Protective effect of ischemic preconditioning on hepatic ischemia-reperfusion injury in mice.
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Alanine Transaminase↗
Biomedical subjects
I Ninomiya
Publications and source records attributed to I Ninomiya.
N-ethylmaleimide-enhanced phosphatidylserine externalization of human pancreatic cancer cells and immediate phosphatidylserine-mediated phagocytosis by macrophages.
The purpose of this study was to examine whether N-ethylmaleimide (NEM) can enhance phosphatidylserine (PS) externalization on the outer surface of cancer cells, and PS-externalized cancer cells can be phagocytosed immediately by macrophages. NEM could externalize PS of cancer cells in concentration- and time-dependent manners. When treated with 5 mM NEM for 1 h, 80% of the carcinoma cells externalized their PS. In phagocytosis assay, these cells were engulfed immediately by macrophages before undergoing apoptosis. These results suggest that NEM can immediately externalize PS of cancer cells, leading to their recognition and phagocytosis by macrophages before undergoing apoptosis morphologically.
Animals↗
[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas].
A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.
Administration, Oral↗
Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer.
S100A4 is known to be involved in cancer cell motility by virtue of its ability to activate nonmuscle myosin. E-cadherin has an important role in the homophilic cell-cell adhesion and is called an invasion suppressor gene. In the current study, we investigate the histological type and metastatic potential of gastric cancer from the aspect of the interrelationship of E-cadherin and S100A4 expression. Expression of E-cadherin and S100A4 in gastric cancer cell lines, primary gastric cancers, and their normal counterparts were analyzed by reverse transcription-PCR, Western blot, and immunohistochemical methods. S100A4 protein and E-cadherin were expressed in five of eight gastric cancer cell lines, and inverse expression of the two proteins are found in four cell lines. In the clinical specimens, E-cadherin mRNA expression in differentiated adenocarcinomas (88%, 14 of 16) was significantly more frequent than that in poorly differentiated adenocarcinomas (50%, 22 of 44; P = 0.015). Western blot analysis demonstrates that S100A4 protein expression in poorly differentiated adenocarcinomas was 1.6-fold higher than in well differentiated adenocarcinoma. Immunohistochemically, S100A4 expression was detected in 51 (55%) of 92 primary gastric cancers. Reduced expression of E-cadherin in primary tumors was found in 66 (72%) of 92 tumors. S100A4 expression in the poorly differentiated adenocarcinomas had a strong relation to positive lymph node involvement or peritoneal dissemination. Reduced E-cadherin expression showed a strong relationship with positive serosal involvement and infiltrating type. Tumors classified as a group with reduced E-cadherin and high expression of S100A4 reveal positive peritoneal dissemination, serosal involvement, and infiltrating type in the growth pattern. Furthermore, these tumors showed a strong correlation with the poorly differentiated adenocarcinoma. In contrast, tumors with preserved E-cadherin and low expression of S100A4 have a close relation to the well differentiated adenocarcinoma and a favorable prognosis. By the Cox proportional hazard model, S100A4 and E-cadherin tissue status was judged as an independent prognostic factor. S100A4 and E-cadherin tissue status may be a powerful aid in evaluating metastatic potential or the prognosis of patients with gastric cancer.
Cadherins↗
Segmental differences in vasodilatation due to basal NO release in in vivo cat pulmonary vessels.
This study was conducted to examine segmental differences in vasodilatation caused by the basal release of nitric oxide (NO) in the serially connected pulmonary vessels and to estimate the relative contributions of endothelial and neuronal NO synthase (NOS), and inducible NOS to the vasodilatation. Using an X-ray TV system on in vivo cat lungs, we measured internal diameter (ID) changes in resistance (100-400 microm ID), small conduit (600-1000 microm) and large conduit (1200-1700 microm) arteries, and veins of the same size. Non-selective NOS inhibitors, L-NAME (30-50 mg/kg i.v.) and L-NMMA (40-60 mg/kg i.v.), decreased the ID of all vessels studied, although their D-isomers had no effect. The decrease was larger in conduit arteries than in resistance arteries, with maximum response of small conduit arteries (25 +/- 2%), while venous segments displayed relatively uniform response (10-12%). L-Arginine completely abolished the ID decrease but hexamethonium bromide and phentolamine had no effect. Selective inhibitors of inducible NOS, L-canavanine (100 mg/kg i.v.) and S-methylisothiourea (10 mg/kg i.v.) did not affect any of the vessels. The data suggest that basal release of NO chiefly derived from endothelial NOS serves to dilate cat pulmonary arteries and veins, particularly small conduit arteries.
