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Biomedical subjects

Koji Sasajima

Publications and source records attributed to Koji Sasajima.

18 recordsLinked to original sources

Young and middle-age associated differences in cytokeratin expression after bone fracture, tissue trauma, and hemorrhage.

BACKGROUND: This study examined whether there is any difference in the lung cytokine and cytokeratin 19 levels between young and middle-aged mice after bone fracture and soft-tissue trauma hemorrhage (Fx-TH). METHODS: Young (6-8 weeks) and middle-aged (12 months) C3H/HeN male mice were subjected to right lower leg fracture, trauma hemorrhage (mean arterial blood pressure to 35 +/- 5 mm Hg for 90 minutes), and resuscitation. RESULTS: The tumor necrosis factor alpha level in the lung increased significantly at 2 hours after Fx-TH in both young and middle-aged mice, whereas at 24 hours the levels remained significantly higher in middle-aged mice. Interleukin-6 levels increased significantly 24 hours after Fx-TH in both groups, whereas interleukin-10 levels increased only in middle-aged mice at 24 hours under those conditions. Monocyte chemoattractant protein-1 levels increased significantly 2 hours after Fx-TH. The protein and messenger RNA levels of cytokeratin 19 were significantly higher in middle-aged mice compared with young mice after Fx-TH. CONCLUSION: These results suggest that age influences the lung inflammatory response after Fx-TH.

Age Factors↗

Liver cytokine production and ICAM-1 expression following bone fracture, tissue trauma, and hemorrhage in middle-aged mice.

Although studies have indicated that hemorrhagic shock and resuscitation produces hepatic damage by mechanisms involving adhesion molecules in endothelial cells and hepatocytes, it is not known if there is any difference in the extent of hepatic damage following bone fracture, soft tissue trauma, and hemorrhage (Fx-TH) between young and middle-aged animals. To study this, young (6-8 wk) and middle-aged (approximately 12 mo) C3H/HeN male mice were subjected to a right lower leg fracture, soft tissue trauma, (i.e., midline laparotomy), and hemorrhage (blood withdrawal to decrease the blood pressure to 35 +/- 5 mmHg for 90 min) followed by resuscitation with four times the shed blood volume in the form of lactated Ringer solution. Mice were euthanized 24 h later, and liver tissues were harvested. Total bilirubin levels in the hepatocyte extract increased markedly following Fx-TH in both groups of mice; however, the increase in middle-aged mice was significantly higher compared with young mice. TNF-alpha and IL-6 levels in the hepatocyte extract following Fx-TH increased significantly in middle-aged mice but remained unchanged in young mice. IL-10 levels significantly decreased in middle-aged mice following Fx-TH but remained unchanged in young mice. Kupffer cells from middle-aged mice produced significantly higher IL-6 and IL-10 levels compared with young mice. Protein levels and mRNA expression of ICAM-1 in hepatocytes were also significantly higher in middle-aged mice compared with young mice following Fx-TH. These results collectively suggest that the extent of hepatic damage following Fx-TH is dependent on the age of the subject.

Aging↗

Quantitative detection of p53 mutations in plasma DNA from tobacco smokers.

In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke.

Baltimore↗

Boerhaave syndrome treated conservatively following early endoscopic diagnosis: a case report.

We report on a 41-year-old man with hematemesis and severe epigastric pain. Three hours after the onset of symptoms, we carefully performed upper gastrointestinal endoscopy for suspected upper gastrointestinal perforation. Endoscopy revealed a 2.5-cm-long longitudinal laceration of the lower esophagus without active gastric or duodenal ulcers. The laceration could be partially closed with endoscopic clipping. Computed tomography of the chest revealed a small amount of extraluminal air in the mediastinum. Neither pleural effusion nor pneumothorax was detected. We treated the patient conservatively on the basis of the following factors: a stable general condition without sepsis, limitation of the esophageal disruption to the mediastinum, and early diagnosis. The treatment course was uneventful, and the patient was discharged from the hospital after we had confirmed with endoscopy that the esophageal ulcer was completely healed. Although Boerhaave syndrome is generally considered to have poor prognosis, conservative therapy may be effective in select cases with early detection of the perforation.

Adult↗

[Practical procedure of totally implanted venous access system for outpatient cancer therapy].

