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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 145 records · Page 8Linked to original sources

Role of the liver in T cell differentiation--generation of CD3-CD4+/CD8+TCRbeta- cells and CD3-4-8-TCRbeta+ cells from CD4-8-TCRbeta- athymic nude bone marrow cells by culture with parenchymal liver cells.

To investigate the influence of the liver on differentiation of hematopoietic stem cells/pro-T cells, TN-NWP-BMC (athymic nude bone marrow cells that were treated with anti-TCRbeta, anti-CD4, and anti-CD8 Abs plus complement and then passed through a nylon wool column) were cultured on parenchymal liver cells. After culture for 2.5 days, CD3-4-8-TCRbeta+ cells and CD3-CD4+/CD8+TCRbeta- cells were developed from TN-NWP-BMC. TCRVbeta8+ cells comprised 19.9% of CD3-4-8-TCRbeta+ cells, and Vbeta8 mRNA was detected in the CD3-4-8-TCRbeta+ cells by reverse transcriptase-polymerase chain reaction. The CD3-CD4+/CD8+TCRbeta- cells contained not only single-positive cells but also CD4+8+ double-positive cells. The CD8 protein consisted of 88.9% CD8alpha+beta-, 10.1% CD8alpha+beta+, and 1% CD8alpha-beta+ molecules. From these results and the finding of co-expressed antigens, CD3-4-8-TCRbeta+ cells and CD3-CD4+/CD8+TCRbeta- cells appear to be immature cells not committed to a certain cell lineage.

Animals↗

Preoperative evaluation of the chemosensitivity of breast cancer by means of double phase 99mTc-MIBI scintimammography.

The chemosensitivity of breast cancer is important for its management, but it is difficult to evaluate preoperatively. Tc-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintimammography has been reported to indicate the expression of P-glycoprotein, which is one factor concerned with multidrug resistance. We developed a chemosensitivity assay by using surgical specimens to investigate whether 99mTc-MIBI scintimammography findings before the operation are related to chemosensitivity according to our assay. Fifteen patients with primary breast cancer were enrolled into the study. Early and delayed images were obtained at 10 and 120 minutes after intravenous injection of 99mTc-MIBI, respectively. Regions of interest were placed on the tumors and the contralateral healthy breasts in each patient to estimate 99mTc-MIBI uptake in the tumor, and retention indices were then calculated to assess the washout of 99mTc-MIBI. Chemosensitivity assay was performed by incubating surgical specimens with anticancer agents such as doxorubicin, epirubicin, pinorubicin, mitomycin C, cisplatin and 5-fluorouracil. 99mTc-MIBI washout on scintimammography was successfully related to inhibition ratios on chemosensitivity tests when compared with 99mTc-MIBI uptake by the tumor. In particular, high correlation coefficients were obtained between the retention index of 99mTc-MIBI and the inhibition ratios of doxorubicin (r = 0.75), epirubicin (r = 0.60) and pinorubicin (r = 0.62), but poor correlation was found for mitomycin C (r = 0.44) and cisplatin (r = 0.31). Our results indicate that the retention index of 99mTc-MIBI is closely correlated to chemosensitivity to anthracyclines, suggesting that double-phase scintimammography allows preoperative prediction of chemosensitivity of breast cancer.

Adult↗

MRI in occipital lobe infarcts: classification by involvement of the striate cortex.

We reviewed the MRI studies of 25 patients with occipital lobe infarcts to clarify the distribution of infarcts in the posterior cerebral arterial territory, focussing on their relationship to the striate cortex. Visual field defects and MRI findings were also correlated in 16 patients. On coronal and/or sagittal images, the distribution of the infarct and its relationship to the striate cortex were classified. Involvement of the cortex of both upper and lower lips of the calcarine fissure was observed in 10 patients, and involvement of the lower lip alone in 15. The upper cortical lesions were always accompanied by lower cortical lesions. The visual field defects were complete hemianopia in nine patients, superior quadrantanopia in six and hemianopia with a preserved temporal crescent in one. All patients with superior quadrantanopia had involvement of the lower cortex alone; there were no cases of inferior quadrantanopia. The characteristic vascular anatomy, and poor development of the collateral circulation in the lower cortical area, may explain the vulnerability of this area to infarcts.

