Detection of metallothionein by western blotting.
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Animals↗
Biomedical subjects
Y Aoki
Publications and source records attributed to Y Aoki.
Paroxysmal speech disorder following left frontal brain damage.
The patient was a 61-year-old female who suffered from the sudden attack of a speech disorder. The episodes of speech disorder lasted for less than 1 min, but occurred several times a day, paroxysmally. A CT revealed a low density area on the surface of the left frontal lobe and an EEG showed an abnormal wave at the frontoparietal area, more dominantly on the left. This condition was diagnosed as a kind of epilepsy. The paroxysmal speech disorder occurred very often during the 2 months after the first episode. However, with therapy using anticonvulsives and antibiotics, the condition began to improve after 4 months and disappeared completely after 6 months. It is assumed that the inflammatory change which occurred at the frontal lobe stimulated the supplementary motor area paroxysmally, and subsequently the speech disorder occurred as a kind of epilepsy.
Brain Damage, Chronic↗
Establishment and characterization of a new Ewing's sarcoma cell line.
A new human Ewing's sarcoma cell line (CADO-ES1) was established from the malignant pleural effusion of a 19-year-old woman. These cells grew both anchorage dependently and anchorage independently. When cultured in bacteriologic dishes, they grew as tightly packed multicellular tumor spheroids; they were also capable of proliferating in soft agar. Flow cytometric DNA analysis demonstrated a nearly diploid DNA content (DNA index = 0.902). Chromosomal studies of cultured cells showed an isodicentric chromosome 8 in all examined cells, but t(11;22)(q24;q12), a translocation reported previously in Ewing's sarcoma, was not detected. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. In addition, immunocytochemical studies showed that vimentin was intensely positive, whereas neurofilament (NF) and neuron-specific enolase (NSE) were weakly positive. Treatment with cyclic AMP (cAMP) induced pronounced morphologic evidence of neural differentiation and strong expression of NF in cultured cells. S-100 protein, glial fibrillary acidic protein (GFAP), desmin, cytokeratin, and epithelial membrane antigen were not detected immunohistochemically in either untreated or cAMP-treated cells, however. These data suggest that this cell line is derived from a highly undifferentiated neural cell with high chromosomal clonality, differentiating into neural features under certain conditions.
Adult↗
Variation of endogenous insulin secretion in association with treatment status: assessment by serum C-peptide and modified urinary C-peptide.
The variation of endogenous insulin secretion in association with fasting plasma glucose (FPG) level and the modality of treatment was assessed using serum C-peptide levels before and after breakfast and the corrected value of 24-h urinary C-peptide (24 h-UCP) in inpatients with non-insulin-dependent diabetes mellitus. The corrected value calculated as 24 h-UCP/(urinary C-peptide to creatinine clearance (CCP/CCR) ratio in the fasting state x 10) was correlated with the sum of day-long serum C-peptide levels (r = 0.93) more closely than the measured value of 24 h-UCP (r = 0.79) in 9 patients. In 52 patients treated with diet alone, 38 with sulfonylurea and 28 with insulin, fasting serum C-peptide level did not vary with FPG level, and the increment of serum C-peptide level after breakfast and the corrected value of 24 h-UCP decreased with the rise in FPG level in each treatment. These indexes were the lowest in insulin treatment among the patients with similar FPG levels. In conclusion, 24 h-UCP was demonstrated to be able to reflect day-long endogenous insulin secretion more faithfully after the correction with the CCP/CCR ratio. It was estimated that the insulin response to breakfast and day-long insulin secretion decreased with the rise in FPG level, but basal insulin secretion was maintained over a wide range of FPG levels in each treatment. Endogenous insulin secretion seemed to be somewhat suppressed or rested by exogenous insulin in insulin-treated patients.
Biomarkers↗
Elevation of serum CA 19-9 in parallel with HbA1c in a diabetic female with the Lewis(a+b-) blood group.