Some outpatient cancer chemotherapy has been replacing inpatient chemotherapy. A totally implanted venous access system is now available for patients who undergo cancer chemotherapy on an outpatient basis. All eleven outpatients who underwent cancer chemotherapy with this system underwent placement of the port and administration of chemotherapy. Complications were observed in two of these eleven patients (18%). Because a subcutaneous abscess occurred in one patient between the placement of the port and her first chemotherapy session, we had to remove the port system once. Another patient developed fungemia, so we discontinued the system after 95 outpatient chemotherapy sessions. When the infection healed, we set up the system again, and no trouble was observed later in these two cases. According to the patients' survey, all patients were satisfied with outpatient chemotherapy using this system. Therefore, we concluded that this system contributes to enhanced quality of life among outpatients who undergo cancer chemotherapy.

Abscess↗

[A case of non-curatively resected colon cancer with liver and lymph node metastases treated by TS-1/CPT-11 combination therapy].

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.

Adenocarcinoma↗

A case of cardiac tamponade following esophageal resection.

We report a rare case of cardiac tamponade after esophageal resection for esophageal cancer. A 69-year-old man underwent subtotal esophagectomy and reconstruction of the gastric tube with cervical anastomosis via the poststernal route and three-field lymphadectomy via a median sternotomy. On postoperative day 4, the patient developed dyspnea, chest oppression, and hemodynamic instability due to cardiac tamponade. Emergency percutaneous catheter drainage was performed to manage the cardiac tamponade. Acute pericarditis due to the original surgical procedure was suspected to be the cause of the tamponade. Although rare, cardiac tamponade should be considered as a cause of hemodynamic instability after esophageal resection.

Aged↗

Comparative study between DNA copy number aberrations determined by quantitative microsatellite analysis and clinical outcome in patients with stomach cancer.

PURPOSE: We detected the relative DNA copy numbers (RCNs) at target loci in patients with stomach cancer with quantitative microsatellite analysis. We additionally clarified the relationship between DNA copy number aberrations and the clinical outcome of the patients. EXPERIMENTAL DESIGN: Fresh frozen samples were obtained from 30 patients who had undergone surgery for stomach cancer. Seven microsatellite loci in chromosomes 8q, 16q, and 20q and one gene-specific locus (ZNF217) were selected as the target loci. The DNA copy number was obtained relatively to a pooled reference consisting of six microsatellite primer sets selected from the regions where few aberrations have been reported in comparative genomic hybridization analysis. On the basis of the TaqMan PCR system, the internal probes used were carrying donor (6-carboxyfluorescein) and acceptor (6-carboxytetramethylrhodamine) fluorescent molecules complementary to CA repeats in the microsatellite markers and to one gene-specific oligomer in the gene-specific marker. RESULTS: Chromosome 8q gain, 20q gain, and 16q loss were detected in 18 (60.0%), 8 (26.7%), and 13 (43.3%) cases, respectively. Gains in the RCNs of D8S1801 and D8S1724 were most frequently found (36.7%). There was a significant correlation between the loss of D16S3026 and reduced survival duration (P = 0.0158), and the simultaneous aberrations of D8S1801 gain and D16S3026 loss (double marker positive) was significantly associated with reduced survival duration (P = 0.0008). According to Cox proportional hazards model, the double marker positive was a significant and independent factor indicating an unfavorable prognostic factor (relative risk, 17.176; 95% confidence interval, 2.782-106.026; P = 0.0022). CONCLUSION: RCN aberrations in tumor tissues determined by quantitative microsatellite analysis enable identification of the prognostic factors that correlate with clinical outcome of the patients with stomach cancer.

Aged↗

Preoperative administration of methylprednisolone attenuates cytokine-induced respiratory failure after esophageal resection.

Proinflammatory cytokines have been implicated in mediating respiratory failure associated with major surgery. We investigated the effect of giving glucocorticoids preoperatively for the prophylaxis of surgical stress and the association of cytokine levels, such as interleukin-6 (IL-6) and interleukin-8 (IL-8), with oxygenation after esophagectomy. We studied 17 patients who underwent subtotal esophagectomy. Seven patients (steroid group) were chosen at random to be given methylprednisolone (10 mg/kg) and 10 patients (control group) to be given saline intravenously before operation. Plasma and bronchoalveolar lavage fluid (BALF) IL-8 levels in the control group were significantly higher than those in the steroid group. In both groups, plasma IL-6 levels were significantly higher than those in BALF, but in contrast, BALF IL-8 levels were significantly higher than plasma levels of IL-8 postoperatively. The PaO(2)/FiO(2) ratio was significantly reduced in the control group. The PaO(2)/FiO(2) ratio of the control group had significantly lower values than that of the steroid group. There was significant correlation between BALF IL-8 levels and the PaO(2)/FiO(2) ratio postoperatively. We conclude that preoperative administration of methylprednisolone may attenuate postoperative reduction of arterial oxygen saturation by suppressing the release of cytokines.