Angiography↗
Effects of mental stress on cardiac and motor rhythms.
To identify whether spontaneous cardiac rhythm and voluntary motor rhythm are modified in parallel or influenced separately when imposing mental stress, we recorded simultaneously the two rhythms during finger tapping as a simple model of rhythmical motion in 10 healthy human subjects (6 males, 4 females each). Each subject performed finger tapping with an arbitrary tapping rhythm. Mental stress was given intermittently three times for 10-15 s at intervals of 40 s during tapping for 150 s. Heart rate (HR) and tapping rate (TR) and their variations (standard deviation; SD) during finger tapping with and without mental stress were compared. HR and TR increased significantly in response to mental stress during tapping. After mental stress was ended, HR returned rapidly to the initial level, but TR remained at a higher level. Moreover, SD of TR, but not SD of HR, during tapping was increased by mental stress. The present results indicate that the cardiac and motor rhythms are influenced simultaneously by mental stress. However, a difference was seen about the sustained effect of mental stress on the two rhythms.
Adult↗
Self-biofeedback control of heart rate during exercise.
To improve cardiac adjustment to exercise, we developed a new self-biofeedback heart rate (HR) controller. Using this device, we analyzed time courses of HR, running speed (RS), stride length (ST) and pitch of gait (PI) in response to various preset HR levels in 7 normal human subjects. When HR was preset at 80 bpm, HR increased rapidly in response to exercise and exceeded the preset level at 12. 1 s with overshoot. At the preset HRs of 100, 120, 140 and 160 bpm, the HRs increased to each preset level at 39.2, 64.5, 58.5 and 83.0 s after the onset of exercise, respectively, and the HRs were adjusted with a range of +/- 4%. For all preset HRs, RS, ST and PI increased more rapidly than the HR and reached the maximum values within 30 s. During exercise, RS, ST and PI remained constant within 1.5-5.5 min. HR, RS, ST and PI increased in proportion to the preset HR. The increases in PI against HR (DeltaPI/DeltaHR) decreased with the higher HR level, and at HRs of 160-170 bpm, HR and PI showed identical rhythm. The increases in RS were produced by 18-59% increases in PI and by 12-44% increases in ST. We concluded that, using our newly developed self-biofeedback HR control system, we could control HR to a given preset value by a change in RS due to PI and ST.
Adult↗
Pulmonary microvascular responses to inhaled prostacyclin, nitric oxide, and their combination in anesthetized cats.
Using an X-ray television system on anesthetized cats, we directly measured internal diameter (ID) changes in identical small pulmonary vessels (100-1,100 microm ID) in response to inhalations of 25, 250, and 2,500 ng/kg/min aerosolized prostacyclin (PGI2), 4 and 34 ppm nitric oxide (NO), and the combination of aerosolized PGI2 and NO. We also compared ID changes during 250 ng/kg/min PGI2 inhalation both with and without an Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg I.V.) pretreatment. In the arteries, inhaled PGI2 increased 100-900 microm vessel ID in a dose-dependent manner but caused no significant, or only slight, ID increases in the vessels larger than this. The greatest ID increase ( approximately 22%) was in the 100-500 microm arteries in response to 2,500 ng/kg/min PGI2 inhalation. PGI2 also increased the ID of the veins (6-12%), but the results were not dose related. NO inhalation also resulted in non-uniform ID response patterns similar to PGI2 with no significant, or only minimal, ID increases of the arteries >900 microm. The simultaneous inhalation of 2,500 ng/kg/min PGI2 and 34 ppm NO increased the arterial ID (maximum approximately 34%) more than either drug alone and to almost the same extent as brought about by injected papaverine (2 mg/kg), a smooth muscle relaxant. Inhaled PGI2 (250 ng/kg/min) decreased pulmonary arterial pressure and increased arterial ID to nearly the same extent with or without L-NAME pretreatment. These results indicate that inhaled PGI2 and inhaled NO locally dilate 100-900 microm pulmonary arteries in a dose-dependent manner and with a similar ID response pattern, and that the combination of these drugs produces a more enhanced vasodilator effect compared to their separate effects and induces the maximum dilated states. The data also suggest that inhaled PGI2 dilates these arteries directly, rather than via secondary release of endogenous NO.
