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Biomedical subjects

Y Fukui

Publications and source records attributed to Y Fukui.

At least 235 records · Page 13Linked to original sources

Role of brain cocaethylene levels in combined cocaine-ethanol lethality in mice.

The purpose of this study was to examine the lethal effects of combining cocaine with ethanol in mice by assaying for cocaethylene at the time of death. After the voluntary oral ingestion of ethanol in the form of a liquid diet containing 35% ethanol-derived calories for 5 days, intraperitoneal cocaine (60 mg/kg) was administered daily for up to 5 days while the ethanol diet continued (ethanol diet group). The mice in the ethanol diet group were paired with control mice that received a control liquid diet containing equivalent carbohydrate calories in the form of sucrose instead of ethanol (control diet group). In order to analyze the drugs, samples (blood, liver and brain) were collected for both groups from the dead animals that could not tolerate the 5 days of cocaine administration. A higher rate of lethality was observed in the ethanol diet group as compared to the control diet group. Furthermore, various patterns of cocaine lethality were revealed under different conditions of ethanol intake. According to the survival times after the last cocaine administration, observed respiratory and locomotive disorders, and drug concentrations, a total of 5 subgroups in the ethanol diet group (Groups E1-E5) and a total of 3 subgroups in the control diet group (Groups C1-C3) were differentiated. The ratio of the mean cocaethylene concentration relative to the mean cocaine concentration was over 30% in the livers of animals in an earliest lethal subgroup (Group E1). In addition, examination of all of the dead animals in the ethanol diet group revealed the prolonged presence of cocaethylene in the brain of the mice that died within 2 hours. Thus, it was suggested that cocaethylene has strong effects on the brain receptors and influences cocaine lethality.

Animals↗

Effects of postnatal cocaine on differentiation of the rat corpus callosum.

We investigated the effects of cocaine on the development of the corpus callosum. Pregnant Wistar strain rats (Thirteenth day of gestation) were used in this study. On the day following birth, litters were culled to 8 pups (4 males and 4 females), and rats were assigned to either a control or drug treatment group. From postnatal day 1 (P1, at birth = P0) to P5, cocaine (50 mg/kg) was subcutaneously injected to the cocaine-treated pups, and saline in the same volume to the control pups. Animals were sacrificed in 110 days and a mid-sagittal section of the callosum was obtained. From this section the morphometric measurement of the corpus callosum was performed. In the control group the rat corpus callosum has a sex difference with the male corpus callosum being larger than the female's. But this sex difference disappeared in the cocaine group. This was attributed to the fact that cocaine-treated male rats indicated a significant reduction of callosal area. These findings suggest that the early postnatal cocaine can abolish the sexual differentiation of the corpus callosum.

Animals↗

Elimination of CO from the body: an experimental study on the rabbit.

Rabbits were exposed to gases containing CO with concentrations ranging from 2.0 to 2.9% for 40 sec, 1 min, or 5 min, and the time course of the change in the arterial blood COHb concentration was followed from immediately after the end of exposure up to 180 min. All rabbits survived. Hypercapnia was not observed. The COHb concentration at the end of the 5-min exposure ranged from 68.8-82.0%. The pattern of the elimination of CO was not linear; the decreasing rate of COHb concentration became slower with the lapse of time. The COHb concentration plotted against the post-exposure time on a semi-logarithmic graph showed three phases. In the first 10 min, the rate of decrease was the fastest. The second phase was followed by the third phase at about 90 min after exposure. In the shorter exposure groups too, the initial phase was observed. The initial phase was considered to be a stage in which CO was distributed throughout the body. The appearance of the third phase is probably explained by the contribution of CO produced endogeneously. The existing equations for predicting COHb concentrations failed to explain the initial and third phases.

Animals↗

Grazing bullet wounds on the tongue and liver.

A 59-year-old man was shot at the wheel of his car while waiting for a traffic light at an intersection. He was shot through the windshield from a distance of about 1 m. He was pronounced dead on arrival at an emergency hospital. X-ray photographs taken there demonstrated the presence of three bullets within the body. The murder weapon was found to be a thirty-eight caliber revolver. In all, five bullet wounds were recognized, one was located in the right side of the neck, one in the lower part of the left temple, and three on the right side of the body. The wound in the right neck was an entrance bullet wound. The bullet had exited at the left temple, after glancing on the root of the tongue. The three wounds on the right side of the body were all entrance bullet wounds. The fatal bullet entered the right chest cavity at the 7th intercostal space and lacerated the right lung and the ascending aorta after glancing on the right lobe of the liver. The cause of death was hemorrhage from the lacerated aorta. The grazing bullet wounds of the tongue and liver were shallow defects of the tissues with irregular margins.

