Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 487 records · Page 27Linked to original sources

PubMed1995

Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.

Plasma thrombin-antithrombin III complex (TAT), FDP-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, and tissue type plasminogen activator (t-PA), PA inhibitor-1 (PAI-I) were significantly increased in patients with acute myocardial infarction (AMI) at onset. These patients exhibited a hypercoagulable state and protein C activation at onset. The plasma PCI level at onset of AMI was within the normal range, but was significantly decreased after percutaneous transluminal coronary angioplasty (PTCA). After PTCA, plasma t-PA, FDP-D-dimer, and plasmin-alpha 2-plasmin inhibitor were increased but APC-PCI complex and TAT were not. The decrease in PCI after PTCA may have been caused by the activation of fibrinolysis. PCI may play an important role in the inhibition of fibrinolysis in stimulated or damaged endothelial cells. These findings suggest that the protein C pathway plays an important role in the onset of AMI and after PTCA.

Angioplasty, Balloon, Coronary↗

PubMed1995

Hemostatic abnormalities and increased vascular endothelial cell markers in patients with red cell fragmentation syndrome induced by mitomycin C.

We examined red cell fragmentation syndrome (RCFS) induced by mitomycin C (MMC) (13 patients), by thrombotic thrombocytopenic purpura (TTP) (17 patients), and by disseminated intravascular coagulation (DIC) (15 patients). Plasma cytokine levels were increased in the TTP and DIC patients, but not in those whose RCFS was induced by MMC, suggesting that the activation of the immune system plays an important role in the pathogenesis of RCFS due to TTP and DIC but did not in RCFS due to MMC. Plasma thrombomodulin, tissue type plasminogen activator, and plasminogen activator inhibitor-I levels were increased in all RCFS patients, suggesting that RCFS, whether MMC induced, or due to TTP or DIC, might be associated with vascular endothelial cell injury. In TTP, von Willebrand factor (vWF) antigen and high molecular weight vWF multimer levels were reduced, possibly as a result of microthrombus consumption. The hemostatic data in this study showed that the TTP patients were in a hypercoagulable state without hyperfibrinolysis, and that DIC patients were in both a hypercoagulable and a hyperfibrinolytic state, whereas hemostatic abnormalities were slight in patients with MMC induced RCFS. These findings suggest that vascular endothelial cell injuries might be associated with RCFS, and that those injuries in MMC-induced RCFS might not be related to microthrombi or an activated immune system.

Adolescent↗

PubMed1995

Expression of the adult T-cell leukemia-derived factor, human thioredoxin, in the allotransplanted canine lung.

The relationship between the expression of adult T-cell leukemia-derived factor, human thioredoxin (ADF/TRX), and rejection in transplanted canine lungs was investigated in this study. Of a total 27 adult mongrel dogs, 24 underwent allotransplantation of the left lung with no immunosuppressant and the other three underwent autotransplantation of the left lung. Of the allotransplanted dogs, five were killed on postoperative day (POD) 1, five on POD 2, seven on POD 3, and seven on POD 5, while all three autotransplanted dogs were killed on POD 5. Histological examination was performed on the 24 allotransplanted left lungs (group A), 12 autologous right lungs (group B), and bilateral lungs of the three autotransplanted dogs (group C). The lung tissue was stained with anti-ADF antibody, and the high-ADF-producing cells (ADFh cells) in a randomly chosen field were counted as an index of ADF expression. As the signs of rejection in the group A lungs became more severe with time, the ADFh cells increased in number: 1.68 +/- 1.15, 6.08 +/- 3.44, 14.03 +/- 6.09, and 47.74 +/- 18.89, on PODs 1, 2, 3, and 5, respectively. However, the number of ADFh cells in the group B and group C lungs did not become significantly different from that on POD 1 in group A. These results suggested that ADF/TRX expression may be useful for the early diagnosis of rejection of transplanted lungs.

Animals↗

PubMed1995

Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia: report of a case.

A case of hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia is reported. The patient had persistent severe jaundice with hepatosplenomegaly. A liver tumor was suspected because of the elevated serum alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor was treated with percutaneous ethanol injection therapy (PEIT). Nine months after initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.

Biliary Atresia↗

PubMed1995

Effects of wortmannin on glucose uptake and protein kinase C activity in rat adipocytes.