Adult↗

A new approach to dynamic graciloplasty.

The reestablishment of anal function by transposition of the gracilis muscle, combined with the implantation of electrodes and a neuromuscular stimulator (dynamic graciloplasty), has recently been developed. With this method, the transposed muscle maintains contraction by electrical stimulation to maintain neoanal pressure without fatigue. It is necessary to convert the fatigue-prone gracilis muscle to fatigue-resistant muscle by long-term electrical stimulation (conditioning). In most patients receiving dynamic graciloplasty, the conditioning is accomplished after the transposition. However, conditioning before graciloplasty should reduce the risk of ischemia in the transposed muscle after the graciloplasty and improve the outcome. This new sequence of procedures is described, in combination with J-pouch construction, in a patient who required abdominoperineal excision of the rectum for lower rectal cancer. The graciloplasty was performed after conditioning of the gracilis muscle in situ; the conditioning did not cause the patient discomfort and resulted in good anal function.

Adenocarcinoma↗

Subtotal duodenectomy with jejunal patch for megaduodenum secondary to congenital duodenal malformation.

BACKGROUND/PURPOSE: This report describes a technique devised for two children with megaduodenum consisting of subtotal duodenal resection with the proximal jejunum used as an onlay patch. METHODS: A 2-year-old boy presented after unsuccessful surgical repairs for duodenal stenosis with web. Another 8-year-old boy returned from the United States after several surgical procedures for complicated congenital left diaphragmatic hernia with gastric outlet obstruction. Both boys manifested postprandial right upper abdominal fullness, occasional vomiting, abdominal pain, and failure to thrive. Upper gastrointestinal contrast study findings showed massively dilated duodenums in both patients that were larger than the stomach. During the operative procedures, about 95% of the duodenal wall was resected, leaving the basal portion that was unified with the pancreatic head and the ampulla of Vater as linguiform flap, which was covered with the proximal jejunum as an onlay patch so as to form the anterior wall of the duodenal bulb. RESULTS: The patients showed markedly improved quality of life and catch-up growth after the operations. The duodenal bulbs were of adequate size in follow-up gastrointestinal series. CONCLUSION: This technique will be useful in cases of functional duodenal obstruction with megaduodenum secondary to congenital duodenal malformations leading to blind loop syndrome.

Child↗

Extra-anal mucosectomy: laparascopic-assisted endorectal pull-through using a prolapsing technique.

BACKGROUND/PURPOSE: The mucosectomy of the aganglionic rectal mucosa has been performed transabdominally in the Soave procedure. Recently, mucosectomy with transanal approach was reported both in the laparoscopic and the open surgical procedure. However, the operative view and working field are restricted because the dissection has to be done in the anal canal. The authors report an innovative approach, an extra-anal mucosectomy, to perform mucosectomy in the Soave procedure for Hirschspung's disease in combination with the laparoscopic-assisted prolapsing technique. METHODS: Four patients underwent laparoscopic surgery for Hirschsprung's disease with extra-anal mucosectomy between 1995 and 1997. One 10-mm and 5-mm ports were used throughout the operation. The rectum was pulled out through the anal canal to create a rectal prolapse and was divided outside the anal canal. The mucosectomy was performed in the everted rectal mucosa outside the anal canal to the level of dentate line. The colon was sutured to the anal mucosa 2 mm above the dentate line. Mean operative time was 3 hours. RESULTS: The present technique made the whole mucosectomy possible under direct observation. CONCLUSION: The extra-anal mucosectomy in conjunction with a laparoscopic-assisted prolapsing technique seems to be a safe and reliable modality in the surgical treatment of Hirschsprung's disease.

