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Biomedical subjects

A Okada

Publications and source records attributed to A Okada.

At least 181 records · Page 10Linked to original sources

Developmental gene expression of gastrin receptor in rat stomach.

Gastrin, which is present in fetal plasma, may have important roles in the development of gastric mucosa, since it is not only a potent stimulator of gastric acid secretion but also a growth promoting factor. Gastrin regulates various cellular functions via its receptors on cell membrane. Therefore, in order to elucidate a role for gastrin in the development of gastrointestinal system during gestation, Northern blot analysis was performed. The results of the study suggested that gastrin receptor is mainly present on parietal cells. Furthermore, proton pump and gastrin receptor gene expressions in parietal cells were strongly stimulated by the administration of exogenous gastrin. In conclusion, gastrin may be involved in the developmental change of parietal cells through its receptors.

Animals↗

Development of the human principal sensory trigeminal nucleus: a morphometric analysis.

The anatomical development of the principal sensory trigeminal nucleus was assessed with morphometric features using serial celloidin sections of 15 human brains, including 12 brains obtained from fetuses and neonates. A microscope and an optical electronic planimeter combined with a computer were employed for morphometric measurements of columnar areas, neuronal numbers, neuronal areas and neuronal perimeters to statistically analyze and evaluate the development of neuronal densities, neuropil indexes and circularity ratios. We could not detect the principal sensory trigeminal nucleus in the specimen of 12 gestational weeks (GW). Microscopic observation disclosed that the fetal principal sensory trigeminal neurons approached those of the adult around 33 GW in terms of cell arrangements, amounts of Nissl bodies and morphology of neurons. Our morphometric analysis showed that the columnar volume, the neuronal area and the neuropil index increased with gestational age. The neuronal density decreased with gestational age, especially from 16 to 32 GW. Comparing the neuronal area with the columnar volume, it developed before the columnar volume during the fetal period. The neurons of the principal sensory trigeminal nucleus matured around 33 GW under microscopic observation and in terms of the distribution of neuronal areas. The development of the neuropil may accelerate after individual neurons of principal sensory trigeminal nucleus mature.

Adolescent↗

Development of the human lateral vestibular nucleus: a morphometric evaluation.

The development of the human lateral vestibular nucleus was studied on serial sections of the brain of 8 fetuses and neonates at 12-40 weeks of gestation, an infant at 2 months of age and an adult of 63 years using a microscope with a drawing tube and an image-analysing computer system. A morphometric analysis revealed that the lateral vestibular nucleus, whose neurons were distinguished from glia after 16 weeks of gestation, divided cytoarchitectonically into the medial and the lateral subnuclei at 21 weeks of gestation onwards, and showed the moderate development in terms of the columnar length and volume, neuronal size and neuropil.

Female↗

Expression of matrix metalloproteinases during rat skin wound healing: evidence that membrane type-1 matrix metalloproteinase is a stromal activator of pro-gelatinase A.

Skin wound healing depends on cell migration and extracellular matrix remodeling. Both processes, which are necessary for reepithelization and restoration of the underlying connective tissue, are believed to involve the action of extracellular proteinases. We screened cDNA libraries and we found that six matrix metalloproteinase genes were highly expressed during rat skin wound healing. They were namely those of stromelysin 1, stromelysin 3, collagenase 3, gelatinase A (GelA), gelatinase B, and membrane type-1 matrix metalloproteinase (MT1-MMP). The expression kinetics of these MMP genes, the tissue distribution of their transcripts, the results of cotransfection experiments in COS-1 cells, and zymographic analyses performed using microdissected rat wound tissues support the possibility that during cutaneous wound healing pro-GelA and pro-gelatinase B are activated by MT1-MMP and stromelysin 1, respectively. Since MT1-MMP has been demonstrated to be a membrane-associated protein (Sato, H., T. Takino, Y. Okada, J. Cao, A. Shinagawa, E. Yamamoto, and M. Seiki. 1994. Nature (Lond.). 370: 61-65), our finding that GelA and MT1-MMP transcripts were expressed in stromal cells exhibiting a similar tissue distribution suggests that MT1-MMP activates pro-GelA at the stromal cell surface. This possibility is further supported by our observation that the processing of pro-GelA to its mature form correlated to the detection of MT1-MMP in cell membranes of rat fibroblasts expressing the MT1-MMP and GelA genes. These observations, together with the detection of high levels of the mature GelA form in the granulation tissue but not in the regenerating epidermis, suggest that MT1-MMP and GelA contribute to the restoration of connective tissue during rat skin wound healing.

