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Biomedical subjects

T Sakurai

Publications and source records attributed to T Sakurai.

At least 91 records · Page 5Linked to original sources

A novel mixed valence form of Rhus vernicifera laccase and its reaction with dioxygen to give a peroxide intermediate bound to the trinuclear center.

Rhus vernicifera laccase, in a novel mixed valence state [T1oxT23red: type 1 Cu as Cu(II), and type 2 and 3 Cus as Cu(I)], was formed by reacting Cu(I) on the type 2 Cu-depleted laccase [T1oxT3red: type 1 Cu as Cu(II) and type 3 Cus as Cu(I)] under argon. Contrary to T1oxT3red, T1oxT23red was highly reactive with dioxygen, and gave the three transient bands at 340, 475, and 680 nm due to the two-electron reduced form of dioxygen [charge transfer bands from peroxide to Cu(II)]. The first order decays were highly dependent on pH, which led to the successful detection of the intermediate for ca. 2 h at pH 7.5. Another mixed valence derivative, T12oxT3red [type 1 and type 2 Cus as Cu(II), and type 3 Cus as Cu(I)] prepared through the action of Cu(II) on T1oxT3red was not reactive with dioxygen, but showed high enzyme activity as to the oxidation of N,N-dimethyl-p-phenylenediamine. The whole reaction mechanism of the reduction of dioxygen by laccase was proposed based on the present results together with data for the former detection and characterization of the three-electron reduced form of dioxygen [Huang, H. et al. (1999) J. Biol. Chem. 274, 46, 32718-32724].

Binding Sites↗

Pamidronate-induced remission of pain associated with hypertrophic pulmonary osteoarthropathy in chemoendocrine therapy-refractory inoperable metastatic breast carcinoma.

We describe an extremely rare case of a woman with pulmonary metastatic disease from breast cancer, who presented with features of hypertrophic pulmonary osteoarthropathy (HPOA). Pain associated with HPOA may be extremely disabling and resistant to treatment. Treatment with pamidronate, an inhibitor of osteoclastic bone resorption, given every 2 weeks by i.v. drip infusion, led to rapid disappearance of uncontrolled pain caused by HPOA.

Adult↗

Purification, characterization, and genetic analysis of Cu-containing dissimilatory nitrite reductase from a denitrifying halophilic archaeon, Haloarcula marismortui.

Cu-containing dissimilatory nitrite reductase (CuNiR) was purified from denitrifying cells of a halophilic archaeon, Haloarcula marismortui. The purified CuNiR appeared blue in the oxidized state, possessing absorption peaks at 600 and 465 nm in the visible region. Electron paramagnetic resonance spectroscopy suggested the presence of type 1 Cu (g(II) = 2.232; A(II) = 4.4 mT) and type 2 Cu centers (g(II) = 2.304; A(II) = 13.3 mT) in the enzyme. The enzyme contained two subunits, whose apparent molecular masses were 46 and 42 kDa, according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-terminal amino acid sequence analysis indicated that the two subunits were identical, except that the 46-kDa subunit was 16 amino acid residues longer than the 42-kDa subunit in the N-terminal region. A nirK gene encoding the CuNiR was cloned and sequenced, and the deduced amino acid sequence with a residual length of 361 amino acids was homologous (30 to 41%) with bacterial counterparts. Cu-liganding residues His-133, Cys-174, His-182, and Met-187 (for type 1 Cu) and His-138, His-173, and His-332 (for type 2 Cu) were conserved in the enzyme. As generally observed in the halobacterial enzymes, the enzymatic activity of the purified CuNiR was enhanced during increasing salt concentration and reached its maximum in the presence of 2 M NaCl with the value of 960 microM NO(2)(-) x min(-1) x mg(-1).

Absorption↗

What do radiographers think about teleradiology in Japan?

In order to understand radiographers' views of teleradiology, we sent questionnaires to all radiographers in Hokkaido, Japan. Questions concerned the understanding of, interest in, need for and problems related to teleradiology. A total of 1275 radiographers responded to the survey (a response rate of 65%). Almost all had heard about teleradiology and about 60% of them were interested in it. However, fewer radiographers working in the central region than in other regions expected to be involved in teleradiology. If teleradiology were to be introduced, 60% of the respondents thought that it should be used for interpreting difficult cases and 30% for emergency cases. Half thought that the system should be managed and operated by the radiographer. Thirty-seven per cent of radiographers expected that there would be problems concerning the management of the system within one facility and between facilities, and 34% predicted problems with the installation costs.

