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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 325 records · Page 18Linked to original sources
PubMed1994

Effect of acute lung injury and coexisting disorders on plasma concentrations of atrial natriuretic peptide.

OBJECTIVE: To clarify how plasma atrial natriuretic peptide concentrations vary with the severity of acute lung injury. The influence of coexisting diseases which trigger acute lung injury was also examined. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Fifty patients who had standard risk factors for acute lung injury including sepsis syndrome, major surgery, prolonged hypotension, aspiration of gastric contents, and burns. Twenty-five of these patients had acute lung injury (group 3) caused by these disorders; the remaining 25 patients had risk factors only (group 2). Ten age-matched normal volunteers were selected as controls (group 1). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Plasma atrial natriuretic peptide concentration was measured in these patients and compared with the severity of acute lung injury. In group 3, a significant increase in the mean plasma atrial natriuretic peptide concentration was observed (188 +/- 78 pg/mL, p < .01) compared with group 2 (54 +/- 28 pg/mL) and the age-matched control group (30 +/- 8 pg/mL). This increase was related to the onset of acute lung injury and returned to control concentrations after recovery. Plasma atrial natriuretic peptide concentrations in group 3 correlated highly with a lung injury score representing the severity of acute lung injury (r2 = .45, p < .01), but did not correlate with other cardiopulmonary variables. CONCLUSION: The results suggest that severity of lung injury, but not other predisposing disorders, may be the key factor leading to the increase in plasma atrial natriuretic peptide concentrations observed in these patients.

Analysis of Variance↗
PubMed1994

[A case report of left limb compartment syndrome associated with laparoscopic surgery].

A 63-year-old male patient with early gastric cancer was attempted for laparoscopic wedge resection of the stomach. After the introduction of anesthesia, bandage of bilateral leg was carried out to prevent deep venous thrombosis during laparoscopic surgery. Although the procedure was converted to open surgery, the bandage has been continued throughout the surgery for 6 hours. After the operation, the swelling and severe tenderness at his left leg was observed. MRI revealed remarkable edema in left deep posterior compartment. Under diagnosis of left limb compartment syndrome, fasciotomy was carried out. Postoperatively the patient did well without any functional disturbance.

Bandages↗
PubMed1994

Reconstruction of anal function by transposed gracilis muscle with electrical stimulation: rabbit model.

For the reconstruction of anal function for fecally incontinent patients, it could be practicable to transpose the gracilis muscle around the anal canal, with electrical stimulation to maintain contraction. It is necessary to keep continuous tonus, so tetanic contraction or "summation" would be essential for fecal continence, with a stimulation which permits prolonged contraction. Transposition of the gracilis muscle around the rectum was performed in thirteen Japanese white male rabbits. The muscles of the conditioning group (n = 8) were stimulated at 10 Hz for 6 weeks before the procedure. By stimulation at 15 Hz, a low frequency to permit prolonged contraction, the neoanal pressure increased maximally to 134.2 +/- 55.6 cmH2O (mean +/- s.d.) in the conditioning group, and to 115.0 +/- 37.1 cmH2O in the non-conditioning group (n = 5) (N.S.). But, the basal pressure with stimulation rose 82.3 +/- 12.4% (mean +/- s.d.) of the increase in the conditioning group, while that of the non-conditioning group remained at resting pressure (p < 0.001). The conditioning made it possible for the rabbit's gracilis muscle to create anal pressure with a sufficient rise in the basal pressure at a frequency permitting prolonged contraction.

Anal Canal↗
PubMed1994

Pathophysiologic role of endothelin-1 in renal function in rats with endotoxin shock.

BACKGROUND: We hypothesized that endothelin-1 (ET-1) is an important mediator in renal dysfunction under septic conditions. This study clarified the pathophysiologic role of ET-1 in renal function under conditions of surgical stress, especially sepsis. METHODS: We investigated the correlation between ET-1 levels and renal function and the effect of anti-ET-1 antibody (AwET-1N40) on renal function in a septic shock rat model. RESULTS: The plasma ET-1 level increased significantly at 30 minutes and remained significantly elevated for 24 hours, reaching a peak (195 +/- 24.4 pg/ml) 3 hours after the endotoxin (lipopolysaccharide derived from Escherichia coli) injection. Increases in plasma creatinine concentration and blood urea nitrogen (BUN) level and decreases in urine volume and urinary sodium excretion were also observed in the early phase after endotoxin injection. The plasma creatinine concentration and the plasma ET-1 level increased significantly at 30 minutes, reached a peak at 3 hours, and then decreased. Anti-ET-1 antibody administration (5 nmol/kg body, four times intravenously) decreased plasma creatinine concentration and BUN level and increased urine volume and urinary sodium excretion 3 hours after endotoxin injection (creatinine, p = 0.07; BUN, p < 0.05; urine volume, p < 0.01; urinary sodium excretion, p < 0.01; anti-ET-1 vs shams). CONCLUSIONS: These results suggest that the increase in endogenous ET-1 induced by sepsis plays an important role in renal dysfunction in the septic state.