Anal Canal↗

Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. BMS-181339 Breast Cancer Study Group.

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.

Adult↗

Lymph node metastasis of early gastric cancer with submucosal invasion.

BACKGROUND: A clinicopathological study of early gastric cancer with submucosal invasion was carried out in relation to lymph node metastasis. METHODS: A retrospective study was conducted of 245 patients with submucosal gastric cancer treated by gastrectomy combined with D2 lymph node resection between 1985 and 1994 in a university hospital. RESULTS: Lymph node metastasis was observed in 34 patients (14 per cent). The mortality rate due to recurrence in patients with lymph node metastasis (three of 34) was significantly higher than in those without lymph node metastasis (five (2 per cent) of 211) (chi2 = 3.95, 1 d.f., P < 0.05). Tumour size, depth of invasion, lymphatic involvement of cancer cells and preoperative diagnosis of advanced cancer correlated significantly with the presence of lymph node metastasis. When the submucosal carcinomas were classified into three categories according to depth of invasion by dividing the submucosal (sm) layer into three equal parts, sm1, sm2 and sm3, the incidence of lymph node metastasis increased from 2 per cent to 12 and 20 per cent respectively. CONCLUSION: When the pathological report reveals sm1 invasion after laparoscopic or endoscopic surgery, reoperation should not be necessary because sm1-carcinomas with diameters of less than 2 cm do not usually metastasize to the lymph nodes.

Adult↗

Pathophysiological response of cytokines and vasoactive agents in patients undergoing total gastrectomy.

OBJECTIVE: To investigate the involvement of vasoactive agents, endothelin (ET)-1, and atrial natriuretic peptide (ANP), and the responses of cytokines in patients undergoing total gastrectomy. DESIGN: Prospective study. SETTING: University hospital, Japan. SUBJECTS: 20 patients with advanced gastric cancer who had undergone total gastrectomy with lymph node dissection. INTERVENTIONS: Serum or plasma samples collected on the day before the operation, at the time of skin closure, and on postoperative days 1, 3, 5, and 7. MAIN OUTCOME MEASURES: Concentrations of acute phase reactants, cytokines (interleukin (IL)-1, tumour necrosis factor (TNF) and interleukin (IL)-6), and vasoactive agents (ET-1 and ANP). RESULTS: There were significant increases in concentrations of IL-6 and acute phase reactants postoperatively. ET-1 and ANP concentrations did not change significantly. CONCLUSION: There was no correlation between concentrations of the vasoactive agents ET-1 and ANP, and those of acute phase reactants or cytokines in serum or plasma in patients undergoing total gastrectomy.

Acute-Phase Proteins↗

Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas.

The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a gene encoding human epidermal growth factor (hEGF). The hybrid human protein was isolated from Escherichia coli inclusion bodies, refolded and purified to homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF receptors (EGFR) and had ribonucleolytic activities approaching those of hpRNase1. Several conformations having different enzymatic activities could be detected after reversed-phase high-performance liquid chromatographic analysis, the less hydrophobic molecules being the most active. The hybrid protein was specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1 had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR-deficient control cells. Taken together, these data suggest that this construct might be useful for targeted therapy of esophageal, lung and other squamous cell carcinomas and also breast cancers overexpressing EGFR, which correlate with a poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules with endogenous human proteins for targeted therapy may alleviate the dose-limiting immunogenicity and toxicity of conventional immunotoxins.

Binding, Competitive↗

An early phase II study of a 3-hour infusion of paclitaxel for advanced gastric cancer.