Animals↗

Rat stromelysin 3: cDNA cloning from healing skin wound, activation by furin and expression in rat tissues.

From a rat skin wound healing cDNA library, a clone encoding stromelysin 3 (ST3) was isolated. The predicted rat ST3 has 491 amino acids, and shows 83, 95 and 58% homology with human, mouse and Xenopus ST3, respectively. COS-1 cells transfected with this rat ST3 cDNA produced the ST3 proform, which could be converted to the mature ST3 form by co-transfection with rat furin cDNA. In addition to healing skin, the rat ST3 gene was found to be strongly expressed in normal adult uterus and ovary, and at lower levels in chemically-induced mammary tumors.

Amino Acid Sequence↗

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function.

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) received endotoxin (10 mg/kg intraperitoneally, n = 9), while the control group (CONT, n = 8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P < 0.05), while the CVP and SMVP increased (P < 0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P < 0.05). The D-xylose concentration in SMV decreased significantly (P < 0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12 h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.

Animals↗

New p57KIP2 mutations in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is characterized by numerous growth abnormalities and an increased risk of childhood tumors. The gene for BWS is localized in the 11p15.5 region, as determined by linkage analysis of autosomal dominant pedigrees. The increased maternal transmission pattern seen in the autosomal dominant-type pedigrees and the findings of paternal uniparental disomy reported for a subgroup of patients indicate that the gene for BWS is imprinted. Previously, we found p57KIP2, which is a Cdk-kinase inhibitor located at 11p15, is mutated in two BWS patients. Here, we screened for the mutation of the gene in 15 BWS patients.

Austria↗

Helicobacter pylori induces proinflammatory cytokines and major histocompatibility complex class II antigen in mouse gastric epithelial cells.

Although Helicobacter pylori has been reported to stimulate the release of various cytokines from gastric tissue, it remains unknown whether normal and nontumorous gastric epithelial cells produce these cytokines. Therefore, in this study, we used a normal mouse gastric surface mucous cell line (GSM06) to determine whether gastric epithelial cells produce proinflammatory cytokines in response to H. pylori. The expression of MHC class II antigen was also examined, to investigate whether gastric epithelial cells participate in the immune response to H. pylori. In the study, GSM06 cells were incubated with H. pylori or its lipopolysaccharide (LPS). Proinflammatory cytokines were detected by Northern and Western blot analysis. The expression of MHC class II antigen was examined by fluorescence activated cell sorter (FACS) analysis. Genetic expression of proinflammatory cytokines such as interleukin-1alpha, tumor necrosis factor-alpha, and cytokine-induced neutrophil chemoattractant-2beta was enhanced by both intact and sonicated H. pylori, but not by H. pylori LPS. The expression of MHC class II antigen was induced by H. pylori more strongly than by interferon-gamma. We conclude that H. pylori induces the expression of proinflammatory cytokines and MHC class II antigen in gastric epithelial cells. Gastric epithelial cells may act as antigen-presenting cells and participate in the immune response to H. pylori infection.

Animals↗

Hyaluronic acid of wound fluid in adult and fetal rabbits.

Fetal wound healing proceeds without fibrosis or scar formation in contrast to adult wound healing. The mechanisms responsible for this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid (HA). Polyvinylalcohol sponge (PVA) wound implants were placed pervertebrally at 24 days' gestation in fetal (N = 118) rabbits and in adult (N = 44) rabbits, and then harvested at 1, 2, 3, 4, 5, and 7 days postwounding. To analyze the fetal and adult wound matrix, the HA concentration of wound fluid within the PVA sponge was quantitated using a newly developed assay. A significantly increased (P < .05) HA deposition on days 1 through 7 in the fetal wounds was found compared with the adult wound. These observations may suggest an important physiologic role in fetal wound healing by providing a more fluid and malleable matrix. These results, coupled with earlier findings of the lack of an acute inflammatory response in the fetus, further support the hypothesis that fetal response to injury is significantly different from adult response in this prescience of an implanted PVA sponge.

