[Leptomeningeal heterotopia].
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Brain Diseases↗
Biomedical subjects
T Sawada
Publications and source records attributed to T Sawada.
Evaluation of serum KL-6, a mucin-like glycoprotein, as a tumor marker for breast cancer.
The utility of serum KL-6 as a tumor marker for breast cancer was evaluated in this study. The sera from 146 patients with breast cancer, 13 with benign breast disease, and 108 healthy individuals were measured for KL-6 titer using a sandwich enzyme immunoassay method. Carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) titers were also tested in the same sera from the patients. The mean KL-6 titer of patients with primary breast cancer was 673 units/ml, which was significantly higher than that of benign and healthy individuals (P = 0.037 and P < 0.0001, respectively). The titer of patients with relapsed breast cancer was 1964 units/ml, which was also higher than that of primary cancer (P = 0.013). KL-6 titer was related to tumor stage, distant metastasis, and relapse site (P = 0.0053, P < 0.0001, and P = 0.0251, respectively). Using the cutoff value of 467 units/ml, the sensitivity of KL-6 was 31% for primary breast cancer (16% for stage I and 29% for stage II) and 73% for relapsed breast cancer (50% for local relapse and 89% for distant relapse). The specificity was 92%. The sensitivity of KL-6 was higher than that of CA15-3 and CEA. Combination of the three markers, followed by KL-6 and CEA, raised the sensitivity for primary breast cancer. Single use of KL-6 demonstrated a higher sensitivity than in each combination for relapsed breast cancer. In conclusion, serum KL-6 may be helpful for clinical use as a tumor marker for breast cancer, and it may play an important role, especially in the surveillance of disease relapse.
Adolescent↗
[Expandable metallic stent for the treatment of left-sided colonic obstruction with malignant disease].
Recently, it was reported that an EMS (expandable metallic stent) was useful for treatment of colorectal obstruction. In our department, EMSs were used for seven patients with left-sided colonic obstruction with unresectable malignant disease. After these treatments with EMS, their symptoms were improved and they were able to intake food. Stomal formation was avoided except in one patient with severe soiling. In conclusion, EMS is thought to be useful for the improvement of quality of life in the patients with unresectable malignant colonic obstruction.
Adult↗
[Neonatal lupus erythematosus].
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Autoantibodies↗
Effects of ethanol on neuronal migration and neural cell adhesion molecules in the embryonic rat cerebral cortex: a tissue culture study.
To investigate whether ethanol has direct effects on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain with thymidine autoradiography. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants with [3H]thymidine, the explants were cultured for 48 h, and then distribution of labeled cells was evaluated autoradiographically. Adding 3.0 or 6.0 mg/ml ethanol to the culture medium caused significantly decreased distribution of labeled cells in the outer intermediate [control: 2.0+/-0.6% (mean+/-S.D.); 1.0 mg/ml ethanol: 2.1+/-1.5%; 3.0 mg/ml ethanol: 0. 5+/-1.5% (P<0.05); 6.0 mg/ml ethanol: 0.4+/-0.5% (P<0.05)] and the inner intermediate-A zones [control: 19.5+/-6.2%; 1.0 mg/ml ethanol: 13.1+/-8.6%; 3.0 mg/ml ethanol: 3.0+/-3.4% (P<0.01); 6.0 mg/ml ethanol: 5.2+/-2.9% (P<0.01)] compared to the control group. The mitotic index after 48-h culture was significantly reduced in the 6. 0 mg/ml ethanol group (0.260+/-0.114%; P<0.01) compared to the control group (0.600+/-0.158%). This suggests that ethanol inhibits neuronal migration in the cerebral cortex, although prolongation of the cell cycle by ethanol may contribute to the decreased number of labeled cells in the outer intermediate and inner intermediate-A zones. Furthermore, an abnormally dense and tortuous staining pattern of immunoreactive products of N-CAM was seen on the surface of migrating neurons in the 3.0 and 6.0 mg/ml ethanol groups, while the L1 staining pattern did not differ between the control and ethanol groups. These results suggest that abnormal expression of N-CAM may be involved in the inhibition of neuronal migration by ethanol.
