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Biomedical subjects

T Asakura

Publications and source records attributed to T Asakura.

At least 109 records · Page 6Linked to original sources

Effects of N-methacryloyl-omega-amino acid primer pretreatment on the bond strength of the resin to acid-etched dentin.

To ascertain the adhesion mechanism of resins to etched dentin treated with hydrophilic primers such as N-methacryloyl-omega-amino acids (NM omega A), the effect of the application of NM omega A primers on the bond strength of the resin and also the characteristics of the "hybrid layer" were investigated. Here, the concept of "hybrid layer" has been proposed previously by Nakabayashi et al. When the demineralized dentin was treated with the NM omega A solution, the bond strength increased remarkably, thus indicating the formation of a hybrid layer. It can be construed that NM omega A primers allowed for diffusion of the bonding agent to the dentinal collageous layer that was exposed by acid etching, and thereby the creation of a hybrid layer. To obtain an understanding of how NM omega A primers improved bond strength at the interface between the resin and dentinal collagen, the 13C-NMR spectra of NM alpha A were observed in the absence and presence of demineralized dentin. The 13C peak intensities of all of the carbons of the NM alpha A species were dramatically reduced in the presence of the dentin. Specifically, the reduction of the carbon peak intensity of carboxylic acid in the NM alpha A species was reduced by 30%. This indicated that the unionized carboxylic acid in the NM alpha A primer interacted with the dentinal collagen. Thus, the composite resin can be considered to adhere to the dentinal collagen through the unionized NM alpha A that interacts with the dentinal collagen.

Amino Acids↗

A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension.

The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n = 6), and patient with hypertension (n = 3), diabetes mellitus (n = 8), and diabetes with hypertension (n = 8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.

Adult↗

Prognostic significance of Ki-67 expression in transitional cell bladder carcinoma after radical cystectomy.

We evaluated the prognostic significance of the Ki-67 labeling index (Ki-67 LI) in 75 patients with transitional cell carcinoma of the bladder who underwent radical cystectomy. Immunohistochemical staining of archival material was performed by the streptavidin-biotin method. Univariate survival analysis showed that Ki-67 LI (p < 0.001), histologic grade (p < 0.05), tumor stage (p < 0.001) and the number of positive lymph nodes (p < 0.001) significantly correlated with prognosis. Multivariate survival analysis indicated that the Ki-67 LI (p < 0.05), histologic grade (p < 0.01), tumor stage (p < 0.01), presence of lymph node metastases (p < 0.05) and use of neo-adjuvant therapy (p < 0.05) had independent prognostic value. The Ki-67 LI is an independent prognostic factor for patients with transitional cell bladder cancer treated by radical cystectomy.

Adolescent↗

Glutathione-doxorubicin conjugate expresses potent cytotoxicity by suppression of glutathione S-transferase activity: comparison between doxorubicin-sensitive and -resistant rat hepatoma cells.

The cytotoxic mechanism of a conjugate of doxorubicin (DXR) and glutathione (GSH) via glutaraldehyde (GSH-DXR) was investigated using DXR-sensitive (AH66P) and -resistant (AH66DR) rat hepatoma cells. GSH-DXR accumulated in AH66DR cells as well as in AH66P cells without efflux by P-gp and exhibited the potent cytocidal activity against both cells compared with DXR. To examine whether thiol from GSH-DXR affected the expression of cytotoxicity, two conjugates of DXR, with modified peptides containing alanine or serine substituted for cysteine in GSH were prepared and their cytotoxicities determined. Substitution of these amino acids for cysteine resulted in an approximately two- to fourfold reduction in cytotoxic activity against both cell lines compared with the effect of GSH-DXR. Depletion of intracellular GSH by treatment of both cells with buthionine sulphoximine did not change the cytotoxic activity of DXR, BSA-DXR or GSH-DXR. By co-treating the cells with tributyltin acetate, an inhibitor of glutathione S-transferase (GST), and either DXR, BSA-DXR or GSH-DXR, the cytotoxicity was markedly increased. Interestingly, GSH-DXR showed non-competitive inhibition of GST activity and its IC50 value was 1.3 microM. These results suggested that the inhibition of GST activity by GSH-DXR must be an important contribution to the expression of potent cytotoxicity of the drug.

Animals↗

The presurgical management with erythrocytapheresis of a patient with a high-oxygen-affinity, unstable Hb variant (Hb Bryn Mawr).