Wortmannin is known to be an inhibitor of myosin light chain kinase and phosphatidylinositol 3-kinase (PI 3-kinase) (J. Biol. Chem. 268, 25846, 1993). We studied the effects of wortmannin on insulin- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced glucose uptake, purified PKC activity and in vitro 80 kDa protein phosphorylation to elucidate the relationship between insulin-induced PI 3-kinase and PKC activations. Pretreatment with 10(-12)-10(-6) M wortmannin for 60 min resulted in a dose-responsive reduction of 10 nM insulin-stimulated glucose uptake in rat adipocytes. Pretreatment with 10(-6) M wortmannin resulted in 80% and 20% decreases of glucose uptake stimulated by insulin and TPA, respectively. Partially purified rat brain PKC activity and 80 kDa protein in vitro phosphorylation of rat adipocyte cytosol by addition of Ca2+ and phospholipid were dose-dependently decreased by 10(-8)-10(-6) M wortmannin; 20% decrease of PKC activity and 50% decrease of 80 kDa protein phosphorylation by 10(-6) M wortmannin were observed. These results suggest that wortmannin has a potent inhibitory effect on PI 3-kinase and a weak inhibitory effect on PKC activity, and both effects cause a significant inhibition of insulin-stimulated glucose uptake in rat adipocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1995

Surgical treatment of small cell carcinoma of the lung: advantage of preoperative chemotherapy.

To assess the effect of chemotherapy on postoperative survival of patients with small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto University between 1976 and 1991 were retrospectively reviewed. Seventeen patients (37.0%) received chemotherapy prior to as well as after surgery (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery (adjuvant therapy group), and the other six received no chemotherapy (non-chemotherapy group). The 5-year survival rate of patients with c-Stage I or II disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be higher, although with no statistical significance, than that in the adjuvant therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c-Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not satisfactory (10.0%), was significantly higher than that in the adjuvant therapy group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5 years. Moreover, multivariate analysis showed that failure to employ preoperative chemotherapy was the strongest prognostic factor causing a poor prognosis (P = 0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II disease postoperatively proved to have mediastinal lymph node involvement (pN2-3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the advantage of preoperative chemotherapy and the discrepancy between c- and p-stage, sufficient chemotherapy prior to surgery should be employed, and may realize a good prognosis in patients with c-Stage I or II disease. In contrast, patients with c-Stage III disease are not appropriate as candidates for surgery even if preoperative chemotherapy is performed.

Aged↗

PubMed1995

Evaluation of cases with combined bronchoplasty and pulmonary arterioplasty for the treatment of lung cancer.

Bronchoplasty and pulmonary angioplasty(PA-plasty) have been performed in recent years for lung cancer invading the bronchus and pulmonary artery. We evaluated the results and complications in patients who underwent such operations. There were 23 cases of bronchoplasty performed between 1988 and October 1993. Of these 23 cases, 9 underwent PA-plasty with bronchoplasty. There were 8 males and 1 female (mean 65.6 year-old). There were 8 patients with primary lung cancer(sq 5, ad 1, la 1, and sm 1) and 1 with metastatic lung tumor of colon cancer. One patient was in p-stage II, 6 in p-stage III, and 1 in p-stage IV. Seven patients underwent right upper lobectomy, 1 did the right upper and middle bilobectomy, and 1 did a left upper lobectomy. Bronchoplasty was performed using sleeve resection in 8 patients, and a wedge resection in 1 patient. PA-plasty was performed using sleeve resection and end to end anastomosis in 2 cases, and using side wall resection and plasty in 7 patients after clamp. Of 9 patients in whom both broncho- and PA-plasty were performed, there was one with the resected bronchial stump of cancer-positive. Total resection of the cancer was possible in the remaining 8 patients. Postoperative complications included 2 pneumonia, 2 empyema, and 1 each, acute cardiac failure, pulmonary thrombus, and chylothorax. The patients with empyema required re-operation using omentopexy or thoracoplasty. Long-term results showed that 2 patients died because of recurrence. Another patient died of respiratory failure. The remaining 6 patients were alive without any evidence of cancer. Pneumonectomy was avoided and the combination of PA-plasty and bronchoplasty was performed instead. However, the incidence of postoperative complications was high, indicating that utmost care must be exercised in the postoperative management of these patients.

Adenocarcinoma↗

PubMed1995

Long-term survival of surgical cases of lung cancer.

