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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 1,009 records · Page 56Linked to original sources

Characterization of anti-IL-1 alpha autoantibodies in the sera from healthy humans.

Previously, we reported that pooled normal human serum contained anti-IL-1 alpha autoantibodies. Further characterization studies have been undertaken with sera from individual healthy humans. Molecular exclusion chromatography demonstrated that 9 of 38 test sera contained anti-IL-1 alpha autoantibodies that specifically bound 125I-IL-1 alpha. The autoantibodies formed immune complexes composed of either one IgG or two IgG molecules bound to one 125I-IL-1 alpha molecule. The data suggest that the autoantibodies recognize at least two separate antigenic sites on IL-1 alpha. The autoantibodies neutralized IL-1 alpha induced IL-2 secretion by mouse thymocytes (EL-4 NOB-1). Further, in an in vitro competitive receptor binding assay, the autoantibodies completely blocked 125I-IL-1 alpha binding to recombinant human IL-1 receptor expressed on CHO cells. Our previous studies have established a correlation between inhibition of 125I-IL-1 alpha binding to receptor bearing cells and neutralization of IL-1 bioactivity in vitro and in vivo. These data suggest that development of anti-IL-1 alpha autoantibodies may play a significant role in modulating the effects of high local or systemic concentrations of IL-1 alpha.

Animals↗

PHA production by activated sludge.

The production of polyhydroxyalkanoate by anaerobic-aerobic activated sludge was reviewed concentrating on the biochemical mechanisms and on the trials to increase polyhydroxyalkanoate (PHA) content in activated sludge. The anaerobic aerobic activated sludge system selects microorganisms with the capabilities to couple glycolysis, polyphosphate degradation, and PHA accumulation for anaerobic substrate uptake. Some of the PHA-related metabolisms observed there have not been seen in pure cultures so far. Such metabolisms are the formation of PHA containing 3-hydroxy-2-methylvalerate, and '3-hydroxyvalerate fermentation' in which glucose or glycogen is converted to 3-hydroxyvalerate-rich PHA while yielding energy. The PHA content of activated sludge can be increased up to 62% by applying a microaerophilic-aerobic activated sludge process. PHA production by activated sludge is worth investigation.

Aerobiosis↗

Growth and behavioral changes in mice prenatally exposed to methylmercury and heat.

Postnatal and behavioral changes in mice exposed prenatally to methylmercury and heat were investigated. Pregnant ICR mice were immersed in water at 37 degrees C or 42 degrees C for 10 min once or twice daily from day 12 through day 15 of gestation. Two hours after the heat exposure on day 12 of age, mice were injected s.c. with 5 mg Hg/kg of methylmercury (MeHg, as chloride) or saline. Prenatal exposure to heat significantly induced inactivity in an open field test (OPF) in males and retarded walking ability in both males and females. Prenatal exposure to MeHg caused significant inactivity in the OPF in females. Although heat did not enhance the effect of MeHg on physical growth or the behavior of pups and vice versa, there were some interactions between the effects of these two agents. Thus, the difference in walking ability in both sexes caused by heat was more distinctive in the saline-treated groups than in the MeHg-treated groups; the difference in locomotion in OPF caused by MeHg in females was more distinctive in the normothermic group than among the hyperthermic groups. The mechanisms underlying these behavioral changes need to be further examined.

Analysis of Variance↗

In utero exposure to methylmercury and Se deficiency converge on the neurobehavioral outcome in mice.

Pregnant female ICR mice, maintained on torula-based diets containing various amounts of Se (0.02, 0.05, or 0.4 mg/kg diet), were given methyl-mercury (MeHg; 0, 5, or 9 mg Hg/kg in total) on the 12-14th days of gestation. The neurobehavioral function of the offspring born to these dams was evaluated with respect to reflex and motor development, thermal preference, and open-field activity. Se deficiency per se as well as exposure to MeHg exerted additive or synergistic effects on the neurobehavioral functions examined. The group of mice most affected was the group given the lowest amount of Se and the highest dose of MeHg. Thus, the neurobehavioral outcome of in utero MeHg exposure and Se deficiency converged. Although the dietary level of Se did not affect the Hg concentration in the fetal brain, the Se concentration and the activity of glutathione peroxidase, a selenoenzyme, were severely depressed by MeHg in the neural tissue. The possibility that functional Se deficiency by MeHg exposure partly accounts for the neurobehavioral toxicity of MeHg is discussed.

Animals↗

Comparison of neurobehavioral changes in three inbred strains of mice prenatally exposed to methylmercury.

