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H Fuji

Publications and source records attributed to H Fuji.

At least 19 recordsLinked to original sources
PubMed1998

Radioresponse of thymomas verified with histologic response.

Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma.

Adult↗
PubMed1997

Comparison of myocardial contrast echocardiography and coronary angiography for assessing the acute protective effects of collateral recruitment during occlusion of the left anterior descending coronary artery at the time of elective angioplasty.

To assess the immediate change in collateral flow distribution within the occluded myocardium and the acute protective effects on myocardial ischemia after coronary occlusion, myocardial contrast echocardiography (MCE) was performed in 15 patients with normal left ventricular function undergoing elective coronary angioplasty of the left anterior descending artery, and the results were compared with those obtained from coronary angiography (CA). The sonicated or nonsonicated contrast material was injected into the right coronary artery before and during coronary occlusion and collaterals were graded on a 4-point scale (none = 0 to good = 3). Development of subjective anginal symptoms, ST-segment shift and wall motion abnormality during coronary occlusion were graded on a 4-point scale (none = 0 to severe = 3). Both MCE and CA detected a significant development in collateral flow during coronary occlusion. There was no significant correlation between MCE and CA collateral grades before or during coronary occlusion. The collateral flow assessed with MCE was inversely but significantly correlated with development of subjective anginal symptoms (r(s) = -0.70, p <0.01), ST-segment shift (r(s) = -0.78, p < 0.005) or wall motion abnormality (r(s) = -0.91, p < 0.001) during coronary occlusion. In contrast, the angiographic collateral flow was not correlated with development of anginal symptoms (r(s) = -0.46, p = 0.10), ST-segment shift (r(s) = -0.41, p = 0.14), or wall motion abnormality (r(s) = -0.26, p = 0.35). The present study suggested that the acute protective effects of coronary collaterals during coronary occlusion were closely associated with myocardial perfusion rather than the angiographic epicardial collateral vessel filling, and thus MCE was useful in assessing the acute protective effects of coronary collaterals during coronary occlusion.

Aged↗
PubMed1996

A one step PCR procedure for analysis of tumor specific T lymphocyte responses.

In an effort to develop optimal conditions for analysis of tumor specific T lymphocyte responses, we have studied the effect of changes in the concentration of oligonucleotide primers on the synthesis of TCR cDNAs in one step PCR procedure using Vbeta10 gene subfamily as a model. It was found that synthesis of the TCR cDNAs increases in a roughly linear fashion at primer concentrations between 0.005-0.05 muM. Evaluation of the use of low concentration (0.005 muM) of primers showed these conditions to be adequate for the analysis of TCR Vbeta subfamilies in the spleen of BALB/c mice, but not in the peritoneal exudate cells (PECs), the latter requiring ten-fold higher concentrations of the variable region primers to compensate for the overall low frequency of T lymphocytes in the PECs in comparison to the spleen. Use of these optimal conditions to detect L1210 tumor specific T lymphocyte responses showed that, in the immunized mice, L1210 specific T lymphocyte responses are detectable in the PECs, but not in the spleen cells from these mice. Thus, upon i.p. immunization of DBA/2 mice with irradiated L1210 lymphoma cells, followed by analysis of the PECs by RT/PCR, three TCR Vbeta subfamilies, including Vbeta8.2, Vbeta15 and Vbeta16 were found to contain specific major TCR cDNA bands. The approach described here is very efficient, as it uses a small amount of the 32P isotope (0.5 muCi) followed by direct analysis of the PCR products on a denaturing acrylamide/urea gel. Furthermore, data is also presented that shows that quantitative differences in the levels of individual TCR cDNAs in a particular Vbeta subfamily are preserved during PCR amplification.

Animals↗
PubMed1996

Impact of biological clearance on tumor radioresponsiveness.