BACKGROUND: Hemoglobin (Hb) Bryn Mawr is an unstable Hb variant resulting in congenital hemolytic anemia. This variant Hb also has an increased affinity for oxygen. The perioperative transfusion management of this disorder is described, and the first genomic analysis of this Hb variant is given. CASE REPORT: An 11-year-old boy, heterozygous for Hb Bryn Mawr, was referred for cholecystectomy. Sequence analysis of genomic DNA confirmed that the patients was heterozygous for a T-->C transition in the codon for amino acid 85, causing a substitution of serine for phenylalanine in the beta-globin chain. On the basis of whole-blood O2 dissociation studies, projected tissue O2 delivery would have been suboptimal during general anesthesia; therefore, a partial red cell exchange transfusion was performed to lower variant Hb and prevent tissue hypoxia during surgery. The red cell mass to be exchanged (50%) was determined from the calculated increase in O2 delivery capacity required to maintain an O2 extraction of 4 to 5 mL of O2 per dL of whole blood. The p50 of whole blood from the patients immediately after the exchange transfusion was 16.0 torr. At the time of surgery, the p50 was normal (25.9 torr). The patient's whole blood 2,3 DPG levels were 4.70 mmol per mL of red cells (before transfusion) (normal range = 4.8 +/- 0.3 mmol/mL red cells), 4.07 mmol per mL of red cells (immediately after transfusion), and 4.55 mmol per mL of red cells (48 hours after transfusion). CONCLUSION: This patient with Hb Bryn Mawr was prepared for surgery with a partial exchange transfusion to prevent tissue hypoxia during anesthesia. Decreased 2,3 DPG levels immediately after transfusion resulted in increased O2 affinity of whole blood; however, 48 hours after exchange transfusion, a normal p50 (due to both removal of variant Hb and regeneration of 2,3, DPG) was observed. Partial exchange transfusion is useful in the preoperative management of patients with Hb variants characterized by increased O2 affinity.

2,3-Diphosphoglycerate↗

Perinatal lethality and multiple craniofacial malformations in MSX2 transgenic mice.

MSX2 is a homeodomain transcription factor that has been implicated in craniofacial morphogenesis on the basis of its expression pattern during mouse development and the finding of a missense mutation (P148H) in humans affected with Boston-type craniosynostosis. We have generated transgenic mice carrying a 34 kb DNA fragment encompassing a human MSX2 gene encoding either wild-type or mutant (P148H) MSX2. Inheritance of either transgene resulted in perinatal lethality and multiple craniofacial malformations of varying severity, including mandibular hypoplasia, cleft secondary palate, exencephaly, and median facial cleft, which are among the severe craniofacial malformations observed in humans. Transgenic mice also manifested aplasia of the interparietal bone and decreased ossification of the hyoid. Transgene-induced malformations involved cranial neural-crest derivatives, were characterized by a deficiency of tissue, and were similar to malformations associated with embryonic exposure to ethanol or retinoic acid, teratogens that cause increased cell death. Together with previous observations implicating MSX2 expression in developmentally-programmed cell death, these results suggest that wild-type levels of MSX2 activity may establish a balance between survival and apoptosis of neural crest-derived cells required for proper craniofacial morphogenesis.

Animals↗

Drug conjugate of doxorubicin with glutathione is a potent reverser of multidrug resistance in rat hepatoma cells.

A recent study has suggested that degraded adducts smaller than 2 kDa in molecular weight of bovine serum albumin (BSA)-conjugated doxorubicin (DXR) (BSA-DXR) might exhibit cytotoxicity against multidrug resistant (MDR) cells. To investigate this notion further, intracellular accumulation and cytotoxicity of DXR coupled to several small peptides, such as glycylglycine (diGly), glycylglycylglycine (triGly), reduced glutathione (GSH) and oxidized glutathione (GSSG), were investigated using DXR-sensitive (AH66P) and DXR-resistant (AH66DR) rat hepatoma cell lines. Against both AH66P and AH66DR cells, diGly-conjugated DXR (diGly-DXR) and triGly-conjugated DXR (triGly-DXR) demonstrated the same cytotoxic activity as DXR, and the accumulation of both conjugates in the two cell lines was almost similar to that of DXR. After treatment of AH66DR cells with 5 microM verapamil [an inhibitor of P-glycoprotein (Pgp)], the intracellular levels of diGly-DXR and triGly-DXR were markedly increased and consequent cytotoxicity was improved. On the other hand, GSH-conjugated DXR (GSH-DXR) showed 9- and 7.5-fold more cytotoxic activity than BSA-DXR against AH66P and AH66DR cells, respectively. GSH-DXR accumulated rapidly in AH66DR cells, probably by the same mechanism as in AH66P cells, because the treatment of AH66DR cells with verapamil did not cause a significant increase in the intracellular drug level as compared with that in cells treated without verapamil. The levels of cytotoxicity and accumulation of GSSG-DXR were the same as those of BSA-DXR for both cell lines. These results indicate that GSH-DXR exerts potent cytotoxicity against both cell lines among the peptide DXR conjugates examined because of the rapid uptake and high accumulation of GSH-DXR similar to that of DXR without efflux.

