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101.
BACKGROUND: Inflammation has been proposed to play essential roles in the pathophysiology of endometriosis, in which neutrophils and mast cells have been suggested to be involved. We studied whether the protease-activated receptor 2 (PAR2), which is activated by enzymes from neutrophils and mast cells, in endometriotic stromal cells (ESC) has any implication in the development of the disease. METHODS: Cultured ESC were stimulated with various concentrations of a specific PAR2 agonist peptide. Proliferating activity of the cells was determined using immunostaining of proliferating cell nuclear antigen (a cell proliferation marker), 5-bromo-2'-deoxyuridine incorporation into DNA and cell count. The concentrations of interleukin (IL)-6 and IL-8 were measured using specific enzyme-linked immunosorbent assay kits. The phosphorylation of three mitogen-activated protein kinases (MAPK), i.e. p38 MAPK, p42/44 MAPK and stress-activated protein Kinase/c-jun N terminal Kinase, in ESC was examined with Western blot analysis. RESULTS: Activation of PAR2 stimulated the proliferation of ESC and the secretion of IL-6 and IL-8 from ESC in a dose-dependent manner. Activation of PAR2 stimulated the phosphorylation of all three MAPK, and inhibitors of each MAPK suppressed the PAR2 activation-induced proliferation of ESC. CONCLUSIONS: The activation of PAR2 in ESC may be involved in the pathophysiology of endometriosis by inducing the growth and inflammation of endometriotic lesions.  相似文献   
102.
 The recently identified prostate cancer susceptibility gene ELAC2 (HPC2) harbors two common missense variants, a serine to leucine substitution at residue 217 (Leu217) and an alanine to threonine substitution at residue 541 (Thr541). We genotyped the two variants in a Japanese cohort consisting of 350 prostate cancer patients 242 male population controls, and 114 male low-risk controls. Both missense alleles, Leu217 and Thr541, were carried at higher frequency in Japanese patients than in the controls (Leu217, P = 0.0012; Thr541, P = 0.0145), and the odds ratios associated with carrying these sequence variants were higher in Japanese than in Caucasians. Although the Leu217 and Thr541 variants of ELAC2 are less common in Japanese than in Caucasians, both variants confer significantly increased risk of prostate cancer in Japanese. Carriage of these variants was not associated with age at diagnosis, tumor stage, or tumor grade in these Japanese prostate cancer patients. The allele-specific pattern of risk observed in Japanese and familial Caucasian patients was qualitatively similar; however, the magnitude of that risk was considerably greater in Japanese than in Caucasians. Received: September 3, 2002 / Accepted: October 2, 2002  相似文献   
103.
We examined the possibility that lumbar skin warming can increase gastrointestinal motility by investigating the electrogastrogram (EGG), blood pressure, and heart rate with psychometric ratings in healthy humans. Scores of mood state profiles showed that lumbar skin warming (42 degrees C, 20 min) decreased tension-anxiety, depression, anger-hostility, fatigue, and confusion of the participants. A multiple bandpass filter analysis of EGGs showed that a postural transition from orthostatic to supine for measurement caused an increase in dominant frequency of 25-29% towards the frequencies of the normal interdigestive migrating motor complex (IMC). The spectral power of the IMC band, 2.55-3.05 cycles/min, was increased by 20 min-warming, reflecting the increase in gastric contractility. No increase in the spectral power was observed in the time-matched control group without skin warming. Therefore, an increase in contractility is a characteristic of lumbar skin warming. The systolic blood pressure increased by 15% during warm stimulation. Interbeat intervals were not influenced by warm stimulation. An analysis of interbeat intervals by a fast Fourier transform method showed that the cardiac sympathetic and parasympathetic nerves did not play a major role in raising the blood pressure. Vasoconstriction of the mesenteric artery was therefore considered to cause a blood pressure increase during warming. It is hypothesized that vasoconstriction of the visceral arteries by lumbar skin warming increases the blood pressure and gastrointestinal contractility.  相似文献   
104.
The expression of variant isoforms of CD44 (CD44v) correlates with the metastatic potential of various carcinomas. In endometrial cancer, however, the significance of CD44v-expression as a prognostic indicator has not been fully investigated, nor has it been compared with that of p53, estrogen receptor or Ki67. Surgical material consisted of 14 atypical endometrial hyperplasias (AEH) and 163 endometrial carcinomas (EC). Expression of CD44s, v3 and v6 in carcinoma tissue, and other prognostic markers were immunohistochemically evaluated. The expression in the squamous differentiation was strictly excluded for the evaluation of immunohistochemistry, because the significance was different from that in the adenocarcinoma component. CD44s was frequently expressed in AEH and EC. On the other hand, CD44v3- and v6-positivities were rare or nonexistent in AEH, but were observed in 8 and 35% of EC, respectively. CD44v3-expression correlated significantly with histologic grade and lymph node metastasis. However, there was no correlation between CD44v6 expression and any clinicopathologic factor, nor were other prognostic markers expressed. Univariate analysis revealed that each CD44 was a prognostic determinant in the patients with EC. However, employing multivariate analysis, there were only three independent factors: p53 overexpression, CD44v6 expression and myometrial invasion. CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients with EC.  相似文献   
105.
Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34(+) cells were transplanted to the peri-ischemic zone. To track the in vivo fate of transplanted cells, CD34(+) cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline-treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell-derived, GFP-positive cells were found incorporated into the vascular structure, and GFP-positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34(+) cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell-derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.  相似文献   
106.
Oral squamous cell carcinoma is the most common oral malignancy, and we performed electron microscopic and immunohistochemical investigation of the tumor. In patients with cervical metastasis, microvilli were developed and a small number of desmosomes were found, regardless of the width of the intercellular spaces. In patients without the metastasis, few microvilli were found in relatively wide intercellular spaces, or numerous microvilli were found in narrow intercellular spaces, and a large number of desmosomes were shown. However, these findings were different from those of tumors that had received radiotherapy, in which numerous microvilli and a small number of desmosomes were found in the nonmetastatic cases. Transferrin receptor, which is a marker of cell proliferation, was localized on the cell membrane, especially in microvilli. Ultrastructural similarity between the primary tumor and the metastatic tumor was recognized, however, the features of microvilli, desmosomes, and the intercellular spaces differed between them in most cases. It is suggested that microvilli might be related to the metastasis of oral squamous cell carcinoma cells. Immunohistochemically, the protein expression of p53 and pRb2/p130 was related to the clinical course of the patients with oral squamous cell carcinoma; the mechanism of the synthesis of these proteins should be investigated in order to understand the biological behavior of the tumor.  相似文献   
107.
Sarcoma of the oral region is extremely rare and ultrastructural studies of the tumor are limited in number. We collected oral sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, alveolar soft-part sarcoma, solitary plasmacytoma, and osteosarcoma, and performed ultrastructural studies of these tumors. The value of these studies for an understanding of the biological behavior of the tumors was then investigated. In these studies, electron microscopic examinations of oral sarcoma were of assistance in our attempt to establish correct diagnosis and histogenesis. Data from the studies of oral sarcoma by light microscopy, electron microscopy, and immunohistochemistry should be accumulated.  相似文献   
108.
Since dendritic cells (DC) play pivotal roles in both innate and adaptive immunity, DC can be a good target for immuno-gene therapy. However, the optimal generation method for gene-modified DC has not yet been well exploited. CD34+ cells from cord blood (CB), bone marrow (BM), or peripheral blood (PB) were expanded in a medium containing stem cell factor (SCF), flt 3 ligand (Flt3L) and thrombopoietin (TPO) with or without HESS-5, a murine BM stromal cell line, for 2 weeks (the first expansion step), then differentiated to DC in a medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF), flt 3 ligand (Flt3L), stem cell factor (SCF), tumor necrosis factor-alpha (TNF-alpha), IL-4, and lipopolysaccharide (LPS) for 9 days (the second differentiation step). DC progenitors were transduced with human immunodeficiency virus (HIV) vectors at different time points during the second step. Use of HESS-5 during the first step resulted in more DC generation than without it (cell expansion: CB, 10,461 vs. 354-fold; BM, 962 vs. 225-fold; peripheral blood mononuclear cell (PBMC), 8,506 vs. 240-fold; %DC: CB, 83.4% vs. 76.9%; BM, 83.6 vs. 69.8%; PBMC, 85.9 vs. 60.5%). Gene transduction to the in vitro expanded DC progenitors at day 3 during the second step, resulted in better final yield of the gene-modified DC than that to those at day 0 or day 6 (as much as 44% of DC expressed green fluorescence protein (GFP) as a transgene) and the transduction efficiency correlated with endocytic ability and percent of S phase. DC transduced with an HIV vector encoding a melanoma antigen, MART-1, were adequately recognized by specific anti-MART-1 CTL. The two-step culture method with HESS-5 is useful for rapid expansion of DC progenitors and subsequent lentiviral gene transduction to DC.  相似文献   
109.
To investigate the possible involvement of the sympathetic nervous system in pressor response during water drinking, muscle sympathetic nerve activity (MSNA), blood pressure (BP), and heart rate (HR) were continuously measured in healthy young volunteers throughout the experiments of a 5-min control, 2 min of drinking 500 ml water, and a 28-min recovery. To avoid the effects of water passing through the oropharyngeal and esophageal regions and/or effects of swallowing, an equal amount of water was directly infused to the stomach through a stomach tube for 2 min. Water drinking caused a transient increase in mean arterial pressure (MAP) and HR immediately after drinking (DeltaMAP, 12.6 +/- 2.1 mmHg; DeltaHR, +19.9 +/- 1.7 beats/min at the peak). An abrupt decrease of MSNA was observed directly during water drinking (Deltaburst rate, -6.9 +/- 1.3 bursts/min; Deltatotal activity, -2,606 +/- 491 U/min), and it increased to the baseline level thereafter. Gastric infusion had little or no effect on MAP, HR, and MSNA. The present study demonstrated that a pressor response during water drinking was associated with the attenuation of MSNA and not generated by gastric infusion of water at the same rate as in this drinking manner. In conclusion, the rapid rise in BP might be caused through stimulations from the oropharyngeal region, swallowing-induced factors, and/or a feedforward mechanism by a central descending signal from the higher brain centers.  相似文献   
110.
Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.  相似文献   
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