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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 559 records · Page 31Linked to original sources

The role of tumor-associated antigen in bovine leukemia virus-induced lymphosarcoma.

Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. To clarify the way in which BLV-infected cattle progress from the asymptomatic stage to the lymphoma stage, we produced a monoclonal antibody (MAb) c143 which recognized a tumor-associated antigen (TAA) that is phosphorylated in the transformed state of BLV-infected B-lymphoid cells. Since the nature of c143 TAA was likely to be that of the major histocompatibility complex (MHC) class II antigens, we isolated cDNAs for bovine MHC (BoLA) class II a-chains and b-chains, produced transfectants that expressed a single type of BoLA class II molecules and analyzed them by flow cytometry with c143 MAb. The c143 MAb recognized the transfectant expressing BoLA-DR but not BoLA-DQ. However, the treatment of lymphocytes with c143 or anti-BoLA-DR MAb induced different effects. Although mixed lymphocyte reaction (MLR) was inhibited by the addition of anti-BoLA-DR MAb, the c143 MAb did not inhibit a proliferative response of T cells in MLR. Increased spontaneous proliferation of lymphocytes in healthy donors was obtained in the presence of c143 MAb but not anti-BoLA-DR MAb, and was much in lymphocytes from the carrier. Moreover, the patterns of immunohistological staining for c143 MAb in BLV-infected sheep showed distinguishing differences from those of anti-BoLA-DR MAbs.

Animals↗

Tumor-associated antigen in lymph nodes during the progression of enzootic bovine leukosis.

A monoclonal antibody, (MAb) c143, that recognizes a tumor-associated antigen (TAA) that is upregulated on neoplastic B cells in cattle with enzootic bovine leukosis (EBL), was used as a marker to study disease progression. Immunohistochemical examination of neoplastic tissue and lymph nodes from animals with EBL, revealed three morphologically definable stages of change in the architecture of lymph nodes associated with infiltration and proliferation of neoplastic cells: 1) presence of c143 positive cells at the marginal sinus with no apparent changes in lymph node architecture at the earliest stage of neoplastic cell accumulation, 2) presence of positive cells extending into and distorting the architecture of the lymph node with clear evidence of proliferation, and 3) presence of positive cells throughout the lymph node with total disruption of lymph node architecture. The results indicated that, at the earliest stages of EBL, neoplastic cells in peripheral blood may accumulate at the marginal sinus area and subsequently proliferate and infiltrate pressing follicles leading to the development of clinical signs of lymphosarcoma.

Animals↗

Point mutation of p53 tumor suppressor gene in bovine leukemia virus-induced lymphosarcoma.

To elucidate the mechanism of leukemogenesis induced by bovine leukemia virus (BLV), the abnormality of p53 tumor suppressor gene was examined using the sequencing method of polymerase chain reaction (PCR)-amplified DNA from peripheral blood lymphocytes (PBL) and tumors from BLV-infected cattle that showed evidence of different stages during the progression of enzootic bovine leukosis (EBL). Mutations of the p53 gene were found in tumor cells from cattle with EBL, but not in PBL from BLV-free normal cattle or BLV-infected cattle without any evidence of tumor, suggesting mutation of p53 gene occurred specifically at the lymphoma stage of the disease. Twelve of eighteen cattle with EBL had seven missense and five silent mutations. The mutations were mapped to the highly evolutionarily conserved regions of p53 gene, and were involved in the DNA binding of p53. Thus, it appeared that the p53 point mutation is one of the critical events leading from the asymptomatic stage to the lymphoma stage.

Animals↗

Chloroquine induces basophilic differentiation of HL-60 cells.

Many agents have been known to induce the differentiation of HL-60 cells. However, only a small number of reports on the basophilic differentiation of this cell line are known. In this study we show that the exposure of HL-60 cells to chloroquine induces to differentiate into basophils. This chloroquine-induced change suggests that the increase in intracellular pH and the upregulation of p21 with subsequent downregulation of cdc2 kinase are triggers for basophilic differentiation of this cell line.

