Biomedical subjects

T Iwai

Publications and source records attributed to T Iwai.

At least 91 records · Page 5Linked to original sources

PubMed1999

Epiphrenic diverticulum composed of airway components attributed to a bronchopulmonary-foregut malformation: report of a case.

Bronchopulmonary-foregut malformation (BPFM), defined originally as pulmonary sequestration with or without communication to the esophagus, has been acknowledged to include congenital foregut diverticula. We present herein the case of a 43-year-old woman with a 9-year history of dysphagia, in whom a barium meal examination demonstrated a 2.5-cm epiphrenic diverticulum and several fistulae. A laparotomy was performed and the lower esophagus without communication to the lung was pulled down and resected, followed by an esophagogastrostomy carried out with fundopexy. Since her operation, the patient has been free of symptoms. Histologically, the diverticulum was observed to be lined by stratified squamous cells, but its shape was formed by mural cartilage, smooth muscle cells, and three ciliated-cell cysts. The dysphagia was considered to have been derived from the kinked esophagus created by the rigid diverticulum, being the possible developmental arrest of a supernumerary lung bud. These findings indicate that this case may involve BPFM in the broad sense. Although several cases of bronchogenic cysts located beneath or across the diaphragm have been reported as a subgroup of BPFM, congenital epiphrenic diverticula has rarely been described.

Adult↗

PubMed1999

Regulation of methionine adenosyltransferase activity by the glutathione level in rat liver during ischemia-reperfusion.

Hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct. After 15 min of ischemia, the hepatic glutathione (GSH) content rapidly decreased. On the other hand, after the start of reperfusion, the hepatic GSH levels promptly increased and reached a peak at about 1 h, and thereafter decreased to a minimum level by 2 h. Under such conditions, we examined the changes in the methionine adenosyltransferase (MAT) activity in the liver. Though the time course of MAT activity was somewhat delayed compared with that of the hepatic GSH levels, both patterns were substantially similar during ischemia-reperfusion. In contrast to the changes in the MAT activity during ischemia-reperfusion, the levels of MAT protein were unchanged during these periods. When endogenous antioxidant coenzyme Q(10) (CoQ(10)) was administered to rats prior to ischemia, both the reduction in the MAT activity and hepatic GSH levels induced by ischemia-reperfusion were protected. Our findings suggest that CoQ(10) may posttranslationally regulate the MAT activity via the changes in the GSH level in the liver.

Animals↗

PubMed1999

Prevention of ischemia-induced hippocampal neuronal damage by 2-deoxy-D-glucose in gerbils.

It has been reported that delayed neuronal death (DND) in the hippocampus following transient forebrain ischemia is associated with internucleosomal DNA fragmentation, indicating apoptosis. This suggests that the process of DND is energy dependent. Transient severe forebrain ischemia was induced in Mongolian gerbils by bilateral occlusion of the common carotid arteries. Post-ischemic administration of 2-deoxy-D-glucose (2-DG), a glucose antimetabolite, markedly reduced the occurrence of ischemia-induced DNA fragmentation and DND in the hippocampus. These results suggest that the reduction of energy dependent metabolism after ischemia may be an attractive therapeutic strategy for preserving hippocampal neurons vulnerable to ischemia.

Animals↗

PubMed1999

Inhibition of concanavalin A-induced hepatic injury of mice by bacterial lipopolysaccharide via the induction of IL-6 and the subsequent reduction of IL-4: the cytokine milieu of concanavalin A hepatitis.