The survival rate and important prognostic factors were studied in patients observed for more than 10 years after surgery for squamous cell carcinoma and adenocarcinoma. The causes of death of long-term survivors and whether 5- or 10-year survival assures complete cure were also examined. The records of 324 patients operated on at Kyoto University Chest Disease Research Institute between January 1976 and May 1984 were analyzed. Five- and 10-year survival of these patients was 34.4 and 26.8%, respectively. There was no difference between the survival rate of adenocarcinoma and squamous cell carcinoma. Significant difference were noted in survival curves between stage I, II and IIIa, and stage IIIa and IIIb cancers (P = 0.001, P = 0.005, and P = 0.001, respectively). A significant difference in the survival curve was also observed between those with complete and with incomplete resection (P < 0.0001). Multivariate analysis using Cox proportional hazards method showed that ages, pathological N-factor, and complete resection were significant prognostic factors. Nine of the 16 patients who died between 5 and 10 years after surgery had recurrent or second primary lung cancer. Five of these nine patients were diagnosed as recurrence or distant metastases. Of the 39 patients who survived disease-free for 10 or more years after surgery, none died of new recurrence. It is speculated that 5-year survival would not indicate complete cure after surgery for lung cancer and patients should be followed up for more than 10 years.

Adenocarcinoma↗

PubMed1995

Band 4.2 Komatsu: 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene associated with total deficiency of band 4.2, hemolytic anemia with ovalostomatocytosis and marked disruption of the cytoskeletal network.

A novel mutation of 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene was detected in a 37-year-old Japanese patient with total lack of band 4.2 protein, designated as allele 4.2 Komatsu. In this patient, moderate uncompensated hemolytic anemia (red cell count 3.38 x 10(6)/microliters, hemoglobin 10.8 g/dl, hematocrit 30.9%, reticulocytes 12.4%, indirect bilirubin 1.84 mg/dl) with ovalostomatocytosis and increased osmotic fragility had been noted since birth. Family studies revealed no overt hemolytic anemia in other family members, essentially normal red cell morphology, and a normal profile of red cell membrane proteins including band 4.2. Genetic studies proved that the proband was homozygous and all the family members studied were heterozygous with respect to the mutation of 523 GAT-->TAT of the band 4.2 gene. Although band 4.2 was completely absent in the proband, trace amounts of 72 kDa and 74 kDa peptides were detected in the red cells of all the family members, in which the mutation of 424 GCT-->ACT at exon 3 of the band 4.2 gene (Nippon type) was not present. Electron microscopic studies with the surface replica method and the quick-freeze deep-etching method showed the most marked disorganization of the cytoskeletal network in the patient's red cells in situ among the cases of band 4.2 deficiencies we have studied. This suggests that the amino acid of the band 4.2 protein, which was affected by the present mutation in exon 4, is much more crucial for the functioning of band 4.2 protein than that at codon 142 in exon 3. The cytoplasmic domain of band 3 in the proband's red cells was essentially normal in protein chemistry and in gene analysis with single-stranded conformation polymorphism (SSCP).

Adult↗

PubMed1995

Flow cytometric functional analysis of multidrug resistance by Fluo-3: a comparison with rhodamine-123.

Using four cell lines including drug-sensitive K562/Parent cells, P-glycoprotein (Pgp)-mediated multidrug resistant (MDR) K562/VCR, K562/ADR and revertant K562/ADR-R cells, two fluorescent agents, Fluo-3 and rhodamine-123 (Rh-123), were compared as indicators in a functional assay of MDR. Cells were incubated with 4 microM Fluo-3 or 1 microM Rh-123 for 45 min and then the intracellular accumulation of the agent was measured using a flow cytometer. Verapamil (20 microM) or cepharanthine (biscoclaurine alkaloid, 10 microM) was added just before the fluorescent agents. Efflux patterns were also studied 60 min after incubation with or without verapamil and cepharanthine. Increased intracellular accumulation and a delayed efflux pattern of Fluo-3 by verapamil and cepharanthine were demonstrated in multidrug resistant K562/VCR and K562/ADR cells, indicating that Fluo-3 is another good indicator of MDR. However, a similar, but lower, increase in uptake and a delayed efflux pattern of Fluo-3 by verapamil and cepharanthine were also demonstrated even in Pgp-non-overexpressed K562/Parent cells. In contrast, accumulation of Rh-123 was not affected by verapamil and cepharanthine. To further study the Pgp dependency of Fluo-3, another cell line, K562/NC16 expressing minimum MDR1 mRNA, was cloned. Increased uptake and a delayed efflux pattern of Fluo-3, but not Rh-123, with verapamil or cepharanthine were again demonstrated in K562/NC16 cells, indicating that intracellular accumulation of Fluo-3 may be non-specifically influenced by verapamil and cepharanthine at very low levels of Pgp-related MDR, while the influx and efflux patterns of Rh-123 may be specifically affected by Pgp overexpression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Expression of adult T-cell leukemia-derived factor in bronchoalveolar lavage cells after canine lung transplantation.