We report a 66-yr-old diabetic female with her serum CA 19-9 levels elevated in parallel with her hemoglobin A1c (HbA1c) levels. She was initially suspected of having pancreatic cancer, but this was later proved to be false. Her serum CA 19-9 levels varied between 58 and 235 U/ml over a 3-yr period, and correlated significantly (r = 0.68, P less than 0.01) with her HbA1c levels (7.2-13.3%). She belonged to the Lewis (a+b-) blood group. Serum CA 19-9 levels were also assessed in 73 diabetic patients (36 males and 37 females) in relation to sex and Lewis blood group. The mean level of serum CA 19-9 was higher in females than in males in each Lewis blood group, and it was the highest in patients with Le(a+b-) and the lowest in Le(a-b-). Patients with a higher level of HbA1c showed a higher level of serum CA 19-9 in Le(a+b-), but patients with Le(a-b-) showed a low level of serum CA 19-9 irrespective of HbA1c level. Patients with Le(a-b+) appeared to intermediate between the patients with Le(a+b-) Le(a-b-). Thus, the elevation of serum CA 19-9 level due to hyperglycemia was indicated to be affected by sex as well as Lewis blood group. The biosynthesis of CA 19-9 seemed to be accelerated in hyperglycemic diabetic patients, especially in females. Consequently, it was considered that the present case was a diabetic female with the Le(a + b -) blood group, which led to showing a relatively high level of serum CA 19-9 correlated with HbA1c level.
Aged↗
Contribution of hyperglycemia and renal damage to urinary C-peptide clearance in non-insulin-dependent diabetic patients.
The variation of urinary C-peptide clearance in relation to hyperglycemia and renal damage was evaluated in 57 patients with non-insulin-dependent diabetes mellitus (NIDDM) with and without overt proteinuria, 14 nondiabetic patients with renal disease (RD) and 18 healthy control subjects. Urinary C-peptide clearance expressed as the ratio of urinary C-peptide to creatinine clearance (CCP/CCR) in the fasting state did not differ in control subjects and RD patients, and was higher equally in NIDDM patients with and without proteinuria. In NIDDM patients without overt proteinuria, urinary levels of C-peptide, beta 2-microglobulin (B2M), N-acetyl-beta-D-glucosaminidase (NAG) and albumin as well as CCP/CCR ratio all decreased significantly with short-term glycemic control (P less than 0.05). Despite a wide range of CCP/CCR ratio (0.07-0.73), a weak but significant correlation (r = 0.56, P less than 0.005) was found between fasting serum and urinary C-peptide levels in NIDDM patients. These results suggest that urinary C-peptide may easily be affected by hyperglycemia per se rather than renal damage, while urinary B2M, NAG and albumin may be affected by both hyperglycemia and renal damage. When the urinary C-peptide level is interpreted, the influence of hyperglycemia on it must be taken into consideration.
Acetylglucosaminidase↗
Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method.
We examined the effect of atrial natriuretic peptide on cerebral edema in 96 rats. Forty-four rats were given 30 (n = 11), 120 (n = 26), or 150 (n = 7) micrograms/kg of the peptide intravenously over 24 hours after occlusion of the left middle cerebral artery to induce cerebral ischemia. We then measured the brain water content, the brain sodium and potassium contents, the in vitro proton nuclear magnetic resonance longitudinal (T1) and transverse (T2) relaxation times, and the area of the edematous regions. Compared with saline treatment (n = 39), peptide treatment decreased the brain water content in a dose-dependent manner and decreased the brain sodium content significantly (p less than 0.05). Peptide treatment also suppressed the lengthening of both T1 and T2 in edematous tissue (p less than 0.05 and p less than 0.01, respectively) and reduced the area of the edematous regions observed by magnetic resonance imaging (p less than 0.01). Atrial natriuretic peptide appears to have a pharmacological effect on ischemic brain edema, possibly by suppressing the elevation of water content through regulation of electrolyte transport in the brain.
Animals↗
Effects of MCPA and other phenoxyacid compounds on hepatic xenobiotic metabolism in rats.
The effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) and other phenoxyacid compounds on hepatic xenobiotic metabolizing enzymes were studied in male rats. These compounds were administered orally 200 mg/kg/day to the rats for 2 weeks. Both MCPA and clofibrate increased the hepatic level of cytochrome P-450. In the MCPA-treated group, the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase increased by 15% and 1.5-fold, respectively. The free acid form of MCPA increased these activities more potently than MCPA. Both MCPA and its free acid did not change the activity of aminopyrine N-demethylase. A marked increase in the activity of aniline hydroxylase was noted in the 2,4-dichlorophenoxyacetic acid-treated group, whereas the aminopyrine N-demethylase activity significantly decreased in the same group. Clofibrate also increased the activities of hepatic microsomal cytochrome P-450-mediated oxidation tested, but to a lesser extent when compared with the effects of MCPA. These results indicate that MCPA may have a potent effect on the hepatic metabolizing enzymes in rats, and also that the induction of xenobiotic metabolizing enzymes may change when the chemical moiety of phenoxyacid compounds is modified.