BACKGROUND/AIMS: Liver natural killer 1.1 antigen (NK1)+ T cells and IL-4 play a crucial role in concanavalin-A (Con-A)-induced hepatic injury in mice, and a T helper (Th) 2 immune response was thus suggested to be involved. This study was designed to examine the effect of bacterial lipopolysaccharide (LPS), a strong inducer of a Th 1 immune response, on Con-A hepatic injury and also to clarify further the cytokine milieu of Con-A hepatitis. METHODS: LPS were injected into mice before Con-A injection to evaluate the effect on hepatic injury. The effect of the pretreatment with various T1 and Th2 cytokines or anti-cytokine antibodies on Con-A hepatitis was also examined. RESULTS: LPS in quantities > or = 500 ng/mouse, when injected 24 h before Con-A injection, abrogated the Con-A-induced elevation of transaminases, hepatocyte destruction and serum IL-4 elevation. This LPS inhibitory effect was blocked when the mice were injected with either anti-IL-6 antibody before LPS injection or IL-4 before Con-A injection. IL-6, but neither IL-10 nor IL-12 pretreatment suppressed Con-A-induced IL-4 production and hepatitis. NK1+ T cells produced IL-4 while both NK1+ T cells and NK1- T cells produced IFN-gamma. Not only anti-IL-4 antibody but also the anti-IFN-gamma antibody pretreatment inhibited Con-A hepatitis. However, although the anti-IL4 antibody suppressed IL-4 alone, the anti-IFN-gamma Ab unexpectedly inhibited both IFN-gamma and IL-4 elevation, while IL-4 injection evoked a moderate Con-A hepatitis even in the anti-IFN-gamma antibody-treated mice. Furthermore, the IL-4 mutant mice did not develop Con-A hepatitis. CONCLUSION: LPS inhibited Con-A hepatitis by inducing IL-6 and thereby inhibited IL-4 synthesis from NK1+ T cells. Although both IL-4 and IFN-gamma were required for the full induction of Con-A hepatic injury, exogenous IL-4 evoked a moderate Con-A hepatitis, even in the absence of IFN-gamma.

Animals↗

PubMed1999

Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat.

Free radicals have been suggested to be largely involved in the genesis of ischemic brain damage, as shown in the protective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent, against ischemic cerebral injury. In the present study, the effects of PBN as well as MCI-186, a newly-developed free radical scavenger, and oxypurinol, an inhibitor of xanthine oxidase, were evaluated in a rat transient middle cerebral aretery (MCA) occlusion model to clarify the possible role of free radicals in the reperfusion injury of brain. The volume of cerebral infarction, induced by 2-h occlusion and subsequent 2-h reperfusion of MCA in Fisher-344 rats, was evaluated. The administration of PBN (100 mg/kg) and MCI-186 (100 mg/kg) just before reperfusion of MCA significantly reduced the infarction volume. In contrast, oxypurinol (100 mg/kg) failed to show any preventive effect on the infarction. These results suggest that free radical formation is involved in the cerebral damage induced by ischemia-reperfusion of MCA, and that hydroxyl radical is responsible for the reperfusion injury after transient focal brain ischemia. It is also suggested that xanthine oxidase is not a major source of free radicals.

Animals↗

PubMed1999

Neuronal apoptosis studied by a sequential TUNEL technique: a method for tract-tracing.

A novel tract-tracing procedure by using a sequential in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) is described. This method identifies fragmented DNA transported into neuronal fibers in tissue sections of gerbil hippocampal CA1 neurons following transient forebrain ischemia. The transported DNA has been confirmed by another method, fluorescence DNA detection technique by DAPI. Many methods have been developed to study the neuroanatomical connections in the central nervous system. Principally, these techniques are based on tract-tracing studies using xenobiotics into the central nervous system. Our tract-tracing method is originated from an intrinsic marker that is produced during the apoptotic process of neurons. Furthermore, the advantage of this method is that only the selected cells undergoing apoptosis are recognized and traced to the end of the related neuronal fiber. Usually, apoptotic cells possess intact intracellular metabolic mechanisms until completion of cell death. Thus, apoptotic neurons retain the axonal transport mechanisms which enables us to detect fragmented DNA moving from nuclei to distal terminals of neuronal fibers. Since TUNEL-positive DNA movement within neuronal fibers occurs only during a limited period, it is essential that a time-course of the TUNEL technique is used to study tract-tracing of apoptotic neurons. Although this method can identify only the apical dendrites of cells that are undergoing apoptosis during the limited period, some projections of the gerbil hippocampal CA1 neurons undergoing apoptosis are clearly demonstrated.

Animals↗

PubMed1999

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Acute Disease↗

PubMed1999

Treatment of esophageal and gastric tumors.

Endoscopic mucosal resection (EMR) has gained increasing popularity in the treatment of esophageal and gastric mucosal cancers in Japan, for complete local resection of the cancer-bearing mucosa. In Western countries, the concept of mucosal cancer and the necessity of treating it are gradually but steadily coming to be accepted. As a treatment for inoperable cases of advanced cancer, on the other hand, intubation with self-expanding metal stents has been widely accepted as a less invasive form of palliation for malignant obstruction of the upper gastrointestinal tract. Tumor ingrowth into the stent can be mechanically avoided by adding a membrane coating to it. In the last two years, applications for therapeutic endoscopy in the treatment of esophageal and gastric tumors have continued to widen.

