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M Kitajima

Publications and source records attributed to M Kitajima.

At least 199 records · Page 11Linked to original sources
PubMed1997

Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury.

BACKGROUND: Oxygen-derived free radicals (FRs) are critical mediators of ischemia/reperfusion injury. Inflammatory cytokines have been shown to play important roles in tissue injury. To examine the relationship between FRs and interleukin-1 (IL-1) in hepatic ischemia/reperfusion injury, we used interleukin-1 receptor antagonist (IL-1ra) to block endogenous IL-1 production in a rat model of hepatic ischemia/reperfusion. METHODS: Female SD rats were subjected to 30 min of hepatic ischemia followed by reperfusion. The animals were divided into two groups, control group and IL-1ra-treated group, according to the rinse solution. In both groups, FR production, histological changes, and interactions between leukocytes and endothelial cells were analyzed in the course of reperfusion. RESULTS: In the control group, production of FRs increased significantly after 60 min of reperfusion. After 60 and 180 min of reperfusion, histological examination showed atrophy and degeneration of hepatocytes. Hepatic microcirculation demonstrated a marked increase in the number of leukocytes adherent to endothelial cells and of injured cells after reperfusion. In the IL-1ra-treated group, IL-1ra pretreatment markedly reduced FR production after 60 min of reperfusion, the number of leukocytes adherent to endothelial cells, and tissue injury. CONCLUSION: These data clearly show an important role for IL-1 in the induction of FR production, leukocyte adhesion, and tissue injury after hepatic ischemia/reperfusion injury.

Animals↗
PubMed1997

Efficacy of intraportal infusion of prostaglandin E1 to improve the hepatic blood flow and graft viability in porcine liver transplantation.

BACKGROUND: Prostaglandin E1 (PGE1) has been reported to have a protective effect in experimental and clinical models of liver damage. The aim of this study was to elucidate the effects of the intraportal infusion of PGE1 on hepatic blood flow and graft viability after orthotopic liver transplantation in pigs. METHODS: First, the hepatic arterial flow (HAF), portal venous flow (PVF), and liver tissue blood flow (LTBF) were measured during the continuous intravenous or intraportal infusion of PGE1. Second, two groups of pigs underwent orthotopic liver transplantation: group A, untreated controls; and group B, animals that received intraportal PGE1 for 2 hr after vascular reconstruction of the allograft. Changes in HAF, PVF, LTBF, and hepatic function were measured. RESULTS: The intraportal infusion of PGE1 significantly increased HAF and had no effect on blood pressure, PVF, or LTBF. In group B, HAF and LTBF increased significantly with time. In group A, HAF remained unchanged and a decrease in LTBF was observed. Group B exhibited a higher arterial ketone body ratio and a greater bile flow compared with group A. A significant elevation in serum glutamic oxaloacetic transaminase concentration was observed in group A, but not in group B. CONCLUSIONS: This study demonstrates that the intraportal infusion of PGE1 improves hepatic allograft blood flow, predominantly through an effect on HAF, and may improve graft viability after orthotopic liver transplantation.

Alprostadil↗
PubMed1997

Active oxidants mediate IFN-alpha-induced microvascular alterations in rat mesentery.

The present study was designed to investigate the influences of IFN-alpha on the microcirculatory hemodynamics. The mesenteric microcirculation of male Wistar rats was observed through an intravital fluorescence microscopic system. The leukocyte behavior, RBC velocity, and albumin leakage were monitored simultaneously before and after a continuous infusion of IFN-alpha. In other rats, the oxidant-sensitive fluorescence probe dihydrorhodamine-123 (DHR) fluorescence was observed in the same set up. Administration of IFN-alpha increased the number of adherent and emigrated leukocytes and decreased the RBC velocity in mesenteric venules. Oxidative stress indicated by DHR fluorescence was exacerbated in microvessels of IFN-alpha-treated rats. Following the leukocyte recruitment and oxidative stress, an exaggerated albumin leakage was observed. Thrombus formation in venules and hemorrhage along venules were frequently observed in rats treated with IFN-alpha. N,N'-dimethylthiourea, a scavenger of hydrogen peroxide and a hydroxyl radical, largely prevented these microvascular responses. Pretreatment of rats with mAb directed against either CD18 or ICAM-1 also attenuated the IFN-alpha-induced microvascular alterations. It is concluded, therefore, that a high concentration of IFN-alpha stimulates CD18/ICAM-1-dependent adhesive interactions with endothelial cells and oxidant production of leukocytes, which leads to microcirculatory derangements characterized by decreased barrier function and reduced anticoagulant activity of venular endothelial cells.