Administration, Inhalation↗
Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer.
Neogenesis of lymphatic vessel and lymphatic invasion is frequently found in the stroma of cancers, but the mechanisms of this phenomenon remain unclear. Vascular endothelial growth factor C (VEGF-C) is known to be the only growth factor for the lymphatic vascular system, and its receptor has been identified as Flt4. To clarify the mechanism of lymphatic invasion in cancer, we studied the expression of VEGF-C and flt4 genes in gastric cancer tissues. VEGF-C mRNA was mainly expressed in primary tumors (15 of 32; 47%), but the frequency of VEGF-C mRNA expression was low in normal mucosa (4 of 32; 13%). In primary tumors, there was a significant relationship between VEGF-C and flt4 mRNA expression. In contrast, Flt4 was mainly expressed on the lymphatic endothelial cells but not in cancer cells. A strong correlation was found between VEGF-C expression and lymph node status, lymphatic invasion, venous invasion, and tumor infiltrating patterns. Cancer cells in the lymphatic vessels frequently showed intracytoplasmic VEGF-C immunoreactivity. Furthermore, there was a close correlation between VEGF-C tissue status and the grade of lymph node metastasis. Patients with high expression of VEGF-C protein had a significantly poorer prognosis than did those in low VEGF-C expression group. By the Cox regression model, depth of wall invasion, lymph node metastasis, and VEGF-C tissue status emerged as independent prognostic parameters, and the VEGF-C tissue status was ranked third as an independent risk factor for death. These results strongly suggest that cancer cells producing VEGF-C may induce the proliferation and dilation of lymphatic vessels, resulting in the development of invasion of cancer cells into the lymphatic vessel and lymph node metastasis.
Biomarkers, Tumor↗
[A case of rectal cancer with lymph node metastasis (N4) successfully treated with low-dose cisplatin and UFT].
A 65-year-old man was admitted to our hospital due to the swelling of bilateral inguinal lymph nodes and anal discomfort. Sigmoidoscopy revealed a type-1 tumor of the lower rectum which was histologically diagnosed as a poorly-differentiated adenocarcinoma, and inguinal lymph node biopsy showed metastatic adenocarcinoma. An abdominal CT scan revealed swelling of the paraaortic lymph nodes. After a full explanation of the treatment options, the patient chose chemotherapy. Treatment by intravenous infusion of 7.5 mg/body/day of cisplatin for 5 days a week and oral administration of 600 mg/day of UFT was carried out. After 4 weeks of treatment, the primary tumor and swelling of the paraaortic lymph nodes had disappeared, and there was a 61% reduction in the inguinal lymph nodes. Four months later, the primary lesion recurred but vanished again following the same treatment regimen for 6 weeks. The patient has been in good health for over 9 months with no adverse effects from the chemotherapy.
Adenocarcinoma↗
Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach.
