Biomedical subjects

R Kawano

Publications and source records attributed to R Kawano.

At least 19 recordsLinked to original sources

PubMed2001

Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs.

BACKGROUND: The role of inflammatory cytokines is still unclear in ischemia-reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR), a newly developed compound that is a potent suppressor of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs. METHODS: The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of the pancreas was removed. A control group (n = 14) and an FR treatment group (n = 11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes, creatinine, IL-1beta mRNA in the peripheral blood, and histopathology. RESULTS: Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041) than did the control group, but there was no remarkable change in endocrine function (P =.422). Pao(2) during the acute phase in the FR treatment group was maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liver and kidneys were unremarkable. CONCLUSIONS: FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may contribute to secondary damage to distant organs.

Animals↗

PubMed2001

The combined use of prostaglandin I2 analogue (OP-2507) and thromboxane A2 synthetase inhibitor (OKY-046) strongly inhibits atherosclerosis of aortic allografts in rats.

BACKGROUND: Atherosclerosis is the main lesion in allografts undergoing chronic rejection. We investigated the effect of OP-2507 (prostaglandin I2 analogue) and OKY-046 (thromboxane A2 synthetase inhibitor) on graft atherosclerosis morphologically and the production of eicosanoids in grafts in a rat aortic allograft model. METHODS: Abdominal aortic allografts of Lewis (RT-1(l)) rats were transplanted orthotopically into fully major histocompatibility complex mismatched Wistar King A/Qdj (RT-1(u)) rats that were subcutaneously administered OP-2507 (0.1 mg/kg/d) or OKY-046 (125 mg/kg/d), or both, with an osmotic pump. Four, 8, or 12 weeks later, the grafts were harvested and examined histologically, and the concentration of eicosanoids in the grafts were analyzed. RESULTS: Lewis aortic allografts in Wistar King A recipients with no treatment displayed atherosclerosis, which involved gradual intimal thickening and medial thinning with continuous inflammation in adventitia. Neither OP-2507 nor OKY-046 treatment affected the intensity of adventitial inflammation. Although inhibition of medial thinning or a decrease in medial nuclear density was not observed, OKY-046 administration alone significantly inhibited an increase in intimal thickness. OP-2507 administration alone significantly inhibited a decrease in medial nuclear density and intimal thickening. Combined treatment with OP-2507 and OKY-046 further decreased the alteration of media and intima. The ratio of thromboxane B2 and 6-keto-prostaglandin F(1alpha) in the grafts was significantly reduced by OKY-046 but not by OP-2507 alone. CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect. Amelioration of balance in eicosanoid production in the grafts by the use of thromboxane A2 synthetase inhibitor and the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for preventing atherosclerosis that results from chronic rejection.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

[Adjuvant GM-CSF cytokine gene therapy for breast cancer].

UNLABELLED: The aim of this study was to examine the enhancement of antitumor immunity of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF) gene-transduced mouse breast cancer cells. METHODS: BALBMC mouse were vaccinated subcutaneously with saline or irradiated mouse breast cancer cells, BALBMC (1 x 10(6)/mouse), infected or not infected with recombinant adenovirus harboring GM-CSF gene on day-7. Mice were injected with parental cells (1 x 10(5)/mouse) on day 0. RESULTS: No mice vaccinated with irradiated GM-CSF producing BALBMC cells developed a tumor during the observation period of up to 16 weeks, whereas 100% of mice injected with saline developed a tumor. CONCLUSION: Our study demonstrates the feasibility of this immunotherapeutic approach as a novel adjuvant cancer therapy after surgery for breast cancer.

Animals↗

PubMed2001

[Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF in 2 cases of advanced breast cancer].

Docetaxel was effective as a second line neoadjuvant chemotherapy after failure of cyclophosphamide, epirubicin and 5-FU (CEF) in 2 cases of breast cancer. In Case 1, 4 cycles of trans-arterial neoadjuvant chemotherapy of docetaxel showed a PR effect after failure of 2 cycles of trans-arterial neoadjuvant chemotherapy with CEF. This patient died of pleuritis carcinomatosa 18 months after surgery for breast cancer (latissimus dorsi muscle myocutaneous flap after radical mastectomy). In Case 2, 6 cycles of neoadjuvant venous drip infusion of docetaxel resulted in a CR effect after failure of 2 cycles of transarterial neoadjuvant chemotherapy with CEF. This patient is alive and disease-free 27 months after the operation for breast cancer (same operation as for Case 1). Docetaxel was effective as neoadjuvant chemotherapy for patients after failure of trans-arterial neoadjuvant chemotherapy with CEF.