Animals↗
PubMed1997

Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat.

The inflammatory cytokines interleukin (IL) 1 and tumor necrosis factor (TNF) may play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the role of IL-1 in hepatic I-R injury, we investigated the effect of pretreatment with IL-1 receptor antagonist (IL-1ra) on the production of IL-1, TNF, histological findings in the liver, and the survival rate for 7 days. Rats were subjected to 90 min of partial liver warm ischemia by clamping the vessels of the left and middle lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before liver ischemia was induced. IL-1alpha and TNF levels were determined in blood and liver at 0, 30, 90, and 180 min after reperfusion. In a second experiment to determine the effect of IL-1ra pretreatment on survival rate, after 90 min of partial liver ischemia, the right lateral and caudate lobes were excised, leaving only the ischemic lobes. In both groups, IL-1alpha was undetectable in blood, but increased in liver tissue. TNF increased in both blood and liver tissue as reperfusion time increased. Histological evidence of tissue injury was minimal in the IL-1ra-treated group. Furthermore, in the IL-1ra-treated group, the production of TNF decreased in both blood and liver tissue compared with the nontreated group. Survival rates in the IL-1ra-treated and nontreated group were 80% and 30%, respectively. The data demonstrated that the production of IL-1 and TNF increases in hepatic I-R injury and that pretreatment with IL-1ra protects the liver from ischemic insult, indicating an important role for IL-1 in I-R injury.

Animals↗
PubMed1997

Antitumor activity of paclitaxel against human breast carcinoma xenografts serially transplanted into nude mice.

BACKGROUND: Paclitaxel (BMS-181339: Taxol) is a promising agent against previously treated breast cancer. The antitumor activity of paclitaxel was evaluated using five human breast carcinoma xenografts in nude mice. METHODS: Paclitaxel at 20 mg/kg dissolved in 0.2 ml ethanol/cremophor EL solution was administered intraperitoneally daily for 5 days. RESULTS: Paclitaxel showed significant antitumor activity against MCF-7 and MX-1, but only limited activity against the other three xenografts (R-27, Br-10, and T-61), suggesting its substantially different antitumor spectrum from conventional antibreast cancer drugs. The different sensitivity of xenografts to paclitaxel was successfully reproduced in vitro using the MTT assay, when the cutoff concentration of paclitaxel was 20 microg/ml. CONCLUSION: Since no significant differences were observed in the pharmacokinetics of paclitaxel in sensitive and resistant tumor cell lines, the efficacy of this agent seemed to depend on the sensitivity of tumor cells rather than the intratumoral concentration of agent.

Animals↗
PubMed1997

The role of stromal cells in the expression of interstitial collagenase (matrix metalloproteinase-1) in the invasion of gastric cancer.

BACKGROUND AND OBJECTIVES: In one of the steps of tumor invasion and metastasis, tumor cells must invade surrounding tissues and degrade the components of the basement membranes. Interstitial collagenase (matrix metalloproteinase-1: MMP-1) has been also investigated in relation to cancer invasion and metastasis. METHODS: We investigated the formation and mechanism of MMP-1 expression using gastric cancer cell lines and gastric fibroblasts derived from normal gastric mucosa by ELISA and immunohistochemistry. RESULTS: Production of MMP-1 protein in gastric fibroblasts was stimulated significantly by adding the conditioned medium of MKN-74. Localization of MMP-1 protein in the xenografted gastric cancer cell lines was heterogeneous according to different cell lines. CONCLUSIONS: These results suggested that the production of MMP-1 protein in tumor invasion was regulated by interaction between stromal cells, particularly fibroblasts, and tumor cells.

