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Biomedical subjects

T Wakabayashi

Publications and source records attributed to T Wakabayashi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma.

We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in recurrent brain tumors. Eligibility required histologic confirmation of glioma recurrence despite standard radiotherapy and chemotherapy as well as enhancement of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total intratumoral dose of 10 mg of ACNU was administered continuously with a microinfusion pump over an average of 13h. Fifteen infusions were given in nine patients. All patients completed the treatment safely. On MRI, necrotic changes surrounded the infusion area in all patients, and tumor progression was inhibited or performance score was improved in seven of nine patients. No symptomatic systemic toxicity was evident, although one patient developed permanent left oculomotor palsy locally after treatment of a left medial temporal tumor. It is concluded that direct microinfusion of ACNU into recurrent gliomas can induce tumor necrosis and inhibit tumor growth.

Adult↗
PubMed2001

High- and moderately high-methionine uptake demonstrated by PET in a patient with a subacute cerebral infarction.

In patients with cerebral tumors, high accumulations of L-methyl-11C-methionine (11C-Met) have been reported in some cases of cerebral ischemic disease, but no high accumulations of 11C-Met in areas where only transient arterial occlusions are most likely to occur have been reported. Herein we present a case of a high accumulation of 11C-Met in an area of frontal interhemispheric cerebral infarction and a moderately high accumulation with an unclear margin in a distant frontal convexity area. A craniotomy revealed a subacute stage of cerebral infarction in the interhemispheric lesion, and an ischemic change in the distant convexity area. Sixteen months after onset, CT scans demonstrated an infarction area in the interhemispheric lesion only, and no atrophic changes were observed in the distant convexity area indicating that no serious tissue damage had occurred.

Adult↗
PubMed2001

Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia.

Heat shock proteins are recognized as significant participants in immune reactions. In this study, we have demonstrated that the cell surface presentation of MHC class I antigen was increased in tandem with increased heat shock protein 70 (HSP70) expression and the immunogenicity of rat T-9 glioma cells was enhanced by hyperthermia. T-9 cells showed growth inhibition for 24 h after the heat treatment at 43 degrees C for 1 h in vitro, but then resumed a normal growth rate. HSP70 expression reached a maximum at 24 h after heating. Flow cytometric analysis revealed a significant increase in MHC class I antigen on the surface of the heated cells. The augmentation of MHC class I surface expression started 24 h after heating and reached a maximum 48 h after heating. The expression of other immunologic mediators, such as intracellular adhesion molecule-1 (ICAM-1) and MHC class II antigens, did not increase. In an in vivo experiment using immunocompetent syngeneic rats (F344), growth of the heated T-9 cells, with augmentation of MHC class I antigen surface expression, was significantly inhibited, while the cells grew progressively in nude rats (F344/N Jcl-rnu). Furthermore, compared with lymphocytes from non-immunized (PBS only injection) rats or rats injected with non-heated T-9 cells, the splenic lymphocytes of the rats in which the heated T-9 cells were injected displayed specific cytotoxicity against T-9 cells. These results suggest that HSP70 is an important modulator of tumor cell immunogenicity, and that hyperthermic treatment of tumor cells can induce the host antitumor immunity via the expression of HSP70. These results may benefit further efforts on developing novel cancer immunotherapies based on hyperthermia.

Animals↗
PubMed2001

Immunohistochemical study of p53, c-erbB-2, and PCNA in barrett's esophagus with dysplasia and adenocarcinoma arising from experimental acid or alkaline reflux model.

PURPOSE: An immunohistochemical study of p53, c-erbB-2, and proliferating cell nuclear antigen (PCNA) in Barrett's esophagus with dysplasia and adenocarcinoma, arising from experimental acid or alkaline reflux, was performed in dogs. METHODS: Cardiectomy was performed in group A (n = 26) as an acid reflux model, and total gastrectomy was performed in group B (n = 24) as an alkaline reflux model. After surgery, the esophageal mucosa was observed and biopsied endoscopically every 3 months over a period of 6 years. Immunohistochemical staining of p53. c-erbB-2, and PCNA was performed, using biopsied specimens. RESULTS: In group A, Barrett's esophagus developed in 14 of the 26 dogs. Low-grade dysplasia occurred in 5 of the 26 dogs, and in 1 of these 5 dogs, it developed into high-grade dysplasia. In this animal, adenocarcinoma arose 63 months after the operation. In group B, Barrett's esophagus developed in 10 of the 24 dogs. Low-grade dysplasia was observed in 4 of the 24 dogs. In 1 of these 4 dogs, the dysplasia became high-grade and adenocarcinoma occurred 66 months after the operation. In group A, PCNA was positive in adenocarcinoma; the PCNA labeling index (LI) was 58. c-erbB-2 and p53 were negative in all animals in group A. In group B, PCNA was positive in Barrett's esophagus with high-grade dysplasia and adenocarcinoma; the PCNA LI was 77. p53 was positive in adenocarcinoma. c-erbB-2 was negative in adenocarcinoma. CONCLUSIONS; The results of this study provided evidence of the dysplasia-carcinoma sequence arising from alkaline reflux, as well as from acid reflux. To the best of our knowledge, this is the first report of the use of an alkaline reflux model and a 6-year study using dogs to observe the course of Barrett's esophagus.

