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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Respiratory function after coronary artery bypass grafting through mini-sternotomy as a factor of early recovery].

OBJECTIVES: Early recovery in patients after minimally invasive coronary artery bypass grafting with mini-sternotomy and cardiopulmonary bypass (MICS-CABG) was compared to standard CABG by assessing preoperative and postoperative (7 to 10 days after) respiratory function. METHODS: Fifteen patients (Group M; mean age 62.1 years) underwent MICS-CABG with a mean of 2.3 distal anastomoses per patient. Ten patients (Group F; mean age 63.8 years) underwent standard CABG through full sternotomy with a mean of 2.4 distal anastomoses per patient. RESULTS: Postoperative coronary angiography showed that the patency rate of the grafts was 97% in Group M and 96% in Group F. Intubation time and hospital stay were significantly shorter (p < 0.01) in Group M (6.2 +/- 2.4 hours, 16.3 +/- 3.1 days) than in Group F (10.8 +/- 2.9 hours, 22.8 +/- 2.5 days). Respiratory function measured as the percentage of postoperative to preoperative values (Group M/Group F; mean +/- standard error) were vital capacity of 95.8 +/- 3.1%/74.6 +/- 3.4% (p < 0.05), 1 sec percentage of forced expiratory volume of 98.8 +/- 2.3%/71.8 +/- 2.8% (p < 0.05) and peak expiratory flow rate of 91.7 +/- 4.2%/89.4 +/- 4.5%. CONCLUSIONS: Quick recovery of the respiratory function after MICS-CABG may be important in the early recovery and short hospital stay of MICS-CABG patients compared with standard CABG patients.

Aged↗
PubMed2000

[Two patients with liver metastasis from gastric cancer who responded remarkably to combined therapy of 5'-DFUR and PSK].

Two patients with liver metastasis from gastric cancer who responded remarkably to a combined therapy of 5'-DFUR and PSK are reported. The first patient had liver metastases 8 months postoperatively. Her AFP level was 513 ng/ml and CEA was 30 ng/ml. After the combined therapy, all liver metastases showed a calcified change. Tumor markers of AFP and CEA decreased remarkably to the normal level within 3 weeks after the therapy. The patient had no relapse as of December 1999. The second patient with liver metastases was treated using the same combined therapy for 14 days preoperatively. The size of liver metastases had decreased remarkably by the time of the operation. A small metastasis of S8 (0.5 x 0.5 cm) was resected. No other liver metastasis was detected by intraoperative ultrasonography. The patient had no relapse as of February 2000. It is reported that PSK produces several cytokines which induce thymidine phosphorylase expression. The present report suggests that the upregulation of PyNPase might enhance the antitumor effect of 5'-DFUR.

Aged↗
PubMed2000

Renal transfer of genetically engineered cells.

For many years, ex vivo gene transfer has been used for genetic manipulation of various organs. In the kidney, ex vivo gene transfer was reported using mesangial cells and macrophages. In rats, cultured cells injected into the renal artery are accumulated selectively in the glomerulus. With this approach, it is possible to transfer genetically engineered cells to normal and diseased glomeruli. The transfer of genetically engineered cells to glomeruli can be used for several purposes. With the use of resident glomerular cells engineered in vitro, it is possible to examine how the cells that overexpress certain genes behave differently in normal and diseased glomeruli. Both gain-of-function and loss-of-function strategies are useful for this purpose. For the latter, stable expression of antisense cDNA, ribosomes, or dominant-negative mutants is available. By transfer of engineered cells producing secretory, recombinant proteins, it is possible to modify glomerular microenvironment in vivo. Transfer of genes encoding therapeutically relevant molecules could be useful for therapeutic intervention. Transfer of engineered leukocytes to the glomerulus also allows investigation of cross talk between leukocytes and resident cells. Transfer of stimulated leukocytes is useful for investigation of the pathologic actions of infiltrating cells on glomerular structure and function. Leukocytes in which certain gene functions are selectively reinforced or deleted would be useful for elucidation of the exact functions of leukocyte-associated genes in glomerular diseases. This article summarizes current experience with the adoptive transfer of engineered cells to the glomerulus for investigation of and therapy for glomerular diseases.