2-Methyl-4-chlorophenoxyacetic Acid↗
Effects of ethyl 4-chloro-2-methylphenoxyacetate on hepatic peroxisomal enzymes in rats.
Effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) and clofibrate on the activities of hepatic lipid metabolizing enzymes in the peroxisomal fraction from rat liver were studied, and these drugs were found to potentiate the peroxisomal enzyme activity. The results imply that MCPA affects lipid metabolism as well as clofibrate.
2-Methyl-4-chlorophenoxyacetic Acid↗
Preparation and partial characterization of a pancreatic cancer-associated glycoprotein expressing CA50.
In our previous study, two antigens associated with pancreatic cancer were prepared from ascites of the patients by using a newly developed affinity chromatography technique; one expressed CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This report describes the other part of the antigens, which was scarcely found in normal sera. This antigen was a glycoprotein with a high molecular weight of 1,000,000 in its native state, estimated by size exclusion chromatography on Sephacryl S400. After sodium dodecyl sulfate polyacrylamide gel electrophoresis and blotting analysis, the antigenic activity was observed on the 200-Kd band, and monoclonal antibody of CA50 showed intense reactivity to it. By means of an enzyme immunoassay, CA19-9 determinant was also recognized on it to a lesser extent, although sialyl SSEA-1 and Dupan-2 determinants were scarcely observed. From these observations, the present antigen was considered to be a serum glycoprotein carrying type-1 polylactosamine determinant and differs from previously reported glycoprotein carrying CA19-9 in its insolubility in perchloric acid solution because of its lesser degree of glycosilation. Serum levels of the antigen measured by enzyme-linked immunosorbent assay demonstrated that highly positive rates were observed in 78% of pancreatic cancers, 82% of biliary tract cancers, and 96% of hepatocellular carcinomas.
Antigens, Neoplasm↗
[Significance of transrectal hyperthermia in the treatment of benign prostatic hyperplasia].
Though the local hyperthermia for the management of benign prostatic hyperplasia has drawn much attention as one non-surgical treatment, no definite conclusion could yet be obtained in terms of the efficacy. In this study local hyperthermia was induced in evaluable 33 cases with benign prostatic hyperplasia using Primus, and the effectiveness of this modality of treatment was investigated by analysing the subjective and objective response following hyperthermia. The prostate was heated trans-rectally up to 43 degrees C with 915 MHz microwave for one hour. Hyperthermia was carried out twice a week for ten times for the sake of thermotolerance. Urinary obstructive symptoms were divided into diurnal and nocturnal frequency, urinary urgency, the degree of urinary stream, hesitancy and dribbling. Each symptom was described before and after the treatment according to the scoring system. Moreover, objective changes of urinary flow and prostatic size were estimated by the residual urine volume, uro-flowmetry, rectal palpation of the prostate and echography. Hyperthermic treatment improved urinary flow markedly, but no appreciable alteration could be observed as to the size of the prostate. The overall efficacy, including subjective and objective response, could be summarized as 37% of effectiveness, and 33% of slight effectiveness, that is, 70% of effective ratio. As to the side effect, anal pain was noted in few cases of the present series. Therefore, transrectal hyperthermia may be a suitable modality for non-surgical treatment of benign prostatic hyperplasia.
Evaluation Studies as Topic↗
[Discrepancy between the serum levels of gamma seminoprotein and prostate-specific antigen in patients with prostatic neoplasms. Both true or either untrue].