Adult↗

Karyotypes and Giemsa C-banding patterns of Zebrina pendula, Z. purpusii and Setcreasea purpurea, compared with those of Tradescantia ohiensis.

It has been proposed that the genera Zebrina and Setcreasea of the family Commelinaceae should be united and reunited, respectively, with the genus Tradescantia, mainly based on morphological studies. In the present study, karyotypes and Giemsa C-banding patterns in the root-tip cells of three Zebrina and two Setcreasea clones were analyzed, and were compared with those of a triploid Tradescantia clone. Z. pendula and Z. purpusii (both 2n = 24) were found to have similar karyotypes (4 M + 6 ST + 14 T; M = meta-, ST = subtelo-, T = telocentric chromosomes), while Z. pendula cv Quadricolor (2n = 23) had a unique karyotype (6 M + 5 ST + 11 T + 1 SA; SA = short acrocentric chromosome). The only clear difference between Z. pendula and Z. purpusii was that one and two subtelocentric chromosomes, respectively, had satellites at the short arms. Two clones of S. purpurea (2n = 24) had karyotypes (8 M + 8 M' + 8 SM; M' = nearly meta-, SM = submetacentric chromosomes) similar to each other. T. ohiensis (2n = 18) had a symmetric karyotype (9 M + 9 SM) consisting of larger chromosomes than S. purpurea. Many clear Giemsa C-bands were detected, in addition to centromeric bands in all chromosomes of all clones. Z. pendula and Z. purpusii commonly had single clear interstitial bands in eight telocentric chromosomes each, but they also had unique telomeric and other interstitial bands, respectively. Z. pendula cv Quadricolor had a unique banding pattern, i.e., satellite bands in the unique short chromosome, telomeric bands at the long arms of all metacentric chromosomes, and single interstitial bands in six telocentric chromosomes. Two clones of S. purpurea had telomeric bands at many chromosome arms and satellite bands in two nearly metacentric and one submetacentric chromosomes, but some differences were found between them. On the other hand, all the chromosomes of T. ohiensis had telomeric bands at both arms, and three submetacentric chromosomes had satellite bands. These result prove structural differentiation of chromosomes occurred among the clones, especially in Zebrina, and show that S. purpurea is relatively close to T. ohiensis, while Zebrina is obviously distant from the other two genera. Therefore, there remains a question cytologically at least for uniting Zebrina with Tradescantia.

Chromosome Banding↗

Sunlight induces N epsilon-(carboxymethyl)lysine formation from glycated polylysine-iron(III) complex.

Sunlight was found to strongly induce the formation of N epsilon-(carboxymethyl)lysine (CML) from glycated polylysine in the presence of Fe(III) ion. The initial step of this Fe(III)-catalyzed CML formation was noted to be similar to that of blueprint photography as was confirmed by the production of Turnbull's blue in sunlight-exposed glycated human serum albumin ferricyanide solution in the presence of Fe(III). Based on this, photoinduced oxidative C-C bond cleavage of the Amadori compound was assumed to be initiated by photochemical single electron transfer front ligand to Fe(III) in the Fe(III)-Amadori compound complex affording the Fe(II)-Amadori compound radical intermediate, which eventually yields either CML or active oxygen species. CML is thus a useful oxidative stress marker. The mechanism proposed here would explain the high accumulation of CML in lens protein and skin actinic elastosis.

Glycation End Products, Advanced↗

Simultaneous onset of type 1 diabetes mellitus and painless thyroiditis following acute pancreatitis.