Animals↗
TRH increases cerebrospinal fluid concentration of kynurenine.
We have analyzed changes in cerebrospinal fluid (CSF) concentrations of monoamine-related substances to clarify the mechanism of the antiepileptic action of thyrotropin-releasing hormone (TRH). TRH-tartrate was administered to 14 patients with intractable epilepsy. Before and 2 weeks after TRH administration, CSF was collected and analyzed for tryptophan and tyrosine metabolites. Among monoamine-related substances, only CSF concentrations of kynurenine were increased after TRH therapy. Considering the fact that kynurenic acid acts as antagonist on the NMDA receptor complex, the results of this study may explain at least one of the mechanisms of the effectiveness of TRH therapy for intractable epilepsy.
Adolescent↗
Immunohistochemical nitrotyrosine distribution in neonatal rat cerebrocortical slices during and after hypoxia.
The peroxynitrite contributions to hypoxic damage in brain slices that arise from N-methyl-D-aspartate (NMDA) receptor activation were studied by following the temporal-spatial course of nitrotyrosine (NT) formation during six conditions: hypoxia (pO(2)<5 mmHg) with or without 10 microM MK-801 treatment; with exposure to 10, 100 and 1000 microM NMDA; and no treatment (control). In each experiment, twenty 350-micrometer thick cerebrocortical slices, obtained from the parietal lobes of ten 7-day-old Sprague-Dawley rats, were metabolically recovered and allowed to respire in a well-oxygenated perfusion system. Thirty minutes exposures to hypoxia or NMDA were followed by 2 h of oxygenated reperfusion. MK-801 administration began 15 min prior to hypoxia and was discontinued during reperfusion. Anti-NT serum immunohistochemistry stains in 20-micrometer frozen sections of slices taken during oxygenated reperfusion, after hypoxia or NMDA exposure, were positive in both neurons and endothelial cells. NT-positive neurons were detected sooner after hypoxia than after NMDA exposure, suggesting that mechanisms of superoxide generation were different in both groups. After hypoxia and even more so after NMDA exposure, more intense NT-positive staining was observed in endothelial cells than in neurons. Cell damage after hypoxia was attenuated by MK-801. MK-801 decreased post-hypoxia counts of NT-stained endothelial cells by 78.5% (p<0. 001) and NT-stained neurons by 54.1% (p<0.05). Our findings suggest that NMDA receptor activation in hypoxic brain slices is associated with increased post-hypoxic peroxynitrite production that contributes to acute neuronal death and endothelial cell injury. Peroxynitrite injury to endothelial cells, caused either by increased peroxynitrite from within or from increased vulnerability to peroxynitrite from without, might play an important role in hypoxic-ischemic brain injury and NMDA-induced brain injury.
Animals↗
Lipoxygenase inhibition decreases neointimal formation following vascular injury.
Our aim was to assess the potential role of lipoxygenase (LO) products in neointimal formation following vascular injury. We investigated the effect of LO pathway inhibition, by phenidone, on the concentration of 12- and 5-hydroxyeicosatetraenoic acid (12- and 5-HETE) in rat whole blood and in aortic tissue. We also examined the effect of phenidone on myoneointimal formation in balloon-injured rat carotid arteries. Phenidone significantly decreases the concentration of HETEs in aortic tissue, and decreases neointimal size even though there is no difference in the BrdU index. These data indicate that the LO product participates in developing neointima following balloon-induced vascular injury, and that the LO blocker phenidone decreases neointimal size possibly by suppressing migration of smooth muscle cells.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Miniaturized ultrathin slab gel electrophoresis with thermal lens microscope detection and its application to fast genetic diagnosis.
