Stromelysin-3 and other stromelysins in breast cancer: importance of epithelial-stromal interactions during tumor progression.
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Breast Neoplasms↗
Biomedical subjects
A Okada
Publications and source records attributed to A Okada.
Influence of glutamine-supplemented parenteral nutrition on intestinal amino acid metabolism in rats after small bowel resection.
Glutamine (Gln)-supplemented total parenteral nutrition (TPN) has been shown to improve mucosal adaptation after massive small bowel resection (SBR); however, its influences on intestinal amino acid metabolism remain unknown. In this study, intestinal amino acid flux, circulating plasma aminogram, mucosal glutaminase activity and protein, and DNA content were measured 7 days after massive SBR in rats receiving either standard (Std) or Gln-supplemented TPN. Sham-operated rats and rats fed chow after enterectomy served as controls. The uptake of Gln and the release of citrulline (Cit) by the remaining intestine was significantly decreased, with reduced mucosal glutaminase activity after SBR in the Chow and Std-TPN groups. Glutamine supplementation resulted in significantly increased gut Gln uptake compared with Std-TPN (P < 0.01). Mucosal glutaminase activity, mucosal protein, and DNA content was also increased by Gln; however, the gut release of Cit remained unchanged (P > 0.05). The subsequent decrease in circulating arginine (Arg) in the Gln-TPN group compared with the Std-TPN group (P < 0.05) was attributed to an insufficient exogenous supply. These findings show that Gln-supplemented TPN improves mucosal growth and gut Gln uptake after SBR. However, the intestinal production of Cit, which remained low in both TPN groups, may lead to an insufficiency of endogenous Arg synthesis. Thus, both Gln and Arg may be essential amino acids after SBR.
Amino Acids↗
Change in digital blood flow with simultaneous reduction in plasma endothelin induced by hand-arm vibration.
Involvement of endothelium-derived relaxing factor (EDRF) or endothelium-derived constricting factor (EDCF) has been proposed as the pathophysiologic mechanism of vibration-induced white finger (VWF). Recent evidence that endothelin is a potent vasoconstrictor peptide indicates that it may play a role in vasoregulation during vibration exposure through the local actions of EDRF or EDCF. Therefore, we examined the effects of grasping (50 N) and hand-arm vibration (50 m/s2 rms, 120 Hz, x-axis) on digital blood flow (DBF) and on the level of plasma endothelin in seven healthy male office workers. Grasping decreased DBF without affecting endothelin, and vibration increased DBF with a simultaneous reduction in endothelin. The grasping-induced decrease in DBF seemed to be due to mechanical compression of the vessels. The negative correlation between DBF and endothelin during vibration exposure suggests that a reduction in release of endothelin from smooth muscle into the vessel cavity during vibration leads to vasodilatation, possibly attributable to the local axon reflex.
Arm↗
Uterine circulatory dysfunction induced by whole-body vibration and its endocrine pathogenesis in the pregnant rat.
Effects of whole-body vibration on normal pregnancy were studied in the rat. Uterine blood flow and five endocrine functions corticosterone (CS), estradiol (E2), progesterone (P), prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) concentration were measured in rats exposed to whole-body vibration with an acceleration of 10 m.s-2 at a frequency of 8 Hz. While no change in uterine blood flow was observed in control rats, uterine blood flow was significantly decreased 75 and 90 min after exposure to vibration. The uterine blood flow at 15 and 30 min was increased by pretreatment with intraperitoneal injections of angiotensin II (AII). In contrast, in AII pretreated rats exposed to the vibration, uterine blood flow was significantly reduced 90 min after exposure. The CS concentration was increased by vibration independently of the pretreatment with AII. Neither E2 nor PGF2 alpha concentration were changed by the vibration with or without AII administration. The P and PGE2 concentrations were both decreased by vibration in the absence of AII, while the decrease in PGE2 induced by the vibration was also found in AII-treated rats. The present results indicated that the pregnant rats subjected to whole-body vibration responded with changes in uterine and ovarian function. The observed decrease in uterine blood flow may have been the result of reduced PGE2 concentration resulting from an indirect effect of vibration.
Animals↗
Stromelysin-3 in the biology of the normal and neoplastic mammary gland.