Adenocarcinoma↗

PubMed1999

The ultrasonic tactile sensor: in vivo clinical application for evaluation of depth of invasion in esophageal squamous cell carcinomas.

BACKGROUND AND STUDY AIMS: We have previously demonstrated that an ultrasonic tactile sensor (UTS) could be used to distinguish between mucosal and submucosal cancer in surgically resected specimens, by providing a measurement of tissue stiffness which could be less prone to subjective errors. In the current study, we evaluated the potential of a newly developed, thin UTS to differentiate in vivo between mucosal and submucosal invasion during clinical endoscopic examination. PATIENTS AND METHODS: Between March and July 1997, 15 patients with esophageal cancer who were not receiving special treatment, underwent preoperative UTS examination during endoscopy. The thin UTS probe was inserted through the biopsy channel of the endoscope. A transparent cap was placed on the distal end of the endoscope in order to facilitate vertical placement of the probe on the tumor. RESULTS: Although the probe used in this study was a prototype, the results of the current in vivo study were in agreement with our previous in vitro study on surgically resected specimens. The mean delta(f) value of the mucosal cancers, which means the magnitude of the frequency shift recorded by the UTS, was -5356.23 Hz, and the corresponding value for submucosal cancers was -4126.56 Hz; this difference was significant. CONCLUSION: The UTS is potentially an essential tool for preoperative evaluation of esophageal cancers. The ability to differentiate between mucosal and submucosal cancers is important because of the differences in surgical management of these tumors, i.e. endoscopic mucosal resection or conventional open esophagectomy.

Carcinoma, Squamous Cell↗

PubMed1999

Perfusion and blood pool scintigraphy for diagnosing soft-tissue arteriovenous malformations.

PURPOSE: Six arteriovenous malformations were assessed to determine the effectiveness of perfusion and blood pool scintigraphy to diagnose arteriovenous malformations of soft tissue. METHODS: After injection of Tc-99m RBC or Tc-99m DTPA-HSA, dynamic perfusion and early and delayed blood pool images were analyzed. RESULTS: Four of six arteriovenous malformations showed increased activity on perfusion images and slightly increased activity on blood pool images; the remaining two arteriovenous malformations showed increased activity on perfusion and normal activity on blood pool studies. CONCLUSIONS: This expansion of the authors' previous studies of hemangiomas shows that perfusion and blood pool scintigraphy are useful methods to differentiate arteriovenous malformations from various types of hemangiomas.

Adult↗

PubMed1999

Frequent allelic imbalance on chromosome 18q21 in early superficial colorectal cancers.

Genetic alterations in early superficial colorectal cancers have rarely been reported. In the present study, we searched for alterations in the APC and p53 genes in 27 superficial (20 depressed and 7 elevated) and 21 protruding colorectal cancers with submucosal invasion by means of PCR-single strand conformation polymorphism. Allelic imbalance (AI) on five loci, i.e., 1p34-36, 8p21-22, 14q32, 18q21 and 22q12-13, was also analyzed. Since a high incidence of 18q21 AI was detected in the superficial depressed cases, we further screened for alterations in Smad2, Smad4 and DCC. APC alterations were observed in three superficial depressed, one superficial elevated, and 11 protruding colorectal cancers, indicating that the frequency of APC alterations in superficial depressed cases was significantly lower than that in the protruding ones. There was no significant association between p53 alterations and macroscopic types. AI on 18q21 (13/20, 65%) was much higher than those on the other four loci in the superficial depressed cases. Moreover, the frequency of 18q21 AI in the superficial depressed cases was significantly higher than that in the protruding ones. Smad4 alterations were only detected in 1 of the 13 superficial depressed and 3 of the 17 protruding cases, while Smad2 and DCC alterations were not detected in any case examined. These data suggest that the carcinogenetic pathways of protruding and superficial depressed colorectal cancers are different, and that alterations of tumor suppressor gene(s) located on 18q21 other than Smad2, Smad4 and DCC might be associated with most superficial depressed colorectal cancers.