Basophils↗

Retrograde cerebral perfusion with pharmacological cerebral protection in the repair of aortic arch aneurysm.

Twenty-six patients underwent resection and graft replacement of an aortic arch aneurysm (proximal arch,5; transverse arch:2, distal arch,8; and type A dissecting aneurysm. Retrograde cerebral perfusion with pharmacological cerebral protection was carried out during aortic arch aneurysm surgery. Prostaglandin E1, thiopental methylpredonisolone were administered for cerebral protection during core cooling. D-Mannitol and deferoxamine mesylate (radical scavengers) were administered for prevention of reperfusion injury. retrograde cerebral perfusion time was 48 +/- 16 minutes (range 20-80 minutes). Perfusion flow was 288 +/- 93 mL/min (range 150-500 mL/min). Since retrograde cerebral perfusion requires no arterial cannulation or aortic cross clamp, the operative field is simplified, and the risks of air and debris emboli to the brain were minimized. Reconstruction was designed to minimize the circulatory arrest time. Eleven cases underwent emergency surgery due to rupture and acute dissection. Five patients (19.2%) died (three from bleeding from the distal anastomosis, one from postoperative DIC and, one from intraoperative dissection). The remaining 21 patients survived neurologically intact. Retrograde cerebral perfusion with pharmacological cerebral protection is a very simple method to prevent air embolism or thromboembolism in aortic arch aneurysm surgery and allows aortic arch replacement in a bloodless field. In spite of the extended circulatory arrest time, recovery of consciousness was complete.

Adult↗

[Treatment of prostate cancer by radiotherapy].

Fifty-seven patients with clinically localized prostate cancer were treated by radical prostatectomy or external radiation therapy following pelvic lymphadenectomy. Comparing the outcome of radiotherapy with that of prostatectomy in 42 T2 patients without lymph node metastasis, the 5-year cause-specific survival did not differ between the radical prostatectomy group (n = 31) and radiotherapy group (n = 11). The 5-year disease-free survival of the prostatectomy group, however, was superior to that of radiotherapy group (p = 0.01). To cure patients with T2 prostate cancer, therefore, it is supposed that radical prostatectomy should be performed. To improve the treatment outcome after radiotherapy, stereotactic radiosurgery for prostate cancer has been attempted in our institution. Phantom experiments using a linear accelerator demonstrated a round dose distribution, and high reproducibility of prostate positioning was confirmed by CT when a thermoplastic immobilization device was used to fix the pelvis. In one patient with localized prostate cancer treated by radiosurgery, acute complication has not been recognized during the 5 week follow-up. Radiosurgery may be available to treat clinically localized prostate cancer.

Humans↗

[Monitoring for spinal cord ischemia by the use of the motor evoked potentials, the evoked spinal cord potential and the segmental evoked spinal cord potential during thoracoabdominal aortic surgery--a case report].

A 55-year-old woman, who was detected an enlargement of the aorta with body CT, was admitted to our hospital. Preoperative examination revealed that the aneurysm was expanded from ascending aorta to the abdominal aorta above the celiac artery. She underwent total arch replacement using elephant trunk technique. Forty-four days after operation, she underwent thoracoabdominal aortic replacement with monitoring for spinal cord ischemia by the use of the motor evoked potentials (MEP), the evoked spinal cord potential (ESCP) and the segmental evoked spinal cord potential (S-ESCP). Under the partial cardiopulmonary bypass with femoral venous drainage and femoral arterial cannulation on normothermia, the aneurysmal part of the aorta was segmentally cross-clamped and the three lumbar arteries and the celiac artery were reconstructed one by one. During the operation, the monitor showed no remarkable change, even while the aorta was cross clamped. Her postoperative course was uneventful without any spinal cord damage. Combined use of MEP, ESCP, and S-ESCP was useful for monitoring spinal cord injury during thoracoabdominal aneurysmal repair.

