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Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 145 records · Page 8Linked to original sources

Relation between tumour necrosis factor alpha and interleukin 1beta producing capacity of peripheral monocytes and pulmonary complications following oesophagectomy.

BACKGROUND: Adult respiratory distress syndrome and pneumonia remain a significant cause of morbidity and death following oesophagectomy. The aim of this study was to clarify the association between tumour necrosis factor (TNF) alpha and interleukin (IL) 1beta with these pulmonary complications. METHODS: The in vitro TNF-alpha and IL-1beta producing capacity of peripheral monocytes with or without lipopolysaccaride (LPS) and serum level of IL-6 was measured in 19 patients with oesophageal cancer before and after surgery and in ten age-matched controls. RESULTS: Six patients had raised TNF-alpha and IL-1beta producing capacity of monocytes without LPS both before operation and on the day after surgery. In these patients plasma elastase and serum IL-6 levels subsequently increased while the ratio of arterial partial pressure of oxygen to fraction inspired oxygen decreased, and they developed bilateral lung infiltration on chest radiography on days 3-7. Five of the six developed pneumonia compared with none of the remaining 13 patients (P < 0.05). CONCLUSION: Pulmonary impairment and pneumonia following oesophageal surgery was associated with raised monocyte producing capacity of TNF-alpha and IL-1beta. These markers may be valuable in the preoperative assessment of patients awaiting oesophagectomy.

Aged↗

Intrahepatic peripheral cholangiocarcinoma: mode of spread and choice of surgical treatment.

BACKGROUND: Classification of macroscopic appearance and standard operative procedures for intrahepatic cholangiocarcinoma (ICC) are still controversial. METHODS: The mode of spread of 12 resected ICCs was examined by light microscopy, and the appropriate operative procedures for the various tumours were considered. RESULTS: Macroscopically, nine tumours were classified as mass-forming type and three as periductal infiltrating type. All patients were treated by major hepatectomy; resection of the extrahepatic bile duct was included in two cases of the periductal infiltrating type. Microscopically, invasion into the portal vein, intrahepatic metastasis and perineural or lymphatic vessel invasion occurred in none, one and all of three tumours of the periductal infiltrating type and in eight, six and six of nine tumours of the mass-forming type. CONCLUSION: ICC of the periductal infiltrating type has a tendency to spread along Glisson's sheath via lymphatic vessels. By contrast, ICC of the mass-forming type tends to invade the liver via the portal vein system; such tumours begin to invade Glisson's sheath through the lymphatic vessels when the tumour has increased in size. Therefore, major hepatectomy with combined resection of the extrahepatic bile duct should be performed for all ICCs of the periductal infiltrating type and for those of the mass-forming type with invasion of Glisson's sheath.

Adult↗

Perigastric lymph node status as a prognostic indicator in patients with gastric cancer.

BACKGROUND: The extent of lymph node dissection and histological examination of dissected lymph nodes varies among countries, which leads to the erroneous nodal stage and different surgical results in gastric cancer (stage migration, 'Will Rogers effect'). The aim of this study was to clarify the prognostic significance of the number of positive perigastric lymph nodes, which could be evaluated simply after D1 gastrectomy. METHODS: A consecutive series of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and lymph node dissection (D2 or D3) was studied. The number of metastatic perigastric nodes (level I, nos 1-6) was examined, and its influence on the survival of patients was analysed. RESULTS: The overall 5-year survival rate was 50.9 per cent; the 5-year survival rate was significantly decreased when positive perigastric nodes exceeded six (62 per cent for one to six nodes versus 23 per cent for seven or more nodes, P< 0.001). Tumours having one to six positive perigastric nodes compared with those having seven or more positive perigastric nodes were more likely to have a size less than 4 cm (29 per cent versus one of 30, P< 0.001), grossly localized type (45 per cent versus seven of 30, P=0.042), absence of serosal invasion (32 per cent versus none of 30, P=0.002) and metastasis limited to the perigastric lymph nodes (70 per cent versus seven of 30, P < 0.001). CONCLUSION: The results indicate that the number of positive perigastric nodes correlates with tumour progression and patient survival. This parameter is a simple and useful prognostic indicator for node-positive gastric cancer, and is available not only for D2 and D3 gastrectomy but also for D1 gastrectomy.