Stromelysin-3 (ST3) is an extracellular proteinase predominantly expressed in fibroblasts. The particular structural features and in vitro functions of this molecule suggest it could be the first member of a new subgroup of the matrix metalloproteinase family. ST3 is transiently expressed during mammary gland post-weaning involution, embryonic implantation, various organogeneses, and during amphibian metamorphosis. Moreover, ST3 is expressed in a panel of human invasive carcinomas including breast, colon, and head and neck carcinomas. Almost all ST3-expressing tissues show intense extracellular matrix remodeling activities including the loss of basement membrane integrity. Thus, either directly, or indirectly in association with other proteinases, ST3 might be involved in tissue remodeling processes occurring in both physiological and pathological processes. In vitro and in vivo studies using malignant cells stably transfected in such a way as to modulate their ST3 expression levels indicate that ST3 modifies neither cell proliferation nor invasive properties, but rather favors tumor cell survival in host tissues. This hypothesis is consistent with clinical data showing that ST3 expression could be predictive of tumor progression leading to metastases.
Animals↗
Pancreaticobiliary maljunction-associated pancreatitis: an experimental study on the activation of pancreatic phospholipase A2.
Congenital dilatation of the bile duct (CDBD), or choledochalcyst, is often complicated by recurrent pancreatitis. Reflux of pancreatic juice into the bile duct through pancreaticobiliary maljunction (PBM), an anomaly commonly associated with CDBD, and ensuing activation of pancreatic enzymes could be involved in the pathophysiologic mechanism of recurrent pancreatitis. A study was undertaken to follow the time course of the activity of phospholipase A2 (PLA2) in animal models of PBM. The assay procedures for PLA2 were evaluated, as were the conditions for separating the active enzyme from its inactive proenzyme (pro-PLA2) by immunoblotting. A rat model was designed according to Block's method with some modifications. The kinetics of prophospholipase A2 (proPLA2) activation in bile was examined by measuring PLA2 activity and by immunoblotting using anti-rat pancreatic enzyme antibody after separating PLA2 from its zymogen under nonreducing conditions. Experimental animals were divided into three groups: group 1 (PBM group) in which bile and pancreatic juice were mixed with occlusion of the papilla; group 2, in which the papilla and hepatic hillus were occluded without mixing the two juices; and group 3, in which simple laparotomy was done. In group 1 animals, pro-PLA2 in bile was activated to its active form. In group 2 animals, where proPLA2 was predominant, there was only slight elevation of PLA2 activity in bile. In group 1 an immunohistologic study demonstrated localization of PLA2 around necrotic foci in the pancreatic parenchyma. These results suggest the involvement of activated PLA2 in the pathogenesis of choledochal cystassociated pancreatitis.
Animals↗
In situ detection of DNA fragmentation and expression of bcl-2 in human neuroblastoma: relation to apoptosis and spontaneous regression.
UNLABELLED: Spontaneous regression occurs in some cases of neuroblastoma, especially stage IVS. The incidence of neuroblastoma has been reported to be increasing since the mass screening program was introduced in Japan. This would indicate that the screening is detecting regressing tumors. However, the mechanism of regression is still unknown. To evaluate the hypothesis that the regression might be related to apoptosis, the authors examined apoptosis by in situ end-labeling of fragmented DNA and expression of the apoptosis-suppressing protein bcl-2. MATERIALS AND METHODS: One hundred eighteen neuroblastoma cases were available for examination. Eighty (67.8%) were detected by the mass screening program. Serial sections were cut from paraffin-embedded tumors. A modified TdT-mediated dUTP nick end-labeling (TUNEL) method was performed to detect apoptosis. Immunohistochemical analysis was performed to detect bcl-2 expression. RESULTS: In cases under 1 year of age or with a favorable clinical stage, the incidence of apoptosis was significantly high. Expression of bcl-2 was associated with N-myc amplification and unfavorable histology (Shimada classification). Tumors in patients under 1 year of age often had areas where cellularity was markedly decreased, and apoptosis was often observed while bcl-2 expression was reduced. In such cases, there was a negative correlation between occurrence of apoptosis and bcl-2 expression. This suggests that apoptosis may be related to spontaneous regression in neuroblastoma.
Age Factors↗
Anomalies of the tracheobronchial tree in patients with esophageal atresia.