Adenocarcinoma↗
PubMed2001

Effects of alpha-tocopherol on cisplatin-induced ototoxicity in guinea pigs.

Cisplatin (CDDP), an antitumor agent widely used in the treatment of head and neck cancers, has dose-limiting side effects such as ototoxicity and nephrotoxicity. Recently, evidence has been accumulated to demonstrate that these side effects are closely related to oxidative stress. In the present study, we attempted to suppress CDDP-induced ototoxicity and nephrotoxicity in guinea pigs by administering alpha-tocopherol, a naturally occurring antioxidant. Hartley albino guinea pigs (250 approximately 300 g) were treated with CDDP (4 mg/kg intraperitoneally (I.P.)) for 3 days in the presence and absence of alpha-tocopherol (50 mg/kg I.P.) injection for 6 days. The combined treatment of animals with alpha-tocopherol distinctly improved the CDDP-induced side effects. These were: loss of Preyer's reflex at high frequencies; distinct elevation of auditory brain stem response threshold at 16 kHz; increased lipid peroxidation in the cochlea determined by the malondialdehyde-thiobarbituric acid method; substantial losses of outer hair cells in the basal and second turns of the cochlea; fragmentation of nuclear DNA detected by the TUNEL method in cochlear hair cells and cells in the stria vascularis; and increases in serum BUN and Cr. These results strongly suggest that alpha-tocopherol suppresses CDDP-induced ototoxicity and nephrotoxicity via the suppression of the increased production of reactive oxygen species.

Animals↗
PubMed2001

Relocation of Cys374 of actin induced by labeling with fluorescent dyes.

Cys374 is an important landmark of actin, because its sulfhydryl group is reactive and can be labeled with various reagents. The atomic coordinates of actin Cys374 have been determined by X-ray crystallography of co-crystals of actin with either profilin or gelsolin. However, the positions of Cys374 in the crystals determined were not consistent with the data obtained through fluorescence resonance energy transfer. Here, we examined its position by means of probabilistic distance geometry using published fluorescence resonance transfer data and found that Cys374 of actin was relocated when Cys374 was labeled with fluorescent dyes that caused steric hindrance. The atomic coordinates of Cys374 after heavy atom labeling have been found to be different from those for the native crystal. This is consistent with our results. Therefore, the position of Cys374 is sensitive to chemical modification that introduces a bulky reagent. This also suggests that the conformation of the C-terminal region of actin could also be sensitive to the environment.

Actins↗
PubMed2001

Quantification of limited augmentation of myocardial (99m)Tc-tetrofosmin uptake at exercise in stable coronary artery disease.

We evaluated the diagnostic accuracy of a new method for quantitative analysis of myocardial perfusion at exercise using (99m)Tc-tetrofosmin tomographic imaging. (99m)Tc-tetrofosmin imaging of an exercise-rest sequence was performed in 30 patients with coronary artery disease (CAD) and eight age-matched control subjects. The exercise-induced myocardial count increase was calculated as the relative value (per cent increase ratio, %IR) to that at rest by correcting for physical decay for (99m)Tc and injected doses and by a subtraction technique. Exercise and rest (99m)Tc-tetrofosmin images were assessed visually and quantitatively using the per cent peak count and %IR of the myocardial count at exercise. Segments with significant coronary stenosis (diameter stenosis=75% or more) showed a significantly lower %IR than did those without significant coronary stenosis in the CAD patients (37+/-19% vs 63+/-21%, P<0.05). The diagnostic efficacy of visual analysis for detecting coronary stenosis was as follows: sensitivity, 58.1% and specificity, 81.4%. When %IR=37% was used for detecting significant coronary stenosis, sensitivity and specificity increased to 74.2% and 93.2%, respectively. Furthermore, the quantitative analysis significantly (P=0.04) improved the overall diagnostic accuracy from 73.3% to 86.7% compared to that of visual assessment. Thus, augmentation of myocardial (99m)Tc-tetrofosmin uptake at exercise is blunted in the myocardium with significant coronary stenosis. The calculation of myocardial count increase at exercise relative to that at rest can improve the diagnostic value of (99m)Tc-tetrofosmin SPECT imaging and may contribute to more accurate quantification of myocardial ischaemia and impaired tracer uptake in coronary artery disease.