PURPOSE: To determine the capacity of biological clearance in tumor regression following radiotherapy by using metastatic brain tumors as a clinical model in which mechanical clearance is negligible. METHODS AND MATERIALS: Thirty-eight tumors (19 nonsmall cell lung cancer, 11 small cell lung cancer, and 8 nonlung cancer) in 23 patients were followed with computed tomography (CT) scans over 3 months or more following initiation of radiotherapy, with doses ranging between 34 and 66 Gy. The tumor regression rate (RR; mm3/day), which represented the capacity of biological clearance, was calculated for each CT observation period. The complete response (CR) rate was calculated. The relationship between RR and tumor diameter was determined with regression analysis in conjunction with the pattern of contrast enhancement and the type of primary disease. The change of the RR also was examined. RESULTS: The CR rate was 60.5% for the total group; it was lower for ring-enhanced tumors (41.7%) than diffusely enhanced tumors (69.2%), which included mostly small cell lung cancer metastases. The RR correlated significantly with the tumor diameter (D), with a regression curve of exponential function (RR = 0.035 *D2.5). The RR varied widely and was rather large until 40 days following initiation of radiotherapy, especially for the subgroups of diffusely enhanced tumors and the small cell lung cancer tumors, and became rather constant thereafter. CONCLUSION: A tumor diameter exponent in the regression curve of smaller than 3.0 indicates that the larger the tumor volume is, the smaller the capacity of biological clearance. The capacity of biological clearance also is dependent on vascularity and cellularity of the tumor components expressed by the pattern of contrast enhancement.

Adult↗
PubMed1996

[Argatroban, a selective thrombin inhibitor, for anticoagulant therapy during and following vascular surgery].

We administered argatroban, a selective thrombin inhibitor, as an anti-coagulant during and following vascular surgery. Activated coagulation time was controlled easily by its continuous intravenous infusion. No abnormal bleeding tendency and thrombus formation in graft and blood vessel were observed. The activity of thrombin was inhibited under the infusion of argatroban. We conclude that argatroban is effective for anti-coagulant therapy during and following vascular surgery.

Aged↗
PubMed1995

[Whole abdominal irradiation for peritoneal dissemination of alimentary tract cancers].

Between January 1986 and August 1991, 19 patients with alimentary tract cancers complicated by peritoneal dissemination received whole abdominal irradiation combined with intraperitoneal chemotherapy postoperatively. Using a moving-strip technique of irradiation, 12.0 Gy was delivered in three fractions to the entire abdominal contents with partial liver and kidney shielding. The primary tumor sites were the stomach in 12 patients, the colorectum in five, and the gall bladder in two. Nine patients with gross residual disease also received a limited field boost of 30.6 Gy in 17 fractions after completion of treatment to the whole abdomen. None of the patients failed to complete the planned dose despite acute gastrointestinal toxicity (nausea and vomiting, 84%, diarrhea and cramping, 78%) and acute hematologic toxicity (leukocytopenia, 84%, thrombocytopenia, 68%). Our follow-up study revealed that the actuarial one-year survival rate was 28.4% and the median survival time was 9.0 months. Survival rates at one-year for patients with colorectal and gastric cancer were 75.0% and 16.7%, respectively. Patients with gastric cancer (n = 12) had a poorer outcome than those with colorectal cancer (n = 5) in the present study. One reason for this difference may have been the presence of cancerous pleuritis, which was frequently observed in patients with gastric cancer. Therefore, more intensive treatment to prevent cancerous pleuritis seems to be necessary to improve the efficacy of whole abdominal irradiation.

Abdomen↗
PubMed1994

Polymorphonuclear leukocytes-induced injury in hypoxic cardiac myocytes.