A miniaturized ultrathin slab gel electrophoresis (MUSGE) apparatus was developed, and fast separation of DNA fragments was obtained using it. To obtain sufficient separation efficiency in a limited space, a discontinuous buffer system was used. In general, it is difficult to cast a discontinuous ultrathin slab gel of adequate quality. However, the miniaturized resolving gel could be cast by taking advantage of the "capillary phenomenon" of the ultrathin channel. A gradient plate was used to control the height of the resolving gel and to form a clear interface between the concentrating gel and the resolving gel. This method was used to cast multiple gels simultaneously and reproducibly. The gradient plate also facilitated sample introduction, which was carried out by using a micropipet. A 25-mm-long and 80-micron thick-resolving gel was used to separate the 100-base pair ladder DNA within 10 min. Bandwidth was reduced to 100-200 microns, thus improving the number of theoretical plates to 22,000, which was comparable to that in conventional slab gel electrophoresis even though the migration distance was reduced to 1/10. Satisfactory lane-to-lane reproducibility (RSD < 1.0%, n = 6) and gel-to-gel reproducibility (RSD < 2.7%, n = 4) were obtained. Finally, the MUSGE apparatus was successfully applied to get a rapid genetic diagnosis.
Apolipoproteins B↗
Critical increment of Lewis blood group antigen in serum by cancer found by photothermal immunoassay.
Lewis blood group antigen levels in human sera were assayed with a highly sensitive photothermal immunoassay which is based on laser-induced photothermal detection. Comparison of 32 colon cancer patients' sera and 34 healthy persons' sera showed that cancer patients' sera contained more Lewis antigens than healthy persons' sera. Le(a) antigen level in Le(a-) type persons and Le(b) level in Le(b-) type persons differentiated healthy persons and colon cancer patients. Furthermore, it was found that in Lewis blood phenotype (a-) several cancer patients' sera specimens changed to (a+). Many reports demonstrated that Lewis phenotype of erythrocytes changed with various conditions, including carcinomas, but they dealt mostly with erythrocytes and salivas or showed immunohistochemical evidence, and there are no reports on the quantitative analysis of ordinary (noncancerated) Lewis antigen levels in human sera. This is because Lewis antigens in sera, unlike those found in saliva, are too small to quantify with conventional immunoassay and there has been no highly selective method to measure Lewis antigens in sera. The increase of Lewis antigen in cancer patients' sera is presumed to antecede the blood type change. Our assay presented here, a highly sensitive assay of Lewis antigens, will greatly contribute to an early detection or diagnosis of cancers.
Animals↗
Malignant rhabdoid-tumor cell line showing neural and smooth-muscle-cell phenotypes.
Malignant rhabdoid tumor (MRT) is a rare and extremely aggressive malignant tumor in childhood. In this study, an MRT cell line, designated KP-MRT-NS, was established from the ascitic fluid taken from an 11-month-old girl, whose tumor had originated from the left kidney. Ultrastructural findings demonstrated the typical aggregation of whorls of intermediate filaments. Chromosome constitution was described as 46, XX, add (10)(q26)[17]/46, idem, dis (1;2)(q22;q31)[3] based on ISCN (1995) and a del (22)(q11.2) was not found in this cell line. The origin of MRT is controversial, various cellular origins having been proposed because of the phenotypic diversity of MRT. Therefore, in this study, to clarify the origin of MRT, the expressions of cytoplasmic proteins including smooth-muscle-specific proteins (alpha-smooth-muscle actin, basic calponin, smooth-muscle-myosin-heavy-chain isoforms of SM1 and SM2) in the primary-MRT tissue and cell line were analyzed. In the primary-tumor tissue, the expressions of neurofilament, vimentin and alpha-smooth-muscle actin were demonstrated by indirect immunofluorescence. In the KP-MRT-NS cell line, the expression of neurofilament, alpha-smooth-muscle actin, basic calponin and smooth-muscle-myosin heavy chain of SM1 and SM2 isoforms was revealed by immunofluorescence, Western blot and/or reverse transcriptase-polymerase chain reaction (RT-PCR). MyoD1 mRNA, determined as a skeletal-muscle-cell lineage marker, was not expressed in the primary-tumor tissue or in the KP-MRT-NS cell line. According to our findings, the MRT cells are of both neural and smooth-muscle cell phenotypes, and support the neural-crest origin of MRT.