To examine associated anatomic anomalies of the tracheobronchial tree and structural abnormalities of the trachea, and their clinical consequences, bronchoscopic examination and follow-up studies were performed in 32 patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) over a 5-year period. To evaluate structural abnormalities of trachea, the ratio of circumferential length of cartilaginous trachea to circumferential length of membranous trachea (C:M ratio) was determined before surgical repair. In patients examined before and after surgical repair, the motion of the posterior tracheal wall was observed under spontaneous respiration. Fifteen of the 32 patients (47%) had abnormalities of the tracheobronchial tree such as ectopic right upper bronchus (12), congenital bronchial stenosis (4), and absence of the right upper bronchus (2). The C:M ratio of the 27 patients with EA (2.0 +/- 0.6) was significantly lower than that of controls (3.0 +/- 0.3); the ratio for the 10 cases with ectopic right upper bronchus (1.7 +/- 0.4) was significantly lower than that of other cases (2.2 +/- 0.5). The C:M ratio for the 12 patients who had atelectasis (1.7 +/- 0.3) was significantly lower than that of the 15 who did not have atelectasis (2.2 +/- 0.6). Of 24 infants, nine had bulging of the posterior tracheal wall synchronized with expiration, and their C:M ratio (1.8 +/- 0.2) was significantly lower than that of the 15 patients without bulging (2.2 +/- 0.6). These data show an association between anatomic anomalies of the tracheobronchial tree and structural abnormalities of the trachea in patients with EA. Because these abnormalities may be related to the occurrence of respiratory disorders such as tracheomalacia and atelectasis, early bronchoscopic examination, including measurement of the C:M ratio and observation of the motion of the posterior tracheal wall under spontaneous respiration, may be useful in the care of patients with EA.
Bronchi↗
Prenatal diagnosis of abdominal wall defects and their prognosis.
To determine whether associated anatomic features may be useful in predicting fetal prognosis, 43 fetuses who had ultrasonographic evaluation for abdominal wall defects during a 13-year period were reviewed. Thirty-one fetuses had omphalocele and were classified into three groups according to fetal ultrasonography results: ruptured omphalocele with exposed liver, giant omphalocele with exposed liver, and small omphalocele without liver herniation. Twelve fetuses had gastroschisis. Ten of the 12 fetuses with gastroschisis survived; one died in utero. Nine of the 12 with a small omphalocele survived. Ten of 12 fetuses with giant omphalocele survived, but six of the seven with ruptured omphalocele died of pulmonary hypoplasia and respiratory insufficiency. Ruptured omphalocele recognized in utero was accompanied by intrauterine growth retardation and liver herniation and frequently was associated with deformity of the spine, diaphragmatic defects, vesicointestinal fissure, and meningocele. These results indicated that, together with the deformity of the spine, rupture and absence of the covering membrane with an exposed liver (noted through fetal ultrasonography) may suggest a poor prognosis because of pulmonary hypoplasia.
Abdominal Muscles↗
An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome.
p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding p57KIP2 is located at 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a cancer-predisposing syndrome, making it a tumour-suppressor candidate. Several types of childhood tumours including Wilms' tumour, adrenocortical carcinoma and rhabdomyosarcoma exhibit a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting is involved. Genetic analysis of the Beckwith-Wiedemann syndrome indicated maternal carriers, as well as suggesting a role of genomic imprinting. Previously, we and others demonstrated that p57KIP2 is imprinted and that only the maternal allele is expressed in both mice and humans. Here we describe p57KIP2 mutations in patients with Beckwith-Wiedemann syndrome. Among nine patients we examined, two were heterozygous for different mutations in this gene-a missense mutation in the Cdk inhibitory domain resulting in loss of most of the protein, and a frameshift resulting in disruption of the QT domain. The missense mutation was transmitted from the patient's carrier mother, indicating that the expressed maternal allele was mutant and that the repressed paternal allele was normal. Consequently, little or no active p57KIP2 should exist and this probably causes the overgrowth in this BWS patient.
Beckwith-Wiedemann Syndrome↗
Peptide-mediated suppression of experimental autoimmune uveoretinitis in mice: development of a peptide vaccine.
Experimental autoimmune uveoretinitis (EAU) is an animal model of antigen-specific, Th cell-mediated, organ-specific autoimmune disease. EAU is induced by immunization of B10.A mice with interphotoreceptor retinoid-binding protein (IRBP). Pre-treatment with synthetic peptide 518-529 derived from IRBP prevented IRBP-mediated EAU. This was accompanied by augmentation of the IRBP-specific IgG1 antibody (Th2) response and down-regulation of the IRBP-specific IgG2a (Th1) response. Consistent with this is the observation that two of two T cell lines established from p518-529-primed mice produced Th2-type cytokines (IL-4 and IL-10), whereas three of three T cell lines obtained from IRBP-primed mice produced Th1-type cytokines (IL-2 and IFN-gamma). Together this suggests the possibility that p518-529 priming causes a shift from a Th1-to a Th2-dominated immune response, thereby playing a pivotal role in the prevention of IRBP-mediated EAU. Furthermore, co-transfer of cells from a CD4+ p518-529-specific T cell line prevented the development of EAU after adoptive transfer of spleen cells from mice with EAU into normal mice. These findings contribute to our understanding of the mechanism of EAU, particularly with respect to the down-regulation of Th1-initiated inflammation, and may prove valuable for designing a peptide vaccine for EAU in the future.