Prognostic significance of c-erbB-2 gene abnormalities is unclear in the poorly differentiated type of gastric carcinoma, because the abnormalities of this gene have been reported to be restricted to the differentiated type of gastric carcinoma. In this study, correlation of c-erbB-2 gene amplification/overexpression of mRNA and protein were studied in the poorly differentiated type of gastric carcinoma. c-erbB-2 gene amplification determined by the slot-blot hybridization was observed in 11 (13%) of 82 gastric cancer, and 8 of 11 tumors were poorly differentiated. In addition, c-erbB-2 mRNA expression was studied by the reverse transcriptase-polymerase chain reaction. Four (17%) of 24 tumors showed overexpression of c-erbB-2 mRNA, and all these four exhibited morphologically a poorly differentiated type. Among 157 poorly differentiated gastric cancers, 20 (13%) tumors showed immunohistochemically c-erbB-2 protein expression. These tumors had significantly higher incidences of larger tumor, serosal invasion-positive tumors, node-positive tumor, or peritoneal dissemination-positive tumor than those without c-erbB-2 expression. Furthermore, patients with c-erbB-2 protein overexpression ran poorer prognoses than those without c-erbB-2 expression. From these results, we conclude that expression c-erbB-2 tissue status may be a good prognostic indicator in poorly differentiated gastric carcinoma.
Adenocarcinoma↗
The significance of atrial monophasic action potentials for monitoring rat cardiac allograft rejection.
BACKGROUND: Changes in the monophasic action potential may be used for detecting early acute rejection in the transplanted rat heart. METHODS: Heterotopic heart transplantations were performed in allogeneic and syngeneic rats. During atrial pacing, monophasic action potentials were simultaneously recorded in the right atrium and ventricle of the transplanted hearts on postoperative days 1, 3, and 5. The amplitude and duration of monophasic action potentials, atrioventricular conduction time, and cardiac intervals were analyzed. Histopathologic examination for rejection was performed on postoperative days 1, 3, and 5. RESULTS: In the allogeneic group, monophasic action potential amplitude progressively decreased, and monophasic action potential duration gradually increased after heart transplantation in the atrium and ventricle. With rejection, the amplitude decreased to a greater extent, and monophasic action potential duration increased to a greater extent in the atrium than in the ventricle on day 3. The atrioventricular conduction time increased on day 5, but the cardiac interval did not change. An inverse correlation between histopathologic grade and the monophasic action potential amplitude, and a positive correlation between histopathologic grade and the monophasic action potential duration existed for both the atrium and ventricle. These electrophysiologic and histopathologic changes were not observed in the syngeneic group. CONCLUSIONS: We conclude that right atrial monophasic action potentials may be a useful and reliable indicator of early acute heart transplant rejection.
Acute Disease↗
Direct observations of sympathetic cholinergic vasodilatation of skeletal muscle small arteries in the cat.
1. The aim of this study was to examine the actual changes of the internal diameter (i.d.) of arterial vessels of skeletal muscle evoked by activation of sympathetic cholinergic nerve fibres during stimulation of the hypothalamic defence area in anaesthetized cats. 2. For this purpose, we have used our novel X-ray TV system for visualizing small arteries (100-500 microm i.d.) of the triceps surae muscle and larger extramuscular arteries (500-1400 microm i.d.) of the hindlimb (the femoral (FA), popliteal (PA) and distal caudal femoral (DCFA) arteries). The passage of a contrast medium from the large extramuscular arteries to the smaller intramuscular arteries was serially measured before and during hypothalamic stimulation. 3. Hypothalamic stimulation increased mean arterial blood pressure, heart rate and femoral vascular conductance. The i.d. of FA, PA, and DCFA did not change during the hypothalamic stimulation, whereas the i.d. of small arteries in the triceps surae muscle increased by 48 +/- 2% (mean +/- S.E.M.) and the cross-sectional area increased concomitantly by 118%. The maximum increase in i.d. of 78 +/- 6%, was observed in arteries of 100-200 microm. These increases in diameter were markedly reduced by intra-arterial injection of atropine or by cutting the sciatic nerve, but not by phentolamine and propranolol given together. 4. The vasodilatation evoked by hypothalamic stimulation was seen in almost all the sections of the small arteries observed under control conditions and was distributed along the entire length of the vessel. In addition, the number of arterial vessels that could be detected increased by 42% during hypothalamic stimulation. The newly detected arterial branches, which ranged from 100 to 300 microm in diameter, mostly arose from the branching points. 5. It is concluded that stimulation of sympathetic cholinergic nerve fibres dilates the small arteries of skeletal muscle ranging from 100 to 500 microm, but not the larger extramuscular arteries.