Aged↗

PubMed2000

Epstein-Barr virus-associated T cell lymphoproliferative disorder following autologous blood stem cell transplantation for relapsed Hodgkin's disease.

Post-transplant lymphoproliferative disorders (PTLD) of T cell type are a rare complication of solid organ and allogeneic hematopoietic cell transplantation (HCT), and usually are not associated with Epstein-Barr virus (EBV) infection. EBV-associated T cell PTLD has not been reported to occur after autologous HCT. We report an unusual case of T cell lymphoproliferation after autologous blood stem cell transplantation (ABSCT). A patient with relapsed Hodgkin's disease developed abdominal lymphadenopathy followed by atypical CD8+ lymphocytosis in the peripheral blood 30 months following ABSCT. DNA studies of the atypical lymphocytes demonstrated rearrangements of the T cell receptor beta gene and a clonal proliferation of EBV.

Clone Cells↗

PubMed2000

["Hetero to homo" allogeneic bone marrow transplantation from a related donor with two HLA loci mismatch].

We describe a 46-year-old HLA-homozygous female patient with CML who received a bone marrow transplant from her son, who had two HLA (A, B) loci mismatch. After conditioning with total body irradiation plus cyclophosphamide, the patient received 4.8 x 10(8) bone marrow cells/kg. Cyclosporin and short-term methotrexate were used for GVHD prophylaxis. She successfully established rapid engraftment with no acute GVHD, and later developed chronic but mild GVHD. Family members with two HLA loci mismatch may be considered as candidate donors for "hetero to homo" bone marrow transplantation.

Bone Marrow Transplantation↗

PubMed2000

[Adult acute lymphoblastic leukemia presenting a near haploid karyotype].

Thirty cases of childhood acute lymphoblastic leukemia (ALL) with a near haploid karyotype (< 30 chromosomes) have been reported so far. However, despite a few cases of severely hypodiploid (30-39 chromosomes) ALL, no near haploid cases have been reported in adult patients. Here, we describe a 64-year-old woman with ALL (L2, CD10+ 19+ 34+ HLA-DR+) presenting a near haploid karyotype of 27, X, +X, +6, +10, +21/54, idem x 2. She died of septic shock during complete remission 6.5 months after the diagnosis.

Female↗

PubMed1999

Adenovirus-mediated local expression of human tissue factor pathway inhibitor eliminates shear stress-induced recurrent thrombosis in the injured carotid artery of the rabbit.

The main cause of acute coronary syndrome may be recurrent thrombosis, which is initiated by the activation of the extrinsic coagulation pathway. Tissue factor (TF) pathway inhibitor (TFPI) efficiently inhibits an early step in this pathway by the formation of a complex with factor VIIa, TF, and factor Xa. We determined whether local TFPI gene transfer can inhibit thrombosis in an injured artery without inducing systemic side effects. Balloon-injured rabbit carotid arteries were infected with an adenoviral vector that expressed either human TFPI (AdCATFPI) or bacterial beta-galactosidase (AdCALacZ). Two to 6 days after gene transfer, thrombosis was induced by the production of constant stenosis of the artery, and blood flow was measured continuously with an electromagnetic flow probe. A cyclic flow variation, which is thought to reflect the recurrent formation and dislodgment of mural thrombi, was observed in all AdCALacZ-infected arteries as well as in saline-infused arteries. In contrast, no cyclic flow variation was detectable in AdCATFPI-transfected arteries, even in the presence of epinephrine (1 microg. kg-1. min-1 infusion). Prothrombin time, activated partial thromboplastin time, and the ex vivo platelet aggregation induced by either adenosine diphosphate or collagen were unaltered in AdCATFPI-infected rabbits. We found that in vivo TFPI gene transfer into an injured artery completely inhibits the recurrent thrombosis induced by shear stress even in the presence of catecholamine, without affecting systemic coagulation status. Adenovirus-mediated local expression of TFPI may have the potential for the treatment of human thrombosis.