Growing evidence suggests that free radicals derived from polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia-reperfusion injury. To elucidate the cellular mechanism by which activated PMNs exacerbate ischemic myocardial damage, we investigated the extent of cell injury, assessed by the morphological deterioration, free radical generation, and lipid peroxidation in mouse embryo myocardial cells coincubated with activated PMNs. The generation of PMN-derived free radicals was related to the extent of myocardial cell injury. When myocardial cell sheets were subjected to hypoxia and glucose-free media, myocardial cells were injured (cristalysis in the mitochondria and disruption of the sarcolemma) after adding various PMN activators, and the injury extended to the adjacent cells. Chemiluminescent emission and production of thiobarbituric acid-reactive substances in the coincubated cells increased markedly compared with myocardial cells or PMNs alone. The augmented lipid peroxidation coincided with the progression of myocardial cell injury. Catalase inhibited the myocardial cell injury by 52%, the chemiluminescence by 46%, and lipid peroxidation by 50%, whereas superoxide dismutase exhibited less pronounced inhibition. These results indicate that a chain reaction of lipid peroxidation in myocardial cells induced by PMN-derived free radicals closely correlates with membrane damage and contributes to the propagation of irreversible myocardial cell damage.

Animals↗
PubMed1994

Alternatively spliced MHC class I mRNAs show specific deletion of sequences encoding the extracellular polymorphic domains.

Analysis of structural diversity at the 5' end of H-2 class I mRNAs showed that a small fraction of Kd mRNA from L1210 lymphoma (approximately 10%) or from various normal tissue (2-3%) of DBA/2 mice carries a precise deletion of the sequences encoding the second extracellular domain. Nucleotide sequence of the coding region of the second domain-lacking Kd mRNA was found to be identical to the known sequence of the Kd gene from DBA/2 liver with the exception of the above deletion and a single nucleotide silent substitution at position 150, suggesting that the novel Kd RNA is a product of the functional Kd gene. In addition, various normal tissues that are known to express varying levels of Kd antigen did not show changes in the expression levels of the second domain-lacking Kd mRNA thus ruling out the possibility that synthesis of this RNA is coupled to control the expression levels of the canonical Kd mRNA, hence the Kd antigen. Analysis by polymerase chain reaction showed that all normal tissues including the testis and sperm express this RNA. Preliminary analysis of the Kb mRNA from the spleen and thymus of C57BL/6 mouse also showed the presence of second domain-lacking Kb mRNA in these mice. Furthermore, preliminary structural analysis of the Dd and Ld mRNAs has revealed additional polymorphic extracellular domain-lacking mRNA species including a first domain-lacking Dd mRNA and two Ld mRNAs that lack sequences encoding either the first extracellular domain or the second extracellular domain respectively. These results together show that H-2 mRNAs lacking sequences that specify individual extracellular polymorphic domains are a frequent feature of the structural diversity at the 5' ends of these mRNAs. Potential significance of these domain-lacking H-2 mRNAs is discussed, particularly with regard to the function of the putative encoded peptides as targets of natural killer cells.

Alternative Splicing↗
PubMed1994

Radiation tolerance of the liver in relation to the preserved functional capacity.

The radiation tolerance of the liver was investigated in 12 patients, 11 of them with liver cirrhosis, treated for hepatocellular carcinoma by partial liver irradiation with doses between 50 and 77 Gy. The tolerance was assessed by the complication probability (Lyman's model), which concerned the injured tissue itself, and by a prediction score used for postsurgical liver failure, which concerned the preserved functional capacity, assuming that the > or = 30 Gy volume was equivalent to the resected volume. The prediction score corresponded better with the observed risk of fatal liver failure than the complication probability. The liver volume after radiotherapy correlated largely with the untreated volume and the low-dose volume. Thus the preserved functional capacity gives a better expression of the radiation tolerance than direct measures of the extent of injured tissue.

Aged↗
PubMed1993

Brief myocardial ischemia affects free radical generating and scavenging systems in dogs.

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.

Animals↗
PubMed1993

Transcardiac alteration of neutrophil function relates to myocardial ischaemia/reperfusion injury.