Animals↗
PubMed1997

CA19-9 as a predictor of recurrence in patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: CA19-9 is a cancer-associated carbohydrate antigen that plays a role in the process of tumor progression as an adhesion molecule. METHODS: We evaluated the prognostic value of CA19-9 tumor expression and CA19-9 preoperative and postoperative serum levels in colorectal cancer patients treated by complete resection. The most powerful discrimination was achieved using the three CA19-9 markers in combination. RESULTS: CA19-9 tumor expression was identified by immunostaining in 71.0% (86/121) of primary carcinomas. Positive CA19-9 serum levels (> or = 37 U/ml) were restricted to cases with positive tumor expression, and CA19-9 was detected more frequently in preoperative serum (20.6%, 25/121) than in 1-month postoperative serum (6.6%, 8/121). Positive tumor expression, positive preoperative serum level, and positive postoperative serum level were all predictive of increased cancer mortality. Patients with three negative parameters had no recurrences and 97.1% 5-year survival, whereas patients with three positive parameters had 62.5% recurrence and 42.8% 5-year survival. CONCLUSIONS: CA19-9 detection in tumor tissue and serum identified patients at high risk of cancer recurrence and death and may be useful in selecting patients for adjuvant therapy.

Adult↗
PubMed1997

Frozen-section-guided breast-conserving surgery: implications of diagnosis by frozen section as a guide to determining the extent of resection.

This study was conducted to analyze retrospectively the results of performing sector resection on 56 breasts in 54 patients with breast cancer. The glands were resected with a 2-cm tumor-free margin on both lateral sides and the distal side, and with more than a 3-cm tumor-free margin on the nipple side. The frequency of positive resection margins for the cancer cells was 7/56 (12.5%) on the nipple side and 12/46 (26.1%) on the lateral sides, with an overall frequency of 15/56 (26.8%). There were positive resected margins for cancer cells on both the nipple and lateral sides in 4/46 patients (9%). Assuming the equivocal margins were positive for cancer cells, an accurate diagnosis by frozen section examination was made in 51 of the 56 operations (91.1%). Additional resection of the margins was performed in all 20 cases of a positive resected margin for cancer cells according to the diagnosis by frozen section. Thereafter, the resected margins became negative in 13 cases (65%), but remained positive in 7 cases (35%). These results show that performing diagnosis by frozen section of the surgical margins is an effective guide to resecting tumors adequately.

Adult↗
PubMed1997

Per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer: the ultimate sphincter-preserving operation.

PURPOSE: The most important goal of sphincter-preserving operations for rectal cancer is to secure a distal surgical margin of safety and the anal sphincter. However, it is not always easy to transect the rectum and to secure a distal surgical margin of safety through the abdominal approach for tumors situated extremely low in the rectum. The aim of this study was to describe and to evaluate a new technique of per anum intersphincteric rectal dissection and coloanal anastomosis. METHODS: The rectum, including the entire width of the internal anal sphincter, is transected circumferentially via the anal route to secure the surgical margin of safety under direct vision and is mobilized proximally as far as possible through the intersphincteric plane. Per anum coloanal anastomosis is performed following transabdominal resection of the rectum. RESULTS: This technique has been used in 12 patients. There have been no instances of short-term or long-term anastomotic complications. CONCLUSIONS: This technique is safe when anastomosis must be performed at the dentate line. It is the best sphincter-preserving operation for lower rectal cancer and does not result in serious postoperative anal dysfunction.

Anal Canal↗
PubMed1997

Basic studies on the application of an artificial esophagus using cultured epidermal cells.

In making an artificial esophagus, the transplantation of the epithelialized granulation tube fabricated by organized synthetic material was studied mainly from the viewpoint of preventing anastomotic leakage and stricture formation. The possibility of epithelialization of the inner surface of a granulation tube using cultured epidermal cells was studied in rats and dogs. A stainless steel mesh tube coated with silicon served as the granulation tube. Epithelialization on the inner surface of a granulation tube was evaluated by seeding cultured epidermal cells. A skin sample was treated with dispase and trypsin to collect epidermal cells, which were cultured in a keratinocyte growth medium. Once confluence was achieved, the epidermal cell suspension was harvested using the following methods: trypsin treatment (n = 15), mechanical separation with a cell scraper (n = 6), and dispase treatment (n = 9). The cultured epidermal cell suspension was then seeded into the lumen of the granulation tubes. The attachment of cultured epidermal cells was attained in 2 of 15 cases by trypsin treatment, and in 5 of 9 cases by dispase treatment. No attachment occurred using the cell scraper method. All attached epidermal cells exhibited a cobblestone appearance on the granulation tissue with a tendency toward stratification. These findings show that the inner surface of a steel mesh granulation tube was epithelialized by cultured epidermal cells.