Forensic Medicine↗

Study of secondary flow in centrifugal blood pumps using a flow visualization method with a high-speed video camera.

Four pump models with different vane configurations were evaluated with flow visualization techniques using a high-speed video camera. These models also were evaluated through in vivo hemolysis tests using bovine blood. The impeller having the greatest fluid velocity relative to the impeller, the largest velocity variance, and the most irregular local flow patterns in the flow passage caused the most hemolysis. Even if the pumps were operated at almost the same speed (rpm) at the same output, the impeller showing more irregular flow patterns had a statistically greater rate of hemolysis. This fact confirms that the existence of local irregular flow patterns in a centrifugal blood pump deteriorates its hemolytic performance. Thus, to optimize the design of the pump, it is very important to examine the secondary flow patterns in the centrifugal blood pump in detail using flow visualization with a high-speed video camera.

Animals↗

Localization of Dictyostelium myoB and myoD to filopodia and cell-cell contact sites using isoform-specific antibodies.

To date, five myosin I heavy chain genes (myoA-E) have been sequenced in Dictyostelium. Among them, myoB, myoC and myoD possess tail domains that contain a putative membrane-binding domain, a nucleotide-insensitive actin-binding site, and an src homology (SH)-3 domain. In this study, we have determined the intracellular localizations of myoB and myoD by immunofluorescence using isoform-specific antibodies raised against bacterially expressed fusion proteins. MyoB is concentrated at the leading edges of lamellipodia and at sites of cell-cell contact in both stationary and aggregation stage cells. Based on its distinctive appearance, we have named the myosin I-rich, interdigitating cell-cell contact structure in the stationary stage cells "zipper". To analyze the staining of filopodia, we employed the ratio imaging technique. We find that myoB is present in filopodia in either a uniform or an apical staining pattern. Like myoB, myoD is concentrated in leading edges of lamellipodia and at sites of cell-cell contact in stationary stage cells. MyoD is also present in filopodia, although the intensity is weaker than that of myoB staining. Despite persistence of myoD protein in the cells, myoD largely disappears from lamellipodia and cell-cell contact regions in aggregation stage cells, suggesting the occurrence of a developmentally regulated relocalization to the cytoplasm. While these results, along with the striking similarity in their tail domain structures, suggest that myoB and myoD have overlapping functions, differences in their localization in developing cells indicate that they have unique functions as well.

Animals↗

Mitochondrial ALDH polymorphism affects ethanol-derived acetate disposition in Wistar rats.

We studied the relationship between polymorphism of aldehyde dehydrogenase (ALDH) and ethanol and acetate kinetics in male Wistar rats. Blood ethanol and acetate concentration time curves after intravenous bolus administration of 1 g/kg of ethanol were estimated by moment analysis. ALDH isozymes in hepatic subcellular fractions were detected by isoelectric focusing (IEF). Blood acetate profiles were divided into two patterns: one-peak type and two-peak type. IEF studies on ALDH isozymes in subcellular fractions showed polymorphism of cytosolic and mitochondrial ALDHs. Polymorphism patterns of ALDH2 corresponded with patterns of blood acetate profiles. Significant differences in mean residence time of acetate and the ratio of area under curves (AUCs) of acetate to ethanol (AUCacetate/AUCEtOH) occurred between different IEF patterns of mitochondrial low K(m) ALDH (ALDH2). Therefore, it was clarified that ALDH2 polymorphism affects ethanol-derived acetate disposition in Wistar rats. Similarity of AUC values of acetate considered, these observations suggest that ALDH2 polymorphism results in change of effects of acetate and acetate-generated adenosine on the central nervous system and other organs during chronic ethanol consumption.

Acetaldehyde↗

Biochemical and pharmacological studies with KT7692 and LY294002 on the role of phosphatidylinositol 3-kinase in Fc epsilon RI-mediated signal transduction.