Animals↗
PubMed1994

[Thoracoscopic surgery for benign esophageal disease].

Two patients with benign esophageal disease were successfully treated by thoracoscopic surgery. First case was a 66 year old male with esophageal diverticulum, who had complained of progressive dysphasia. The esophagogram showed a giant epiphrenic diverticulum which was 8 cm in diameter. Entire procedure was performed thoracoscopically under general anesthesia, while left side univentilation was applied. A flexible videoelectronic thoracoscope was introduced into thoracic cavity at the 5th intercostal space, and 4 additional trocars were inserted. The pleura over the diverticulum was divided, and the diverticulum was fully dissected and exposed. A multifire endoscopic stapler, an Endo GIA, was applied to resect the diverticulum. For security, uninterrupted suture of muscular layer of the esophagus over the stapled line was performed. Second case was a 60 year old male with esophagobronchial fistura, who had complained of choking during liquid intake for 20 years. The bronchogram showed a communication between a esophageal diverticulum and a right B6 bronchus. The operation was performed thoracoscopically. A thoracoscope was introduced as mentioned above, and the esophagus and the peripheral lung around the fistura was dissected and fully exposed. The diverticulum was divided at its base using an Endo GIA, and the fistura was resected with lung parenchyma using also an Endo GIA. The postoperative courses of the both patients were uneventful. The patients started diet on the 4th and the second postoperative day respectively, and the symptoms had disappeared after surgery.

Aged↗
PubMed1993

A novel "patient-like" treatment model of human pancreatic cancer constructed using orthotopic transplantation of histologically intact human tumor tissue in nude mice.

Pancreatic cancer is a disease with essentially no effective treatment. To increase the potential for discovering effective treatment, we have developed a new treatment model whereby a human pancreatic cancer line, PANC-4, was orthotopically transplanted to the pancreas of nude mice as histologically intact tumor tissue. The tumor grew with subsequent invasive local tumor growth and liver and peritoneal metastases. The antitumor activity of 5-fluorouracil (5-FU) and mitomycin C (MMC) against PANC-4 was initially determined in the in vitro collagen-sponge-gel supported histoculture drug-response assay with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide end point. Inhibition rates were 5.6% for 5-FU and 39.4% for MMC indicating higher efficacy of MMC than 5-FU against PANC-4. When the antitumor activities of 5-FU and MMC against PANC-4 were determined in vivo using the nude mouse orthotopic transplant treatment model, slight local tumor growth inhibition with equivalent incidence of metastases to the liver and the peritoneum as the control were observed in the mice treated with 5-FU, while those treated with MMC had considerably reduced local tumor growth without liver and peritoneal metastases. Thus the histoculture drug-response assay in combination with the orthotopic transplant metastatic models provides for the first time a paradigm for evaluation of agents which may be effective against not only locally growing human pancreatic cancer but resulting metastases as well.

Animals↗
PubMed1993

Molecular cloning and initial characterization of a novel fibrinogen-related gene, HFREP-1.

We have isolated HFREP-1, a gene that is overexpressed in a hepatocellular carcinoma from a lambda gt10 cDNA library constructed from the mRNA of the hepatocellular carcinoma specimen using subtractive and differential cDNA cloning. The largest cDNA insert contained 1231 base pairs encoding 312 amino acids. The deduced protein sequence contained a hydrophobic leader peptide and the putative protein sequence showed marked homology with beta- and gamma-subunits of fibrinogen and other fibrinogen-related proteins. However, the HFREP-1 protein lacked a platelet-binding site, a cross-linking region and a thrombin-sensitive site, which are crucial for fibrin clot formation. The expression of the gene was studied in various organs in the rat and in several human carcinoma cell lines, and was found to be specific to liver and hepatocellular carcinoma cell lines. We suggest that the HFREP-1 gene is a new member of the fibrinogen family and that further data on the gene are important for a better understanding of the development of hepatocellular carcinomas.

Amino Acid Sequence↗
PubMed1993

Thymosin beta-4 expression is correlated with metastatic capacity of colorectal carcinomas.

We constructed a "non-metastatic cell (SW837)--metastatic cell (PMCO1)" subtraction library and identified one cDNA that was strongly expressed in SW837 but weakly expressed in PMCO1. The nucleotide sequence of the cDNA revealed that it encoded thymosin beta-4. Four non-metastatic cell lines, which produced no experimental liver metastasis in nude mice, showed high expression of thymosin beta-4. However three of four metastatic cell lines showed weak expression of thymosin beta-4. Among surgical materials, thymosin beta-4 expression was high in tumors without metastasis in comparison with non-tumorous mucosa, but one case with liver metastasis showed decreased expression in both the primary and metastatic tumors. We suspect that down-regulation of thymosin beta-4 expression is correlated with the metastatic capacity of colorectal carcinomas.