Animals↗

Apoptosis in transitional cell carcinoma of the renal pelvis and ureter: association with proliferative activity, bcl-2 expression and prognosis.

PURPOSE: We attempted to clarify the significance of apoptosis in tumor development and progression in 64 cases of transitional cell carcinoma of the renal pelvis and ureter by investigating apoptosis, proliferative activity and bcl-2 expression. MATERIALS AND METHODS: We used in situ deoxyribonucleic acid nick end labeling for apoptotic cells and immunohistochemical staining for bcl-2 on archival tumor material. RESULTS: The apoptotic index correlated significantly with mitotic index, histological grade and pathological stage. There was no significant relationship between apoptotic index and bcl-2 expression. Patients with an apoptotic index greater than or equal to 0.22 had a poor prognosis. CONCLUSIONS: Apoptosis is closely related to proliferative activity, tumor differentiation and depth of invasion in transitional cell carcinoma of the renal pelvis and ureter.

Adult↗

Bone mineral density and the results of chiari pelvic osteotomy for osteoarthritis of the hip.

The aim of this study was to discover the involvement, if any, by bone mineral density (BMD) in the results after osteotomy for osteoarthritis of the hip (OA). The BMD, the Bombelli classification and the postoperative results in 36 joints after Chiari pelvic osteotomy for OA in the advanced and late stage were investigated for any correlations. The Bombelli hypertrophic type showed significantly better improvement than the atrophic type, but there was no correlation between the value of the BMD, and the postoperative result.

Adult↗

[Intracellular distribution of bovine serum albumin-conjugated doxorubicin and multidrug resistance].

The intracellular distribution of bovine serum albumin (BSA)-conjugated [14C] doxorubicin (DXR) was investigated in a rat hepatoma cell line (AH66P) and its anthracycline resistant subline (AH66DR). After the conjugate had been taken up into the cells by endocytosis and degraded in the lysomes, active adducts with a molecular mass of approximately 2 kDa were distributed to target organellae such as nuclei and mitochondria. Drug accumulation in the nuclear fraction was lower in AH66DR cells than in AH66P cells, but the level of drug radioactivity in the DNA fraction, which was extracted from the same nuclear fraction, was higher in the AH66DR cells than in AH66P cells. It is presumed from these results that the intercalated level of the drug into DNA was sufficient to exhibit cytotoxicity against AH66DR cells as well as AH66P cells. A part of the active adducts was effluxed from AH66DR cells by P glycoprotein (Pgp) in the same manner as DXR because the efflux of the adducts was suppressed by verapamil, an inhibitor of Pgp. The IC50 values of BSA DXR conjugate was decreased from 120 nM to 2 nM for AH66DR cells and from 3 nM to 0.6 nM for AH66P cells by the co-treatment with 5/M verapamil, respectively.

Animals↗

[Bellini duct carcinoma of kidney with invasive growth pattern: a case report].

We report a case of Bellini duct carcinoma of the left kidney with invasive growth pattern. A 39-year-old man was admitted to our hospital with the chief complaint of gross hematuria. Ultrasonography showed left renal swelling but normal reniform configuration of the kidney was maintained. Computed tomography demonstrated a low density tumor infiltrating into the renal cortex and with tumor extension into the renal vein. Renal angiography revealed a hypovascular tumor. We suspected a left renal cell carcinoma with tumor extension into the left renal vein, and performed radical nephrectomy. Macroscopically, the resected kidney had a normal outer contour. The tumor with infiltrative growth pattern existed in renal medulla. Histopathologic examination revealed a papillary adenocarcinoma originated in Bellini duct (pT3bN2M0). The patient underwent systemic chemotherapy (M-VAC). This case showed invasive growth pattern, which were different from the usual renal cell carcinoma and Bellini duct carcinoma.

Adenocarcinoma, Papillary↗

[Metastatic renal tumor originating from esophageal cancer: report of 2 cases].