Adoptive Transfer↗
Alanyl-glutamine dipeptide-supplemented parenteral nutrition improves intestinal metabolism and prevents increased permeability in rats.
OBJECTIVE: The authors determined the effects of alanyl-glutamine-supplemented total parenteral nutrition (TPN) on mucosal metabolism, integrity, and permeability of the small intestine in rats. METHODS: Male Sprague-Dawley rats were randomized to receive TPN supplemented with a conventional amino acids mixture (STD group) or the same solution supplemented with alanyl-glutamine; both solutions were isocaloric and isonitrogenous. On the seventh day of TPN, D-xylose and fluorescein isothiocyanate (FITC)-dextran were administered orally. One hour later, superior mesenteric vein (SMV) D-xylose and plasma FITC-dextran concentration were measured. Intestinal blood flow and calculated intestinal substrates flux were measured with ultrasonic transit time flowmetery. RESULTS: Plasma FITC-dextran increased significantly in the STD group. Intestinal blood flow and SMV D-xylose concentration did not differ between the groups. Mucosa weight, villus height, mucosal wall thickness, mucosal protein, and DNA and RNA content in jejunal mucosa were significantly increased in the alanyl-glutamine group. Jejunal mucosal glutaminase activity and net intestinal uptake of glutamine (glutamine flux) were significantly higher in the alanyl-glutamine group as compared with the STD group. CONCLUSION: Addition of alanyl-glutamine dipeptide to the TPN solution improves intestinal glutamine metabolism and prevents mucosal atrophy and deterioration of permeability.
Animals↗
The convergence of axon terminals from the mediodorsal thalamic nucleus and ventral tegmental area on pyramidal cells in layer V of the rat prelimbic cortex.
We investigated the ultrastructural basis of the synaptic convergence of afferent fibres from the mediodorsal thalamic nucleus (MD) and the ventral tegmental area (VTA) on the prefrontal cortical neurons of the rat by examining the synaptic relationships between thalamocortical or tegmentocortical terminals labelled with anterograde markers [lesion-induced degeneration or transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP)] and randomly selected unlabelled apical dendrites of layer V pyramidal cells in the prelimbic cortex. WGA-HRP-labelled terminals from the VTA ranged in diameter from 0.7 to 2.8 microm and established synaptic contacts with large dendritic profiles, i.e. proximal segments of apical dendritic shafts and spines from layer V pyramidal cells. Symmetrical synapses, i.e. inhibitory synapses, were more often seen than asymmetrical ones. Degenerating terminals from the MD formed asymmetrical synapses on dendritic spines or occasionally on small dendritic shafts of apical dendrites from layer V pyramidal cells, which received tegmentocortical synapses, mostly within layer III. Thalamocortical synapses were more distally distributed over common apical dendrites than tegmentocortical synapses, although some of them overlapped. The numerical density of direct synaptic inputs from the MD and VTA was low. These results suggest that fibres from the VTA exert their inhibitory effects directly on pyramidal cells in layer V via synaptic junctions with apical dendrites of these pyramidal cells, and that the tegmentocortical fibres are in an ideal anatomical position to modulate the reverberatory circuits between the MD and the prelimbic cortex.
Afferent Pathways↗
Presence of prostaglandin EP4 receptor gene expression in a rat gastric mucosal cell line.
RGM-1 is an epithelial cell line established from gastric mucosa of adult Wistar rats. In this study, we characterized this newly established cell line by Northern blot analysis. We also investigated deoxyribonucleic acid (DNA) synthesis and hexosamine production in RGM-1 by PGE2. Northern blot analysis did not detect any transcript of proton pump, gastrin receptor, histidine decarboxylase, somatostatin and pepsinogen 1, indicating the absence of characteristics of parietal, ECL, D and chief cells in RGM-1 cells. However, this periodic acid-Schiff (PAS)-positive cell line expressed prostaglandin EP4 receptor mRNA but not EP1 and EP3 receptor mRNAs. [3H]-thymidine incorporation into DNA of the cells was not increased by PGE2. In contrast, PGE2 increased hexosamine content in RGM-1 cells. These results suggest that RGM-1 may be a useful model of gastric mucosal cells and that PGE2 plays a role on mucin synthesis in RGM-1 cells possibly via EP4 receptors.