Adult↗
PubMed2001

Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings.

The aim of this study was to assess the imaging findings of pathologically proven intraductal papillary-mucinous tumors of the pancreas and the natural history of follow-up cases, and to optimize the therapeutic management of patients with these tumors according to their imaging findings. All nine patients with main duct type tumors were histologically diagnosed as having adenocarcinoma or adenoma, with no hyperplastic lesion. The images failed to discriminate between the two histologic types. In 26 patients with branch duct type tumors, all but one with intraductal mural nodules or tumors of > or = 30 mm had adenocarcinoma or adenoma, regardless of the caliber of the main duct. Of the nine patients with tumors < 30 mm and no mural nodules. three had adenoma, and six had hyperplasia. All of four patients had hyperplasia, with the additional caliber of the main duct being < 6 mm. In a series of 23 cases in which the patient was followed-up, no apparent progression was found in 17 patients who had no mural nodules and tumors of < 30 mm. Given these results, patients with main duct type tumors, and those with branch duct type tumors showing mural nodules or a tumor diameter of > or = 30 mm, are at high risk of developing neoplasms, including adenocarcinoma, for which surgical resection should be considered, whereas those patients with tumors < 30 mm and no mural nodules can be followed.

Adenocarcinoma↗
PubMed2001

Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes.

Magnetoliposomes (MLs) conjugated with an antibody fragment to give specificity to a tumor were applied to hyperthermia for cancer. The Fab' fragment of the G250 antibody, which binds to MN antigen on many types of human renal cell carcinoma, was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The targetability of the G250-Fab' fragment-conjugating MLs (G250-FMLs) was investigated using the mouse renal cell carcinoma (mRCC) and MN antigen-presenting cell, MN-mRCC. The amount of G250-FMLs uptake reached 67 pg / cell against MN-mRCC cells in an in vitro experiment using plastic dishes and this value was about 6 times higher than that in the case of MLs. In an in vivo experiment using MN-mRCC-harboring mice, 1.5 mg of the FMLs per carcinoma tissue accumulated (tumor weight was 0.19 g), which corresponded to approximately 50% of the total injection. This value was 27 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using alternating magnetic field irradiation. The temperature of tumor tissue increased to 43 degrees C and the growth of the carcinoma was strongly arrested for at least 2 weeks. These results indicate the G250-FMLs could target renal cell carcinoma cells in vitro and in vivo, and are efficiently applicable to the hyperthermic treatment of carcinoma.

Animals↗
PubMed2001

Pancreatitis-associated protein levels in pancreatic juice from patients with pancreatic diseases.

BACKGROUND: Pancreatitis-associated protein (PAP), the acute-phase protein of the pancreas, is overexpressed in acute pancreatitis. Serum PAP levels were reported to be useful as an indicator of the severity, prognosis and healing of acute pancreatitis. Although PAP was originally identified in pancreatic juice, there has been no clinical report on PAP levels in pancreatic juice. This study was conducted to determine levels of PAP in pancreatic juice (PJ-PAP) in various human pancreatic diseases. METHODS: PAP levels in endoscopically aspirated PJ were measured by enzyme-linked immunosorbent assay in 86 patients with pancreatic diseases. RESULTS: 55% of 22 patients with pancreatic cancer (PC) and 25% of 49 patients with chronic pancreatitis (CP) were positive (> 350 ng/ml) for PJ-PAP. PJ-PAP levels were significantly higher in PC than in CP, in which PJ-PAP was also significantly higher than in 15 control subjects. There was no significant correlation between PJ-PAP and serum PAP, and combination assay of serum PAP and/or PJ-PAP detected 80% of PC cases and 44% of CP cases. CONCLUSIONS: We have demonstrated that human PAP could be detected in pancreatic juice from patients with pancreatic diseases. Determination of PAP in pancreatic juice might be helpful for early detection of pancreatic injury.

