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Biomedical subjects

K Iwase

Publications and source records attributed to K Iwase.

At least 55 records · Page 3Linked to original sources

The Relation between Superoxide Dismutase in Cancer Tissue and Clinico-pathological Features in Breast Cancer.

The localization of Cu/Zn- and Mn-superoxide dismutase (SOD) in breast cancer tissue (12 papillotubular carcinomas, 21 solid-tubular carcinomas, 16 scirrhous carcinomas, 1 medullary carcinoma, 1 secreting carcinoma, 1 lobular carcinoma, 1 Paget's disease) was investigated via an immunohistochemical technique using antihuman Cu/Zn- and Mn-SOD antibodies in 10%formalin fixed-paraffin embedded thin sections. Both SODs stained strongly in the normal breast gland, but not clearly in many cancer tissues. Furthermore, Cu/Zn-SOD stained more strongly in well differentiated tubular carcinomas than in poorly differentiated tubular carcinomas. It tended to stain less in tumors which recurred or had a poor outcome, and in tumors with a diploid pattern on DNA flow cytometry. Mn-SOD staining was similar to that of Cu/Zn-SOD, but no significant differences among subgroups was found, since the incidence of positively staining tumors was too small in all groups. The intensity of SOD staining seems to change in relation to cell proliferation and differentiation in breast carcinoma, and may be a prognostic indicator, since SOD decreased in poorly differentiated carcinoma and in tumors which developed distant metastasis. Thus, the localization of SOD in breast cancer tissue can provide useful information for cancer treatment.

Journal Article↗

Inhibition of neurotensin-induced pancreatic carcinoma growth by a nonpeptide neurotensin receptor antagonist, SR48692.

BACKGROUND: Recently, a nonpeptide neurotensin (NT) receptor antagonist, SR48692, was developed that selectively antagonizes the high affinity, biologically active NT binding site. The effect of SR48692 on NT-mediated growth of a human pancreatic carcinoma, MIA PaCa-2, was determined both in vitro and in vivo. METHODS: (125)I-NT binding and Northern blot analyses were performed for evaluation of the NT receptor in MIA PaCa-2 cells. Intracellular calcium ([Ca2+]i) mobilization and inositol phosphate (IP3) levels were measured. Cell growth studies were performed by counting cell numbers. Athymic nude mice were inoculated with MIA PaCa-2 cells and randomized into four groups to receive either vehicle (NT or SR48692) or NT + SR48692. RESULTS: MIA PaCa-2 cells possess both a high affinity, SR48692-sensitive and a levocabastine-insensitive NT binding site; Northern blot analysis demonstrated expression of the NT receptor. SR48692 inhibited [Ca2+]i mobilization, IP3 turnover, and MIA PaCa-2 cell growth induced by NT in a dose-dependent fashion. In in vivo experiments, NT significantly increased the size, weight, and DNA and protein content of xenografted MIA PaCa-2 tumors; SR48692 inhibited the effect of NT. CONCLUSIONS: The novel NT receptor antagonist SR48692 will be a valuable agent to delineate further the cellular mechanisms responsible for peptide-mediated growth of normal and neoplastic gut tissues.

Animals↗

Thoracoscopic enucleation of a large leiomyoma located on the left side of the esophageal wall.

Thoracoscopic enucleation through the right thorax was successfully performed for a large leiomyoma located on the left wall of the upper-middle esophagus. Using intraoperative esophagoscopy, the exact location of the tumor was identified by trans-illumination. Two sling tapes passed around teh esophagus made the procedure as easy as that for tumor located on the right wall of the esophagus. We considered that the thoracoscopic approach through the right thorax can be applied to various types of esophageal leiomyoma, even a large one located on the left side of the esophagus.

Adult↗

Laparoscopic cholecystectomy and time-course changes in renal function. The effect of the retraction method on renal function.