Serum levels of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate-specific antigen (PSA) were determined simultaneously in 57 patients with benign prostatic hyperplasia (BPH) and in 50 untreated patients with prostatic cancer (adenocarcinoma, N = 47 and non-adenocarcinoma, N = 3). The correlations between the serum levels of gamma-Sm and PSA in these patients were assessed by linear regression analysis. Some fundamental studies were added for explaining the causes of discrepancy between the serum levels of gamma-Sm and PSA. All of BPH group underwent transurethral resection of the prostate (TURP) and the sera were obtained for measurements before, immediately after and 18 hours after TURP. The gamma-Sm correlated well with the PSA in the sera obtained before (r = 0.76) and 18 hours after (r = 0.73) TURP. However, there was no correlation (r = 0.26) between them in the sera obtained immediately after TURP. In 47 untreated patients with adenocarcinoma of the prostate, no significant correlation (r = 0.19) between serum levels of gamma-Sm and PSA was observed, although there was correlation (r = 0.51) between those of PAP and PSA. When these patients were classified into two groups, M0 (stage A-C; N = 26) and M1 (stage D; N = 21), however, the serum gamma-Sm correlated with the serum PSA in M0 group (r = 0.57), but didn't in M1 group (r = 0.11). Furthermore, the differences in the means of PAP (p less than 0.05) and PSA (p less than 0.001) between M0 group and M1 group were statistically significant, although the serum gamma-Sm failed to distinguish M0 from M1. The anti-PSA antibody of "PSA Kit" reacted against the standard gamma-Sm adopted from "gamma-Sm Kit". Surprisingly, the anti-gamma-Sm antibody of "gamma-Sm Kit" also reacted against the standard PSA adopted from "PSA Kit". The gamma-Sm and PSA apparently cross-reacted each other. The quantitative analyses with serial dilution of the sera were done by using each assay in 3 patients whose serum levels of gamma-Sm were markedly different from those of PSA. The dilution curve for PAP appeared to be rectilineal, and that for PSA also appeared to be approximately rectilineal. However, the gamma-Sm assay failed to be proportional. In conclusion, the correlation between serum levels of gamma-Sm and PSA was absent in certain circumstances, when the true values of them were expected to be much higher than those determined.(ABSTRACT TRUNCATED AT 400 WORDS)
Acid Phosphatase↗
[Effects of various growth factors on the growth of trophoblast cells in long-term culture].
Trophoblasts taken from placental tissue of the 1st trimester and molar tissue, and GCH-1 (gestational choriocarcinoma cell line) cells were cultured in collagen coated dishes. The medium used was a mixture of DME and Ham's F-12 (1:1), containing EGF, PDGF, insulin, GM-CSF, IL-1, -2, -3, PGE1 and PGE2 in various concentrations. 3H-TdR uptake of the cultured cells was measured as a marker of cell growth. The growth of normal trophoblasts was enhanced by PDGF or insulin, and remarkably by EGF + PDGF + insulin + GM-CSF. The growth of molar trophoblasts was accelerated by EGF or insulin. Under these culture conditions, normal trophoblasts have been successfully cultured and maintained for 12 months and molar trophoblasts for 9 months to date. The cultured cells were identified with trophoblasts by immunohistochemical staining with CAM 5.2 monoclonal antibody. No effect of growth factors was observed in GCH-1 cells.
Alprostadil↗
[Assessment of therapeutic effects of cisplatin-phosphatidyl-choline-lipiodol (CPL) suspension for hepatocellular carcinoma].
Sixty-three patients with unresectable hepatocellular carcinoma (HCC) were treated with cisplatin-phosphatidyl-choline-Lipiodol (CPL) suspension. Partial response (PR) and minor response (MR) were obtained in 3 of 14 cases (21.4%) by one shot therapy, and in 13 of 43 cases (30.2%) by TAE therapy. AFP decreased in 11 of 15 patients (73.3%) by one shot therapy, and in 32 of 33 patients (97%) by TAE therapy. PIVKA II also decreased. The one-year survival rate was 74% in TAE therapy, and 52% in one shot therapy. The two-year survival rate was 53% in TAE therapy, and 28% in one shot therapy. Nausea, vomiting and fever were noted in most cases as adverse effects, but they were slight. The concentration of free-CDDP in the peripheral venous blood was lower and continued longer than that of CDDP on the market. These results suggest that CPL was useful as an anticancer agent for arterial chemotherapy or TAE therapy for unresectable HCC.
Carcinoma, Hepatocellular↗
[A clinical study of pulmonary tuberculosis in lung cancer patient].
