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Biomedical subjects

S Asakura

Publications and source records attributed to S Asakura.

At least 37 records · Page 2Linked to original sources

Allogeneic peripheral blood stem cell transplantation for the treatment of refractory follicular lymphoma.

A 38-year-old male with follicular lymphoma at clinical stage IV failed to achieve complete remission (CR), and developed leukemic change. After the patient was further treated with intensive chemotherapy for acute lymphoblastic leukemia, lymphoma cells in the peripheral blood and bone marrow disappeared, but the bulky mass persisted. Then, the patient received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from his human lymphocyte antigen (HL A)-identical brother following high-dose cyclophosphamide and 12 Gy total body irradiation, and the patient achieved CR with the disappearance of Bcl-2 rearrangement. The patient is now alive in continuous CR for more than 19 months after allo-PBSCT.

Adult↗

D-amino-acid oxidase is not present in the mouse liver.

Since there are conflict reports on the presence of D-amino-acid oxidase in the mouse liver, this problem was examined. D-Amino-acid oxidase activity was not detected in the homogenates of the mouse liver, lung, or heart, whereas it was detected in the homogenates of the mouse kidney and brain. Western blotting showed that a protein which reacted with the antiserum against pig D-amino-acid oxidase was present in the homogenates of the mouse kidney and brain but not in those of the liver or heart. Northern hybridization using a D-amino-acid oxidase cDNA probe detected a hybridizing signal in poly(A)+ RNAs extracted from the mouse kidney and brain but not in those from the liver, heart, or lung. Reverse transcription-polymerase chain reaction using three primer pairs always amplified D-amino-acid oxidase cDNA fragments of expected sizes in the mouse kidney and brain but very rarely did so in the liver, heart, or lung. The results indicate that D-amino-acid oxidase is not present in the mouse liver in a measurable amount.

Animals↗

Fibroblasts spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptor alphavbeta3 on their surface.

Human and murine fibroblasts were found to spread far more avidly on fibrin monomer monolayers than on immobilized fibrinogen, indicating that removal of fibrinopeptides by thrombin is a prerequisite for the fibrin-mediated augmentation of cell spreading. In fact, cell spreading was not efficiently augmented on monolayers of a thrombin-treated dysfibrinogen lacking the release of fibrinopeptide A due to an Aalpha Arg-16 --> Cys substitution. Since a synthetic Arg-Gly-Asp (RGD)-containing peptide inhibited the fibrin-mediated cell spreading, subsequent dissociation of the carboxyl-terminal globular domain of the Aalpha-chains appears to render the RGD segments accessible to the cell-surface integrins. In support of this, fibrin-augmented cell spreading was inhibited by an antibody recognizing a 12-kDa peptide segment with gamma Met-89 at its amino terminus, which is located in close association with the RGD segment at Aalpha 95-97 in the helical coiled-coil interdomainal connector. The fibrin-mediated augmentation of cell spreading was inhibited not only by an antibody against human vitronectin receptor (LM 609) but also by an antibody against the beta1 subunit of integrin (mAb13), suggesting that the beta1-class integrin together with a vitronectin receptor, alphavbeta3, is mobilized onto the surface of fibroblasts upon contact with the fibrin monomer monolayer.

Animals↗

Quinoline-induced chromosome aberrations and sister chromatid exchanges in rat liver.

Induction of chromosome aberrations and sister chromatid exchanges (SCEs) was studied in hepatocytes of F344 rats exposed in vivo to the hepatocarcinogen quinoline (Q). Hepatocytes were isolated 4-48 hr after a single dose of 200 mg/kg body weight or 24 hr after 28 repeated doses (once a day) of 25-200 mg/kg body weight/day by gastric intubation, and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 hr. A single dose of Q induced chromosome aberrations in up to 22% of metaphase cells, and SCEs with a frequency of up to 1.27 per chromosome 12 hr after the dose, while the control values were 1% and 0.63 per chromosome, respectively. Treatment with 28 repeated doses of Q induced significant chromosome aberrations and SCEs dose-dependently. Cytogenetic damage induced induced in the liver by repeated doses of Q was greater than induced by a single dose. Furthermore, Q induced replicative DNA synthesis in the liver, but failed to induce micronucleus formation in the bone marrow. The noncarcinogen 8-hydroxyquinoline was also examined and found to be essentially non-genotoxic to rat liver. These results show that Q is a genotoxic carcinogen to rat liver and the present method of in vivo cytogenetic assay should be useful for evaluating the genotoxicity of hepatocarcinogens.