Adenoviridae↗

PubMed1999

[Surgical treatment of N2 involved non-small cell lung cancer--the systematic extended lymph node dissection based on the regional lymphatic drainage].

From the study on regional lymphtic drainage, we have decided the extent of lymphadenectomy as follows; a) For the left lung cancer and the right upper lobe primary, systematic bilateral mediastinal dissection (R3 alpha) through a median sternotomy, b) For the cases with the highest mediastinal node involvement, lower half of radical neck dissection (R3 gamma) through a cervical collar incision in addition to a). The cN diagnosis by CT interpretation and pN diagnosis were compared. The under estimated rates of N were 32% of 137 patients with the left lung primary. 46 patients with pN2(+) included 14 patients (31%) with pN3 disease. As for the right upper lobe primary, 17 patients with pN2(+) included 13 patients (76%) with pN3 disease. Postoperative survival rates calculated with Kaplan-Meiermethod; 1) The five-year survival rates were 43% of 46 patients with pT1-3 N2-3 of the left lung primary. 2) As for the right upper lobe primary, the two-year survival rates were 51% of 17 patients with pT1-4 N2-3. 3) The three-year survival rates of 26 patients with pN3 gamma diagnosed as cN0-3 alpha preoperatively were 41%. These systematic extended dissection (R3 alpha, R3 gamma) would bring better prognosis in the patients with pN2-3 disease.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Graft persistence effectively induces and maintains donor-specific unresponsiveness.

BACKGROUND: In the present study we attempted to evaluate the role of the graft as an alloantigen in induction and maintenance of donor-specific prolongation of allograft survival by short course(s) of FK506 treatment in rat heart transplantation. Materials and methods. In the WKA/Qdj-to-LEW combination group, FK506 (3 mg/kg/day, 7 days, s.c.) was administered from Day 0 after cardiac transplantation. A second WKA/ Qdj cardiac graft was transplanted on Day 14 into the LEW recipient after removal of the first graft on Day 3 or Day 7. In other groups an additional course of FK506 (3 mg/kg/day, 7 days, s.c.) was given from Day 35. A second WKA/Qdj cardiac graft was transplanted on Day 49 into the LEW recipient after removal of the first graft on Day 7 or Day 28. RESULTS: A short course of FK506 treatment allowed for survival prolongation of a cardiac allograft [mean survival time (MST) = 42.8 days]. Removal of the first graft on Day 7 (MST = 16.4 days) but not on Day 3 (MST = 10.2 days) caused donor-specific prolongation of the second allograft survival, which was significantly shorter than that in the recipient without the graftectomy (MST = 32.8 days). When graftectomy was performed on Day 3, there were immunohistochemically detectable levels of donor class II expressing cells in the recipient spleen on Day 7, indicating that the presence of the graft more effectively induced unresponsiveness than microchimerism alone. The additional course of FK506 treatment on Day 35 maintained graft survival (MST > 90.6 days). Removal of the first graft on Day 7 (MST = 13.5 days) or Day 28 (MST = 24.7 days) did not show significant prolongation of the second allograft survival, whereas significant survival prolongation of the second graft was observed in the recipient without the graftectomy (MST = 38.8 days). However, marked survival prolongation of the second donor-specific allograft in half of the recipients that had received the second course of FK506 treatment after graftectomy on Day 28 indicates that residual donor antigen can function as tolerizing antigen with an FK506 supplement. CONCLUSIONS: We concluded that the persistence of a graft more effectively induces and maintains donor-specific unresponsiveness than does the chimeric state of graft-derived cells alone under immunosuppression by FK506 in the rat heart transplantation model.

Animals↗

PubMed1997

Pitfalls of intervention therapy in a patient with anomalous origin of the right coronary artery from the left sinus of Valsalva associated with organic stenosis.