Lung transplantation is now an accepted therapeutic option for patients with end-stage lung disease, and an early diagnosis of rejection is essential in the management of these patients. Adult T-cell leukemia-derived factor (ADF), known as a human homolog of thioredoxin, has been shown to be induced by a variety of stresses. In this study we examined ADF expression in lung tissues and bronchoalveolar lavage cells after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Allotransplantations were performed in adult mongrel dogs, and immunosuppression was performed from the day of operation to the fifth postoperative day. No immunosuppressant was given from the sixth to the tenth postoperative days. Animals were put to death on the tenth postoperative day. Bronchoalveolar lavage was performed on the fifth and tenth postoperative days, and the lavage cells and lung tissues were examined immunohistochemically with anti-ADF antibody. The grades of rejection were as follows: grade 1 in two animals, grade 2 in three animals, and grade 3 in two animals. The percentages of ADF high-producer cells in bronchoalveolar lavage cells on the fifth and tenth postoperative days were 4.29% +/- 2.65% and 26.6% +/- 3.99%, respectively (p < 0.01). The percentages of ADF high-producer cells in normal healthy dogs and in those with grade 1, grade 2, and grade 3 rejection were 3.00% +/- 1.64%, 20.5% +/- 9.00%, 25.5% +/- 6.06%, and 34.5% +/- 6.50%, respectively. The percentage in each rejection group was significantly higher than that in normal healthy dogs (p < 0.05). These results suggest that examination of bronchoalveolar lavage cells with ADF staining may be useful in the early diagnosis of rejection.

Animals↗

PubMed1995

Reliable cryopreservation of trachea for one month in a new trehalose solution.

We previously reported that trehalose, a reduced disaccharide, was effective in the preservation of lungs. In this study, we investigated the possibility of prolonged cryopreservation of tracheas in a preservative solution containing trehalose. Five rings of cervical trachea were removed and immersed in the preservative solution. The harvested tracheas were then cryopreserved and stored in a deep freezer at -85 degrees C. One month later, five rings of mediastinal trachea were removed. The cryopreserved cervical tracheas were thawed and autotransplanted in place of the excised mediastinal trachea (n = 6). The anastomotic site and graft were then covered with an omental pedicle. All six animals survived for more than 6 months. All grafts survived without any evidence of atrophy or stenosis. Microscopic examination of the grafts showed that the integrity of the tracheal tissues was maintained. Our findings show that consistent cryopreservation of the trachea for 1 month is possible in a preservative solution containing trehalose.

Animals↗

PubMed1995

Improved 20-hour canine lung preservation with a new solution--ET-Kyoto solution.

We developed a new solution, ET-Kyoto (ET-K) solution, and compared its efficacy in 20 h lung preservation with that of Euro-Collins (EC) solution in a canine left lung transplantation model. The lungs were flushed with ET-K solution (ET-K group, n = 5), with EC solution plus prostaglandin E1 (PGE1) pretreatment (EC + PGE1 group, n = 6) or with EC solution (EC group, n = 6), and were stored at 4 degrees C for 20 h. The function of left lung grafts was assessed 40, 70, and 130 min after transplantation. The arterial pressure of oxygen (PaO2) in the ET-K group was significantly greater than in the EC + PGE1 group (p < 0.05 or p < 0.01) and in the EC group (p < 0.01). The peak inspiratory pressure and wet to dry weight ratio in the ET-K group were significantly lower than in the EC + PGE1 group and in the EC group (p < 0.05 or p < 0.01). Pulmonary vascular resistance in the ET-K group 130 min after reperfusion was significantly lower than in the EC group (p < 0.05). All the transplanted lungs in the EC + PGE1 group and the EC group showed histological evidence of pulmonary edema, whereas all in the ET-K group showed no signs of edema. We concluded that ET-K solution is superior to EC solution with or without PGE1 pretreatment in 20 h canine lung preservation.