Animals↗
PubMed2000

[Thymidylate synthase and dihydropyrimidine dehydrogenase activity in a metastatic liver tumor from colorectal cancer].

The value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) activity in metastatic liver tumor from colorectal cancer as predictive parameters for hepatic artery infusion (HAI) chemotherapy with 5-FU was investigated. Thirteen patients with metachronous liver metastases underwent hepatic resection and primary site colectomy. We measured TS and DPD activity in normal colonic mucosa, primary colon tumor, and metastatic liver tumor in these patients. The TS (pmol/g-tissue) of primary tumor, metastatic tumor, and normal colonic mucosa was 6.6 +/- 1.40 (mean +/- SE), 3.2 +/- 0.83 and 2.5 +/- 0.83 respectively. The DPD (pmol/min/mg/protein) of primary tumor, metastatic tumor, and normal colonic mucosa was 31.7 +/- 5.49, 82.1 +/- 12.5 and 50.6 +/- 8.46, respectively. There was significant relationship between DPD activity level and recurrence. It is suggested that 5-FU catabolism in metastatic liver tumor was increased, and DPD activity may be a valuable predictive marker for tumor response to HAI therapy.

Antimetabolites, Antineoplastic↗
PubMed2000

Patient access to medical records: problems and strategies for inpatient charts.

Fasing the impending introduction of patient access to medical charts, we have attempted to include a more substantial description of medical activity in specific areas. Using the guidelines published jointly by the Ministry of Health and Welfare and the Tokyo Metropolitan Office in October 1998, the staff of the medical records division examined and evaluated the layout and description of items on individual hospital charts, with excellent results. To encourage the continued improvement of medical chart recording in the future, incentives should be implemented to avoid insufficient descriptions, encourage regular chart inspections, and promote education regarding the need for a systematic approach to charts and chart recording.

Forms and Records Control↗
PubMed2000

[Role of hepatocyte growth factor in invasion of prostate cancer cell lines through tumor-stromal interaction].

We examined how prostate stromal cell-derived hepatocyte growth factor (HGF) affects invasion of prostate cancer cells through tumor-stromal interaction. The effects of HGF, various growth factors [transforming growth factor (TGF)-alpha, TGF-beta 1, basic fibroblast growth factor, keratinocyte growth factor, and platelet-derived growth factor], and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC-3 and DU145) were determined by collagen gel invesion assay. DU145 cells and PrSC were co-cultured for matrigel invasion chamber assay. LNCaP and PC-3 cells did not respond to any of the factors examined. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF-beta 1, but not by any of the other factors tested. When DU145 cells were cultured in CM from PrSC or co-cultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF-beta 1. Induction activity of CM from cancer cells to stimulate HGF production by PrSC was studied by ELISA method and Western blotting. Native type HGF production in PrSC was enhanced by some unknown inducer(s) produced by cancer cells. In summary, PrSC-derived HGF enhanced invasive activity of the prostate cancer cell line DU145 through tumor-stromal interaction wherein DU145 cells secreted some HGF-inducer(s) for PrSC.

Cell Communication↗
PubMed1999

Dual potential of extracellular signal-regulated kinase for the control of cell survival.

Extracellular signal-regulated kinase (ERK) controls cell proliferation positively or negatively depending on the cellular contexts in which ERK is activated. In this report, we address differential roles of transient and constitutive activation of ERK in cell survival. Under a basal culture condition, mesangial cells showed modest, sustained ERK activity. The activity of ERK was transiently upregulated (15-60 min) in response to hydrogen peroxide (H(2)O(2)). The cells exposed to H(2)O(2) exhibited shrinkage of the cytoplasm, condensation/fragmentation of nuclei and DNA ladder typical of apoptosis. Inhibition of the transient ERK activation by MEK inhibitor PD098059 attenuated the H(2)O(2)-induced apoptosis. In contrast, inactivation of the constitutive ERK by PD098059 induced morphologic and biochemical features of apoptosis under the unstimulated, basal culture condition. Consistently, transfection with dominant-negative mutants of ERK1 and ERK2 inhibited H(2)O(2)-induced apoptosis, whereas it facilitated apoptosis of unstimulated cells. These results suggested the novel, dual potential of ERK for the regulation of cell survival. Transient upregulation of ERK participates in the induction of apoptosis, whereas basal, constitutive activity of ERK is required for the maintenance of cell survival.