Adult↗

Inhibition of mitochondrial gene expression by antisense RNA of mitochondrial transcription factor A (mtTFA).

Mitochondrial transcription factor A (mtTFA) plays an important role in regulating the expression of mitochondrial genes. To gain a better understanding of the relationships between mitochondrial gene expression and mtTFA, the mtTFA gene was inserted into a mammalian expression vector, both in the sense orientation and in the antisense orientation. After construction, these plasmids were transfected into COS-7 cells. In antisense-transformed cells, the expression of the cytochrome c oxidase subunit I and subunit III genes encoded by mitochondrial DNA was inhibited and there was an accompanying reduction of the level of mtTFA protein. These results provide direct evidence that the expression of mitochondrial genes is under the control of mtTFA.

Animals↗

Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer.

Liver metastasis is the gravest prognostic factor in colorectal cancer. To identify a reliable indicator for liver metastasis, we evaluated macroscopic features and seven established histopathological findings at the cut section containing the deepest penetration using univariate and multivariate analyses in 417 colorectal cancers. Macroscopic features were divided into two types, streak type and non-streak type, according to the presence or absence of white streak(s) at the advancing margin of tumor invasion. Streak type was observed in 109 patients (26%). The frequency of liver metastasis in streak type tumors (56%) was significantly higher than that in non-streak type tumors (13%) (p < 0.001). The white streak corresponded histologically with cancer cells showing focal dedifferentiation with marked stromal and perivascular fibrosis extending towards the serosa or adventitia. In 343 curatively treated patients, univariate analysis showed that recurrent liver metastasis was significantly associated with macroscopic features, venous invasion, focal dedifferentiation and lymph node metastasis. Multivariate analysis disclosed that macroscopic features and lymph node metastasis were independent indicators of liver metastasis. These macroscopic features, corresponding histologically to stromal behavior against invading cancer cells, are a simple and useful indicator of liver metastasis of colorectal cancer.

Colonic Neoplasms↗

Low-dose cisplatin-5-fluorouracil prevents postoperative suppression of natural killer cell activity in patients with gastrointestinal cancer.

BACKGROUND: The effect of administering low-dose cisplatin (CDDP)-5-fluorouracil (5-FU) postoperatively on the activity of the immune system is not known. To clarify the effect on natural killer (NK) cell activity of treatment with low-dose CDDP-5-FU, we compared NK cell activity after surgery for gastrointestinal cancer in patients treated with low-dose CDDP-5-FU, a bolus dose of mitomycin C (MMC) or no anticancer drug. METHODS: Sixty-two patients consisted of three groups: low-dose CDDP-5-FU (n = 15), MMC (n = 20) and no-drug (n = 27). Chemotherapy was initiated immediately after surgery. NK cell activity was measured on the day before surgery (pre-op) and on postoperative days 7 (POD7) and 21 (POD21). RESULTS: The NK cell activities of the CDDP-5-FU group were 37.7% at pre-op, 36.1% on POD7 and 33.6% on POD21. However, the NK cell activities in the no-drug and MMC groups were significantly decreased on POD7 (from 36.6 to 24.8% and from 31.4 to 16.6%, respectively). The NK cell activity in the MMC group remained depressed on POD21 (18.6%) whereas that in the no-drug group recovered (31.6%). CONCLUSIONS: Consecutive administration of low-dose CDDP-5-FU appears to be useful as postoperative adjuvant chemotherapy because of its preventive effect on NK cell suppression after surgery.

Aged↗

Distribution of lymph node metastasis and level of inferior mesenteric artery ligation in colorectal cancer.