Aging↗

Experience in tracheobronchial reconstruction with a costal cartilage graft for congenital tracheal stenosis.

Although successful surgical management of congenital tracheal stenosis has been reported, it is still controversial as to the best operative procedure. Eleven infants with congenital tracheal stenosis were evaluated to confirm the efficacy of tracheobronchial reconstruction with costal cartilage graft. Symptoms ranged from recurrent respiratory infection to severe respiratory failure. All infants had other congenital anomalies in addition to tracheal stenosis. Notably, five infants had pulmonary artery sling and four infants had patent ductus arteriosus. Definitive diagnosis was made by bronchoscopy, results of which showed complete tracheal rings in all patients with severely compromised tracheobronchial lumens. Five infants had elongated stenosis involving nearly the whole length of the trachea, and five infants had segmental stenosis involving nearly one half the length of the trachea. One infant had bilateral stenosis of the main bronchi. Early experience included two deaths from problems related to the repair. The involvement of the carina and the distal portion of the trachea was associated with increased complications and a higher mortality rate. Currently, our preferred technique facilitated by extracorporeal membrane oxygenation (ECMO) includes carinal reconstruction with a thin-wall intraluminal stent. Bronchoscopy is essential for accurate intraoperative incision of the trachea, post-operative airway management for several weeks, and removal of the intraluminal stent.

Bronchi↗

Nitric oxide inhalation therapy for an infant with persistent pulmonary hypertension caused by misalignment of pulmonary veins with alveolar capillary dysplasia.

Misalignment of pulmonary veins with alveolar capillary dysplasia (MPV) has been reported to be a rare cause of persistent pulmonary hypertension of the newborn (PPHN) and to be fatal despite extracorporeal membrane oxygenation (ECMO). A full-term female neonate with PPHN was brought to the hospital for ECMO therapy at 2 days of age. On the 14th day of life, she was extubated early after the second run of ECMO, and underwent nitric oxide (NO) inhalation therapy in the incubator. She died of catheter-related sepsis on the 61st day of life. After autopsy findings revealed MPV, the longest survival with this disease was documented. NO inhalation therapy in the incubator may provide time for lung transplantation.

Administration, Inhalation↗

Factors influencing the outcome of liver transplantation for biliary atresia.

BACKGROUND/PURPOSE: This study examined the factors present before liver transplantation (LTx) influencing the outcome in 14 patients who had biliary atresia (BA) who underwent LTx. RESULTS: Nine patients survived (Group A), whereas five died primarily of infection (Group B). Rate of the attempted multiple hepatic portoenterostomy (HPE) and existence of intestinal stoma was significantly higher in Group B than in Group A. Pre-LTx parameters showed significant difference between the two groups as follows: total bilirubin, 15.9 +/- 7.9 versus 29.1 +/- 14.5 mg/dL (P = .0446); gamma-glutamyl transpeptidase, 170.0 +/- 97.6 versus 65.2 +/- 38.8 IU/L (P = .0425); the body weight deviation score, 0.17 +/- 0.88 SD versus -1.46 +/- 0.30 SD (P = .0029); total cholesterol, 129.4 +/- 33.5 versus 52.2 +/- 20.4 mg/dL (P = .0008) in Group A versus Group B. Total cholesterol level and body weight for age remained within normal range until the advanced stage and rapidly decreased according to deterioration of the general condition before LTx. CONCLUSIONS: From these results, avoidance of multiple HPE and closure of stoma before LTx may be preferable. LTx should be performed before failure to thrive or hypocholesterolemia develops.

Analysis of Variance↗

Esophageal atresia in Osaka: a review of 39 years' experience.