A 64-year-old man visited our hospital with a complaint of exertional chest discomfort. Exercise electrocardiography revealed ST segment depression in the V4-V6 leads, and exercise thallium myocardial scintigraphy demonstrated myocardial ischemia in the area of the right coronary artery, suggesting effort angina. Diagnostic coronary angiography revealed an anomalous origin of the right coronary artery from the left sinus of Valsalva and 90% organic stenosis at the proximal portion. We performed percutaneous transluminal coronary angioplasty (PTCA), but repeat PTCA was required 3 months later because of restenosis. Follow-up angiography 1 year later showed regression of the stenotic lesion to less than 50% diameter compared with the data obtained 3 months after the second PTCA. However, exercise 99mtechnetium-tetrofosmin myocardial scintigraphy disclosed obvious myocardial ischemia in the inferior region. These results suggested that the myocardial ischemia in this particular patient was caused not only by the organic stenosis but also by the anatomic anomaly which might reduce coronary blood flow during exercise. Such patients should be followed up cautiously with much more sophisticated methodology.

Angioplasty, Balloon, Coronary↗

PubMed1996

Effects of K-ras gene mutations in the development of lung lesions induced by 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1-butanone in A/J mice.

The relationship between the development of peripheral lung lesions induced by tobacco-specific 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and K-ras gene mutation in A/J mice, and the correlations between histological alterations and the course of lung lesion development after NNK treatment and K-ras gene mutation were investigated. The acquisition of a selective growth advantage by the lung lesions with mutations was also examined using immunohistochemical labeling with bromodeoxyuridine. Thirty female 5 weeks old A/J mice were each injected intraperitoneally with a single dose of NNK (100 mg/kg body weight) and subdivided into 6 groups according to the time after NNK treatment. The lung lesions were characterized histologically as alveolar/bronchiolar hyperplasia, adenoma and adenocarcinoma, and point mutations in codons 12 and 61 of the K-ras gene were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and dideoxy sequencing methods. K-ras gene mutations were identified in 7 (58.3%) of 12 hyperplasias, 42(75.0%) of 56 adenomas and 3 (75.0%) of 4 adenocarcinomas. The most frequent K-ras gene mutation was a G-to-A transition at the second base of codon 12 and this accounted for 86.5% of all the mutations detected. Neither the frequency of activation of this gene nor the specific mutation was affected by the time after NNK treatment and there was no positive correlation between the proliferative activity of lung lesions and the presence of K-ras gene mutations. Thus, K-ras gene mutation is closely associated with the development of NNK-induced peripheral lung lesions in A/J mice, but it plays no role in the selective growth advantage of these lesions.

Animals↗

PubMed1996

p16/CDKN2 gene and p53 gene alterations in Japanese non-smoking female lung adenocarcinoma.

Primary lung adenocarcinomas in non-smoking females are increasing in the USA and Japan. Environmental factors such as passive smoking, asbestos, domestic radon, and hormonal effects have been implicated, but the etiology is still uncertain. We therefore analyzed point mutations of p16 gene, a newly characterized tumor suppressor gene, and compared the results with alterations of p53 gene in 28 primary lung adenocarcinomas in non-smoking Japanese females. There were no cases with somatic point mutation of p16 gene, except for one case with two germline mutations (silent mutations). In contrast, six out of 16 informative cases showed loss of heterozygosity of p53 gene using a TP53 microsatellite marker and 19 out of 28 cases showed expression of oncoprotein using DO-7 immunohistochemistry. These findings suggest that p16 gene alteration is a rare event in primary lung adenocarcinomas in Japanese non-smoking females, compared with alterations of the p53 gene.

Adenocarcinoma↗

PubMed1996

Alteration of the p53 gene of lung carcinomas with sarcomatous transformation (spindle cell carcinoma): analysis of four cases.