Adult↗

PubMed1999

Expression of tumor necrosis factor-alpha gene during allograft rejection following rat liver transplantation.

BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF-alpha) is believed to play a role in hepatic allograft rejection. However, the specific cellular population responsible for TNF-alpha production during hepatic allograft rejection is not known. Circulating monocyte-macrophage cells are the primary systemic sources of TNF-alpha. In the liver, Kupffer cells are the main producers of TNF-alpha. In this study, we determined which cells are involved in TNF-alpha production during allograft rejection after orthotopic liver transplantation. METHODS: In situ hybridization was used to identify cells with TNF-alpha mRNA in the liver. Immunohistochemical staining with ED2 and ED3 was used to differentiate between cellular types (Kupffer cells versus infiltrating monocytes). To detect DNA fragmentation in liver cells, TdT-mediated biotin-dUTP nick-end labeling (TUNEL) was done. Studies were performed in the rat liver transplant model using rejecting (ACI to LEW) and non-rejecting (ACI to ACI) donor/recipient combinations. RESULTS: In the control group, cells with TNF-alpha mRNA were rarely observed. In the rejection group, TNF-alpha mRNA was observed in mononuclear cells that were mainly within the vessels of the portal region and occasionally in the sinusoids. The cells with the signals for TNF-alpha mRNA were ED2-negative and ED3-positive. DNA fragmentation was observed in hepatocytes as well as infiltrating mononuclear cells. CONCLUSIONS: The main producer of TNF-alpha may be infiltrating mononuclear cells such as monocyte-macrophage cells rather than Kupffer cells during allograft rejection after liver transplantation. Circulating monocyte-macrophages may play a role in the control of allograft rejection.

Animals↗

PubMed1999

Intestinal metaplasia at the esophagogastric junction in Japanese patients without clinical Barrett's esophagus.

OBJECTIVE: The significance of intestinal metaplasia found in biopsy specimens taken from healthy appearing squamocolumnar junction is unclear. The aim of the present study was to investigate the prevalence of intestinal metaplasia at the esophagogastric junction in Japanese patients with no clinical diagnosis of Barrett's esophagus. METHODS: A total of 103 specimens from consecutive surgeries were studied. All subjects underwent surgical resection for squamous carcinoma of the esophagus. Microscopic examination was performed from the squamocolumnar junction to 4 cm distal to the squamocolumnar junction. The extent of intestinal metaplasia was investigated in detail. Microscopic columnar-lined esophagus was defined as columnar epithelium with esophageal-type submucosal glands. RESULTS: The extent of intestinal metaplasia varied and was usually identified at intervals. Intestinal metaplasia exactly at the squamocolumnar junction was identified in 29 of 103 specimens (28%). Microscopic columnar-lined esophagus was identified in five of the 103 (5%), four of which had intestinal metaplasia in the columnar-lined esophagus. CONCLUSION: Intestinal metaplasia occurs frequently in the region of the esophagogastric junction in Japanese patients with squamous cell cancer of the esophagus.

Adult↗

PubMed1999

Involvement of adenosine receptor, potassium channel and protein kinase C in hypoxic preconditioning of isolated cardiomyocytes of adult rat.

A possible mechanism for hypoxic preconditioning of adult rat cardiomyocytes was pharmacologically investigated. Isolated cardiomyocytes in all experimental groups were incubated for 120 min under hypoxic conditions followed by 15-min reoxygenation (sustained H/R). Sustained H/R decreased rod-shaped cells. Exposure of the cardiomyocytes to 20-min of hypoxia/30-min reoxygenation (hypoxic preconditioning) attenuated the sustained H/R-induced decrease in rod-shaped cells. The effects of hypoxic preconditioning were abolished by treatment with the protein kinase C (PKC) inhibitor polymyxin B, but abolished by neither the adenosine A1/A2-antagonist sulfophenyl theophylline (SPT) nor the ATP-sensitive potassium channel (K(ATP) channel) blocker glibenclamide. In another series of experiments, cardiomyocytes were incubated without hypoxic preconditioning in the presence of either the PKC activator PMA, adenosine or K(ATP)-channel opener nicorandil and then subjected to sustained H/R. Treatment of the cells with PMA, adenosine or nicorandil mimicked the effects of hypoxic preconditioning. The effects of treatment with adenosine and nicorandil were abolished by polymyxin B treatment. Combined treatment with both SPT and glibenclamide abolished the effects of hypoxic preconditioning, whereas it failed to abolish PMA-induced cytoprotection. These results suggest that the activation of PKC in hypoxic preconditioned cardiomyocytes coupled independently with stimulation of adenosine receptor or opening of K(ATP) channel, either of which is fully enough to exert the cytoprotective effects.