Animals↗
PubMed1997

Surgical management of gastric leiomyosarcoma: evaluation of the propriety of laparoscopic wedge resection.

Laparoscopic surgery has been applied to malignant gastric tumors. To evaluate the propriety of laparoscopic wedge resection for gastric leiomyosarcoma it is necessary to question whether lymph node dissection is necessary for the surgical management of gastric leiomyosarcoma. A retrospective study on open surgery cases of gastric leiomyosarcoma was performed to address this issue. The clinical records of 28 patients with gastric leiomyosarcoma who had had surgery were examined. The patients who underwent open surgery were divided into a systematic lymph node dissection (SLND) group (n = 9) and a nondissection (non-D) group (n = 19). No patient had lymph node metastasis at the time of operation or recurrence, and statistical analysis showed no difference between the SLND and non-D groups in terms of survival rates. These data suggest that SLND might not be necessary for the surgical management of gastric leiomyosarcoma and that laparoscopic wedge resection of the stomach can be considered a first-line treatment for gastric leiomyosarcoma.

Adult↗
PubMed1997

Impaired expression of neural cell adhesion molecule L1 in the extrinsic nerve fibers in Hirschsprung's disease.

Immunohistochemical studies on the ganglionic and aganglionic segment in Hirschsprung's disease (HD) were carried out using antibodies against three neural membrane proteins, Thy-1, integrin alpha5, and L1. Enteric neural elements were immunostained with antibodies against neurofilament, which is the neuronal cytoskeletal protein. In ganglionic segments, neurofilament-immunoreactivity was detected in neuronal cell bodies and fine nerve fibers of the myenteric and submucosal plexuses. All of these neural elements were immunopositive for Thy-1, integrin alpha5, and L1. In aganglionic segments, no intrinsic neurons were detected, and instead, hypertrophied nerve bundles were observed in intermuscular space, in submucosa, and in circular muscle layer by immunochemistry for neurofilament. These hypertrophied nerve bundles were immunopositive with anti-Thy-1 and anti-integrin alpha5 antibodies. However, they were not immunostained with anti-L1 in all five cases. These findings indicate that the expression of L1 molecule, which plays an important role in cell adhesion, neural cell migration, and neurite outgrowth, is impaired in the extrinsic nerve fibers in aganglionic colon. And this may perturb neural crest migration and adequate neurite outgrowth, with resulting aganglionic segment and abnormal nerve bundles of extrinsic fibers in HD.

Antigens, CD↗
PubMed1997

Anti-interleukin-8 monoclonal antibody reduces free radical production and improves hemodynamics and survival rate in endotoxic shock in rabbits.

BACKGROUND: Although high levels of interleukin-8 (IL-8) have been found in patients with sepsis and a monoclonal antibody (MoAb) against IL-8 has been successfully used in some animal models of inflammation, no specific therapeutic agent against IL-8 has been tested for the treatment of sepsis. We studied the effects of a MoAb against IL-8 in the treatment of endotoxic shock with a prospective randomized rabbit endotoxic shock model. METHODS: Twenty New Zealand white rabbits were anesthetized and divided into four groups: normal, anti-IL-8, control-Ab, and lipopolysaccharide (LPS). Anti-IL-8 and control-Ab groups received a MoAb (immunoglobulin G, 3 mg/kg) 5 minutes before the LPS injection. All groups, except the normal group, received a continuous 20-minute infusion of LPS (500 micrograms/kg). The normal group received NaCl (0.9%) rather than LPS. RESULTS: The 7-day survival rates were 100% for normal group, 80% for anti-IL-8 group, 40% for control-Ab group, and 0% for LPS group. Compared with the LPS group, anti-IL-8 rabbits had a smaller decrease in mean arterial blood pressure (p < 0.05) and increased urinary volume (p < 0.05). Anti-IL-8 rabbits had lower plasmatic levels of IL-1 beta, less free radical production (p < 0.05), and a higher survival rate (p < 0.01). CONCLUSIONS: IL-8 plays a significant role in endotoxic shock, and IL-8 blockage results in attenuation of the hypotensive and tachypneic effects of LPS, reduced free radical production, and an increased survival rate after lethal endotoxic shock.

Animals↗
PubMed1997

Influence of estrogen metabolism on proliferation of human breast cancer.