BACKGROUND: Recently, the retraction method has been used to reduce intraabdominal pressure (IAP) during laparoscopic surgery. The purpose of this study was to determine the serial changes in renal function during laparoscopic cholecystectomy (LC) using the retraction method. METHODS: Urine output, effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) were measured serially in seven patients who underwent LC with 12 mmHg pneumoperitoneum (High-IAP group) and five who underwent LC using the retraction method with 4 mmHg pneumoperitoneum (Low-IAP group). RESULTS: Urine output, ERPF, and GFR were decreased during pneumoperitoneum in the High-IAP group, whereas no significant changes in any of these parameters were observed in the Low-IAP group. CONCLUSIONS: Our findings demonstrate that reduction of IAP to 4 mmHg using the retraction method prevents the transient renal dysfunction caused by prolonged 12 mmHg pneumoperitoneum during LC, suggesting that the retraction method reduces the risk of perioperative renal dysfunction during laparoscopic surgery.

Adult↗

Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin.

BACKGROUND & AIMS: Gastrin (G-17) stimulates the growth of certain gastric and colon cancers mostly through gastrin/cholecystokinin (CCK)-B receptors. Glycine-extended gastrin (Gly-G) stimulates growth of a rat pancreatic acinar cell line; however, the effect of Gly-G on human gastric cancers is not known. The purpose of this study was to characterize the trophic effect of G-17 and Gly-G on two human gastric cancer cell lines, AGS and SIIA. METHODS: Binding analyses were performed, and cell growth was assessed by counting cells over a time course. RESULTS: G-17 stimulated growth of both AGS and SIIA cells. In AGS cells, gastrin/CCK-B receptor antagonists inhibited the effect of G-17 and competitively antagonized 125I-G-17 binding, whereas the CCK-preferring (CCK-A) receptor antagonists had no effect. In contrast, CCK-A receptor antagonists inhibited the stimulatory effect of G-17 in SIIA cells, whereas CCK-B receptor antagonists had no effect. Gly-G stimulated the growth of AGS and SIIA cells; neither the CCK-B nor the CCK-A receptor antagonists blocked this effect. CONCLUSIONS: G-17 stimulates proliferation of AGS cells through the CCK-B receptor; however, G-17-mediated growth of SIIA acts through a CCK-A-like receptor. Furthermore, Gly-G stimulates growth of human gastric cancer cell lines, possibly through a receptor other than the CCK-B or CCK-A receptor.

Cell Division↗

Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders.

To clarify whether the changes of free radicals and its scavengers are induced by thyroid disorders, we measured levels of free radical scavengers and checked O2 radical generating systems in the human thyroid gland. Thyroid specimens from patients with Graves' disease, follicular adenoma, and papillary and follicular carcinomas contained significantly higher concentrations of xanthine oxidase (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal thyroid tissue. Catalase concentration was significantly lower in thyroid specimens from patients with Graves' disease and significantly lower in thyroid specimens from patients with follicular adenoma, compared to those in the normal thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was significantly lower in the specimens from follicular adenoma and papillary carcinoma and Mn SOD concentration was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide concentration, expressed as malondialdehyde (MDA) concentration, was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. These findings suggest that the levels of free radicals are increased and are scavenged and catalyzed in the thyroid of Graves' disease, whereas free radicals and lipid peroxide are not completely scavenged in papillary carcinoma tissues, suggesting that these substances affect some role in cell function of thyroid tumors.

Adenocarcinoma, Follicular↗

Role of endogenous somatostatin in postprandial hypersecretion of neurotensin in patients after gastrectomy.

OBJECTIVE: The purpose of this report is to elucidate the mechanism of the hypersecretion of neurotensin (NT) after gastrectomy. SUMMARY BACKGROUND DATA: NT secretion induced by fat ingestion is increased after pancreatoduodenectomy or distal gastrectomy. The hypersecretion of NT in the patients undergoing resection of the upper gastrointestinal tract is suppressed by an exogenous somatostatin (SST) analog. METHODS: We observed simultaneously the secretion of NT and SST in the same patients before and after gastrectomy (n = 7). We also observed the secretion of these hormones induced by intraduodenal (ID) fat infusion in the normal volunteers (n = 6). RESULTS: The response of plasma NT to fat ingestion was significantly increased after gastrectomy compared with that before gastrectomy. The response of plasma SST after gastrectomy was significantly suppressed. The response of plasma NT and SST after ID fat infusion in the normal volunteers was similar to the gastrectomized state. CONCLUSION: Diminution of SST secretion, probably caused by the lack of SST cells in the distal part of the stomach, may play a role in augmenting NT secretion after gastrectomy.

