7). Prostaglandin E2 and the protein kinase A inhibitor H8 also blocked the Ang-(1–7) effect. Blockade of vasopressin V1 receptors by antagonists did not change the Ang-(1–7) effect, but pre-treatment with a V2 antagonist abolished the effect of Ang-(1–7) on P
f. Similarly, pre-treatment with A-779 inhibited AVPs effect on P
f. Forskolin-stimulated P
f was blocked both by A-779 and by the V2 antagonist. Finally, Ang-(1–7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V2 antagonist. These data provide evidence that Ang-(1–7) interacts via its receptor with the AVP V2 system through a mechanism involving adenylate-cyclase activation. 相似文献
996.
Deckert M Lütjen S Leuker CE Kwok LY Strack A Müller W Wagner N Schlüter D 《European journal of immunology》2003,33(5):1418-1428
Under various inflammatory conditions, cell adhesion molecules are up-regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)-1 in Toxoplasma encephalitis (TE) was addressed using VCAM(flox/flox MxCre) mice. Neonatal inactivation of the VCAM-1 gene resulted in a lack of induction of VCAM-1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM-1 on choroid plexus epithelial cells and the ependyma was unaffected; in these animals, resistance to T. gondii was abolished, and VCAM(flox/flox MxCre) mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti-T. gondii-specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T. gondii-specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM-1-mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM-1-mediated homing across cerebral blood vessels. 相似文献
997.
998.
童家明 《中国医学物理学杂志》2006,23(3):233-235
根据七年制医学生培养要求,在“生物物理技术”教学中,除介绍有关物理方法与技术的原理及在生物医学中的应用外,还尝试了小论文写作和渗透科研思路、方法培养的探索。 相似文献
999.
Flow cytometry immunolabeling, tube agglutination tests, and thin-layer chromatography immunostaining with two different anti-A
monoclonal antibodies (anti-A mAb1 and anti-A mAb2) and one anti-B mAb were used to demonstrate differences in expression
of the A and B antigens among erythrocytes from type A and four different type AB cats. Although the flow cytometric patterns
of reactivity and agglutination scores for erythrocytes from types A and B cats detected with the anti-A and anti-B mAbs were
consistent, reactivity among erythrocytes of different type AB cats was variable. By flow cytometric analysis, 99.9% of type
A erythrocytes, no type B erythrocytes, 2.5–4.0% of erythrocytes from type AB cats 1, 3, and 4, and 60.7% of erythrocytes
from type AB cat 2 had detectable A antigen when anti-A mAb1 was used. In contrast, 86.4% of type A erythrocytes, no type
B erythrocytes, 20.2–38.0% of erythrocytes from type AB cats 1, 3, and 4, and 68.5% of erythrocytes from type AB cat 2 had
detectable A antigen when anti-A mAb2 was used. In addition, 86.9% of type B erythrocytes, no type A erythrocytes, 83.1–96.8%
of erythrocytes from type AB cats 1, 3, and 4, and 73.0% of erythrocytes from type AB cat 2 had detectable B antigen when
the anti-B mAb was used. Agglutination scores of type AB cats were comparable to the percent binding on flow cytometry. Thin-layer
chromatography immunostains confirmed differences in the amount of A antigen between erythrocyte glycolipids of type A and
AB cats and those of type AB cats 1 and 2. These results suggest that at least two different phenotypes exist within the feline
AB blood type, which differ in the amount of A antigen expressed on the erythrocyte surface. 相似文献
1000.