Pregnant mice of three inbred strains (BALB/c, C57BL/6J, C57BL/6Cr) were orally given methylmercury (MMC; 3 x 3 mg/kg body weight) or the equivalent volume of phosphate-buffered saline during days 12-14 of gestation and allowed to deliver. The behaviors of their male offspring were evaluated in an open field and their home cage and in a Morris water maze. In the open field test, the BALB/c and C57BL/6Cr MMC groups exhibited less total locomotor activity than did their respective control groups. However, there was no significant difference observed between the MMC and control C57BL/6J strain. In the BALB/c strain, the MMC group exhibited significantly more central locomotion and significantly less peripheral locomotion than did the control group. These results indicated that the prenatal exposure to MMC caused decreases in open-field activity in the C57BL/6Cr and BALB/c strains, concomitantly with a change in emotional status in BALB/c strain. For spontaneous activity in their home cage, all groups moved more actively in the dark phase than in the light phase except BALB/c MMC group. The BALB/c MMC group moved in the light phase as much as in the dark phase, indicating a disturbance of nocturnal rhythm of spontaneous activity. In the Morris water maze, the C57BL/6Cr and C57BL/6J control groups perform very well over the 5 consecutive days. The prenatal exposure to MMC caused significantly prolonged latency in the C57BL/6Cr and C57BL/6J, but not in BALB/c strain. This result indicated that the prenatal exposure to MMC impaired the performance in the Morris water maze differently among the strains. This study provides a basis for evaluating strain-specific neurobehavioral changes when the widely used three inbred strains of mice are chronically exposed to MMC.

Animals↗

Computer-aided diagnosis for pulmonary nodules based on helical CT images.

In this paper, we present a computer-assisted automatic diagnostic system for lung cancer that detects nodule candidates at an early stage from helical CT images of the thorax. Our diagnostic system consists of analytical and diagnostic procedures. In the analytical procedure, first we extract the lung and the pulmonary blood vessel regions using the fuzzy clustering algorithm, then we analyze the features of these regions using image-processing techniques. In the diagnostic procedure, we define diagnostic rules utilizing the extracted features which support the determination of the candidate nodule locations. We show the effectiveness of our system by giving the results from its application to image data for mass screening of 450 patients.

Algorithms↗

Representation of molecular configurations by CAST coding method.

A configurational CAST (CAnonical representation of STereochemistry) coding method, which represents relative and absolute configuration, is described. The configurational CAST codes are constructed by canonical rotation of the dihedral angles of the input structure before the CAST codes are assigned. Using the configurational CAST, configurational differences can be distinguished independently of conformational differences. Representation of enantiomers is also achieved by a mirror image conversion method. The CAST representation shows the distinctive characteristics of several diastereomers and conformers that were examined. The method clearly represents the differences in configurations. Applications to organic molecules having complex stereochemistry are also demonstrated.

Journal Article↗

Induction of apoptosis by castration in epithelium of the mouse seminal vesicles.

Castration on days 0, 5, 10, 20, 40, and 60 caused increases in an apoptotic index (% of apoptotic cells) in seminal vesicle (SV) epithelium, peaking 1-3 days after castration. The peak apoptotic indices after castration on days 0, 5, 10, and 20 were significantly lower than peak apoptotic indices observed after castration on days 40 and 60. DNA extracted from mouse SVs 2 days after castration on days 0, 5, 10, and 60 showed a ladder pattern on agarose gel electrophoresis. The secretion of androgen by testes was confirmed by the growth retardation of the SVs after castration on days 0, 5, 10, and 20. It would appear that a proportion of SV epithelial cells dependent on testicular androgens for survival is smaller before day 20 than after day 20.

Animals↗

Morphological classification of dental lesions induced by various antitumor drugs in mice.

To characterize and compare maxillary incisor lesions caused by various antitumor drugs, male BALB/c mice were given a single intravenous injection of an estimated 10% lethal dose (LD10)) of 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C (MMC), vinblastine sulfate (VBL). taxotere (TXR), irinotecan hydrochloride (CPT-11), DX-8951f, or cisplatin (CDDP). After 3, 5, 10, 15, and 60 days, the animals were sacrificed, and the maxillary incisors were examined microscopically. The dental lesions observed were classified into 4 different types on the basis of their morphological features. The lesion due to 5-FU was characterized by focal defects in the dentin, and this injury was reversible (transient dentin injury). ADR- or MMC-induced lesions were defined by abnormal structure of the apical aspect of the tooth and irregular odontogenesis, lasting for a long period (persistent apical injury). Treatment with VBL or TXR showed irregular enamel formation and abnormal dentinogenesis. Their targets were considered to be both immature and mature odontogenic cells (diffuse dental injury). Exposure to CPT-11, DX-8951f, or CDDP elicited minor reductions in a few precursor cells in the epithelial sheath on day 3, but no prominent dental abnormalities were seen thereafter (nontoxic injury). In conclusion, antitumor drugs can cause a variety of dental lesions that vary temporally and spatially, making histopathological examination of the maxillary incisor an important component of the safety assessment process for novel antitumor drugs.