Aged↗

Nitric oxide in the rat spinal cord in Freund's adjuvant-induced hyperalgesia.

To elucidate the involvement of nitric oxide in spinal nociceptive processing, the correlation of thermal withdrawal latency with nitric oxide synthase-stained neurons in the rat lumbar dorsal horn was analyzed after adjuvant-induced inflammation. From 4 hr through 5 days after subcutaneous injection of complete Freund's adjuvant into the hind paw, a marked thermal hyperalgesia was observed for heat stimulus applied to the affected region. NADPH-diaphorase- and nitric oxide synthase-positive neurons increased significantly in the superficial layers of the dorsal horn ipsilateral to the inflamed hind paw at day 3 of adjuvant-induced inflammation. No change in NADPH-diaphorase-positive neurons was observed at 1 hr and 1 day of adjuvant-induced inflammation. The intravenous administration of N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg), an inhibitor of nitric oxide synthase, significantly blocked the adjuvant-induced thermal hyperalgesia at day 3 of inflammation, but not at day 1; and it had no effect in non-inflamed rats. This anti-hyperalgesic effect of L-NAME at day 3 of inflammation was reversed by the prior administration of L-arginine (600 mg/kg, i.p.), a substrate of nitric oxide synthase. These data suggest that nitric oxide producing neurons in the spinal dorsal horn are involved in maintaining and facilitating the hyperalgesia associated with chronic nociception.

Animals↗

Laparoscopic cholecystectomy in patients with cardiac disease: hemodynamic advantage of the abdominal wall retraction method.

We examined the use of an abdominal wall retraction method instead of pneumoperitoneum in laparoscopic cholecystectomy for patients with cardiac disease to prevent the hemodynamic deterioration associated with pneumoperitoneum. Eight patients with cardiac diseases, mainly valvular or coronary artery diseases, underwent laparoscopic cholecystectomy under hemodynamic monitoring. Five patients without cardiac disease served as controls. As hemodynamic parameters, heart rate, mean systemic arterial pressure (mAP), mean pulmonary arterial pressure (mPAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) were measured. The patients with cardiac disease showed significantly elevated mPAP and PCWP compared with the control group under pneumoperitoneum, and one patient showed critically decreased CI due to increased tricuspid regurgitation under pneumoperitoneum. These changes, however, were resolved on the abdominal wall retraction. There was no major perioperative complication. This abdominal wall retraction method is, therefore, favorable for patients with underlying cardiac disease to minimize the hemodynamic deterioration during laparoscopic cholecystectomy.

Abdominal Muscles↗

Endoderm-specific gene expression in embryonic stem cells differentiated to embryoid bodies.

Mouse embryonic stem cells can differentiate into various cell types within cell aggregates called embryoid bodies (EBs). This structure consists of ectodermal, mesodermal, and endodermal tissues, which resemble the embryo of egg-cylinder stage. After 8-10 days in culture, about half of the EBs expand into large cystic structures homologous to visceral yolk sac of postimplantation embryos. To study endoderm differentiation at molecular level, we examined expression of endoderm marker genes during the processes of EB development. alpha-Fetoprotein (AFP) and transthyretin (TTR) transcripts increased at the stage when embryoid bodies began to form yolk-sac-like structures and were expressed strongly thereafter. Expression of hepatocyte nuclear factor (HNF) 4, a variant form of HNF1 (also called HNF1beta), and HNF3beta started before the onset of AFP and TTR expression. HNF1 (also called HNF1alpha) expression began a few days after the onset of the expression of the transcription factors described above. Serum albumin (ALB) transcript was only found in late large cystic EBs. Also, AFP gene expression preceded ALB gene expression. These results suggest that the patterns of endoderm gene expression during EB development reflect the order found during mouse development in vivo, and EB formation may serve as an in vitro system to study the differentiation process.

Animals↗

NADPH-diaphorase in the developing rat: lower brainstem and cervical spinal cord, with special reference to the trigemino-solitary complex.