A 24-year-old female suffered from acute pancreatitis, followed by simultaneous onset of painless goiter, elevation of thyroid hormones and diabetic ketoacidosis. Two months later, her insulin secreting function was severely decreased and positive for anti-GAD and anti-islet cell antibodies, whereas the serum glucagon level was normal, suggesting an autoimmune-related destruction specifically of beta cells. In addition, the initial hyperthyroid state was followed by a hypothyroid phase which later recovered to an euthyroid state, suggesting an initial destruction of thyroid cells. Because anti-thyroidal antibodies were positive, it is likely that the thyroidal destruction was also autoimmune-related. This case implies common pathogenic mechanisms in the autoimmunity related destruction of beta cells and thyroid cells.

Acute Disease↗

Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and leiomyoma.

Angiogenesis is essential for tumor growth and metastasis. Some angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) are involved in increased angiogenic activity and disease progression in many carcinomas. However, there is little information regarding the association between angiogenic factors and leiomyosarcoma. Although there are abundant vessels in the sarcoma which enable it to easily receive nutrition and medicinal components, chemotherapy cannot effectively treat leiomyosarcoma. This means the resistance to anticancer drugs in leiomyosarcoma is very strong. However, the resistant mechanism is still unclear. In this study, expressions of VEGF, PD-ECGF, TGF-alpha, bFGF, intratumoral microvessel density (IMVD), and p53, Bcl-2 and Bax were examined by immunohistochemistry in 30 patients with leiomyosarcoma and 21 patients with leiomyoma. With regard to angiogenesis, PD-ECGF and TGF-alpha were closely associated with an increase in IMVD (p=0.012, 0.0196, respectively), and VEGF and PD-ECGF were significantly expressed in leiomyosarcoma compared with leiomyoma (p=0.041, 0.041, respectively). Although p53 expression in leiomyosarcoma was significantly higher than in leiomyoma (p=0.016), the frequency of p53 positivity was not so high (47%). On the other hand, the ratio of Bcl-2/Bax in leiomyosarcoma was significantly higher than that in leiomyoma (p=0.033). The findings of this study suggest that in leiomyosarcoma, angiogenic factors, such as PD-ECGF, VEGF and TGF-alpha expression may be involved in tumor angiogenesis, and the frequently high ratio of Bcl-2/Bax and expression of p53 gene mutation might be related to chemoresistance mechanism.

Angiogenesis Inducing Agents↗

Four strains of spontaneously hyperlipidemic (SHL) mice: phenotypic distinctions determined by genetic backgrounds.

Spontaneously hyperlipidemic (SHL) mice are Japanese wild mice (KOR) with disruption of the apolipoprotein E (Apo E) gene. These mice (KOR-Apoe(shl)) are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis is relatively mild compared with Apo E knockout mice. First, we tested whether this distinction is due to additional mutation of the Apoc1 and/or Apoc2 genes in KOR-Apoe(shl). Southern blot analysis, but found no gross disruption of these genes. Next, we tested whether the phenotypic distinction is due to differences in the genetic background. To this end, we established three lines of congenic SHL mice with a genetic background of C57BL/6, BALB/c or C3H/He, and named them, respectively, C57BL/6.KOR-Apoe(shl) (B6.KOR-Apoe(shl)), BALB/c.KOR-Apoe(shl) (C.KOR-Apoe(shl)) and C3H/He.KOR-Apoe(shl) (C3.KOR-Apoe(shl)). Hypercholesterolemia was most severe in KOR-Apoe(shl) followed the by others as follows; KOR-Apoe(shl)>>C3.KOR-Apoe(shl)>C.KOR-Apoe(shl)>B6.KOR-Apoe(shl). In contrast, atherosclerosis was most severe in B6.KOR Apoe(shl) followed by the others: B6.KOR-Apoe(shl)>C.KOR-Apoe(shl)>>C3.KOR-Apoe(shl)> or =KOR-Apoe(shl). This order, however, did not match that in xanthoma, which was highly prominent in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KORApoe(shl). This order, however, did not match that in xanthoma, which was highly prominant in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KOR-Apoe(shl). These distinctions suggest that the severity of each of the phenotypes is determined by distinct genetic backgrounds which probably are composed of polymorphism of lipid metabolism-related proteins. We found that apolipoprotein A-I is decreased in each SHL strain and polymorphic between B6.KOR-Apoe(shl) and the other strains examined. This polymorphism may be related to the most severe atherosclerosis observed in B6.KOR-Apoe(shl). It is most likely that combination of such polymorphisms is due to the genetic background accountable for phenotype distinctions.