Animals↗
PubMed1999

Prostate stromal cell-derived hepatocyte growth factor induces invasion of prostate cancer cell line DU145 through tumor-stromal interaction.

BACKGROUND: In prostate cancer, several growth factors derived from stromal cells regulate tumor cell growth. Hepatocyte growth factor (HGF) possesses biological activities that promote cancer proliferation and invasion through tumor-stromal interaction. We examined how prostate stromal cell-derived HGF affects invasion of prostate cancer cells through this interaction. METHODS: The effects of HGF, various growth factors (transforming growth factor (TGF)-alpha, TGF-beta1, basic fibroblast growth factor, keratinocyte growth factor, and platelet-derived growth factor), and conditioned medium (CM) from prostate stromal cells (PrSC) on prostate cancer cells (LNCaP, PC-3, and DU145) were determined by collagen gel invasion assay. DU145 cells and PrSC were cocultured for Matrigel invasion chamber assay. Induction activity of CM from cancer cells to stimulate HGF production by PrSC was studied by the ELISA method and Western blotting. RESULTS: LNCaP and PC-3 cells did not respond to any of the factors examined. Invasion of DU145 cells into the collagen gel matrix was induced by HGF and TGF-beta1, but not by any of the other factors tested. When DU145 cells were cultured in CM from PrSC or cocultured with PrSC, the cells acquired invasive potential, and this invasion was inhibited by an antibody against HGF, but not against TGF-beta1. Native-type HGF production in PrSC was enhanced by some unknown inducer(s) produced by cancer cells. CONCLUSIONS: PrSC-derived HGF enhanced invasive activity of the prostate cancer cell line DU145 through tumor-stromal interaction, wherein DU145 cells secreted some HGF-inducer(s) for PrSC.

Cell Communication↗
PubMed1999

Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds.

By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability-positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1999

Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Gastric Cancer Surgical Study Group.

BACKGROUND: To study the survival benefit of adjuvant chemotherapy in gastric cancer, seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer. METHODS: 579 patients were enrolled in the study, stratified by disease stage (T1, n=188; T2, n=323), and allocated randomly adjuvant chemotherapy or no further treatment. 285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible. Six cases were excluded because they did not fulfill the entry criteria. The treatment group had intravenous mitomycin (1.4 mg/m2) and fluorouracil (166.7 mg/m2) twice weekly for 3 weeks after surgery, and oral UFT (uracil plus tegafur, 300 mg daily) for 18 months. Analyses were by intention to treat. FINDINGS: No serious toxic effects were observed in the treatment group. At median follow-up of 72 months, 59 patients in the control group and 47 in the treatment group had died. There was no significant difference in survival between the groups (5-year survival 82.9% control vs 85.8% treated; hazard ratio 0.738 [95% CI 0.498-1.093]). 5-year survival of patients with T1 (mucosal or submucosal) cancer in the control and treatment groups was 94.9% versus 92.0%, and that of patients with T2 (muscularis propria or subserosa) cancer was 76.9% versus 83.0%. However, a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response. INTERPRETATION: There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer (T1 and T2) after curative gastrectomy. Patients with T1 cancer can be excluded from future trials, because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy.

Adenocarcinoma↗
PubMed1999

Suppression of apoptosis by all-trans-retinoic acid. Dual intervention in the c-Jun n-terminal kinase-AP-1 pathway.