Lung carcinoma with sarcomatous transformation (LCST) is highly aggressive and characterized by local invasion and/or distant metastasis, which leads to a shorter survival than ordinary lung carcinomas. Therefore, to elucidate whether the malignant potential of the spindle cell element in LCST is associated with the alteration of the p53 gene, four cases were examined by analyses of overexpression of the p53 oncoprotein, mutation of the p53 gene and loss-of-heterozygosity (LOH) at chromosome 17p. In two cases overexpression of the p53 oncoprotein of the spindle cell component showed a higher degree of staining than that of the carcinoma component; LOH was identified in both carcinoma and sarcomatous components in one case, while in contrast, another case showed LOH in the sarcomatous component only. Mutations were clearly detected in two cases; one showed a CTT to CGT transversion in codon 194 of exon 6 in both components, whereas the other showed a CTG to CAG transversion in codon 265 of exon 8 in the sarcomatous component only. On the basis of these observations, it suggested that the sarcomatous component shows a higher frequency of p53 gene abnormalities in comparison to the carcinoma component. These results also suggested that the acquisition of malignant potential in the sarcomatous component, or the morphological alteration of carcinoma cells, is correlated with abnormalities associated with the p53 gene.

Adenocarcinoma↗

PubMed1996

Sudden death during Holter electrocardiogram monitoring in a patient with variant angina.

We report a case of sudden death due to variant angina during Holter electrocardiogram (ECG) monitoring. The patient, a 60-year-old man, had been aware of chest discomfort lasting less than one minute at midnight 2 days earlier. Because variant angina or arrhythmia was suspected, Holter ECG monitoring was performed. The patient spent a whole day without a recurrence of chest pain before going to bed, but at midnight he developed sudden chest pain, and died immediately after taking a sublingual tablet of isosorbide-dinitrite. Analysis of the Holter ECG revealed ventricular fibrillation after several ventricular premature beats following ST-segment elevation in both the CM5 and NASA leads. This case shows that sudden death from variant angina may occur within a few days after the first onset, and also highlights whether priority should be given to making a definite diagnosis or giving treatment when variant angina is strongly suspected.

Angina Pectoris, Variant↗

PubMed1995

Role of point mutation of the K-ras gene in tumorigenesis of B6C3F1 mouse lung lesions induced by urethane.

In order to elucidate the role of point mutation of the K-ras gene in the tumorigenetic process of lung tumors, an experimental model of lung lesions in mice induced by the administration of urethane was used. A total of 135 B6C3F1 male mice, 6 weeks old, were given urethane in the drinking water at 0, 6, 60, 600 or 1200 ppm, and were then killed after varying periods of time. The lung lesions were histologically characterized as hyperplasia, adenoma and adenocarcinoma. Point mutations in codons 12 and 61 of the K-ras gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by using dideoxy sequencing analysis. K-ras gene mutation was identified in 9 (23.7%) of 38 lesions classified as hyperplasia, 31 (46.3%) of 67 adenomas, and 3 (50%) of 6 adenocarcinomas. The most frequent mutation was an AT-to-TA transversion at the second base of codon 61 and this pattern accounted for 65% of the three mutant forms observed. These results suggest that the point mutation of K-ras gene is involved in all stages of mouse lung tumorigenesis, i.e., activation of this gene can also influence the later stages of lung lesions.

Adenocarcinoma↗

PubMed1989

The thallium-201 time activity curve in thyroid cancer: a role for the detection of metastases.

The Tl-201 Cl time activity curves were evaluated in 17 patients with histologically proven benign nodules and papillary carcinoma of the thyroid gland. In the dynamic studies, the uptake at the region of interest was counted every 10 sec for 20 min after the intravenous injection of 2mCi Tl-201 Cl. The curves from frame 21 to 100 were transformed to linear plots for clinical evaluation. Papillary carcinoma could not be differentiated from benign lesions by means of the values of the washout rate. However, the "relative washout rate" in papillary carcinoma was lower than that of benign lesions (P less than 0.05). Although the average values of the "relative extrapolated uptake" in papillary carcinoma appeared to be greater than those in benign lesions, the difference was not statistically significant. The difference in the washout rates between lymph node metastases and local recurrences, and pulmonary metastases of the papillary carcinoma was significant (P less than 0.05).

Adenoma↗

PubMed1987

Parathyroid adenoma imaged by gallium-67 citrate. A case report.

A parathyroid adenoma imaged by Ga-67 citrate in a 17-year-old man with primary hyperparathyroidism and a palpable solid tumor in the neck is presented. Although preoperative examination and intraoperative findings suggested a parathyroid carcinoma, histologic studies showed a parathyroid adenoma with predominant chief cell type.

Adenoma↗