Animals↗

Pelvic arteriovenous malformation with iliac vein thrombosis. A case report.

BACKGROUND: Congenital arteriovenous malformations (AVMs) of the pelvis are relatively rare and are difficult to treat because of diffuse extension and the number of feeding vessels. METHODS: We describe a patient with a pelvic AVM with shunts who also developed iliac vein thrombosis. The AVM was diagnosed during evaluation of what had initially appeared to be a venous stasis ulcer. RESULTS: The ulcer was successfully treated by Palma s procedure, partial resection of the feeding vessels, and transcatheter arterial embolization. CONCLUSIONS: Coexistence of a pelvic AVM with an iliac vein thrombosis has not previously been reported.

Aged↗

[A case of docetaxel-resistant breast cancer responsive to paclitaxel therapy].

A 73-year-old woman underwent docetaxel therapy for lung metastasis from breast cancer after having received CAF therapy. Because of the progressive disease due to secondary resistance to docetaxel, the patient was given three courses of paclitaxel therapy (60 mg/m2, day 1, 8, 15 and 22, repeated every 6 weeks). The paclitaxel therapy brought about no adverse effects and a 51%-reduction in the size of the metastatic lung tumor (PR). Although the duration of the response to the paclitaxel therapy was limited to about one month due to progression of a brain metastasis, paclitaxel therapy may be effective against docetaxel-resistant breast cancer.

Aged↗

[Non-small cell lung cancer with liver metastasis responsive to gemcitabine--a case report].

A 56-year-old male patient underwent a right upper lobectomy and lymph node dissection for non-small cell lung cancer in March 1994. Multiple lung metastases in the right lung were found 45 months after the operation, and chemotherapy with docetaxel was administered. A liver metastasis was detected 11 months later, and it was refractory to docetaxel. Therefore, the patient was treated with cisplatin, mitomycin C and vinorelbine, which resulted in no change to the liver metastasis. He was next treated with gemcitabine, which resulted in a partial response of the liver metastasis. The adverse effects of gemcitabine were Grade 3 thrombocytopenia and Grade 2 neutropenia. The response duration for gemcitabine therapy was three months.

Adenocarcinoma↗

[A case of bronchioloalveolar carcinoma with multiple cystic shadows on chest CT].

A 68-year-old woman was admitted to our hospital in 1998 with shortness of breath on exertion. On the first admission, chest radiography revealed multiple nodular shadows and areas of ground-glass appearance mainly in the basal lung fields, and chest CT scans showed multiple thin-walled cystic lesions in both lung fields. Bronchioloalveolar carcinoma was diagnosed by transbronchial lung biopsy. The CA 19-9 level in the serum was abnormally high. The disease progressed, and the patient died 7 months after diagnosis. We report this case because CT scans showed multiple cystic lesions, which is very rare. The mechanism of cystic formation in this case of lung cancer may have involved disruption of the alveolar structure and enlargement of disrupted spaces or of the check valve mechanism.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Effect of actarit combination therapy in patients with active rheumatoid arthritis resistant to gold agents].

We investigated the utility of combination therapy of actarit with gold agents in patients with active rheumatoid arthritis resistant to gold agents even after the administration of gold agents for longer than 24 weeks in principle. 1. In the final global improvement rate by the combination therapy of actarit with gold agents, the ratio of "improved" and/or better was 30.8% (12/39). 2. The clinical evaluation items which showed significant improvement were grip strength, ESR, number of painful joints, number of swollen joints, active joint count, duration of morning stiffness and Lansbury's activity index. 3. ADRs were observed in 6 patients per 75 patients (8.0%), but there was no serious ADR.

Aged↗

Development of a cryopreservation procedure employing a freezer bag for pancreatic islets using a newly developed cryoprotectant.