Animals↗
Erythropoietin stimulates proliferation of rat-cultured gastric mucosal cells.
Most anemic patients with chronic renal failure have gastric mucosal lesions. However, these gastric lesions are often improved after the administration of recombinant human erythropoietin (rHuEPO). We have used the rat gastric mucosal cell line RGM-1, to examine the possibility that rHuEPO might directly stimulate the growth of gastric mucosal cells in vitro. Our results show that rHuEPO dose-dependently increased [3H]thymidine incorporation into RGM-1 cells and their expression of c-myc gene. In addition, 125I-rHuEPO specifically bound to RGM-1 cells, and moreover, erythropoietin receptor gene expression was detected by RT-PCR. We conclude that rHuEPO has a direct growth-promoting effect on RGM-1 cells, suggesting possible usefulness of rHuEPO administration for the treatment of gastric mucosal damage in patients with chronic renal failure.
Animals↗
Distribution of amyloid bodies in the aged human vestibulocochlear nerve.
We tried to elucidate the localization and distribution of amyloid bodies (Corpora amylacea) in the human vestibulocochlear nerve stained with luxol fast blue-periodic acid Schiff-hematoxylin using of a combination of an image analyzing computer system and a microscope fitted with a drawing tube. After having observed each section of the vestibulocochlear nerve from the brain stem to the fundus of the internal auditory meatus, we counted the numbers of amyloid bodies in three different parts for each of three corpses, and measured the areas. We found that amyloid bodies of the vestibulocochlear nerve are concentrated to the limiting glial portion of the nerve more than to the nerve parenchyma, and amyloid bodies are not seen in the vestibulocochlear nerve peripheral to the transitional zone. Our quantitative trial proved that the amyloid body was larger in the 8th decade than in the 6th or 7th decade of life.
Aged↗
[A case of nutcracker esophagus associated with ischemic heart disease].
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Aged↗
Quantification of intestinal blood flow by ultrasonic transit time flowmetry in fed and endotoxaemic rats.
OBJECTIVE: To compare the dye dilution method with ultrasonic transit time flowmetry (UTTF) for quantifying intestinal blood flow in the same experimental animals. DESIGN: Open experimental study. SETTING: University hospital, Osaka, Japan. MATERIAL: 11 (experiment 1) and 25 (experiment 2) adult male Sprague-Dawley rats. INTERVENTIONS: In experiment 1, the rats were fasted overnight. In experiment 2, endotoxin, Escherichia coli lipopolysaccharide (endotoxin) or saline (sham) was injected intraperitoneally. MAIN OUTCOME MEASURES: Superior mesenteric venous and abdominal aortic blood flow. RESULTS: Experiment 1: intestinal blood flow measured by UTTF was significantly decreased by 17% (p < 0.05) and 56% (p < 0.05) after 30 minutes infusion through the tertiary branch of the mesenteric vein and during simultaneous drawing of blood samples from both the carotid artery and the superior mesenteric vein over a 1.5 minute period, respectively. The intestinal blood flow measurements obtained by UTTF at different intervals before simultaneous drawing of blood from the carotid artery and the superior mesenteric vein differed significantly (p < 0.05) from those obtained by the dye dilution method. Experiment 2: intestinal blood flow was also decreased by 21%-34% (p < 0.05) during similar simultaneous drawing of blood. Aortic blood flow in the endotoxin group was reduced by 66% (p < 0.05) compared with fed animals and 63% (p < 0.05) compared with sham animals. Simultaneously, intestinal blood flow in the endotoxin group was also reduced by 57% (p < 0.05) compared with fed or 48% (p < 0.05) compared with sham treated animals. CONCLUSION: Real intestinal blood flow might not be measured by the procedure of simultaneously drawing blood from the carotid artery and the superior mesenteric vein in rats as is usually done in the dye dilution method. Intraperitoneal endotoxin reduced aortic as well as intestinal blood flow. We propose that UTTF is an alternative method for quantifying intestinal blood flow in fed and endotoxaemic animals.
Animals↗