A previous study indicated that in adult rat, a distinctive neuronal group in the dorsomedial division of the subnucleus oralis of the spinal trigeminal nucleus (SpVo) and the rostrolateral part of the nucleus of the solitary tract (Sn) is stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), and suggested that the labeled structures are involved with sensorimotor reflexive functions. This study aimed to characterize the developmental expression of NADPH-d in SpVo and Sn, including other areas of the lower brainstem and cervical spinal cord, by means of the enzyme histochemical staining technique, from the prenatal through the postnatal period. On embryonic day 12 (E12), no neurons in the brain were stained for NADPH-d, whereas blood vessels were stained. Labeling in the vessels was consistently present throughout pre- and postnatal periods but decreased with development. On E15, labeled neurons appeared in the dorsomedial part of SpVo and the rostrolateral part of Sn, but not in the other nuclei. The labeled neurons in both nuclei increased in numbers drastically to E17. Postnatally, they tended to increase gradually in Sn, but to decrease slightly in SpVo. The cell size of labeled neurons reached a plateau at E17 in SpVo, but at postnatal day 4 (P4) in Sn. In other nuclei on E17, labeling appeared in the lateral paragigantocellular reticular, intermediate reticular, medullary reticular, pedunculopontine tegmental, and spinal vestibular nuclei, and laminae V, VI, and X of the cervical spinal cord. On E20 and P0, labeling appeared in the dorsal column, laterodorsal tegmental, raphe obscurus, parvocellular reticular, ventral gigantocellular reticular, and parahypoglossal nuclei, and laminae IX of the cervical spinal cord. On P4 labeling appeared in the parabrachial and median raphe nuclei, medial and caudolateral Sn, the magnocellular zone of subnucleus caudalis of the spinal trigeminal nucleus (SpVc), and laminae III/IV of the cervical spinal cord. On P10, labeling appeared in the paratrigeminal and dorsal raphe nuclei, the superficial zone of SpVc, and laminae I/II of the cervical spinal cord. No newly labeled neurons appeared in any nuclei after P14. The very early appearance of NADPH-d staining in SpVo and Sn, which precedes the appearance of NADPH-d elsewhere in the brainstem, suggests that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system has an important role for primitive orofacial sensorimotor reflexive functions. Furthermore, the pattern of developmental expression of NADPH-d in SpVo and Sn suggests that the NO/cGMP system is organized in a distinct manner in different nuclei.

Afferent Pathways↗

Effect of pneumoperitoneum on interatrial pressure gradient during laparoscopic cholecystectomy.

Alterations of the left atrial/right atrial pressure gradient were determined using a Swan-Ganz thermodilution catheter in 20 patients who underwent laparoscopic cholecystectomy with 12 mmHg pneumoperitoneum (LAP) and 13 patients who underwent minilaparotomy cholecystectomy (MINI). Right and left atrial pressures were both elevated by pneumoperitoneum. A diminished or reversed left/right interatrial pressure gradient was recognized during pneumoperitoneum in 4 of the 20 patients (20%) in the LAP group, whereas it was not recognized during operation in any of the 13 patients in the MINI group. Evaluation of the elevation of intrathoracic pressure during pneumoperitoneum using peak inspiratory airway pressure or pulmonary arterial pressure could not predict the occurrence of this paradoxical interatrial pressure gradient.

Atrial Function, Left↗

Intraoperative manometry during laparoscopic operation for esophageal achalasia: does pneumoperitoneum affect manometry?

The effects of pneumoperitoneum on the lower esophageal sphincter (LES) were evaluated during laparoscopic operation for esophageal achalasia. Intraoperative manometry was performed in three patients who underwent laparoscopic cardiomyectomy with Dor's fundoplication and five patients who underwent laparoscopic cholecystectomy (LC). The LES pressure and the length of the high-pressure zone (HPZ) did not change during pneumoperitoneum in either the achalasia and the LC group. In the achalasia group the LES pressure was sufficiently decreased following completion of cardiomyectomy, and the length of the HPZ was found to be sufficiently long after completion of fundoplication. The postoperative courses of the achalasia patients were uneventful, and they have had no symptoms of achalasia or gastroesophageal reflux since the operation. Accordingly, intraoperative manometry during 12 mmHg pneumoperitoneum was considered to be available for laparoscopic surgery for esophageal achalasia.

Adult↗

Bilateral internal carotid artery agenesis in a child with psychomotor developmental delay.

In a 2-year-old boy with severe psychomotor developmental delay and a dysmorphic face, a chromosome study revealed a balanced translocation: 46XY,t-(1;3)(p31.2;p21). With magnetic resonance angiography, bilateral internal carotid artery agenesis was diagnosed. Periventricular high-intensity areas were evident on T2-weighted imaging, but no major cerebral malformation was observed.