Animals↗

PubMed1995

Treatment of Pancoast tumors. Combined irradiation and radical resection.

Eighteen patients underwent combined preoperative irradiation and radical resection for a Pancoast tumor at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1977 and 1993. Four patients were applied a full radiation dose of 50-70 Gy and fourteen patients were applied a reduced dose of 33-40 Gy preoperatively. Eleven of these fourteen were applied a supplemental dose postoperatively up to a total dose of at least 50 Gy. Fourteen lobectomies, three partial resections, and one pneumonectomy were performed with combined resection of chest wall or adjacent structures: rib in 14, vertebra in 4, brachiocephalic vein in 3, subclavian artery in 2, spinal nerve in 3, sympathetic truncus in 2, phrenic nerve in 2 cases. Chest walls were reconstructed with marlex mesh in 5 patients, and two subclavian arteries and one brachiocephalic vein were repaired with artificial grafts. In 13 patients complete resections were achieved, but in the other 5 only incomplete resections leaving residual tumor were achieved. Incomplete resections consisted of 4 positive stumps at the brachial plexus of the apex and one aortic involvement by a metastatic lymph node. There was one operative death. Median survival was 21.6 months and the 5-year-survival rate was 38.5% for all 18 patients. In the complete resection group 5-year-survival was 56.4%, but in the incomplete-resection group 0%, showing a significantly more favorable result for the complete resection group. It is considered that evidence of incomplete resection influences the prognosis and that particularly tumor invasion to the brachial plexus may serve as a limiting factor for surgery.

Adult↗

PubMed1995

Pulmonary metastasis of polymorphous low-grade adenocarcinoma of the minor salivary gland.

A surgical case of pulmonary metastases of polymorphous low-grade adenocarcinoma (PLGA) originating from the minor salivary gland in the soft palate in a 62-year-old woman is reported. PLGA has been to be a locally invasive carcinoma without distant metastases; thus our case is the first reported case with histologically-proven distant metastases to the lung. We emphasise that attention should be paid to distant metastases especially to the lung even in case of PLGA.

Adenocarcinoma↗

PubMed1995

Tissue factor expression in endothelial cells in health and disease.

Plasma tissue factor (TF) antigen can be detected in healthy volunteers and may be significantly increased in patients with disseminated intravascular coagulation (DIC). Plasma TF antigen level in patients with DIC was significantly reduced after therapy. The TF activity of human umbilical vein endothelial cells (HUVEC) cultured with lipopolysaccharide (LPS), cytokines and the medium of cultured mononuclear cells (MNC) was significantly increased. TF expression was induced in HUVEC and MNC by incubation with lipoproteins, suggesting that hyperlipidaemia is a direct risk factor in thrombotic disease. TF activity in HUVEC was significantly increased in the presence of plasma and this activation was higher in patients with thrombotic thrombocytopenic purpura (TTP) and DIC. Enhanced TF production by endothelial cells may be important in the pathogenesis of thrombotic diseases.

Cells, Cultured↗

PubMed1995

Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis.

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.

Aged↗

PubMed1995

Characterization of the murF gene of the cyanobacterium Synechocystis sp. PCC 6803.

The murF gene encodes UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2, 6-diaminopimeloyl-D-Ala-D-Ala synthetase (EC 6.3.2.15), which catalyses the final step in the synthesis of UDP-N-acetylmuramoyl-pentapeptide, the precursor of murein. An open reading frame identified as the murF gene was found in the genome of the cyanobacterium Synechocystis sp. PCC 6803. The murF gene encodes a polypeptide of 454 amino acid residues with a predicted molecular mass of 48 kDa. The murF gene is present as a single-copy gene in the genome of Synechocystis sp. PCC 6803. The amino acid sequence deduced from the murF gene is 39% identical to that of the product of the murF gene of Escherichia coli. The cyanobacterial murF gene complemented a temperature-sensitive mutation in a murF-deficient strain of E. coli, restoring the mutant's ability to synthesize a cell wall and to survive at high sublethal temperatures.

Amino Acid Sequence↗