Aorta, Thoracic↗

Rupture of a dissecting aneurysm into the superior vena cava in Marfan's syndrome.

Aneurysmal dilatation of the aorta with subsequent dissection or rupture occurs frequently in patients with Marfan's syndrome. These complications are among the major causes of death. We report the case of a 51-year-old man with annulo-aortic ectasia in Marfan's syndrome. Acute aortic dissection and rupture into the superior vena cava occurred 8 years after aortic valve replacement. The preoperative diagnosis was made by right heart catheterization and computed tomography. A markedly increased left-to-right shunt occurred with rapid enlargement of the fistula due to the fragility of the aortic wall characteristic of Marfan's syndrome. Postmortem examination demonstrated severe medial necrosis with rupture of the aortic wall into the superior vena cava which was adherent to the suture line of the aortotomy from the previous surgery. Type A aortic dissection with severe congestive heart failure strongly suggested rupture into the pulmonary circulation.

Aortic Dissection↗

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: independence of tubular necrosis and sulfhydryl depletion.

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin (TRX). ADF/TRX is a conserved multifunctional reductant presumably associated with redox regulation of the cellular environment; it works in vitro as a cytokine, free radical scavenger, activator of transcription factors, and substrate for several enzymes. In the present series of experiments, we studied the expression and intracellular localization of ADF/TRX in mouse kidney from two different renal tubular injury models: a free radical-associated model with ferric nitrilotriacetate (Fe-NTA) and a free radical-independent model with HgCl2. Markers of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine, thiobarbituric acid-reactive substances, and 4-hydroxy-2-nonenal-modified proteins, were significantly increased in kidney from male C57B/6 mice 1 hour after a single intraperitoneal injection of Fe-NTA (5 mg iron/kg). However, in kidney from mice given a subcutaneous injection of HgCl2 (5 mg Hg/kg), none of these markers were increased, despite tubular necrosis with sulfhydryl depletion. In the Fe-NTA model only, Northern and Western blot analyses of the kidney revealed induction of ADF/TRX (> 2.5-fold) after 16 hours and translocation of ADF/TRX from the cytoplasmic to nuclear fraction (> 3.5-fold) after 24 hours. Immunohistochemistry showed a patchy distribution of ADF/TRX in the normal renal proximal tubules. In ex vivo experiments using serial normal kidney frozen sections, it was found that renal proximal tubules with low expression of ADF/TRX were more vulnerable to oxidative stress mediated by Fe-NTA. Collectively, these data suggest that: (a) ADF/TRX is induced and translocated to nuclei by oxidative damage mediated by Fe-NTA in the renal proximal tubules; (b) induction of ADF/TRX is independent of tubular necrosis or sulfhydryl depletion; and (c) ADF/TRX is involved in the cellular defense mechanisms in vivo against oxidative damage.

8-Hydroxy-2'-Deoxyguanosine↗

[Abnormal agglutination by reducing surface charge of red cell membrane as source of error in ABO typing and actual cases of incompatible ABO blood transfusion due to various factors].

T activation of red cells results from the effects of microbial sialidase catalysing the cleavage of sialic acid from red cell membrane. Abnormal agglutination may be induced when human-derived antiA,B antibodies containing antiT are used. By the using of mouse-derived antiA,B monoclonal antibodies this type of polyagglutination as source of error could be overcome. Most common cause of ABO mismatch is due to more simple technical or clerical error resulting in transfusion of the wrong blood to the recipient. Three such cases with non-fatal hemolytic transfusion reaction are described.

Adolescent↗

Characterization and targeting of the murine alpha2-antiplasmin gene.