Acute-Phase Proteins↗
PubMed2001

Opposite effects of microtubule-stabilizing and microtubule-destabilizing drugs on biogenesis of mitochondria in mammalian cells.

Distribution of mitochondria as well as other intracellular organelles in mammalian cells is regulated by interphase microtubules. Here, we demonstrate a role of microtubules in the mitochondrial biogenesis using various microtubule-active drugs and human osteosarcoma cell line 143B cells and rat liver-derived RL-34 cells. Depolymerization of microtubules by nocodazole or colchicine, as well as 2-methoxyestradiol, a natural estrogen metabolite, arrested asynchronously cultured cells in G(2)/M phase of cell cycle and at the same time inhibited the mitochondrial mass increase and mtDNA replication. These drugs also inhibited the mitochondrial mass increase in the cells that were synchronized in cell cycle, which should occur during G(1) to G(2) phase progression in normal conditions. However, stabilization of microtubules by taxol did not affect the proliferation of mitochondria during the cell cycle, yet a prolonged incubation of cells with taxol induced an abnormal accumulation of mitochondria in cells arrested in G(2)/M phase of cell cycle. Taxol-induced accumulation of mitochondria was not only demonstrated by mitochondria-specific fluorescent dyes but also evidenced by the examination of cells transfected with yellow fluorescent protein fused with mitochondrial targeting sequence from subunit VIII of human cytochrome c oxidase (pEYFP) and by enhanced mtDNA replication. Two subpopulations of mitochondria were detected in taxol-treated cells: mitochondria with high Delta(psi)(m), detectable either by Mito Tracker Red CMXRos or by Green FM, and those with low Delta(psi)(m), detectable only by Green FM. However, taxol-induced increases in the mitochondrial mass and in the level of acetylated (alpha)-tubulin were abrogated by a co-treatment with taxol and nocodazole or taxol and colchicine. These data strongly suggest that interphase microtubules may be essential for the regulation of mitochondrial biogenesis in mammalian cells.

Animals↗
PubMed2001

Impaired exercise-related myocardial uptake of technetium-99m-tetrofosmin in relation to coronary narrowing and diabetic state: assessment with quantitative single photon emission computed tomography.

Despite the diagnostic efficacy of stress myocardial perfusion imaging, the correlation between the actual perfusion tracer activity and diseased state of a coronary artery has not been studied in detail. We estimated exercise-related perfusion augmentation in relation to disease states of a coronary artery in diabetic and non-diabetic patients by a newly developed quantitative technetium (Tc)-99m-tetrofosmin myocardial imaging technique. Tc-99m-tetrofosmin tomographic imaging with an exercise-rest protocol was performed in 26 stable coronary patients and in 8 age-matched controls. Percent increase (%IR) in myocardial count during symptom-limited submaximal exercise-stress was calculated in 16 non-infarcted polar map segments and in each coronary territory by a subtraction technique with corrections for physical decay and injected tracer doses, and the results were compared with those of angiographically quantified coronary diameter stenosis (%DS). Percent IR and peak heart rate during exercise showed a positive linear correlation both in coronary territories with significant stenosis (%DS > or = 75%) and in control or nonstenotic (%DS < 75%) territories. The regression line in stenotic regions was, however. significantly (p < 0.01) shifted downward compared to that in non-stenotic regions. Percent IR in stenotic regions showed a significant inverse correlation with %DS. Coronary stenosis of 75% or more was identified by a %IR cutoff value of 40% with 77% sensitivity, 70% specificity, and an accuracy of 72%. In coronary territories with a %DS of less than 75%, %IR in diabetic patients was significantly lower (46+/-15%) than that in nondiabetic patients (61+/-25%). Thus, blunted exercise-related augmentation of myocardial uptake of Tc-99m-tetrofosmin correlates with the severity of coronary narrowing and diabetic state.

Adult↗
PubMed2001

Crow-Fukase syndrome with ischemic cardiomyopathy.