Wortmannin inhibited phosphatidylinositol 3-kinase (P13-kinase) and Fc epsilon RI-mediated histamine secretion in RBL-2H3 cells to a similar degree, with IC50 values of 3 and 2 nM, respectively. Although P13-kinase is an acknowledged regulator of intracellular trafficking and secretion, wortmannin has proved to be a difficult drug to use in assessing the role of P13-kinase because it inhibits another important enzyme, myosin light-chain kinase (MLCK; IC50 = 200 nM). In the present study we synthesized a unique derivative of wortmannin, O-acetyl-delta 16-wortmannin-17-ol (KT7692), that has an inhibitory potency against PI3-kinase one-hundredth that of wortmannin, but retains a similar potency to wortmannin against MLCK. Histamine secretion was influenced 100-fold more by wortmannin than by KT7692.2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a structurally different PI3-kinase inhibitor from wortmannin, inhibited PI3-kinase with an IC50 of 2 microM but had little effect on MLCK activity in this concentration range. LY294002 also inhibited histamine secretion in RBL-2H3 cells with an IC50 of 5 microM. These results provide further evidence that PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion after stimulation of Fc epsilon RI. Furthermore KT7692 in combination with wortmannin and LY294002 would be a powerful tool for clarifying the involvement of PI3-kinase as distinct from that of MLCK in signal transduction systems of various cellular responses.

Androstadienes↗

Phosphatidylinositol 3-kinase is involved in TRE-dependent gene expression in response to arginine vasopressin.

We identified arginine vasopressin (AVP) as a potent activator of TPA-response element (TRE)-dependent gene expression in rat 3Y1 fibroblasts. In order to examine the involvement of phosphatidylinositol 3-kinase (PI3-kinase) in TRE-mediated gene expression, we examined the effect of the overexpression of PI3-kinase mutant. The overexpression of p110 alpha, the catalytic subunit of PI3-kinase, enhances TRE-reporter expression in response to AVP. On the other hand, the overexpression of the p110-EcoS mutant, which contains the binding site for the regulatory p85 subunit but lacks the catalytic domain, results in decreased TRE reporter expression in response to AVP. These results suggest that PI3-kinase is involved in TRE-dependent gene expression in response to AVP.

Animals↗

Region-related Fos expression in hypothalamic dopaminergic neurons of rats by intraperitoneal administration of an endogenous satiety substance, 2-buten-4-olide.

An effect of 2-buten-4-olide (2-B4O), an endogenous satiety substance, on hypothalamic dopamine neurons of rats was studied by double-label immunohistochemistry for c-Fos and tyrosine hydroxylase (TH). Intraperitoneal administration of 2-B4O induced Fos-like immunoreactivity in TH-immunoreactive neurons in the periventricular area and paraventricular nucleus but not in the arcuate nucleus. Thus, the present results suggest that tuberohypophysial dopamine neurons are regulated under the influence of endogenous 2-B4O.

4-Butyrolactone↗

Pancreatitis associated with choledochal cyst and other anomalies in childhood.

Fifty-one children with anatomical anomalies of the pancreatic duct developed pancreatitis associated with either congenital dilatation of the bile duct (choledochal cyst; n = 48) or other rare causes (n = 3). Among those with choledochal cyst, 41 underwent primary surgical resection of the dilated bile duct, while five of the remaining seven patients receiving cystenterostomy underwent secondary resection of the cyst.

Adolescent↗

Prevalence of dry eye in Japanese eye centers.

BACKGROUND: The purpose of the investigation was to ascertain the prevalence of dry eye in new outpatients. METHODS: A total of 2127 consecutive new outpatients seen in eight Japanese centers from April 1992 to January 1993 underwent comprehensive examinations, including double vital staining and measurement of tear film break-up time, basal tear secretion, and tear clearance. Dry eye was diagnosed if patients had abnormalities of both the tear film and the ocular surface. RESULTS: Three hundred fifty-nine patients (17%) had dry eye. There was no seasonal pattern for dry eye. The condition was significantly more common in Tokyo than in suburban areas (P < 0.01). The prevalence of dry eye in visual display terminal (VDT) users and contact lens (CL) wearers was significantly higher than in non-VDT users and non-CL wearers (P < 0.05 and P < 0.02, respectively). CONCLUSION: Our findings suggest that dry eye is one of the most common ocular disorders encountered by physicians. Furthermore, if patients use VDTs or wear CLs, the likelihood of dry eye occurring is higher.

Adolescent↗

Effect of human leukemia inhibitory factor on in vitro development of IVF-derived bovine morulae and blastocysts.