Animals↗
Renal sympathetic nerve activity and the weight of the remaining kidney in unilateral nephrectomized rats.
To examine compensatory response of the kidney to reduction in renal mass, acute and chronic effects of unilateral nephrectomy on renal sympathetic nerve activity (RNA) and weight of the remaining kidney were analyzed in rats. Under acute nephrectomy, RNA decreased significantly due to ligation of the renal vessels, ureter and nerves. With acute unilateral renal denervation, basal mean RNA (MRNA) did not change but the reflex inhibition of RNA due to ligation disappeared. Chronic effects of nephrectomy were analyzed at 3, 7, 14 and 28 days after surgery. At 3, 7, 14 and 28 days after nephrectomy, MRNA were about two times larger than the values obtained in sham operation group (p < 0.01). Changes in arterial pressure and heart rate were not significant after unilateral nephrectomy. When the maximal MRNA due to dimethylphenylpiperazinium iodide (DMPP) administration was set as 100%, relative basal MRNA at 3, 7, 14 and 28 days were estimated in sham and nephrectomy groups. Also, relative basal MRNA increased about two times in nephrectomy group. After unilateral nephrectomy, the remaining kidney weight per unit body weight increased significantly by 18-35%. These findings indicate that the RNA in the remaining kidney was reflexly inhibited by the activation of afferent input due to ligation of renal vessels, ureter and nerves under acute nephrectomy. Under chronic unilateral nephrectomy, basal MRNA and the weight of the remaining kidney were increased significantly. The RNA per unit of kidney weight in unilateral nephrectomized rats was increased at 3 and 7 days and then it was relatively constant at 14 and 28 days.
Action Potentials↗
Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats.
1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100-1100 microns i.d.) by use of an X-ray television system on the in vivo cat lung. 2. Under control (resting vascular tone) conditions, AM injections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100-1100 microns arteries (4 +/- 1, 11 +/- 2, and 17 +/- 2% with 0.01, 0.1, and 1 nmol kg-1 AM, respectively) was significantly larger than that for the veins (1 +/- 1, 5 +/- 2, and 7 +/- 2% with 0.01, 0.1 and 1 nmol kg-1 AM, respectively) whatever the injected dose of AM. 3. When unilobar hypoxia (5% O2) had decreased the i.d. of the 100-1100 microns arteries and veins by 16 +/- 3 and 6 +/- 3%, respectively, AM (0.1 nmol kg-1) was able to induce significantly larger i.d. increases in the arteries (28 +/- 3%) and veins (11 +/- 3%) than those under control conditions. 4. The AM-induced i.d. response pattern in the serially connected pulmonary arteries was quite different from that induced by CGRP; AM caused a greater increase in smaller vessels (100-500 microns) than in larger vessels (500-1100 microns). In the case of CGRP, a greater increase was observed in the larger vessels. 5. CGRP8-37 (100 nmol kg-1, i.v., followed by a continuous infusion of 0.2 nmol kg-1 min-1) had no significant effect on the i.d. increase induced by AM (0.1 nmol kg-1) in any serial segments of the arteries and veins. 6. The results indicate that, in the cat, AM induces greater vasodilatation in small pulmonary arteries and lesser vasodilatation in small veins, the maximum dilatation being in the more peripheral arterial segment (100-500 microns). The vasodilator effect of AM was enhanced when vascular tone was elevated. The data suggest that the AM-induced pulmonary vasodilatation is not mediated by CGRP receptors but by its own specific receptor.
Adrenomedullin↗
Endogenous nitric oxide attenuates hypoxic vasoconstriction of small pulmonary arteries and veins in anaesthetized cats.
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Anesthesia↗
Radical cyclization in heterocycle synthesis. II. Total synthesis of (+/-)-anantine and (+/-)-isoanantine.
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Cyclization↗
[Effects of repetitive physical training on neurogenic regulation of heart rate in healthy subjects].
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Adolescent↗