Retinoic acid induces apoptosis of various cells, whereas little is known about its anti-apoptotic potential. In this report, we describe an anti-apoptotic property of all-trans-retinoic acid (t-RA) in mammalian cells. Mesangial cells exposed to hydrogen peroxide (H2O2) exhibited shrinkage of the cytoplasm, membrane blebbing, condensation of nuclei, and DNA fragmentation. Pretreatment with t-RA attenuated the morphologic and biochemical hallmarks of apoptosis. t-RA also inhibited apoptosis of mesangial cells triggered by pyrrolidine dithiocarbamate, whereas it did not prevent tumor necrosis factor-alpha-induced apoptosis. The anti-apoptotic effect against H2O2 was similarly observed in NRK49F fibroblasts, but not in Madin-Darby canine kidney epithelial cells and ECV304 endothelial cells. Mesangial cells exposed to H2O2 undergo apoptosis via the activator protein 1 (AP-1)-dependent pathway. We found that t-RA abrogated the H2O2-induced expression of c-fos/c-jun and activation of AP-1. Furthermore, t-RA inhibited H2O2-triggered activation of c-Jun N-terminal kinase (JNK), and dominant-negative inhibition of JNK attenuated the H2O2-induced apoptosis. These data disclosed the novel potential of retinoic acid as an inhibitor of apoptosis. The anti-apoptotic action of t-RA was ascribed, at least in part, to dual suppression of the cell death pathway mediated by JNK and AP-1.

Animals↗
PubMed1999

Selective sensitization to tumor necrosis factor-alpha-induced apoptosis by blockade of NF-kappaB in primary glomerular mesangial cells.

Recent data have implicated nuclear factor kappaB (NF-kappaB) in the prevention of apoptosis in transformed cell lines exposed to tumor necrosis factor alpha (TNF-alpha). However, it is obscure whether NF-kappaB plays an anti-apoptotic role in nontransformed cells, and it is not clear whether NF-kappaB inhibits apoptosis triggered by other mediators. We investigated the effect of specific inhibition of NF-kappaB on cytokine-induced apoptosis of glomerular mesangial cells, which is important in determining the outcome of glomerulonephritis. Cultured rat mesangial cells were stably transfected with the dominant negative mutant inhibitor of NF-kappaB (IkappaBalphaM). IkappaBalphaM was resistant to stimulus-dependent degradation and suppressed NF-kappaB activation induced by TNF-alpha (10 ng/ml) or IL-1beta (10 ng/ml). IkappaBalphaM significantly sensitized mesangial cells to TNF-alpha-induced apoptosis in a dose- and time-dependent manner but had no significant effects on the level of apoptosis in the presence of proinflammatory or apoptosis-inducing stimuli including Fas ligand, IL-1alpha, IL-1beta, hydrogen peroxide, lipopolysaccharide, cycloheximide, or serum deprivation. Moreover, IkappaBalphaM-mediated sensitization to TNF-alpha overcame the protective effect of mesangial cell survival factors present in serum, which usually inhibit killing of mesangial cells by the proapoptotic stimuli used. These data show that inhibition of NF-kappaB selectively sensitizes primary adult glomerular mesangial cells to TNF-induced apoptosis but not to other mediators of cell death including the Fas ligand.

Animals↗
PubMed1999

Bystander macrophages silence transgene expression driven by the retroviral long terminal repeat.

The Moloney murine leukemia virus (MLV)-based retroviral vector has been widely used for transfer of exogenous genes to various organs and tissues. Although the long terminal repeat (LTR) of MLV allows for transgene expression in a wide range of cell type, its activity is often silenced in vivo. In reporter macrophages transduced with a MLV-based retroviral vector, activity of the LTR was transiently and reversibly suppressed following stimulation by lipopolysaccharide (LPS). When unstimulated reporter macrophages were co-cultured with LPS-stimulated, untransduced macrophages, the LTR activity was similarly depressed. Activity of the LTR in retrovirus-transduced, mesangial cells was also down-regulated when co-cultured with activated macrophages. This suppressive effect was reproduced by cross-feeding with culture media conditioned by activated macrophages. LPS-stimulated macrophages abundantly expressed cytokines including IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1). When externally added, TNF-alpha and/or TGF-beta1, but not IL-1beta, depressed activity of the LTR in reporter macrophages and reporter mesangial cells. These results raise a possibility that expression of transgenes driven by the MLV-LTR may be silenced in vivo when the retrovirally-transduced cells are co-localized with activated macrophages.