BACKGROUND: One hundred fifty-nine patients who had esophageal atresia with or without tracheoesophageal fistula have been treated at Osaka University Medical School and its affiliated hospitals since the initial (Japanese) experience of Dr T. Ueda in 1957. METHODS: These cases were divided chronologically into three groups. With earlier recognition of surgical neonates and the development of perinatal care, the long-term survival of these patients has steadily improved over 39 years from 28% in the first period (1957 to 1967) to 80% in the third period (1980 to 1995). Of 141 patients treated in the second and third periods (1968 to 1995), 92 (65.2%) had associated anomalies. Cardiovascular and gastrointestinal malformations were the most frequently seen major anomalies. VATER or VACTER association was seen in 12.8% (18 of 141) of these patients. Survival of these cases according to Waterston risk factors was 100% for group A, 100% for group B, and 50% for group C, whereas the new classification proposed by Spitz showed survival of 92% for group 1, 50% for group 2, and 0% for group 3, showing better differentiation among the three groups. RESULTS: There was a long gap between the proximal and distal esophageal ends in seven patients (type A), in all of whom primary anastomosis was possible after 28 to 128 days of elongation by bouginage. Although the survival of esophageal atresia patients dramatically improved in recent years, there is still a high incidence of early and long-term postoperative complications, ie, anastomotic leakage (26.5%), recurrent fistula (7.2%), anastomotic stricture (49.1%), postoperative pneumonia or atelectasis (57.0%), tracheomalacia (25.8%), and gastroesophageal reflux (52.0%). CONCLUSIONS: Recently, there have been changing patterns in the occurrence of complications, which are mainly attributed to technical improvement, better perinatal care and early recognition of pathophysiologic conditions such as tracheomalacia and gastroesophageal reflux.

Abnormalities, Multiple↗

Immunohistochemical assessment of the MIB-1 Labeling Index in human hepatoblastoma and its prognostic relevance.

BACKGROUND/PURPOSE: The MIB-1 monoclonal antibody has been raised against recombinant parts of the Ki-67 antigen, which is a cell cycle-related nuclear protein that is elevated in late G1 and S phases. The aim of the study was to analyze the expression pattern of MIB-1 in hepatoblastoma and to assess whether it provides any prognostic information in clinical practice. METHODS: Sections from formalin-fixed paraffin embedded tissues were collected from 18 patients who had hepatoblastoma and stained with MIB-1 antibody according to streptavidinbiotin method. A percentage score of positively stained nuclei, MIB-1 Labeling Index (LI), was determined and correlated with clinical variables. MIB-1 LI ranged from 0% to 39.5% with a mean value of 13.5%. Among them in 14 patients, who received preoperative chemotherapy, the authors analyzed the result of MIB-1 staining. RESULTS: Although there were no significant correlations between MIB-1 LI and age, sex, or histological type, a statistically significant correlation was found between clinical stage and MIB-1 LI. Mean MIB-1 LI was lower in patients with stage I and II than in those with stages III and IV (P < .05). Metastatic lesions showed higher MIB-1 LI than primary lesions, indicating that metastatic tumor cells have an increased rate of cellular proliferation. Kaplan Meier survival curve showed that patients with MIB-1 higher than 10% (n = 3) had a worse survival rate than those with lower than 10% MIB-1 LI (n = 11), whereas there was no significant difference because of the limited number of cases. Because high MIB-1 LI was correlated with clinical stage and poor survival rate, MIB-1 LI may be considered an important prognostic factor in hepatoblastoma. CONCLUSION: Although further studies, including larger series of patients, are required, the authors consider MIB-1 immunostaining an easy method to assess proliferative activity that provides useful prognostic information in hepatoblastoma.

Antibodies, Monoclonal↗

Mutation analysis of p53 gene in childhood malignant solid tumors.

Alterations of the p53 gene have been extensively investigated in a wide variety of human malignancies. However, data on childhood malignant solid tumors are still limited. Mutations of the p53 gene on exons 5 through 8 were examined in 82 childhood malignant solid tumors by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method, and the nature of these mutations was confirmed by direct sequencing. The 82 tumors examined included neuroblastomas (n = 44), Wilms' tumors in = 13), hepatoblastomas (n = 11), rhabdomyosarcomas (n = 10), extraosseus Ewing sarcomas (n = 2), undifferentiated sarcoma of the liver (n = 1), and fibrosarcoma (n = 1). Two sarcoma samples were identified as having point mutations. One was a rhabdomyosarcoma with a missense mutation at codon 273, substituting histidine (His) for arginine (Arg). Another was an undifferentiated sarcoma of the liver with a missense mutation at codon 245, substituting serine (Ser) for glycine (Gly). No mutations were detected among neuroblastomas, Wilms' tumors, or hepatoblastomas. The two sarcomas with mutations were localized tumors. Both patients who had these tumors are disease free for 8 and 5 years after treatment, respectively. The overall incidence of p53 mutations was low (2.4%, 2 of 82). However, the incidence, when calculated for sarcomas, was higher at 14.3% (2 of 14). These data indicate that p53 mutations are generally uncommon in childhood malignant solid tumors examined. However, in some childhood sarcomas, p53 mutations appear to have a causative role in the development of these tumors.