Animals↗
PubMed1993

Differential chemosensitivity of local and metastatic human gastric cancer after orthotopic transplantation of histologically intact tumor tissue in nude mice.

We have established a metastatic model of human gastric cancer using orthotopic transplantation of histologically intact tissue in nude mice, and have used this model to evaluate the effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) against SC-I-NU, a human stomach cancer line. One-quarter or one-half maximum tolerated doses (MTDs) of 5-FU or MMC resulted in a significant reduction of stomach tumor growth, while liver metastases were not reduced, possibly due to suppression of natural killer (NK)-cell activity by both drugs. On the other hand, when combined with OK-432, half MTDs of 5-FU and MMC significantly reduced liver metastases, with synergistic reduction of stomach tumor growth, possibly reflecting a rescue of NK-cell activity by treatment with OK-432. This metastatic model of human stomach cancer shows that locally growing and metastatic tumors may have different chemosensitivities, and provides the opportunity to test both with various treatment regimens.

Adenocarcinoma↗
PubMed1993

Ad4BP regulating steroidogenic P-450 gene is a member of steroid hormone receptor superfamily.

Bovine cytochrome P-450(11 beta) gene (CYP11B) has six different cis-acting elements, Ad1, Ad2, Ad3, Ad4, Ad5, and Ad6, in the promoter region. The Ad4 site also exists in the promoter regions of other steroidogenic P-450 genes as well as in CYP11B1. An Ad4-binding protein (Ad4BP) which specifically binds to the Ad4 site was purified from bovine adrenal cortex nuclear extract, and its molecular mass was 53 kDa. A complementary DNA encoding Ad4BP was isolated from a bovine adrenal cortex cDNA library. The cDNA clone contained an open reading frame of 1383 base pairs encoding 461 amino acids, whose calculated molecular weight was 51,020. The predicted amino acid sequence of Ad4BP revealed that the protein has a zinc finger domain and a ligand binding/dimerization domain. Ad4BP is a novel member of the steroid hormone receptor superfamily. Comparison of the primary structures of the hormone receptor superfamily showed that Ad4BP was highly homologous to FTZ-F1, which regulates the fushi tarazu gene, and ELP, which is expressed in the murine embryonal carcinoma cells. Transfection of a Ad4BP expression plasmid into CV-1 cells activated the transcription of the CAT reporter gene carrying the Ad4 sequence in the promoter region.

Amino Acid Sequence↗
PubMed1993

Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue.

Nude mice have been used to develop s.c. growing human stomach tumors, but these rarely metastasize. Recently, I. J. Fidler and others have developed orthotopic implantation metastatic models using cell suspensions which are inoculated into the corresponding organ of nude mice from which the tumor cells were originally derived in the human. However, recent work has indicated that disaggregated cell suspensions may not always express their full metastatic potential. In this light, we have recently developed an orthotopic implant model utilizing intact tissue such as that obtained directly from surgery. This approach has yielded high take rates and frequent metastases in colon cancer, bladder cancer, lung cancer, pancreatic cancer, and prostate cancer. We report here the application of this intact tissue orthotopic implant technique to stomach cancer resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject stomach cancer cells at the same site, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of using intact tissue to allow full expression of metastatic potential. Injuring the serosa similar to that occurring in intact tissue transplantation did not increase the metastatic rate after orthotopic injection of cell suspensions of stomach tumor cells. This intact tissue orthotopic implantation model should allow development of new treatment modalities and further study of the biology of human stomach cancer.

Animals↗
PubMed1993

Orthotopic transplantation of histologically intact clinical specimens of stomach cancer to nude mice: correlation of metastatic sites in mouse and individual patient donors.

Fresh surgical specimens derived from 36 patients with advanced stomach cancer were orthotopically transplanted in nude mice using histologically intact tissue. Twenty of 36 patient tumors gave rise to locally growing tumors in the mice. All 20 patients whose stomach tumors resulted in local growth in the nude mice had clinical lymph-node involvement, whereas 8 of the other 16 patients whose tumors were rejected had lymph-node involvement. There was a statistical correlation (p < 0.01) between local tumor growth in nude mice and clinical lymph-node involvement. Of the 20 cases resulting in local growth in the nude mice, 5 had clinical liver metastases and all 5 cases resulted in liver metastases in the nude mice. Of the 20 cases, 6 had clinical peritoneal involvement of their tumor, and of these 5 resulted in peritoneal metastasis in the nude mice. There were statistical correlations (p < 0.01) for both liver metastases and peritoneal involvement between patients and mice. These results indicate that, after orthotopic transplantation of histologically intact stomach cancers from patients to nude mice, the subsequent metastatic behavior of the tumors in the mice closely correlated with the course of the tumors in the patients.