To investigate the distribution of lymph node metastasis along the inferior mesenteric artery (IMA) and clarify whether high ligation of the IMA is important or not, we examined the surgical results of 172 patients with cancer of the sigmoid colon and rectum. Histologically, lymph node metastasis was absent in 108 (63%) patients and present in 64 (37%) patients. The distribution was adjacent to the wall of the rectum (35.5%) and sigmoid colon (10.5%), along the IMA (7.7%) and sigmoid colic artery (6.3%), and at the root of the IMA (0.7%, 1 of 135 patients). The presence of lymph node metastasis was predicted by the operative findings of lymph node metastasis (p < 0.01) and serosal invasion (p < 0.05) and by the histologic type of tumor (p < 0.05). These results indicate that lymph node metastasis at the root of the IMA is rare, and complete removal of the pericolic and intermediate nodes (D2 dissection) without high ligation of the IMA is feasible for cancer of the sigmoid colon and rectum.

Adenocarcinoma↗

Moyamoya disease and pregnancy: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Many female patients with moyamoya disease are of childbearing years, including those who were diagnosed before entering their childbearing years. However, there have been no extensive reviews of the management of pregnancy and delivery in association with moyamoya disease. The purpose of this report is to describe the case of a patient with moyamoya disease complicated by pregnancy and to review the literature on other such cases. CLINICAL PRESENTATION AND INTERVENTION: We report a 23-year-old primipara with moyamoya disease who delivered uneventfully by cesarean section under spinal anesthesia at 38 weeks of gestation. In the literature, 30 cases were reported of patients who had been diagnosed with moyamoya disease before pregnancy and delivery, and 23 patients who were symptomatic and were diagnosed for the first time with moyamoya disease in association with pregnancy. CONCLUSION: There is no evidence that pregnancy increases the risk of cerebrovascular accident or that bypass surgery decreases its risk. Poor prognosis of the patient or the newborn is mostly caused by cerebral hemorrhage and not by cerebral ischemia. It is important to control blood pressure and especially to avoid toxemia during pregnancy. Either cesarean section or vaginal delivery can be accomplished safely. Any anesthetic method can be used, provided special attention is given to avoiding hypocapnia, hypotension, and hypertension. Oral contraceptives should be avoided.

Adult↗

Fibronectin in saliva inhibits Porphyromonas gingivalis fimbria-induced expression of inflammatory cytokine gene in mouse macrophages.

The aim of this study was to examine whether fibronectin in saliva plays a regulatory role in Porphyromonas gingivalis fimbria-mediated pathogenesis in adult periodontal disease. Our previous study demonstrated that fibronectin is one of the binding proteins of P. gingivalis fimbrillin. In the present study, we observed that fibronectin in saliva binds specifically to the fimbrillin. The fibronectin content in saliva of adult periodontal patients was significantly lower than that of healthy subject. In addition, the inhibitory action of salivary fibronectin from adult periodontal patients toward P. gingivalis fimbria-induced expression of the neutrophil chemoattractant KC gene in mouse macrophages was clearly weak compared with that of the fibronectin from healthy subjects. These results suggest that fibronectin in saliva plays an important role as a regulator in the pathogenesis of P. gingivalis fimbriae in adult periodontal disease.

Adult↗

Porphyromonas gingivalis fimbriae use beta2 integrin (CD11/CD18) on mouse peritoneal macrophages as a cellular receptor, and the CD18 beta chain plays a functional role in fimbrial signaling.