Animals↗

PubMed1999

EXTL3/EXTR1 alterations in colorectal cancer cell lines.

We previously demonstrated that metastasis-related tumor suppressor gene(s) may exist on chromosome 8p21-22 on allelotype analysis of early colorectal carcinomas (CRC) with lymph node metastasis. Here, we searched for target gene(s) in this chromosomal region in the UniGene database. The EXTL3 (also called EXTR1) gene was selected as a candidate because of its homology to EXT1 and EXT2, putative tumor suppressor genes. We screened 12 CRC cell lines for mutations by means of polymerase chain reaction (PCR)-single strand conformation polymorphism. Three cell lines showed EXTL3 mutations, all of which were located within exon 3 and caused amino acid substitutions. Reverse transcription-PCR analysis showed that the EXTL3 expression was lacking in 1 of the 12 colorectal cancer cell lines. Although there is still no definitive evidence that EXTL3 is a tumor suppressor gene for CRC, these data suggest that inactivation of the EXTL3 gene may at least offer a selective growth advantage for some CRC cell lines.

Adenomatous Polyposis Coli↗

PubMed1999

[Metastatic testicular tumor requiring inferior vena cava resection with polytetrafluoroethylene graft replacement: a case report].

A 31 year-old man with a biopsy-proved retroperiotoneal yolk sac tumor was referred to our clinic. Physical examination revealed a thum- tip sized left supra-clavicular mass, a huge right abdominal mass and a tiny hard mass of the right testis. On CT scan, the abdominal tumor, 13 cm in diameter, encircled the inferior vena cava. Serum levels of LDH, AFP and hCG-beta were 2,585 U/l, 19,922 ng/ml and 6.6 ng/ml, respectively. No visceral metastasis was found. Following the right high orchiectomy, 4 cycles of VIP chemotherapy consisting of ifosfamide, etoposide and cisplatin were given, which resulted in partial response of the retroperitoneal mass and complete regression of the supraculavicular node with normalization of all tumor markers. Thus, retroperitoneal lymph node dissection was carried out. Because of the marked adhesion to the tumor, the inferior vena cava was segmentally resected together with the tumor, which was followed by reconstruction of the vena cava using a 16 cm long polytetrafluoroethylene graft, since no collateral venous route was found on the pretreatment venacavography. Histologically, the tumor was nearly necrotic with mature teratoma in small part. Postoperative clinical course was uneventful except feeling of numbness at the right tip toe, and the inferior vena cava has been patent 18 months after the operation with no evidence of recurrence.

Adult↗

PubMed1999

[A patient operated for occlusion of the superior mesenteric artery].

A 40-year-old woman presented with fever, dysarthria, and left hemiparesis. Diagnostic imaging detected an infarction in the right cerebrum; lupus anticoagulant was positive. A T4N3M0 adenocarcinoma coexisted in the left lung, which was irradiated once. Two days later, the superior mesenteric artery was occluded. The bowel was widely resected but she died of hepatic infarction. The lung cancer may have triggered catastrophic antiphospholipid syndrome.

Adenocarcinoma↗

PubMed1999

[Assessment of blood flow by Doppler method].

There are two categories including Doppler sound and color-duplex sonography to assess blood flow using Doppler principle. Ankle pressure measurement has been a useful method to assess the severity of lower limb by Doppler sound. Color-duplex sonography could recognize total occlusion with no signal and significant stenosis with jet and turbulence, which could also differentiate embolism from thrombosis. Internal carotid lesion could be delineated to provoke minor stroke, and transient ischemic attack by this method. Ruptured aneurysm couldn't be diagnosed precisely by the color-duplex sonography. Doppler sound has been used to evaluate deep vein patency; however, recent available color-duplex sonography as well as gray scale ultrasonography could recognize thrombus formation precisely around the femoral, popliteal, and infrapopliteal deep vein.

Blood Circulation↗