Aged↗

Biological behavior of mucoepidermoid carcinoma of the esophagus.

Mucoepidermoid carcinoma of the esophagus (MEC) is uncommon and has not been fully investigated. The biological behavior and clinical aspects of MEC were studied. The clinical features of eight patients with MEC were compared with 51 cases of squamous cell carcinoma of the esophagus (SCC). Proliferating cell nuclear antigen (PCNA), p53, and carcinoembryonic antigen (CEA) were stained in the resected specimens by immunohistochemistry. Seven out of 8 cases (87.5%) had stage III by TNM classification. Four cases died of widespread metastases and 2 cases died of local recurrence within 2 years after the surgery. Neither chemotherapy and radiotherapy were effective against MEC. Overall median survival periods were 10.8 months for MEC and 32.1 months for SCC (P<0.05). When patients in stage III alone were compared, MEC tended to have a worse prognosis than SCC (P=0.058). Immunohistochemical studies revealed that the positive rates of PCNA and CEA were significantly higher in MEC than in SCC (P<0.05), while there was no significant difference in p53 positive rate. Esophageal MEC had an aggressive biological nature and was resistant to adjuvant therapies. The poor prognosis of esophageal MEC may be caused by high proliferative and metastatic potential.

Aged↗

[Effect of nedaplatin, 5-FU, and leucovorin combined with radiation therapy in unresectable esophageal carcinoma].

A 51-year-old male was assessed as having esophageal squamous cell carcinoma with trachea invasion and cervical lymph node metastasis. After one course of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU) and Leucovorin (LV), the patient had progressive disease (PD) of the primary lesion and metastatic lymph nodes, and a side effect of severe nausea. One course of nedaplatin, 5-FU and LV combined with radiation was performed alternatively. The effect was evaluated as a partial response (PR) of the primary lesion and metastatic lymph nodes. There were no adverse side effects such as nausea or renal dysfunction except for pancytopenia of grade 2. Increased serum levels of vascular endothelial growth factor (s-VEGF) decreased after the chemoradiotherapy and increased again during continued radiotherapy alone. More information is needed as to whether changes in s-VEGF relate to the clinical effects of the treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Role of L-selectin in the development of ventilator-associated pneumonia in patients after major surgery.

BACKGROUND: The circulating level of soluble L-selectin (sL-selectin) has been reported to be low in adult respiratory distress syndrome and acute lung injury. This study explores the role of L-selectin in the development of ventilator-associated pneumonia (VAP) in patients undergoing major surgery. PATIENTS AND METHODS: Thirty-four patients who underwent esophagectomy were maintained by mechanical ventilation in a surgical intensive care unit. Fourteen patients developed VAP by postoperative day (POD) 7, while 20 patients did not. The plasma levels of soluble adhesion molecules and elastase were measured serially by ELISA or EIA. The expression of L-selectin on polymorphonuclear neutrophils (PMNs) was analyzed by flow cytometry. RESULTS: In multiple logistic regression analysis, only the preoperative plasma level of sL-selectin was significantly associated with VAP. The plasma sL-selectin level before surgery was significantly lower in the patients who developed VAP compared with the patients who did not develop VAP. After surgery, the level of sL-selectin did not change. The plasma level of soluble intercellular adhesion molecule-1 increased in the patients with and without VAP. The plasma level of soluble vascular cell adhesion molecule-1 was significantly higher in the patients with VAP. L-selectin expression on PMNs showed a peak on POD 2 in the patients without VAP, whereas it was impaired in the patients with VAP. CONCLUSIONS: Determination of the preoperative plasma level of sL-selectin may help to identify patients at high risk for VAP after esophagectomy.

Cell Adhesion Molecules↗

Comparative analysis of telomere lengths and erosion with age in human epidermis and lingual epithelium.

We investigated progressive telomere shortening in normal human epidermis and lingual epithelium during aging, and attempted, in particular, to ascertain whether the telomere shortening that accompanies aging occurs at the same rate in different tissues. We studied telomeric DNA integrity, and estimated annual telomere loss, in 52 specimens of epidermis and 48 specimens of lingual epithelium collected at autopsy from subjects who had died at ages between 0 and 101 y. Most of the DNA samples were measured twice by southern blot hybridization. In addition, the correlation between telomere lengths in the two types of tissues was examined. The telomere reduction rates in epidermis and lingual epithelium were 36 bp and 30 bp per y, respectively, and these were significantly different. The rates obtained by the second measurements in epidermis and lingual epithelium were 39 and 32 bp per y, respectively, and these were also significantly different. The mean telomere lengths in the epidermis of eight neonates and the lingual epithelium of seven neonates were 13.2+/-1.0 and 13.8+/-1.0 kb, respectively. Comparison of telomere lengths in the two tissues for 41 paired samples showed that the mean telomere length in the epidermis (10.7+/-2.3 kb) was less than that in the lingual epithelium (12.4+/-2.5 kb); however, statistical analysis revealed a very significant relationship between epidermal and lingual epithelial telomere length (r=0.842, p<0.0001). These results indicate that the telomeres in epidermis and lingual epithelium are characterized by tissue-specific loss rates.