In this study, we demonstrate that Porphyromonas gingivalis fimbriae use molecules of beta2 integrin (CD11/CD18) on mouse peritoneal macrophages as cellular receptors and also show that the beta chain (CD18) may play a functional role in signalling for the fimbria-induced expression of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) genes in the cells. Using a binding assay with 125I-labeled fimbriae, we observed that fimbrial binding to the macrophages was inhibited by treatment with CD11a, CD11b, CD11c, or CD18 antibody but not by that with CD29 antibody. Western blot assays showed that the fimbriae bound to molecules of beta2 integrin (CD11/CD18) on the macrophages. Furthermore, Northern blot analyses showed that the fimbria-induced expression of IL-1beta and TNF-alpha genes in the cells was inhibited strongly by CD18 antibody treatment and slightly by CD11a, CD11b, or CD11c antibody treatment. Interestingly, intracellular adhesion molecule 1 (ICAM-1), a ligand of CD11/CD18, inhibited fimbrial binding to the cells in a dose-dependent manner. In addition, ICAM-1 clearly inhibited the fimbria-induced expression of IL-1beta and TNF-alpha genes in the cells. However, such inhibitory action was not observed with laminin treatment. These results suggest the importance of beta2 integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease.

Animals↗

Molecular mechanisms of impaired stimulation of DNA synthesis in cultured hepatocytes of aged rats.

We examined epidermal growth factor (EGF)- and epinephrine-stimulated mitogen-activated protein kinase kinase (MEK) 1 and MEK2 activities, DNA polymerase alpha activity, and EGF-stimulated E2F DNA binding activity in primary cultured hepatocytes from 6- and 24-mo-old rats. MEK stimulation by either EGF or epinephrine was not altered with aging. However, stimulation of DNA polymerase alpha activity by these agents was 70% and 50% lower, respectively, in cells of aged compared with cells of young rats, consistent with a lesser increase in [3H]thymidine incorporation. EGF-stimulated E2F (a transcription factor that regulates expression of the DNA polymerase alpha gene) binding to DNA was reduced with age. PD-098059, a specific inhibitor of MEK, inhibited EGF-stimulated MEK1 and MEK2 activities in hepatocytes from 6- and 24-mo-old rats. Although PD-098059 inhibited EGF-stimulated DNA synthesis in hepatocytes from 6-mo-old rats, it had no effect in 24-mo-old rats. Thus the age-related impairment appears to occur before E2F activation, and signal transduction sequences other than the mitogen-activated protein kinase pathway may be involved in stimulated DNA synthesis in hepatocytes from old rats.

Aging↗

Exogenous ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like factor in rats.

Ouabain has been isolated as an endogenous pathogenetic factor in salt-induced hypertension and has been shown to be rich in the adrenals. In this study, organ accumulation of orally administered [3H]ouabain was examined in rats. Exogenous [3H]ouabain was accumulated in high levels in the adrenals, especially in the zona intermedia, and was not metabolized in the rat. Accumulated [3H]ouabain mimicked the movement of "endogenous" digitalis-like factor, since 1) the plasma [3H]ouabain level decreased in bilaterally adrenalectomized rats, 2) the plasma [3H]ouabain level increased accompanied by a decrease in [3H]ouabain content in the adrenals in reduced renal mass hypertensive rats, and 3) [3H]ouabain levels in plasma and in the adrenals increased in spontaneously hypertensive rats, as compared with those in respective control animals. Moreover, the rat diet contained a relatively high amount of ouabain-like immunoreactivity (OLI), and the ratio of the [3H]ouabain content to OLI in each organ was comparable to that of the daily intake of dietary [3H]ouabain to OLI. Furthermore, high 3H-radioactivities were also observed in the adrenals of rats that ingested [3H]digoxin and [3H]digitoxin. These data suggest that exogenous ouabain, related cardiotonic glycosides of plant origin, or both accumulate in the adrenals and, at least in part, act as "endogenous" digitalis-like factor(s).

Adrenal Cortex↗

Detection of ras gene mutations in peripheral blood of carcinoma patients using CD45 immunomagnetic separation and nested mutant allele specific amplification.