The purpose of this study was to evaluate the feasibility and efficacy of 3-hour infusional paclitaxel for the treatment of advanced gastric cancer with measurable metastatic diseases. Eligibility criteria included no more than one regimen of prior chemotherapy. Paclitaxel was administered as an intravenous infusion over 3 hours at a dose of 210 mg/m2 every 3 weeks. Premedication of dexamethazone, ranitidine, and diphenhydramine were given to all patients. Sixteen patients were registered in the study. One patient did not receive paclitaxel because of gastrointestinal bleeding before the initiation of drug's administration. Thirteen of the 15 patients had a prior history of chemotherapy. Although 10 patients (67%) developed grade 4 neutropenia, no serious infections occurred during the study. Nonhematologic toxicities were generally mild. Three (20%) patients who showed evidences of resistance to the previous intensive regimen achieved a partial response. In conclusion, a 3-hour infusion of paclitaxel is a safe and promising treatment for advanced gastric cancer. Paclitaxel appears to be non-cross resistant to other agents that are commonly used for gastric cancer. A large-scale phase II study is now underway.

Adult↗

Case report: Metachronous early gastric carcinoma in a reconstructed gastric tube after radical operation for oesophageal carcinoma.

The incidence of double cancer has increased as a result of the significant advances in both diagnostic procedures and anti-cancer therapy, and as the outcome of oesophageal squamous cell carcinoma (ESCC) has improved, the number of cases of double cancer of the oesophagus and stomach has also increased. Two patients with metachronous early gastric carcinoma in a reconstructed gastric tube were successfully treated after subtotal oesophagectomy for ESCC. These cases have shown that early diagnosis of second cancer is very important for curative therapy.

Adenocarcinoma↗

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats.

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.

Animals↗

[Laparoscopic surgery for early gastric cancer--its advantages and pitfalls].

We have successfully established two different laparoscopic procedures for early gastric cancer since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method and laparoscopic intragastric mucosal resection. The indication is as follows; (A) mucosal cancer, (B) < 25 mm, if the lesion is elevated type, (C) < 15 mm and Ul (-), if the lesion is depressive type. The advantages of these methods are; 1) minimally invasiveness, 2) sufficient surgical margin, 3) feasibility of detailed histology, 4) feasivility of perigastric lymph node dissection. In contrast, there are several problems to be solved, which are; 1) preoperative diagnostic accuracy of the depth of cancer invasion, 2) possibility of reoperation because of sm invasion or lymphatic or venous invasion in final histology, 3) possibility of postoperative stenosis after laparoscopic intragastric mucosal resection for the lesion near the cardia, 4) incidence of metachronous multiple gastric cancer. In conclusion, if the indication is properly selected, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.

Gastric Mucosa↗

[Telomerase assay for diagnosis of esophageal cancer].

Esophageal squamous cell carcinoma is one of the aggressive diseases that has poor outcome. Therefore it is appeared that early diagnosis is very important for improving its outcome. Iodine staining method is useful for detecting the abnormal squamous epithelium and unstaining lesions by iodine contain the early esophageal cancers. Recently, telomerase activity that provides an immortal capacity for the cells has been measured in many tissues. We measured the telomerase activity in the samples of unstaining lesion by iodine using a polymerase chain reaction-based assay and described the relation between telomerase activity and histopathological findings.

Biomarkers, Tumor↗

[Recent progress of matrix metalloproteinase (MMP) research and its clinical application for cancer therapy].

The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound zinc-endopeptidases. These enzymes are capable of degrading the extracellular matrix, including collagens, laminin, proteoglycan and fibronectin. In some human cancers, a positive correlation has been demonstrated between MMP expression and the likelihood of developing metastasis. An imbalance between MMPs and the tissues inhibitor of metalloproteinases (TIMPs) may play a significant role in the invasive phenotype of cancers. Although TIMPs have been shown to inhibit tumor metastasis in some in vivo models, they are not suitable for pharmacologic applications due to their short half-life in vivo and large molecular size. In this paper, recent advances in MMP research and reports of clinical applications of synthetic MMP inhibitors for cancer patients are reviewed.

Humans↗