Animals↗

Morphological and immunohistochemical characteristics of the heterogeneous prostate-like glands (paraurethral gland) seen in female Brown-Norway rats.

Morphological and immunohistochemical characteristics of the prostate-like glands (paraurethral gland) seen spontaneously in female Brown-Norway (BN) rats were investigated by gross, and light and electron microscopic examination. At 9- to 10-weeks-old, the paraurethral gland was detected in 50 out of 52 female animals examined (96.2%), and it was observed as single or paired structures located ventrolaterally in the urethra just caudal to neck of the urinary bladder. Microscopically, the glandular acini consisted of flat to cuboidal secretory epithelium surrounded by the smooth muscle. The glands displayed modest secreting activity, and a few secreting materials were observed in the acinar lumens. The main peripheral ducts were located in the urethral wall, and drained into the urethra on both sides. Ultrastructurally, abundant rough endoplasmic reticulum (RER), numerous mitochondria and lysosomes, and secretory granules in the apical portion of the epithelial cells were noted, and basal cells were also observed. These gland epithelial cells showed positive reactions when stained for androgen receptor (AR), prostate specific antigen (PSA), or prostate specific acid phosphatase (PSAP). The nature of this paraurethral gland resembled that of the prostate gland in male rats. Thus, the paraurethral glands seen in the females were considered homologous to the prostate gland in males.

Acid Phosphatase↗

Synthesis and antiviral activities of 5-substituted 1-(2-deoxy-2-C-methylene-4-thio-beta-D-ertythro-pentofuranosyl)uracils.

Various 5-substituted 1-(2-deoxy-2-C-methylene-4-thio-beta-D-erythro-pentofuranosyl)uracils (4'-thioDMDUs) were synthesized from D-glucose via sila-Pummerer-type glycosylation. All of the beta-anomers of 5-substituted 4'-thioDMDU, except the 5-hydroxyethyl derivative, showed potent anti-HSV-1 activity (ED50 = 0.016-0.096 microgram/mL). 5-Ethyl- and 5-iodo-4'-thioDMDUs were also active against HSV-2 (ED50 = 0.17 and 0.86 microgram/mL, respectively). 5-Bromovinyl-4'-thioDMDU was particularly active against VZV (ED50 = 0.013 microgram/mL).

Antineoplastic Agents↗

Detection of the integrated feline leukemia viruses in a cat lymphoid tumor cell line by fluorescence in situ hybridization.

Feline leukemia virus (FeLV) is a type-C retrovirus associated with lymphoid and hematopoietic malignancies in cats. The FeLV-induced tumors are thought to be caused, at least in part, by somatically acquired insertional mutagenesis in which the integrated provirus may activate a proto-oncogene or disrupt a tumor suppressor gene. This study was undertaken to enumerate and map the acquired proviral insertions in the genome of a feline thymic lymphoma cell line (FT-1) infected with FeLV. Fluorescence in situ hybridization (FISH) combined with tyramide signal amplification was applied on the chromosome specimen of FT-1 cells and normal cat lymphocytes, with an entire FeLV-A genome used as a probe. Specific hybridization signals were detected from only the metaphases of the FT-1 cells, not from those of normal cat lymphocytes. Statistically based on the Poisson's distribution, at least six loci of chromosomal regions, A2p23-p22, B2p15-p14, B4p15-p14, D4q23-q24, E1p14-p13, and E2p13-p12, appeared to be positive for FeLV integration. Consistently, Southern blot hybridization analysis using an FeLV LTR-U3 probe specific for exogenous FeLV showed the integration of at least six FeLV proviral genomes in FT-1 cells. The cytogenetic technique employed here will provide valuable molecular tags to reveal unidentified tumor-associated genes in FeLV-associated tumor cells.

Animals↗

Comparison between pulsatile and nonpulsatile circulatory assist for the recovery of shock liver.