One of the most important requirements for success in clinical islet transplantation is the use of a large number of viable donor islets. To achieve this, the ability to cryopreserve islets and to establish an islet bank are critical. Previously, we developed a two-step cryopreservation procedure with freezing tubes utilizing low and high concentrations of dimethyl sulfoxide (DMSO) and using a fully automated cryomachine for human pancreatic islets and porcine islet-like cell clusters (ICCs). Based on these experiments, we developed a simple and efficient cryopreservation procedure of a freezer bag for isolated islets using a fully automated computer-controlled cryomachine with a newly developed cryoprotectant consisting of ethylene glycol (EG) instead of DMSO for decreasing injury of the islets by freezing. A 250 ml Cryocyte blood freezer bag and our newly developed cryoprotectant containing ethylene glycol (EG) were used in the freezing procedure. The islets were frozen by a fully automated computer-controlled cryomachine (GE 9,000) with our original program of slow cooling. Nucleation occurred at -8 degrees C, and the frozen islets were stored at -196 degrees C in a liquid nitrogen tank. The frozen-stored islets were subsequently rapidly thawed in a 37 degrees C water bath and cultured before viability testing. In vitro function, the stimulation index of insulin release during the static incubation test for rat islets cryopreserved in a freezer bag vs. nonfrozen islets as control, was 2.13 +/- 0.42 and 2.02 +/- 0.38 (94.8% compared with control), respectively (n = 5, p = NS). The islet recovery compared with the nonfrozen control group was 85% (n = 5) in insulin content. When 1000 rat islets cryopreserved in a freezer bag were transplanted into the renal capsule of diabetic athymic mice, all the mice became normoglycemic within 7 days from transplantation. Before nephrectomy, the intravenous glucose torelance test (IVGTT) was performed. The fractional decay constant of the glucose level (K value) of the frozen-thawed group was 0.42 +/- 0.06%/min. A histological study of renal subcapsular grafts demonstrated the morphological integrity of the islets. These results demonstrate the utility of our cryopreservation procedure of a freezer bag for isolated islets using a fully automated computer-controlled cryomachine with a newly developed cryoprotectant for the maintenance of viability and function of frozen-stored islets both in culture and after transplantation. Cryopreservation using freezer bags with the new cryoprotectant is an effective and simple method for making an islet bank for clinical trials of islet transplantation.

Animals↗

Effect of basic fibroblast growth factor on insulin secretion from microencapsulated pancreatic islets: an in vitro study.

Microencapsulation of pancreatic islets represents a potentially effective method to prevent graft rejection in allotransplantation or xenotransplantation without the need of immunosuppression. Adequate insulin secretion and glucose responsiveness of microencapsulated pancreatic islets has been regarded as a prerequisite for successful transplantation. The microencapsulated pancreatic islets were respectively cultured in bFGF+ RPMI-1640 medium (bFGF+) or bFGF- RPMI-1640 medium (bFGF-) for 21 days. The functional activities of microencapsulated pancreatic islets were assessed by measuring basal insulin secretion and stimulated insulin release at different time points. The results revealed that microencapsulated pancreatic islets in the presence of bFGF demonstrated an increase in basal insulin secretion. Furthermore, microencapsulated pancreatic islets in the presence of bFGF demonstrated a marked stimulated insulin release and relative stability of stimulation indices (SI). The results in the perifusion study showed that microencapsulated pancreatic islets in the presence of bFGF maintained good glucose responsiveness over the course of culture period as well. These results indicate that bFGF has a beneficial effect on insulin secretion from microencapsulated pancreatic islets during in vitro culture. New strategies for preserving and improving function of microencapsulated pancreatic islets prior to transplantation may be developed by application of growth factors or other factors.

Animals↗

[Surgical voice restoration after pharyngolaryngoesophagectomy].

Although pharyngolaryngoesophagectomy (PLE) offers the only reliable possibility for cure in patients with advanced carcinomas of the cervical esophagus, the majority must reconcile themselves to subsequent voicelessness. Various surgical methods for voice restoration have been devised to solve this problem. Among these methods, the most common following PLE are the tracheogastric shunt, double tracheo-esophagogastric shunt, elephant trunk-shaped tracheo-esophageal shunt, tracheo-jejunal shunt, and tracheo-ileocecal shunt. The basic premise of these procedures is to introduce expiratory air from the trachea into the reconstructed esophagus to produce voice without aspiration of liquid or food during deglutition. The resultant speech is acceptable in most patients.

Esophageal Neoplasms↗

[A case of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil].

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.

Aged↗