We developed a sensitive technique of detecting circulating tumor cells in carcinoma patients, using CD45 immunomagnetic separation to isolate epithelial cells in blood samples and specific polymerase chain reaction analysis to identify point mutations of the K-ras gene. The method is based on the fact that the peripheral blood mononuclear cells (PBMC) that express CD45 antigen are trapped with anti-CD45 conjugated supramagnetic microbeads while the carcinoma cells that do not express CD45 antigen are not trapped and pass through the magnetic fields. This method concentrated the number of carcinoma cells 3.3 times. After this separation, the modified method of mutant allele specific amplification was applied and this method was able to ten control carcinoma cells in a background of 107 PBMC. A preliminary clinical study demonstrated that six cases of end-stage carcinoma with K-ras mutations in the primary tumor showed the same mutations in the peripheral blood samples, while two cases without K-ras mutation in the primary tumor and 10 healthy volunteers showed no mutation in the peripheral blood samples. The results suggest that this method may be very useful to detect circulating carcinoma cells in the patient whose primary tumor shows K-ras mutations.

Aged↗

Loss of heterozygosity on chromosome 18q in cohesive-type gastric cancer is associated with tumor progression and poor prognosis.

Although loss of heterozygosity (LOH) on chromosome 18q is frequently found in gastric cancer, the clinical significance of this abnormality has not been well documented. We examined LOH on chromosome 18q22-23 in DNA extracted from the tissues of gastric cancer patients using the PCR-based dinucleotide repeat assay with two microsatellite markers, D18S61 and D18S58. We investigated LOH in 100 samples of DNA extracted from formalin-fixed, paraffin-embedded tissues of cohesive-type gastric cancer patients operated on between 1984 and 1993. Thirty-two of 83 informative cases (39%) showed LOH on chromosome 18q22-23 at one or two loci. The LOH correlated significantly with serosal invasion of the tumor (P = 0.004) and hematogenous recurrence (P = 0.035). In 60 cases who were cured, the 5-year survival rate in patients with LOH (54%) was lower than that in patients without LOH (81%; P = 0.019). These results suggest that 18q22-23 LOH in cohesive gastric cancer is associated with tumor progression and a patient's poor prognosis.

Aged↗

Tumor size of colorectal cancer: indication for laparoscopic surgery.

Port site metastasis often occurs after laparoscopic colorectal resection of Dukes B and Dukes C tumors. To evaluate the feasible indication for laparoscopic surgery for the cure of colorectal cancer, we performed a clinicopathologic study with special reference to tumor size. A total of 233 patients who underwent curative resection of colorectal cancer at our department during 15 years were examined. There were 59 Dukes A tumors, and their mean size was 2.86 cm. Tumors < 2 cm, compared with tumors > 2 cm, were characterized by grossly superficial type (68% vs. 9%, p < 0.01), negative serosal invasion (95% vs. 24%, p < 0.01), and absence of lymph node metastasis (91% vs. 60%, p < 0.01). Among tumors < 3 cm, node-negative cases were distinguished by location in the colon (73% vs. 22%, p < 0.05) and by histologically well-differentiated type (75% vs. 11%, p < 0.01) in comparison with node-positive cases. All 14 patients with Dukes A tumor undergoing laparoscopic colectomy were free of recurrence during a mean follow-up period of 34 months. The results indicate that all cancers < 2 cm and well-differentiated colon cancers < 3 cm are good candidates for laparoscopic colorectal surgery for cure.

Adenocarcinoma↗

[Application of ultrafast 3D-CT in cervical spine injury].

The authors investigated the usefulness of the ultrafast three-dimensional computed tomography (UF-3D-CT) in cervical spine injury. At Osaka City General Hospital, between April 1995 and March 1998, the authors examined 38 patients with cervical spine injury using UF-3D-CT. The ultrafast CT reduces scanning time. There were no complications associated with the examination. We examined 12 patients with vertebral body fracture, 11 patients with lamina fracture, 8 cases with subluxation including locking facet, 2 patients with atlanto-axial dislocation and 8 patients without bony abnormality. Results suggested that UF-3D-CT was very useful for helping us to understand the bony deformity and the relationship between the bone and the important vessels. UF-3D-CT is very useful for preoperative evaluation and pathophysiological evaluation in cervical spin injury.

Adolescent↗