We report 2 cases of esophageal cancer metastatic to the kidney. The first case was in a 57-year-old man who complained of severe right flank pain. He had underwent an operation for esophageal cancer 2 months previously. A computerized tomography (CT) scan revealed a wedge-shaped, low-density mass in the right kidney. Right nephrectomy revealed squamous cell carcinoma. He has remained free of recurrence 3 months postoperatively. The second case was in a 57-year-old man with esophageal cancer treated by radiation therapy. Severe right flank pain and gross hematuria appeared after 1 year. A CT scan showed a wedge-shaped, low-density tumor in the right kidney accompanied with a tumor thrombus in the inferior vena cava. Right nephrectomy as well as resection of the thrombus were performed. Pathological diagnosis was squamous cell carcinoma. He died of cancer 2 months postoperatively.

Carcinoma, Squamous Cell↗

Prognostic value of Ki-67 for recurrence and progression of superficial bladder cancer.

PURPOSE: We retrospectively reviewed 104 cases of superficial bladder cancer to ascertain whether the Ki-67 labeling index predicts recurrence and progression. MATERIALS AND METHODS: Archival specimens from superficial bladder cancer cases were immunostained with Ki-67. RESULTS: The recurrence rate was significantly higher in cases with a Ki-67 labeling index of 5.35 or greater than in those with a value less than 5.35 (p < 0.001). The recurrence rate at 2 years was 70% in cases with a Ki-67 labeling index of 5.35 or greater and 22% in those with an index less than 5.35 (p < 0.001). Using multivariate analysis the index predicted recurrence of bladder cancer (p < 0.005). Median Ki-67 labeling index in cases with progression was significantly higher than in those without progression (p < 0.01). CONCLUSIONS: The Ki-67 labeling index is an independent predictive factor for recurrence of superficial bladder cancer.

Adult↗

[Mitral valve re-replacement in patients aged 70 years and older: is age alone not operative risk factor?].

We analyzed the risk of mitral valve re-replacement (re-MVR) in patients over 70-year-old. Surgical and late follow-up results were compared between 14 elderly patients over 70-year-old (group I) and 23 patients aged from 60 to 69-year-old (group II) who underwent re-MVR due to primary tissue failure (PTF). Donation of autologous blood and a rate of replaced valve prosthesis (mechanical/biological) were different between the two groups. There were no differences in the other factors such as clinical profile, preoperative organ function, operative characteristics, post operative relating factors. No operative death occurred in both groups. There was one hospital death in group I (a hospital mortality rate of 7.1%). The cause of death was related to massive cerebral infarction due to anticoagulant-related thromboembolic event. 4-64 months after re-MVR, the improvement of a NYHA function class was I-II in the two groups. With improvement in myocardial protection and intraoperative strategies, the operative risk in patients undergoing re-MVR over 70-year-old has been markedly reduced. Surgical results in aged patients were satisfactory and age alone is not a contraindication for this operation. The re-MVR in aged patients should be done at the early stage of PTF before progress of cardiac failure.

Age Factors↗

[Clinical results of single-stage mobilization of pectoral muscle flaps and omental transposition for infected mediastinitis after open heart surgery].

The purpose of this study was to retrospectively evaluate the outcome of refractory infected mediastinitis managed primarily with mobilization of pectoral muscle flaps and omental transposition. From January 1992 to December 1995, infected mediastinitis occurred in 11 (2.5%) of 447 consecutive patients. All patients required sternal debridement. The wound was thoroughly irrigated with a solution of 0.5% povidone-iodine in physiological saline after debridement and then the defect was repaired. Reconstruction of the chest wall was attained using pectoral muscle flaps in seven patients and pectoral muscle flaps and omental transposition in four. Antibiotic therapy was provided for 6 weeks or more according to the regimen in North America. No hospital deaths occurred after surgery. Significant early complications occurred in four patients. The reasons for the prolonged hospitalization were a recurrent wound infection, prosthetic valve endocarditis and saphenous vein graft pseudoaneurysm formation caused by Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus epidermidis (MRSE). Length of stay in ICU after surgical treatment was range 1 to 140 days (an average of 11 +/- 3 days in 9 patients without complications in ICU). Duration between surgical treatment and discharge was range 47 to 300 days (an average of 58 +/- 8 days in 7 patients without significant early complications). At the time of this report, the patients are doing well with no signs of recurrence of infection. The mean follow-up was 28.8 months (range 8 to 48 months). We conclude that single-stage mobilization of pectoral muscle flaps together with omental transposition is very usefull for managing refractory infected mediastinitis. But careful follow-up is needed after this procedure in case of MRSA-caused mediastinitis because of its tendency to recur.

Adult↗