Animals↗

Analysis of cytogenetic effects and DNA adduct formation induced by safrole in Chinese hamster lung cells.

Safrole (1-allyl-3,4-methylenedioxybenzene) was tested for its ability to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) and to form DNA adducts in Chinese hamster lung (CHL) cells, in order to investigate the relationship between cytogenetic effects and DNA adduct formation under the same treatment conditions. The cells were treated with 0.025-0.2 mg/ml safrole in the presence or absence of rat liver postmitochondrial supernatant fraction (S9). Safrole induced significant SCEs and CAs dose-dependently in the presence of S9. SCEs ranged in number from 15.6 to 21.1 SCEs/cell and CAs were observed in 4-37% of cells. Using the 32P-postlabeling assay, two major and two minor safrole-DNA adducts were detected in DNA digests obtained from CHL cells in the presence of S9. The levels of total DNA adducts ranged from 1.3 to 22.8 adducts/10(7) nucleotides. The two major adducts were shown to be guanine derivatives since these adducts comigrated on polyethylenimine plates with the adducts produced by the reaction of safrole with 2'-deoxyguanosine 3'-monophosphate. A correlation was seen between DNA adducts and SCEs or CAs. Neither induction of SCEs and CAs nor formation of DNA adducts was observed in the absence of S9. These findings suggest that SCEs and CAs induced by safrole result from covalent DNA modification metabolically activated by S9 in cultured cells.

Animals↗

A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen.

Two groups of anti-plasminogen monoclonal antibodies, whose epitope was either in the kringle 1 + 2 + 3 domain (F3P2, F11P5, F11P6, and F12P18) or the kringle 5 domain (F1P6 and F12P16), were isolated and their effects on the conformation of plasminogen were explored. All antibodies except F1P6 had 3- to 10-fold higher affinity toward Lys-plasminogen than Glu-plasminogen. F1P6 exhibited a comparable affinity to Glu- and Lys-plasminogen. Among these, only F11P5 binding was inhibited by epsilon-amino-nu-caproic acid (EACA) in a concentration-dependent manner, with half maximal inhibition at 3 mM. From a competition assay, we concluded that the epitopes of F11P5, F11P6, and F12P18 should be very close, and located at or near the low affinity lysine binding site on the kringle 2 + 3. These three antibodies dramatically enhanced the binding of Glu-plasminogen to the other antibodies, except to F1P6. Interestingly, F3P2, whose non-overlapping epitope was in the kringle 2 + 3 domain, also augmented the binding of Glu-plasminogen to the other antibodies. In contrast, we did not observe enhanced binding of Lys-plasminogen to one antibody in the presence of the other antibodies, and the binding of Glu-plasminogen to these antibodies did not increase in the presence of 10 mM EACA. In the presence of these antibodies, including F1P6, Glu-plasminogen bound more efficiently to immobilized degraded fibrin, with a binding profile similar to Lys-plasminogen. All antibodies except F1P6 enhanced the conversion rate of plasminogen to plasmin remarkably. Taken together, we propose that these two groups of monoclonal antibodies can dissociate the intramolecular interactions of Glu-plasminogen and induce the conformational transition of Glu-plasminogen to Lys-plasminogen. In addition, the kringle 2 + 3 and kringle 5 structures of Glu-plasminogen liganded with EACA are distinct from the Lys-plasminogen structure.

Animals↗

[Two cases of tracheal injuries secondary to blunt trauma].

We present two cases of injury to the cervical trachea and the tracheal bifurcation due to blunt trauma. A 20-year-old man sustained complete disruption of the cervical trachea during a traffic accident. He underwent end-to-end anastomosis of the disrupted trachea. Nevertheless, 3 weeks after the initial surgery, tracheostomy was required because of suture failure. Two months after the second procedure, he underwent closure of the tracheostoma. Granulation developed temporarily, but diminished thereafter. The second case was a 14-year-old boy. He sustained a longitudinal laceration about 3 cm from the tracheal over the membranous portion during a traffic accident. The laceration was successfully repaired by interrupted sutures with absorbable materials. Our experiences emphasize the importance of debridement of the injured cartilageous portion during treatment of tracheal injury due to blunt trauma and the difficulty in managing complete disruption of the cervical trachea with bilateral paralysis of the recurrent nerve.