Animals↗
PubMed1999

NF-kappaB-mediated self defense of macrophages faced with bacteria.

NF-kappaB is a ubiquitous transcription factor that is extensively exploited by immune cells involved in host defense mechanisms. Macrophages participate in the first line of defense against microorganisms, but little is known about whether and how NF-kappaB is involved in the handling of microbes by macrophages. To explore this issue, NF-kappaB-inactive macrophages, NIKMAC(NR), were created by overexpression of a super-repressor mutant of IkappaB alpha. When co-cultured with Escherichia coli, the NIKMAC(NR) macrophages exhibited impairment of bactercidal activity. Microscopic analysis revealed that NIKMAC(NR) cells faced with bacteria underwent rapid and fulminant apoptosis. Similary, NIKMAC(NR) macrophages cultured in the presence of a bacterial component, lipopolysaccharide, showed dramatic apoptosis. Inhibition of RNA synthesis or protein synthesis failed to block the apoptosis of NIKMAC(NR) cells, indicating that macrophages possess a pre-existing, apoptotic pathway that can be triggered by bacteria. Apoptosis was not observed in NIKMAC(NR) macrophages exposed to non-microbial stimuli including phorbol ester and opsonized zymosan. However, NIKMAC(NR) cells were more susceptible to apoptosis triggered by TNF-alpha and reactive oxygen intermediates, both of which are produced abundantly by macrophages when faced with bacteria. These data suggest a critical role for NF-kappaB in the survival of macrophages at the site of bacterial infection.

3T3 Cells↗
PubMed1999

Esophageal cancer associated with right aortic arch: report of two cases.

We report herein two cases of thoracic esophageal cancer with a right aortic arch. Both cases were elderly males who complained of dysphagia. Computed tomography and aortography revealed a right aortic arch with a mirror-image branching and a diverticulum of the right descending aorta in both cases. They underwent an esophagectomy and a mediastinal lymph node dissection in a left thoracotomy, and we also added a median sternotomy in the second case for a lymph node dissection in the right mediastinum. The ductus arteriosus was divided in the first case, but he died of a rupture of the aortic diverticulum 13 months later. In conclusion, for a successful esophagectomy and mediastinal lymph node dissection, a median sternotomy should be added to the left thoracotomy, while careful attention should also be paid to the aortic diverticulum and the ductus arteriosus.

Aged↗
PubMed1999

Postoperative lung volume calculated by chest computed tomography in patients with esophageal cancer.

It has been reported that, due to the severe surgical stress of thoracotomy, respiratory function after esophagectomy under thoracotomy worsened as late as a month after surgery. To investigate the mechanism of the reduction of the respiratory function, we utilized chest CT to analyze separately the changes in the lung volume of the thoracotomized side and the other side. Here, we reported the results of our comparative study of lung volume and respiratory function, which was performed by spirogram before esophagectomy and 6 months afterwards. We selected twenty-three patients who had undergone esophagectomy under right thoracotomy. Fourteen of the selectees received standard thoracotomy, while the other nine had the anterior serratus muscle and the latissimus dorsi muscle preserved. Total lung volume was found to have decreased from a preoperative value of 4077 +/- 674 ml (mean +/- SD) to a postoperative value of 3964 +/- 774 ml, and right-lung volume significantly decreased from 2229 +/- 397 to 2023 +/- 397 ml, while left-lung volume tended to increase. While right-lung volume in standard thoracotomy displayed a significant decrease from 2264 +/- 334 to 1949 +/- 424 ml, that in muscle-preserving thoracotomy showed almost no change. Spirogram revealed that vital capacity had decreased from 3574 +/- 601 to 2666 +/- 576 ml, and forced expiratory volume in the first second showed a significant decrease from 2680 +/- 500 to 2249 +/- 485 ml. Comparing the decreasing rate, the correlation coefficients between right-lung volume and %VC was 0.58. These results suggested that a change of lung volume in the thoracotomized side could play a role in the post-operative decrease of vital capacity and that muscle-preserving thoracotomy might induce less surgical stress than standard thoracotomy.

Adult↗