We have reviewed 442 patients with lung cancer. There were 323 male patients with a mean age of 65.8 yr and 119 female patients with a mean age of 66.0 yr. Histological types of lung cancer were squamous cell carcinoma 177 patients (40.0%), adenocarcinoma 167 (37.8%), small cell carcinoma 75 (17.0%), large cell carcinoma 17 (3.8%) and undifferentiated carcinoma 6 (1.4%). When lung cancer was diagnosed, 55 patients (12.5%) showed tuberculous lesions on the initial chest X-ray film. The majority of these tuberculous lesions were old changes, but only one with cavitary lesion was confirmed to be active. Although there was no statistical significance, the incidence of squamous cell carcinoma was higher in the 55 patients with tuberculous lesions than in the remaining 387 patients without ones. In the present study, five patients developed active pulmonary tuberculosis while on a therapy of lung cancer. All of these five patients were male and they had advanced lung cancer on admission. The diagnosis of active tuberculosis was made by autopsy in two patients and by culture--positive after death in two. Only one patient was identified to have active tuberculosis by broncho-alveolar lavage. Three of 5 patients showed old tuberculous lesions on the initial chest X-ray film, but all of five patients showed caseoinfiltrative shadows when active tuberculosis occurred. In addition, the prevalence of active pulmonary tuberculosis was significantly higher in the patients with old tuberculous lesions (5.6%: 3 out of 54 patients) than in those without ones (0.52%: 2 out of 387 patients). Finally, all of the five patients died. The causes of death were lung cancer in three patients, both pulmonary tuberculosis and lung cancer in one and pulmonary tuberculosis in one.
Adenocarcinoma↗
Pharmacological actions of chemically-modified phospholipase A2 from the venom of Trimeresurus flavoviridis on the smooth muscle of the rat stomach fundus.
The pharmacological activities of Trimeresurus flavoviridis phospholipase A2 (PLA2) and their chemically-modified PLA2 were characterized by measuring the contraction of rat stomach fundus strips. The native PLA2 produced a contraction of rat fundus strips. The alpha-amino-modified enzyme induced an almost identical contraction of the fundus with that of the native enzyme, whereas His-modified and Lys-modified enzymes induced a markedly decreased contraction as compared with the native enzyme. These results demonstrate that lysine and histidine residues but not the alpha-amino group in the PLA2 molecule are essential for contractile activity of the stomach fundus.
Animals↗
Different distribution of cadmium in the liver supernatant between in vivo and in vitro.
Distribution of cadmium (Cd) in liver supernatant was examined by gel filtration chromatography after injecting Cd intravenously into female Wistar rats and also by adding Cd in vitro into the control supernatant. Supernatants were analyzed on an HPLC Asahipak GST-520 column and on-line ICP (inductively coupled argon plasma-atomic emission spectrometer) analysis of the eluate (HPLC-ICP). The relative intensity of the three main Cd-associated peaks changed with time after injection of Cd into rats. The three peaks were tentatively assigned as Cd-binding protein-I and -II (Cd-BP-I and -II) and metallothionein (MT) in the order of respective elution from the column. Relative affinities of Cd for the three peaks were determined by injecting different doses of Cd into rats as follows: MT greater than Cd-BP-II greater than Cd-BP-I. Cd-BP-II was assigned as the major Cd-BP other than MT in the liver supernatant and it contained zinc that can be replaced by Cd. Comparison between the in vivo and in vitro Cd distributions indicated that the former distribution is not reproducible under any in vitro conditions examined and the latter distribution is dependent mostly upon incubation temperature.
Animals↗
Binding of cadmium to alcohol dehydrogenase in the liver before induction of metallothionein.
The cadmium-binding protein (Cd-BP) with the highest affinity to Cd other than metallothionein (MT) is assumed to be the target molecule for the toxicity of Cd and one of the major zinc (Zn)-containing proteins in the liver supernatant of rats has been identified as the Cd-BP before induction of MT. In the present study the Zn-containing Cd-BP was assumed to be alcohol dehydrogenase (ADH) from the similarity in several characteristic properties such as molecular size, isoelectric point, Zn content and enzyme activity. Zn bound to non-active site in ADH was replaced with Cd both in vivo and in vitro. Cd bound to ADH to an extent more than the replacement in vitro and the enzyme activity was decreased in vitro by Cd. However, the ADH enzyme activity was not affected in vivo despite the replacement of Zn with Cd and binding of Cd to ADH. This difference was explained by the weaker affinity of Cd to the active site than the other binding sites for Cd in other high molecular weight proteins. The result also suggested that ADH sequesters Cd temporally before induction of MT and reduces the toxicity of Cd without being affected its enzyme activity and that the target molecules for the toxicity are other Cd-BPs.
Alcohol Dehydrogenase↗