Child↗

Expression of endothelial constitutive nitric oxide synthase mRNA in gastrointestinal mucosa and its downregulation by endotoxin.

Endothelial nitric oxide exerts local vasodilatory actions in the gastrointestinal (GI) microvasculature and is proposed to play a role in enteric vasomotor regulation. The aims of this study were to characterize the tissue distribution of mRNA for endothelial nitric oxide synthase (NOS-III) and to examine its response to endotoxin challenge in vivo. We demonstrate the expression of NOS-III mRNA and protein in mucosa throughout the gastrointestinal tract and show for the first time that NOS-III mRNA expression in the GI mucosa was down-regulated in the rats treated with endotoxin. The ubiquitous expression of NOS-III mRNA in digestive tissues is consistent with the proposed role of NOS-III in the physiology of the gastrointestinal tract. The decreased NOS-III mRNA, in parallel to induction of inducible NOS (NOS-II) mRNA, may contribute to the impaired endothelium-dependent relaxation and damaged mucosal integrity during sepsis.

Animals↗

Beneficial effects of growth hormone combined with parenteral nutrition in the management of inflammatory bowel disease: an experimental study.

BACKGROUND: Growth hormone (GH) improves net protein anabolism and stimulates wound healing. Although GH is also known to exert the trophic effect on the intestinal tract, its role in the healing of intestinal ulceration is not known. The aim of this study was to evaluate the effects of exogenous GH coinfused with parenteral nutrition (PN) in an experimental model of inflammatory bowel disease in rats. METHODS: All rats underwent central venous cannulation and were randomized to two groups after induction of small intestinal ulceration with indomethacin. Both groups received the same PN formula. In addition, the GH group (n = 10) received subcutaneous injections of human GH at a dose of 1.0 IU/kg daily for 4 days, whereas the control group (n = 10) received injections of normal saline solution. Nitrogen balance, macroscopic inflammation score, intestinal myeloperoxidase activity, DNA content, and mucosal permeability were determined for each rat. Insulin-like growth factor-I (IGF-I) mRNA was detected by reverse transcription and polymerase chain reaction. RESULTS: Administration of GH significantly improved the cumulative nitrogen balance, ameliorated the gross inflammation score, and decreased intestinal myeloperoxidase activity. Similarly, intestinal permeability was significantly decreased in the GH group as compared with the control group. GH treatment resulted in increased plasma concentration of IGF-I and IGF-I mRNA expressions in both the liver and the small intestine compared with those in the control group. CONCLUSIONS: Exogenous GH plays an important role in accelerating intestinal healing in an experimental model of small bowel ulceration in rats. The mechanisms may include the stimulated IGF-I production, which thereafter augments intestinal epithelial cell growth.

Animals↗

Lock method using sodium hydroxide solution to clear occluded central venous access devices.

Occlusion of central venous access devices (CVADs) is not an uncommon problem duringlong-term parenteral nutrition. A number of techniques have been developed to deal with obstructed CVADs. This study investigated the effectiveness of the sodium hydroxide (NaOH) lock method for gradual CVAD occlusion. When a progressively declining flow was noticed, 0.1 N NaOH solution was injected into the CVAD and locked. Nineteen CVAD occlusions in 11 home parenteral nutrition patients were treated Sixteen of 19 trials cleared the occlusions, whereas 3 of 19 failed. One of the failures was due to a mechanical occlusion and the other two were able to be restored by using ethanol. There were no significant complications. The benefits of this method are: (1) a shorter treatment time and a lower dose than NaOH infusion therapy, (2) it does not require hospital admission and (3) it does not result in bursting of the catheter.

Journal Article↗