Accidents, Traffic↗

A gamma Gly-268 to Glu substitution is responsible for impaired fibrin assembly in a homozygous dysfibrinogen Kurashiki I.

A new type of gamma Gly-268 (GGA) to Glu (GAA) substitution has been identified in a homozygous dysfibrinogen by analyses of the affected polypeptide and its encoding gene derived from a 58 year-old man manifesting no major bleeding or thrombosis. The functional abnormality was characterized by impaired fibrin assembly most likely due to failure to construct properly aligned double-stranded fibrin protofibrils. This presumption was deduced from the following findings: (1) Factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains progressed in a normal fashion, indicating that the contact between the central E domain of one fibrin monomer and the D domain of another took place normally; (2) Nevertheless, factor XIIIa-catalyzed cross-linking of the fibrinogen gamma-chains was obviously delayed, suggesting that longitudinal association of D domains of different fibrin monomers, ie, D:D association was perturbed; (3) Plasminogen activation catalyzed by tissue-type plasminogen activator was not as efficiently facilitated by polymerizing fibrin monomer derived from the patient as by the normal counterpart. Therefore, gamma Gly-268 would not be involved in the 'a' site residing in the D domain, which functions as a complementary binding site with the thrombin-activated 'A' site in the central E domain, but would be rather involved in the D:D self association sites recently proposed for human fibrinogen. Thus, the gamma Glu-268 substitution newly identified in this homozygous dysfibrinogen seems to impair proper alignment of adjacent D domains of neighboring fibrin molecules in the double-stranded fibrin protofibril, resulting in delayed fibrin gel formation.

Afibrinogenemia↗

Tissue localization of transforming growth factor-beta1 in pulmonary eosinophilic granuloma.

Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma.

Collagen↗

[A case of congenital ejaculatory duct obstruction].

We report a case of congenital ejaculatory duct obstruction treated successfully by transurethral incision. A 33-year-old man was referred for evaluation of primary infertility. His semen analysis showed volumes of 1.7 ml at average and azoospermia. Clinical examinations revealed right undescended testicle, absence of the left kidney and axial rotation of right kidney. Left vasogram showed dilated but intact seminal vesicle with no contrast material visible in the bladder. Following removal of right undescended testicle, transurethral incision of the left side of the prostatic urethral floor near the vermontanum was performed. Transurethral vesiculogram showed dilated but not cystic ejaculatory duct. Eight months postoperatively semen analysis showed a volume of 3.5 ml, a concentration of 61.3 x 10(6)/ml and motility rate of 51.8%. However, semen analysis 18 months postoperatively showed azoospermia again. After re-transurethral incision, his sperm concentration increased to 15.2 x 10(6)/ml. However, his wife didn't become pregnant yet.

Adult↗

[Renal cell carcinoma accompanied with ossification: a case report].

Renal cell carcinoma accompanied with ossification reported in Japan is very rare. We report a case of renal cell carcinoma with ossification pathologically in a 61-year-old woman. She suddenly presented with hypercalcemia that caused acute renal failure, 6 months after the operation and died shortly thereafter. We discuss the relationship between the tumor and the hypercalcemia.

Acute Kidney Injury↗

Biodegradation of toluene diamine (TDA) in activated sludge acclimated with aniline and TDA.

The biodegradability of toluene diamine (TDA) which has been regarded as a "recalcitrant compound" was examined in activated sludges. In this study, a microorganic-enzyme system which metabolized TDA was obtained by acclimating the activated sludge with aniline and TDA. In the sludge subject to be 200 days' acclimation, the considerable increase in respiration rate with the addition of TDA, accompanied the sharp decrease in its concentration. This indicated that TDA was metabolized fortuitously. The rate of biodegradation of TDA in the absence of aniline was first order with respect to its concentration when the initial TDA concentration was less than about 5 mg/l. The rate constant in this relation was proportional to mixed liquor suspended solid (MLSS). However, when the initial TDA concentration exceeded 5 mg/l, the plots were deviated from a first order rate equation.