A 31-year-old man was admitted to our hospital for further evaluation of heart failure symptoms. Crow-Fukase syndrome was diagnosed on the basis of findings of polyneuropathy, hepatomegaly, monoclonal hypergammaglobulinemia, and hypertrichosis. Dipyridamole-stress thallium-201 perfusion imaging, contrast left ventriculography, and coronary angiography revealed a markedly dilated and dysfunctioning left ventricle, extensive reversible ischemia with fixed defect, and multiple coronary lesions. Histopathology of myocardial biopsy specimens demonstrated ischemia-induced myocardial necrosis. These findings suggested that ischemic cardiomyopathy, probably due to inflammatory reactions of coronary arteries in Crow-Fukase syndrome, was responsible for the heart failure symptoms and left ventricular dysfunction in this patient.

Adult↗
PubMed2001

Efficacy of adjuvant therapy with procarbazine, MCNU, and vincristine for oligodendroglial tumors.

An adjuvant chemotherapy regimen consisting of procarbazine, MCNU, and vincristine (PMV) was evaluated for the treatment of malignant oligodendroglial tumors. Ten patients with histologically proven oligodendroglial tumors were treated with PMV therapy and the effectiveness was assessed using magnetic resonance imaging. Four patients with primary tumors underwent PMV after radiation therapy, and six patients with recurrent tumors were treated using PMV only. Tumor response was defined as radiological evidence of mass size change after completion of three courses of PMV. Complete or partial responses (more than 50% reduction in tumor mass) were noted in six patients, and tumor growth stabilized in four patients. In particular, inhibition of tumor growth using PMV was achieved in three patients with recurrent oligodendroglial tumors, despite the initial response after chemoradiation therapy (interferon-beta, MCNU, radiation) or nitrosourea chemotherapy (ACNU, MCNU). This PMV regimen (a modified PCV regimen using drugs available in Japan) is effective for treating malignant oligodendroglial tumors despite recurrence after other initial treatment procedures.

Adult↗
PubMed2001

Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death.

UNLABELLED: Cardiac (123)I-labeled metaiodobenzylguanidine (MIBG) activity has significant incremental prognostic value, but the difference between the long-term prognostic value of MIBG imaging for ischemic cardiomyopathies and the long-term prognostic value of MIBG imaging for idiopathic cardiomyopathies is not clear. This study aimed to determine whether assessment of cardiac (123)I-MIBG activities in ischemic and idiopathic cardiomyopathies have equally prognostic values and whether the kinetics are different because of the underlying etiologies. METHODS: After quantitative (123)I-MIBG imaging, 76 ischemic and 56 idiopathic cardiomyopathy patients were prospectively followed up for 54 mo. In addition to conventional parameters, cardiac (123)I-MIBG activity was quantified as a heart-to-mediastinum ratio (H/M) for early and late images and the washout kinetics were calculated using tomographic imaging. The data were compared with those obtained from 16 healthy volunteers. RESULTS: During follow-up, 29 deaths from heart failure, 11 sudden cardiac deaths, 2 deaths from arrhythmia, and 5 deaths from acute myocardial infarction were documented. Multivariate discriminant analysis using the Cox proportional hazards model showed that, in comparison with other variables, late H/M was the most powerful independent predictor of a lethal clinical outcome in ischemic (Wald chi(2) = 18.6502; P = 0.0000) and idiopathic (Wald chi(2) = 5.3394; P = 0.0208) groups. When patients with left ventricular ejection fraction (LVEF) < 40% were considered, late H/M had the greatest statistical power in both groups. Kaplan-Meier analysis showed late H/M to have an identical threshold (1.82) for both groups for identifying patients at risk of cardiac death. Likewise, when analysis was restricted to patients with an LVEF < 40%, the upper cutoff value of late H/M was 1.50 (P = 0.0358; log rank = 4.41) for ischemic patients and 2.02 (P = 0.0050; log rank = 7.86) for idiopathic patients. For patients with an LVEF < 40% and a late H/M less than the identified threshold of late H/M, the annual rate of cardiac death was greatest, 18.2%/y for the ischemic group and 11.9%/y for the idiopathic group. CONCLUSION: Cardiac (123)I-MIBG activity has the most powerful independent long-term prognostic value for both ischemic cardiomyopathy patients and idiopathic cardiomyopathy patients, indicating that both disease processes have common pathophysiologic and prognostic implications of impaired cardiac sympathetic innervation. Although combined testing of cardiac function and (123)I-MIBG activity is most likely to identify patients at increased risk of cardiac death, the underlying etiology of cardiac dysfunction may affect the threshold of (123)I-MIBG activity for the differentiation of high-risk patients.

3-Iodobenzylguanidine↗