Abnormalities, Multiple↗

Induction of the C/EBP beta gene by dexamethasone and glucagon in primary-cultured rat hepatocytes.

The synthetic glucocorticoid, dexamethasone, and glucagon cooperatively elevated the level of mRNA for the transcription factor CCAAT/enhancer binding protein beta (C/EBP beta) in primary-cultured rat hepatocytes. In response to dexamethasone and/or glucagon, C/EBP beta mRNA started to increase as early as 30 min, reached a maximum within 2 h, and then gradually decreased. The administration of cycloheximide, a protein synthesis inhibitor, led rather to an increase in C/EBP beta mRNA, which suggested that a labile negative protein factor(s) is involved in regulation of the C/EBP beta mRNA level. Cycloheximide further augmented the increases in C/EBP beta mRNA by dexamethasone and/or glucagon. Therefore, C/EBP beta mRNA accumulation in response to these hormones is apparently independent of ongoing protein synthesis. The elevation of the C/EBP beta mRNA level by these hormones was accounted for by increases in the rate of transcription of the C/EBP beta gene, as deduced on nuclear run-on analysis. Gel mobility shift analysis revealed that the DNA-binding activity of C/EBP beta was increased cooperatively by dexamethasone and glucagon. These results suggest that the C/EBP beta gene is primarily induced by glucocorticoids and/or glucagon and that the accumulated C/EBP beta protein is then involved in secondary activation of target genes in response to these hormones in the liver.

Animals↗

An effect of somatostatin on neurotensin secretion.

A somatostatin analog (SMS201-995) was administered subcutaneously to six totally pancreatectomized (TP) patients at five dose levels from 0 microgram/kg (control) to 2.5 micrograms/kg before ingestion of a liquid test meal, and plasma levels of neurotensin (NT) were measured. There were no significant differences in basal levels of NT between the doses of somatostatin. The NT levels were significantly elevated after ingestion of the test meal in the normal controls (n = 14). In the TP patients postprandial hypersecretion of NT was observed. The hypersecretion of NT in the patients was suppressed by SMS201-995 dose-dependently.

Adult↗

Cloning of cDNAs encoding argininosuccinate lyase and arginase from Rana catesbeiana liver and regulation of their mRNAs during spontaneous and thyroid hormone-induced metamorphosis.

Thyroid hormones are responsible for a change in the expression of many target genes during amphibian metamorphosis. In this study we cloned and sequenced cDNAs encoding two of the five urea cycle enzymes, argininosuccinate lyase and arginase, from adult liver of Rana catesbeiana. The cDNAs for the bullfrog argininosuccinate lyase and arginase encoded proteins of 467 and 321 amino acids with predicted molecular weights of 52,257 and 35,088, which were 72-75 and 64-68% identical to the mammalian enzymes, respectively. The accumulation of the mRNAs for argininosuccinate lyase and arginase in liver increased 26 and 4-times in a coordinated manner during spontaneous metamorphosis. Thyroid hormone-treatment induced about 5 and 10-times accumulation of mRNAs for argininosuccinate lyase and arginase in liver from premetamorphosing tadpoles within 4 days. These results suggest that the mRNA levels of the two enzymes in liver are upregulated by thyroid hormone during metamorphosis.

Amino Acid Sequence↗

Laparoscopic extramucosal myectomy with anterior fundoplication (Dor) for esophageal achalasia using intraoperative manometry.

Laparoscopic extramucosal myectomy with anterior fundoplication according to the Dor technique was performed on a 24-year-old-woman. Intraoperative inflation of a pneumatic balloon made the operative procedures such as extended submucosal dissection quite easy. Intraoperative gastrofiberscopy was useful for confirming that the remaining mucosal layer was not injured after completion of myectomy. Intraoperative manometry confirmed a complete decompression of the high-pressure zone in the lower esophageal sphincter. Complete relief of the symptoms has been recognized for 6 months after operation without any medication. It is considered that these laparoscopic procedures including intraoperative inflation of a pneumatic balloon, gastrofiberscopy, and intraoperative manometry can be used as a standard operation for esophageal achalasia.

Adult↗