Blotting, Western↗
Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma.
BACKGROUND: Recently many studies have demonstrated that the degree of tumor angiogenesis is related to the aggressiveness of the tumor and clinical outcome. Vascular endothelial growth factor (VEGF) is a well characterized inducer of angiogenesis. In this study, the authors investigated the prognostic significance of VEGF expression in patients with early gastric carcinoma together with p53 gene abnormality and tumor cell proliferation. METHODS: One hundred ninety-five endoscopically biopsied specimens obtained preoperatively from patients with early gastric carcinoma were studied immunohistochemically. RESULTS: According to conventional clinicopathologic factors, submucosal invasion, lymph node metastases, and tumor size were associated significantly with the incidence of disease recurrence. According to conventional biologic factors, VEGF expression was observed more frequently in patients with disease recurrence compared with those without disease recurrence whereas neither p53 abnormality nor tumor cell proliferation were correlated with prognosis. Moreover, multivariate analysis indicated that VEGF expression (as well as submucosal invasion and lymph node metastases) is an independent predictor of disease recurrence. CONCLUSIONS: The results of the current study show that VEGF expression may be a useful prognostic factor for patients with early gastric carcinoma.
Adult↗
A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion.
Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.
Amyloid beta-Protein Precursor↗
Measurement of carnitine precursors, epsilon-trimethyllysine and gamma-butyrobetaine in human serum by tandem mass spectrometry.
Methods using tandem mass spectrometry for measurement of epsilon-trimethyllysine and gamma-butyrobetaine in human serum are described. Precursor ion scan analysis of a methylated sample was applied for gamma-butyrobetaine measurement. However, for epsilon-trimethyllysine measurement, homoarginine interfered with the methylated sample during precursor ion scan analysis. To overcome this interference, the sample was propylated and acetylated prior to precursor ion scan analysis. The obtained values resembled those obtained by enzymatic or HPLC measurement. Using tandem mass spectrometry, all members of the carnitine family, free carnitine, acylcarnitines, gamma-butyrobetaine, epsilon-trimethyllysine can be analyzed in 0.1 ml of serum. Thus, the proposed method appears to be suitable for clinical application, especially in the pediatric field.
Betaine↗
Effect of sports activity on carnitine metabolism. Measurement of free carnitine, gamma-butyrobetaine and acylcarnitines by tandem mass spectrometry.
The effects of sports activity on carnitine metabolism were studied using mass spectrometry. Serum levels of free carnitine, acylcarnitines (acetylcarnitine, propionylcarnitine, C4-, C5- and C8-acylcarnitine) and gamma-butyrobetaine, a carnitine precursor, were determined by tandem mass spectrometry in liquid secondary ion mass ionization mode. The coefficients of variation at three different concentrations were 2.8-7.9% for gamma-butyrobetaine, and 1.2 to approximately 6.7% for free carnitine. The recoveries added to serum were 109.1% for gamma-butyrobetaine, 89.3% for free carnitine. Sports activity caused increased serum levels of gamma-butyrobetaine, acetylcarnitine, C4- and C8-acylcarnitines and decreased serum levels of free carnitine. This method requires a small amount of sample volume (20 microl of serum) and short total instrumental time for the analysis (1 h for preparation, 2 min per sample for mass spectrometric analysis). Therefore, this method can be applied to study carnitine metabolism under various conditions that affect fatty acid oxidation.
Betaine↗
Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms.