Animals↗
PubMed1993

Colorimetric chemosensitivity testing using sulforhodamine B.

A colorimetric chemosensitivity test was investigated using sulforhodamine B (SRB), which stains protein synthesized by cells, as an end-point marker. Four cultured cell lines, 9 human tumor xenografts serially transplanted into nude mice, and 14 fresh surgical specimens were subjected to this assay. The optimal conditions for the assay were 3-5 x 10(4) cells per well in a 96-microplate, an SRB concentration of 4%, and an incubation time of more than 10 minutes. When mitomycin C, doxorubicin, cisplatin, and 5-fluorouracil were assessed by the SRB assay, the concentration-effect curves revealed a sharp slope between plateaux at low and high concentrations, suggesting that this assay has an excellent sensitivity which can assess the effect of drugs as "all or none." Although this high sensitivity resulted in good reproducibility of the assay for cultured cell lines, the predictive rate of the SRB assay for the chemosensitivity of human tumor xenografts in vivo was limited to 63.9%. As a result, this SRB assay is thought to be useful for evaluating the chemosensitivity of cultured cells as all or none, since it can assess directly cellular protein synthesis, which is one of the most important parameters of cell renewal, with excellent sensitivity.

Animals↗
PubMed1993

Experimental cancer chemotherapy using a liver metastatic model of human colon cancer transplanted into the spleen of severe combined immunodeficient mice.

We have developed a liver metastatic model of human colon cancer using severe combined immunodeficient (SCID) mice. Liver metastases were observed in all the SCID mice on day 28 after intrasplenic injection with 5 x 10(6) dissociated tumor cells of COL-2-JCK, a human colon cancer strain serially transplanted in nude mice. When this model was applied for chemotherapeutic experiments, 5-fluorouracil (5-FU) demonstrated significant antitumor effects in preventing liver metastases, whereas the efficacy of 5-FU was limited in the currently used sc-ip chemosensitivity assay in nude mice. When the human LDH-5 isozyme was evaluated in the homogenized metastatic liver tissue of SCID mice, a good correlation was obtained between the liver tumor weights and LDH-5 isozyme, suggesting that it could be a promising quantitative indicator for metastases. This model would be useful for further studies on the treatment of liver metastases of colon cancer.

Animals↗
PubMed1993

Western blot analysis of glycoproteins bearing Lewis(a) and sialyl-Lewis(a) antigens in human colorectal mucosa.

Glycoproteins (GPs) bearing Lewis(a) and sialyl-Lewis(a) antigens (Le(a), sialyl-Le(a)) derived from human colorectal carcinomas and their surrounding non-neoplastic mucosa (normal mucosa) were analyzed using Western blotting. GPs bearing Le(a) were detected mainly as segmental bands of M(r) 310, 220, 160, and 80 kDa in 80% of the normal mucosa, but these GPs were detected predominantly as broad bands ranging from high to low molecular weight (MW) in 71% of the carcinoma tissues. GPs bearing sialyl-Le(a) were detected only in 23% of the normal mucosa and limited on huge MW bands, i.e., more than 400 kDa, whereas these GPs were detected predominantly as broad bands in 49% of the carcinoma tissues. In the cases with lymph node metastasis, the MW of GPs bearing sialyl-Le(a) varied over a wide range and were detected as broad bands, compared with the cases without metastasis. In conclusion, the MW of GPs bearing Le(a) and sialyl-Le(a) in normal colorectal mucosa was different from that in colorectal carcinomas. That is, the MWs of GPs bearing Le(a) varied more in carcinoma tissues, and the GPs bearing sialyl-Le(a) from carcinoma tissues had lower MWs than those from normal mucosa. It was, furthermore, suggested that the increased expression of lower MW GPs bearing sialyl-Le(a) are associated with an increased metastatic potential of the tumor cells.

Blotting, Western↗
PubMed1993

Synergistic antitumor activity of mitomycin C and cisplatin against gastric cancer cells in vitro.

The synergistic antitumor activity of mitomycin C (MMC) and cisplatin (DDP) against the gastric cancer cell lines MKN-28 and MKN-45 was assessed in vitro using the MTT assay. The synergism of the two agents was evaluated in terms of the interaction index (I.I.). The sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence against MKN-28 and MKN-45, and the intracellular concentration of platinum was significantly increased in MKN-45 by preincubation with MMC, suggesting that MMC modulates cellular permeability to DDP or the ability of DDP to intercalate DNA. Since these two antitumor agents show different types of toxicity clinically, i.e., myelotoxicity by MMC and nephrotoxicity by DDP, this combination chemotherapy could be advantageous by providing synergistic antitumor activity without increased toxicity.

Adenocarcinoma↗