In patients with prior shock and liver injury, mechanical circulatory assist still has a high risk of hepatic failure. The purpose of this study was to evaluate the effect of mechanical circulation using pulsatile or nonpulsatile blood pumps on shock organs, particularly shock liver. In 14 dogs, a shock liver model was produced by clamping the descending aorta above the diaphragm. After 60 minutes of ischemia, left atrial-femoral artery bypass (LHB) was started while the clamp remained in place. A pneumatic pulsatile pump (Toyobo; Tokyo, Japan) was used in seven dogs (Gr-PP) and a centrifugal pump (Biomedicus; Minneapolis, MN) in seven (Gr-NPP). In both groups the mean arterial pressure was maintained at 80 mmHg. The mean bypass flow was 96 +/- 14 ml/kg/min for Gr-PP, and 95 +/- 35 ml/kg/min for Gr-NPP. In both groups the bile flow and arterial ketone body ratio decreased significantly after ischemia, and recovered to normal after 120 min of LHB. There was no significant difference between the two groups in this model. The other parameters (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic transaminase, lactate dehydrogenase, mitochondrial GOT) were independent of the period of ischemia and reperfusion, and there was no difference between the two groups. In conclusion, these results suggest that nonpulsatile circulatory assist may not be disadvantageous for the circulatory support and recovery of liver function in the setting of shock liver.

Animals↗

P-selectin monoclonal antibody may attenuate the whole body inflammatory response induced by cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been reported to be involved in the initiation of this inflammatory response by promoting the adhesion of neutrophils to endothelial cells in postcapillary venules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the effect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceutical) on the response of inflammatory cytokines and lung injury in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minutes (80 ml/kg per minute, 34 degrees C) under one of two conditions. In group P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circuit (n = 10). Saline alone was given to group C (n = 10). Inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1beta, IL-6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchange ability were measured 1) before the initiation of CPB, 2) at the termination of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1beta was detected during the experimental period in either group. The plasma levels of IL-6 and IL-8 increased after CPB in both groups, but they were significantly lower in group P than in group C. The RI value increased in a pattern similar to that of the inflammatory cytokines and was significantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of inflammatory cytokines and attenuates CPB induced lung injury in rats. Thus, P-selectin may play a role in the augmentation of CPB induced inflammatory response, and the use of its inhibitory monoclonal antibody seems to be a promising strategy for the treatment of CPB induced lung injury.

Animals↗

Effects of etafenone and antiarrhythmic drugs on Na and Ca channels of guinea pig atrial muscle.

Since Ca-mediated electrophysiological phenomena seem to be important in the generation of various arrhythmias, we quantitatively compared the effects of quinidine, disopyramide, procainamide, lidocaine, propranolol, and etafenone, a new coronary vasodilator with antiarrhythmic properties, on Na and Ca channels in normal and depolarized guinea pig atria. The maximum rate of rise of the normal action potential and the amplitude of the depolarized, Ca-mediated action potential were measured to examine the Na and Ca channel activity, respectively. In both preparations, the contractile force was determined concomitantly in order to establish the role of Ca influx in the inotropic effects of the drugs. All six drugs suppressed the Na channel, the effect being strongest with etafenone, followed in order by quinidine, propranolol, disopyramide, lidocaine, and procainamide. Only quinidine, disopyramide, and propranolol suppressed the Ca channel and only in concentrations higher than those required to block the Na channel. Etafenone and procainamide decreased Ca influx, while lidocaine had no effect on it. The negative inotropic effects of propranolol and disopyramide may be due to decreases in Ca influx, but the order drugs seem to have other mechanisms for their inotropic effects.

Action Potentials↗

Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs.

The effects of parathyroid hormone and related polypeptides on the heart were examined using the canine heart-lung preparation supported by a donor. Synthetic bovine parathyroid hormone (PTH) containing 34 amino acids [PTH-(1--34)] and natural bovine PTH containing 84 amino acids [PTH-(1--84)] showed slight positive chronotropic and inotropic action and prominent coronary vasodilator action. The effects of the two compounds were very similar. The cardiac stimulatory action was not blocked by pindolol. The coronary vasodilation occurred without increase in the myocardial oxygen consumption, suggesting that it is due to a direct action on the coronary vasculature. All effects occurred soon after intra-arterial injection, lasted only about 20 min, and were not accompanied by changes in plasma Ca and Pi levels. Fragments of PTH, PTH-(24--34) containing 11 amino acids. PTH-(24--28) containing 5 amino acids, and PTH-(25--27) containing 3 amino acids showed very weak transient coronary dilatory action without cardiac stimulatory effects.

Animals↗

Spontaneous regression of multiple emphysematous bullae.

The etiology of emphysematous bullae is not well known; thus, the management of bullous lung disease is often difficult because of concomitant underlying emphysema and coexisting cardiac conditions. The present paper reports a case in which near complete resolution of multiple emphysematous bullae in the right lung occurred spontaneously. This case is of interest, not only because of the rarity with which spontaneous regression of multiple emphysematous bullae has been reported in the literature, but also because of the accompanying dramatic improvements in radiological results and pulmonary function of the patients.

Chest Tubes↗