In order to investigate the influence of estrogen metabolism on human breast cancer, estradiol 2- and 16 alpha-hydroxylase (2- and 16 alpha-OHase) activities were determined in the microsomal fractions of cancer tissues by using reverse phase HPLC. 2-OHase activity was detected in most cancer tissues and noncancerous tissues, but the activity was significantly lower in cancer tissues than in the paired noncancerous tissues (0.01 < p < 0.02). Interestingly the patients without lymph node metastasis had significantly higher 2-OHase activity in cancer tissues than those with lymph node metastasis (0.02 < p < 0.05). No correlation was observed between ER status and 2-OHase activity in cancer tissues. On the other hand, 16 alpha-OHase activity was detected only in one third of the breast cancer tissues examined. The activity was not significantly different from that in noncancerous tissues, although it was relatively higher in ER-positive cancer tissues when compared with that in ER-negative ones (0.05 < p < 0.1). Estrone sulfatase activity measured simultaneously in the cytosol fractions of some specimens was much higher in cancer tissues than in noncancerous tissues (0.02 < p < 0.05). We found, however, no correlation between estrone sulfatase activity and estradiol hydroxylase activity. Taken together, our results suggest that the increase in 2-OHase activity prevents the proliferation of breast cancer and that estradiol metabolism is regulated independently of the local biosynthesis of estrogen.

Aryl Hydrocarbon Hydroxylases↗
PubMed1997

Suppressed production of nitric oxide as a cause of irregular constriction of gastric venules induced by thermal injury in rats.

Microcirculatory disturbance is a crucial step in development of gastric mucosal lesions. In this study we investigated the influence of nitric oxide (NO) on the irregular constriction of gastric venules observed in rats subjected to thermal injury. Male Wistar rats were anesthetized and a 30% full skin thickness dorsal burn was inflicted. Microvascular images in the submucosal layer and basal region of the gastric mucosa were obtained through an intravital microscope. Distribution of constitutive-type nitric oxide synthase (cNOS) was observed by the immunofluorescence method. Venule walls were basically smooth in the control group (no injury), whereas irregular constrictions tended to be observed in the 5-h group (5 h after thermal injury). Venule diameter was significantly smaller in the 5-h group. In the control group, cNOS-associated fluorescence was found on the venule endothelium, whereas it was almost negligible after thermal injury. A NO donor, 3-morpholinosydnonimine hydrochloride, simultaneously diminished the thermal injury-associated venule constriction and irregularity of venule walls. Therefore, the present study suggests that venule constriction, which is observed 5 h after thermal injury, is related to decreased NO production by endothelial cNOS and is a cause of irregularity of the venule walls.

Animals↗
PubMed1997

Matrix metalloproteinase gene expression in chronic gastric ulcer: a potential role of eosinophils in perforation.

Gene expression of matrix degrading enzymes was investigated in surgical specimens of perforated gastric ulcers. In these ulcers, the inflammatory cells infiltrating into the granulation tissue were granulocytes, particularly eosinophils. The extracellular matrix of the stomach wall consists mainly of collagen types I and III, which are selectively degraded by matrix metalloproteinase-1 (MMP-1). MMP-1 mRNA was detected in the cytoplasm of infiltrating cells, suggesting that eosinophils play an important role in ulcer recurrence and in perforation of the stomach wall. The degree of eosinophil infiltration into an ulcer base may be a useful marker for the risk of perforation. Patients showing this marker may benefit from a prophylactic therapy for preventing severe complications. The control of MMP gene expression represents a potential strategy for the treatment of recurrent gastric ulcer.

Adult↗
PubMed1997

Expression of interstitial collagenase (matrix metalloproteinase-1) in gastric cancers.

The expression of matrix metalloproteinase-1 (MMP-1) gene and the presence of MMP-1 protein in gastric cancer were examined by in situ hybridization and immunohistochemistry. Expression of the interstitial collagenase (MMP-1) gene was detected within the stroma of the neoplastic glands, and infiltration of eosinophils was observed to be associated with regions of MMP-1 gene expression. The degree of eosinophilic infiltration correlated with the level of MMP-1 mRNA expression. Immunostaining showed localization of MMP-1 protein in the stromal cells, and additionally in the neoplastic glands. These findings indicate that the stromal cells may play an important role in the expression of MMP-1, and suggest a pathophysiological role for MMP-1 in the invasion and metastasis of gastric cancer.

Adenocarcinoma↗