Aniline Compounds↗

Comparison of autoradiography, liquid scintillation counting and immunoenzymatic staining of 5-bromo-2'-deoxyuridine for measurement of unscheduled DNA synthesis and replicative DNA synthesis in rat liver.

Different methods for evaluating unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) were studied in hepatocytes of F344 rats exposed in vivo to dimethylnitrosamine (DMN) or CCl4. Hepatocytes were isolated and incubated in Williams' medium E supplemented with either [3H]thymidine for autoradiography or 5-bromo-2'-deoxyuridine for immunoenzymatic staining. In the method of liquid scintillation counting, the cells were incubated with [3H]thymidine with or without hydroxyurea. The nuclear fraction was isolated and the incorporation of [3H]thymidine into nuclear DNA was determined by a liquid scintillation counter. DMN at doses of 0.625-5 mg/kg body weight induced UDS of 1.6-37.9 (0 dose; -6.9) net grains/nucleus measured by autoradiography and 337-1377 (0 dose; 177) dpm/microgram DNA in the presence of hydroxyurea measured by a liquid scintillation counter. CCl4 at doses of 50-400 mg/kg body weight induced RDS in 1.5-12.1% (0 dose; 0.12%) and 1.8-14.6% (0 dose; 0.16%) of cells with the methods of autoradiography and immunoenzymatic staining, respectively, and of 2991-24256 (0 dose; 324) dpm/microgram DNA in the absence of hydroxyurea with the method of liquid scintillation counting. Similar dose-dependent induction of UDS and RDS was observed with these methods. These results suggest that the methods of liquid scintillation counting and immunoenzymatic staining have almost the same sensitivity for measuring UDS and RDS as that of autoradiography.

Animals↗

Well-differentiated fetal adenocarcinoma of lung.

Well-differentiated fetal adenocarcinoma (WDFA) histologically resembles pulmonary blastoma, and is thought to be a subtype of pulmonary blastoma which has differentiated epithelial features resembling the fetal lung among its epithelial features and sarcomatous features. We recently encountered one patient who underwent surgery for WDFA. This case is reported with a discussion of the literature. A 33-year-old woman had a tumor shadow in the lower lobe of the right lung. The tumor was diagnosed as pulmonary blastoma as a result of echographic biopsy, and right total pneumonectomy was performed. No sarcomatous features were observed on postoperative histological assessment, and the patient was diagnosed as having WDFA. Its prognosis is believed to tend to be better than that of biphasic blastoma, in which sarcomatous features are mingled with epithelial features. However, it is reported that chemotherapy or radiotherapy has seldom been effective. Complete surgical resection is essential for long-term survival.

Adenocarcinoma↗

[Carcinoma of the renal pelvis and ureter following bladder carcinoma].

We followed 135 primary bladder carcinoma patients for at least 3 years. Subsequent carcinomas of the upper urinary tract were found in 5 patients (3.7 per cent) an average of 67 months after an initial treatment of the bladder tumors. Two patients underwent radical cystectomy and the remaining 3 patients received transurethral resections or partial cystectomy five to seven times for bladder lesions. Primary bladder tumor was multiple in all and one of them was accompanied by carcinoma in situ in the bladder and urethra. Except for one patient who presented with gross hematuria, four patients had no symptoms referable to the upper urinary tract tumor. However two of them had high stage disease. Positive urinary cytology was observed in only one patient. All patients underwent nephroureterectomy and the four got well but one died of acute heart failure. Regular urinary cytology and IVP should be done for an extended period of time for early detection of renal pelvic and ureter cancers in patients who had multiple and recurrent bladder cancers.

Adult↗

[A case of tongue cancer effectively treated with tegafur].

We administered a slow-release formulation of tegafur (SF-SP) to a patient with cancer of the tongue. We would like to report the findings of this case which showed clear improvement. SF-SP was administered at 800 mg/day to a 58 year-old male for cancer of the tongue (T4N1). By the 17th day after the start of SF-SP administration, the tumor had shrunk, and by the 37th day the submandibular lymph nodes could not be located by touch. At the completion of the test on the 60th day, no cancer cells were detected. Following the completion of the test, there have been no symptoms of recurrence and a complete response was observed. At present, we are continuing administration of SF-SP and making observations.

Adenocarcinoma↗