Adolescent↗

Oncocytic adenocarcinoma of the stomach: parietal cell carcinoma.

We report 10 cases of an unusual type of gastric adenocarcinoma that occurred in elderly patients 58-81 years of age. Histologically, the tumors were well to moderately differentiated tubular adenocarcinomas with very eosinophilic, finely granular cytoplasm. Immunohistochemical stains for antimitochondrial antibody were strongly positive. Ultrastructurally, the tumor cells had numerous mitochondria in their cytoplasm and occasional intracytoplasmic lumina with associated long microvilli. These histologic and ultrastructural features are similar to those of parietal cells in normal gastric fundic mucosa, but immunohistochemical staining of the tumors using four different antiparietal cell antibodies (anti-H(+)-K(+)-adenosine triphosphatase antibodies) was negative in all cases. Therefore, we think that these tumors were not parietal cell carcinomas but could be termed oncocytic adenocarcinomas, or adenocarcinomas with oncocytic differentiation. Previously reported cases of parietal cell carcinoma have been said to have a favorable prognosis, but it will be necessary to study a larger number of cases to determine the prognosis of oncocytic adenocarcinoma.

Adenocarcinoma↗

Serum levels of vascular endothelial growth factor, basic fibroblast growth factor and endostatin in human metastatic liver tumors.

BACKGROUND/AIMS: Angiogenic factors are related to the malignant potential of tumors. This study aimed to investigate the relationship of serum angiogenic factors to liver metastasis. METHODOLOGY: The serum levels of vascular endothelial growth factor, basic fibroblast growth factor and endostatin were measured using EIA in 25 patients with metastatic liver tumors and were compared with those of 12 cancer patients without metastasis and 15 controls. RESULTS: The serum vascular endothelial growth factor concentration was significantly higher in the liver metastasis group (503 +/- 84 pg/mL) than in the no metastasis group (205 +/- 38 pg/mL) and the control group (201 +/- 26 pg/mL). The three groups had similar serum basic fibroblast growth factor concentrations. There was no significant difference in serum levels of endostatin among the liver metastasis group (18.8 +/- 1.5 ng/mL), the no metastasis group (23.9 +/- 4.9 ng/mL), and the control group (17.1 +/- 1.5 ng/mL). CONCLUSIONS: Angiogenic response is more prominent than anti-angiogenic responses in liver metastasis. These findings support the rationale for anti-angiogenesis therapy such as endostatin therapy in patients with liver metastasis.

Collagen↗

Detection of lymph node micrometastasis in esophageal carcinoma.

BACKGROUND/AIMS: The presence of lymph node metastasis is the most important prognostic factor in esophageal squamous cell carcinoma. Molecular biology techniques have improved the ability to recognize micrometastasis in lymph nodes, bone marrow, and peripheral blood. Previous studies have demonstrated that cytokeratin 19 reverse transcriptasepolymerase chain reaction can detect tumor cells even when lymph nodes appear normal histologically. However, the presence of pseudogenes for cytokeratin 19 have reduced the specificity of reverse transcriptase-polymerase chain reaction, thereby reducing its clinical worth as a sensitive diagnostic technique. METHODOLOGY: We examined the expression of mRNA for cytokeratin 19 using a newly designed set of primers, and compared the results with data from histologic examinations. Samples were obtained from tumors, intact tissues, resected lymph nodes and in 10 patients who underwent esophagectomy via right thoracotomy with lymph node dissection in the neck, mediastinum and abdomen. RESULTS: All tumors, non-cancerous tissues were positive for cytokeratin 19 by reverse transcriptasepolymerase chain reaction. However, 2 of the 6 lymph nodes that appeared normal on histologic examination were positive for cytokeratin 19; sensitivity and specificity were 100% and 67%, respectively. CONCLUSIONS: Reverse transcriptase-polymerase chain reaction using new primers for cytokeratin 19 detected micrometastasis in specimens of lymph nodes from patients with squamous cell carcinoma. This method may increase the accuracy of tumor staging and provide clinicians with valuable information that will help individualize treatment options.

Esophageal Neoplasms↗