BACKGROUND: Galectin-3 is a beta-galactoside-binding protein that has been reported to be expressed preferentially in thyroid malignancies. The current study was designed to substantiate this finding further and to establish a presurgical diagnostic modality of differentiating between benign and malignant thyroid neoplasms by analyzing galectin-3 expression in fine-needle aspirates. METHODS: The expression of galectin-3 was examined immunohistochemically in total of 172 specimens: 45 primary and 20 metastatic papillary carcinomas, 8 primary and 2 metastatic follicular carcinomas, 5 primary and 3 metastatic anaplastic carcinomas, 3 primary medullary carcinomas, 25 follicular adenomas, 3 goiters, and 58 adjacent normal thyroid tissue. Alternatively, epithelial cells were isolated from the fine- needle aspirates of 14 thyroid nodules and subjected to immunoblotting analysis of galectin-3. RESULTS: Immunohistochemical analysis revealed that all thyroid malignancies of follicular cell origin (including papillary, follicular, and anaplastic carcinomas) showed high and diffuse expression of galectin-3, whereas one of the three medullary carcinomas of parafollicular cell origin displayed weaker and focal expression of galectin-3. In contrast, neither benign thyroid adenomas, goiters, nor normal thyroid tissues expressed galectin-3. Immunoblot analysis of the isolated epithelial cells detected galectin-3 in nine thyroid nodules that were proven histologically to be malignant ( eight papillary carcinomas and one follicular carcinoma) after surgical intervention, whereas galectin-3 was not detected in five nodules proven to be benign follicular adenomas. CONCLUSIONS: Galectin-3 serves as a marker of thyroid malignancy of follicular cell origin. Analysis of galectin-3 expression in fine-needle aspirates enhances the differential diagnostic accuracy between benign and malignant thyroid neoplasms.
Antigens, Differentiation↗
Relationship between chimerism and tolerance in a kidney transplantation model.
The persistence of donor leukocytes in recipients of organ allografts has been associated with long-term graft acceptance. However, it remains unclear whether this peripheral donor cell microchimerism plays an active role in graft acceptance or is simply a consequence of the maintenance of sufficient immunosuppression to avoid rejection. A model of kidney transplantation between swine leukocyte Ag (SLA)-matched miniature swine, in which tolerance can be established with or without immunosuppressive treatment, has been used to study the correlation between donor leukocyte chimerism and kidney graft acceptance. SLA-identical kidney transplants were performed from animals positive for an allelic pig leukocyte Ag to animals negative for this marker. SLA-identical kidney transplant recipients given a 12-day course of cyclosporine (CyA) (n = 3) became tolerant, showing stable serum creatinine levels (1-2 mg/dl) after cessation of CyA treatment. Donor cell chimerism (0.2-0.7%) was present by FACS in all three animals with peak levels detected at 3 wk. Two control animals receiving SLA-identical kidney grafts without CyA also showed stable serum creatinine levels and became tolerant. However, in neither of these animals could donor leukocytes be detected in the peripheral blood beyond 1 wk following transplantation. In one additional control animal, ureteral obstruction occurred at day 10, and was associated with additional peripheral chimerism, presumably related to inflammation rather than to immune status. These results indicate that the persistence of donor cell chimerism is not a requirement for the maintenance of tolerance to organ allografts in this model.
Animals↗
Inhibiting neuronal migration by blocking NMDA receptors in the embryonic rat cerebral cortex: a tissue culture study.
To investigate the role of the NMDA receptor on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants by [3H]thymidine, the explants were cultured for 48 h. Then distribution of labeled cells was evaluated autoradiographically. Blocking NMDA receptors by adding the NMDA receptor antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801: 1 or 10 microM) or d(-)-2-amino-5-phosphonopentanoic acid (d-AP5: 100 microM) to the culture medium, caused significantly decreased distribution of labeled cells in the outer intermediate zone (control 14.2+/-5.5%, 1 microM MK-801 5.8+/-7.2%, 10 microM MK-801 3.6+/-1.4%, and d-AP5 8.6+/-4.0%; mean+/-S.D.). This suggests that blocking NMDA receptors inhibits neuronal migration in the cerebral cortex. Furthermore, the influence of decreased intracellular Ca2+ concentration on neuronal migration was examined by adding intracellular Ca2+ chelator, 1, 2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester (BAPTA-AM: 5 or 25 microM). This also resulted in inhibited neuronal migration. Therefore, it seems that neuronal migration in the cerebral cortex is regulated by intracellular Ca2+ concentration, which the NMDA receptor may influence.
2-Amino-5-phosphonovalerate↗