Alpha2-Antiplasmin (alpha2-AP) is the main physiological plasmin inhibitor in mammalian plasma. As a first step toward the generation of alpha2-AP deficient mice, the murine alpha2-AP gene was characterized and a targeting vector for homologous recombination in embryonic stem (ES) cells constructed. Alignment of nucleotide sequences obtained from genomic subclones allowed location of exons 2 through 10 of the alpha2-AP gene, but failed to identify the 5' boundary of exon 1. Compared to the human gene, exons 2 through 9 in the murine gene have identical size and intron-exon boundaries obeying the GT/AG rule. The 5' boundary of exon 10 is identical in both genes while the 3' non-coding region is 64 bp longer in the human gene. Introns 2, 3, 6 and 8 have similar sizes in the mouse and human genes; intron 1 is 6-fold smaller, introns 5, 7 and 9 are 2- to 3-fold smaller, whereas intron 4 is about 2-fold larger in the mouse gene. Compared to the human 5' flanking sequence, an insertion of a simple repeat region with sequence (TGG)n has occurred. The open reading frame of the mouse alpha2-AP gene encodes a 491-amino-acid protein comprising the experimentally determined NH2-terminus of the mature protein Val-Asp-Leu-Pro-Gly-. A targeting vector, pPNT.alpha2-AP, was constructed by introducing a homologous sequence of 8.3 kb in total in the parental pPNT vector. In pPNT.alpha2-AP, the neomycin resistance expression cassette replaces a 7 kb genomic fragment comprising exon 2 through part of exon 10 (including the stop codon), which represents the entire sequence encoding the mature protein, including the fibrin-binding domain, the reactive site peptide bond and the plasmin(ogen)-binding region. Electroporation of 129R1 embryonic stem (ES) cells with the linearized vector pPNT.alpha2-AP yielded three targeted clones with correct homologous recombination at the 5'- and 3'-ends, as confirmed by Southern blot analysis of purified genomic DNA with appropriate restriction enzymes and probes. These targeted clones will be used to generate alpha2-AP deficient mice.

Amino Acid Sequence↗

[Treatment outcome of radical cystectomy during a 10-year period (June 1984-September 1994) at Department of Urology, Fukui Medical School].

The treatment outcome was evaluated in 63 patients with bladder cancer more than 2 years after cystectomy. Cisplatin-based combination chemotherapies were given to 40 patients after the operation as an adjuvant therapy and two patients with T4 or N2 bladder cancer received chemotherapy before the operation as a neoadjuvant therapy. The extent of infiltration of the removed tumors was pTa in 5, pT1 in 18, pT2 in 8, pT3a in 6, pT3b in 17, and pT4 in 9 cases. Regional lymph node metastases were present in 10 cases (16%). Nineteen patients died of tumor recurrences. The 5-year acturial survival rates at each stage were 60% for stage pTa, 78% for stage pT1, 63% for stage pT2, 83% for stage pT3a, 33% for stage pT3b and 38% for stage pT4, respectively. A significant difference (p < 0.05) in survival curve was observed between pT3a and pT3b. The prognosis of patients with tumors extending beyond the bladder muscles is extremely unfavourable, with the exception of bladder cancers infiltrating the neighboring organ (pT4a), the removal of which may result in lasting survival in a part of the cases. Effective adjuvant treatment is required for patients with bladder tumors penetrating the bladder wall.

Adult↗

Pulmonary hemodynamics modify the rat pulmonary artery response to injury. A neointimal model of pulmonary hypertension.