OBJECTIVE: The aim was to define the relation between transcardiac changes in neutrophil function in myocardial ischaemia and the progression of myocardial necrosis. METHODS: Samples of blood from carotid artery, jugular vein, and cardiac vein streaming from the ischaemic area were taken simultaneously in a canine coronary occlusion-reperfusion model of myocardial infarction. Neutrophil function was evaluated by neutrophil count, whole blood chemiluminescence and leucocyte infiltration into the ischaemic myocardium. Myocardial necrosis was assessed by plasma creatine kinase and dual staining technique using Evans blue dye and triphenyltetrazolium chloride. Effects of a free radical scavenger, N-2-mercaptopropionyl glycine (MPG), initiated 15 min before reperfusion and continued during the reperfusion phase, were also examined. RESULTS: Whole blood chemiluminescence of the cardiac vein was reduced at 90 min after coronary artery occlusion as compared to carotid artery [5.8(SEM 0.5) v 7.5(0.7) count x 10(3) cell neutrophil-1 x 10 min-1, p < 0.05], and then increased abruptly after reperfusion to peak after 10 min of reperfusion [7.1(0.7) count x 10(3) cell neutrophil-1 x 10 min-1]. The neutrophil count in cardiac venous blood was significantly reduced within 5 min of reperfusion. MPG significantly attenuated the reperfusion associated increase in cardiac vein whole blood chemiluminescence and the decrease in the cardiac venous blood neutrophil count. The increase in myocardial free radical generation 1-3 h after reperfusion, as assessed by the electron paramagnetic resonance spin trapping technique, was reduced markedly, as was the extent of leucocyte infiltration into the ischaemic myocardium. Under these conditions, administration of MPG significantly reduced myocardial infarct size [40.3(4.5)% v 21.4(4.2)%, p < 0.05]. A marked increase in transcardiac creatine kinase release after reperfusion observed in control dogs was also reduced significantly. CONCLUSIONS: A transient alteration of neutrophil function occurs in the coronary circulation immediately after reperfusion, which may augment neutrophil infiltration and free radical generation in the ischaemic myocardium, leading to the propagation of myocardial ischaemia/reperfusion injury.

Animals↗
PubMed1993

Sublethal ischemia alters myocardial antioxidant activity in canine heart.

We examined antioxidant activity in the pre-conditioned canine myocardium with four 5-min episodes of regional ischemia and reperfusion. Immediately after repetitive brief ischemia, mitochondrial Mn-superoxide dismutase (SOD) activity in the ischemic myocardium significantly increased compared with that in the nonischemic myocardium (18.7 +/- 2.1 vs. 14.9 +/- 1.0 U/mg protein, P < 0.05). Although no difference was seen in the activity between these regions after 3 h of the sublethal ischemia, a significant increase in the activity of the ischemic myocardium reappeared after 24 h compared with that of the nonischemic myocardium (26.7 +/- 0.9 vs. 20.8 +/- 0.9 U/mg protein, P < 0.05). Mn-SOD content increased gradually in the ischemic myocardium after sublethal ischemia, with a peak after 24 h (2.8 +/- 0.1 vs. 2.1 +/- 0.1 microgram/mg protein, P < 0.05). There were no differences in the activity and content of Cu, Zn-SOD between these regions after sublethal ischemia. Activities of glutathione peroxidase and reductase were significantly higher and lower, respectively, in the ischemic myocardium than those of the nonischemic myocardium immediately after repetitive brief ischemia, but no differences between these regions were seen in activities after 3 or 24 h. These results indicate that a brief ischemic insult alters myocardial antioxidant activity not only immediately after but also 24 h after sublethal ischemia.

Animals↗
PubMed1993

Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.

The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p < 0.01]; and for the delayed occlusion, 18.8 +/- 3.4% versus 35.1 +/- 4.6%, respectively [p < 0.05]); however, when the infarction was induced 3 hours (31.2 +/- 3.7% versus 37.5 +/- 4.2%, respectively) or 12 hours (25.4 +/- 4.8% versus 35.0 +/- 5.3%, respectively) after repetitive ischemia, the infarct size did not differ. No differences were seen in regional myocardial blood flow or rate-pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning.

Animals↗
PubMed1992

Tumorigenicity of interleukin-2 (IL-2)-cDNA-transfected L1210 lymphoma and its in vivo variants is modulated by changes in IL-2 expression; potential therapeutic implications.

To study parameters that affect the tumorigenicity of L1210 lymphoma we have analyzed the structure of MHC class I antigens of this tumor. In addition this tumor was transfected with interleukin-2 (IL-2) cDNA in order to determine the effects of high concentrations of IL-2 within the tumor environment. The nucleotide sequence of the class I Kd, Dd and Ld mRNAs from this tumor showed that the encoded amino acid sequence of the corresponding antigens is normal, thus suggesting that the tumorigenicity of L1210 lymphoma is not due to defective antigen presentation to tumor-specific cytotoxic T cells. In contrast, induction of IL-2 expression by cDNA transfection led to loss of tumorigenicity of the IL-2-secreting tumor cells. However, a fraction of long-term-surviving mice developed progressively growing variant tumors that showed substantial decrease or loss of IL-2 expression. These results suggest that IL-2 secretion by tumors is suicidal but, because of tumor heterogeneity, IL-2-loss-variant tumors may arise that are able to escape the immune defenses of the host. The observed consistent loss of IL-2 expression in variant tumors implies that specific targeting of large quantities of IL-2 to tumor cells may be a valuable approach to immunotherapy of cancer. In addition we find that under specific gamma ray irradiation IL-2-secreting tumor cells lose their ability to multiply yet continue to secrete IL-2 at levels equivalent to those secreted by unirradiated cells. Such IL-2-secreting irradiated tumor cells were found to be superior immunogens in comparison to the irradiated parental tumor cells, suggesting their use as tumor vaccines.

Animals↗
PubMed1991

Transcardiac alteration of neutrophil function before and after coronary thrombolysis in human myocardial infarction.

We examined function of isolated neutrophils taken from aorta and coronary sinus before and after thrombolytic reperfusion in 17 patients whose infarct-related coronary arteries were totally occluded. Before reperfusion in left coronary artery disease, free radical generation by activated neutrophils in coronary sinus, assessed by ferricytochrome c reduction (phorbol myristate acetate, 10 ng/ml) and luminol-enhanced chemiluminescence (A23187, 2 microM), was reduced by 20% (P less than 0.05) and 30% (P less than 0.05), respectively, compared with those in aorta. Neutrophil aggregation (A23187, 10 microM) and chemotactic activity (formyl-methionyl-leucyl-phenylalanine, 5 microM) were also reduced in coronary sinus by 21% and 20%. After reperfusion the extent of such neutrophil function in coronary sinus recovered and was similar to that in aorta. There were no significant differences between neutrophil counts in aorta and coronary sinus before and after reperfusion. In right coronary artery disease, no significant changes were seen in these functions of neutrophils of aorta and coronary sinus before and after reperfusion. These results indicate that function of neutrophils passing through coronary circulation fluctuated significantly in association with reperfusion, suggesting (1) factor(s) that depress neutrophil function are produced in coronary circulation during myocardial ischemia and their effects are overcome after reperfusion or (2) activated neutrophils, trapped in the ischemic coronary bed, are washed out to coronary sinus after reperfusion.

Chemotaxis, Leukocyte↗
PubMed1991

Neutrophil-induced myocardial cell damage and active oxygen metabolites.

Free radicals derived from polymorphonuclear leukocytes (PMN) have been suggested to play an important role in myocardial ischemia-reperfusion injury. To define the mechanism by which activated PMN exacerbate ischemic myocardial damage, we investigated the extent of cell injury, free radical generation and lipid peroxidation in embryo mouse myocardial cells co-incubated with activated PMN. The generation of free radicals derived from PMN correlated with the extent of myocardial cell injury. Among the cell sheets preconditioned with hypoxic and glucose free medium, PMN-adhered myocardial cells were initially injured after adding PMN activator, extending to adjacent cells. Chemiluminescence emission and thiobarbituric acid reactive substance in the co-incubated cells were markedly increased and sustained compared with those in each cell monoincubation. The augmented lipid peroxidation was related to the progression of myocardial cell injury. These results indicate that PMN-derived free radicals cause membrane disruption, contributing to the progression of myocardial injury.

Animals↗