Hemodynamic factors have profound influences on blood vessels. To test the hypothesis that hemodynamic conditions modify the pattern of remodeling in response to injury, monocrotaline (MCT) injury in Sprague-Dawley rats was followed 1 week later by left pneumonectomy to increase blood flow to the right lung. Right pulmonary artery remodeling in these MCT plus pneumonectomy animals was compared with animals receiving MCT or pneumonectomy alone. Neointimal changes developed in more than 90% of all right lung intra-acinar vessels 5 weeks after MCT injury (4 weeks after pneumonectomy). Neointimal lesions did not develop in untreated animals or in animals receiving MCT or pneumonectomy only. Animals with a neointimal pattern of remodeling developed severe right ventricular hypertrophy (RVH) whereas animals with a medial hypertrophy pattern of remodeling (MCT only) developed moderate RVH compared with control animals. Neointimal lesions and RVH were similar whether injury preceded pneumonectomy or vice versa. To exclude the possibility that neointimal lesions resulted from injury plus post-pneumonectomy compensatory lung growth, rather than injury plus increased flow, a left subclavian-pulmonary artery anastomosis was substituted for pneumonectomy. Neointimal lesions and severe RVH developed in these animals but were not seen in animals receiving either MCT or anastomosis only. These studies demonstrate an important role for hemodynamics in determining the pattern of pulmonary vascular remodeling after injury.

Actins↗

Rapid quantitative analysis of oleandrin in human blood by high-performance liquid chromatography.

A simple and rapid method for quantitation of oleandrin in human blood has been developed using an Extrelut column and high-performance liquid chromatography (HPLC). Blood samples spiked with oleandrin were mixed with distilled water and applied to an Extrelut column for elution with ethyl acetate before HPLC. The HPLC separation of the compound from endogeneous impurities was generally satisfactory with the use of a reversed-phase column. Oleandrin showed excellent linearity in the range of 0.05-10 micrograms/g and the limit of detection was 0.02 microgram/g for human blood. The recovery of the compound, which had been spiked to human blood, was more than 90%. The present method is simple and more rapid than those so far reported, and seems useful for analysis of oleandrin in the cases of oleander poisoning.

Cardenolides↗

[Low flow anesthesia using a fresh gas flow of 600 ml.min-1 for 5 hours].

Low flow anesthesia (LFA) using a fresh gas flow (FGF) of 600 ml.min-1 with oxygen and nitrous oxide flow each set at 300 ml.min-1, and dial setting of sevoflurane 3% was administered to 30 patients for a duration of 5 hours. There were no problems such as unsuitable concentrations of nitrous oxide and sevoflurane in inspired and expired gases or low FIO2 below 0.3 during anesthesia in 15 patients of group A. Their body weight was 53 +/- 5 kg. FIO2 decreased below 0.29 at about 4 hours in 7 patients of group B weighing 62 +/- 6 kg, and at about 1 h in 8 patients of group C weighing 71 +/- 7 kg. In group A and B, the sum of concentrations of oxygen, nitrous oxide and sevoflurane in inspired gas decreased for a moment and recovered as anesthesia progressed, but in group C, it kept decreasing without recovery. The body weight was significantly different among the 3 groups (P < 0.05). It was suggested that in group A the FGF per body weight was suitable; in group B though oxygen flow was larger than oxygen consumption, hypoxia occurred due to saturation of nitrous oxide in the body; and in group C the FGF was insufficient. The compound A was detected in the breathing circuit, and the concentration was around 20 ppm and it did not depend on the duration of LFA. It was concluded in this study that LFA using the FGF of 600 ml.min-1 with setting of 3% sevoflurane, 50% oxygen and nitrous oxide, could be performed safely without risks such as hypoxia and severe delay of induction for patients weighing 53 +/- 5 kg for a duration of 5 hours.

Adult↗

[A case of advanced primary ureteral squamous cell carcinoma responding to combination chemotherapy with cisplatin and 5-fluorouracil].

A 63-year-old female with left ureteral tumor metastasizing to the left iliac lymph node was treated with left total nephroureterectomy. The histopathological diagnosis was squamous cell carcinoma of the ureter, G1 INF beta, pT2, pR0, pV1 and pL0. Three cycles of chemotherapy were performed postoperatively with cis platin and 5-fluorouracil. A major response was obtained (tumor regression rate, 57%). She received 60 Gy radiotherapy to the left iliac region postchemotherapy (postradiotherapy tumor regression rate, 74%). No evidence of the tumor relapse was found 7 months after irradiation.

Antineoplastic Combined Chemotherapy Protocols↗