This study was conducted to investigate whether human leukemia inhibitory factor (hLIF) improves the subsequent development of IVF-derived bovine morulae and blastocysts. To obtain IVF-derived bovine morulae, ova were matured and fertilized in vitro and cultured in 0.5 ml of synthetic oviduct fluid (SOF) medium supplemented with 10% human serum (HS) for 5 d at 39 degrees C under a gas atmosphere of 5% CO(2), 5% O(2), 90% N(2). Morulae and early blastocysts at Day 5 of culture were cultured in 0.5 ml of SOF medium with or without 5000 U/ml recombinant hLIF for 2 or 3 d (2 groups). To investigate the effect of addition of hLIF on the subsequent development of morulae, SOF medium was supplemented with 8 mg/ml BSA instead of HS. To test whether hLIF affects the subsequent development of IVF-derived bovine blastocysts, only good blastocysts that developed from SOF medium with or without hLIF at Days 7 and 8 of culture were frozen by a conventinal slow freezing method and again cultured in SOF medium with or without the addition of hLIF for 3 d after thawing (4 groups). Survival of frozen-thawed bovine embryos was evaluated for re-expansion and hatching of blastocysts during 3 d of culture. There was no significant difference in the developmental rate of Day 5 embryos to blastocysts between those cultured with (47.8%) and without (47.6%) addition of hLIF. However, the addition of hLIF before freezing significantly increased the hatching rate of IVF-derived bovine morulae (P < 0.05), whereas addition of hLIF after thawing did not increase the subsequent development of blastocysts. These results suggest that hLIF added at the Day 5 morula stage may contribute to bovine embryonic development through the hatching process.

Journal Article↗

A quantitative study of the effects of prenatal X-irradiation on the development of cerebral cortex in rats.

Pregnant rats were exposed to a single whole body X-irradiation on day 15 of gestation at a dose of 1.0 Gy. The offspring showed microcephaly at 7 weeks of age. Their body weight, brain weight, cortical thickness and the numerical density of neurons and synapses in the somatosensory and visual cortex were examined. Significant decreases in cortical thickness in both somatosensory (25%) and visual (16%) cortex were observed. However, there were no significant changes in the numerical density of neurons and synapses, nor in synapse-to-neuron ratios in both cortical regions between control and X-irradiated groups. These results suggest that prenatal X-irradiation can decrease the number of neurons, and the neurons which survive X-irradiation proliferate and elaborate connections in a normal fashion. This is in contrast to the animals exposed to ochratoxin A, in which numerical density of neurons in the somatosensory cortex is increased, with normal numerical density of synapses, resulting in low synapse-to-neuron ratios. The discrepancy in the synapse-to-neuron ratios between the X-irradiation and ochratoxin A-treatment might derive from a different effect on the developing neurons.

Animals↗

A computerized control system for cardiopulmonary bypass.

A pump control system using a microcomputer for cardiopulmonary bypass has been developed. The parameters monitored by the computer are central venous pressure, aortic pressure, blood volume in a reservoir, and collapsing of a small vinyl bag in a venous withdrawal tube. Both pumps in the arterial infusion and the venous withdrawal lines are automatically controlled through an interface unit throughout cardiopulmonary bypass. The system regulates central venous pressure with a proportional-integral control algorithm to maintain intravascular volume constant. A screening algorithm is devised to remove artifacts introduced to the pressure measurement. During the weaning period, a perfusionist can select either the central venous pressure control or a reservoir blood volume control. Computerized pump perfusion was applied on 15 children during cardiac operations. Perfusion flow and central venous pressure were controlled satisfactorily with stable operation. Compared with conventional manually controlled pump perfusion, no significant difference was noted in mean aortic pressure, central venous pressure, net fluid balance, total urination, blood chemistry, and urinalysis. This system is useful and is expected to improve the safety of pump perfusion.

Algorithms↗

Production of monoclonal antibodies specific to the carboxyl terminal region of the 85 kDa subunit of phosphatidylinositol 3-kinase: use of the antibodies in recognition of mutant p85.

We have established two hybridomas producing mAb to the carboxyl terminal region of phosphatidylinositol-3 kinase 85 kDa subunit type alpha (p85 alpha). Analysis using deletion mutants of p85 revealed that epitopes for the two mAb were located on the border of the src homology 2 (SH2) sequence located at the carboxyl end of p85. They immunoprecipitated free p85 efficiently, but reactivity to p85 bound to p110 was very weak. Together with the mAb which we have reported previously, a panel of mAb that covered the various parts of p85 alpha was obtained. Using this panel, we characterized two mutants of p85 (70 and 50 kDa) expressed in the human colon carcinoma cell line, HCC2998. No wild-type p85 was detected in these cells. A mAb specific to the carboxyl terminal region detected p70 but not p50, suggesting that this region is missing in p50. The panel of mAb is a useful tool to use to analyse mutant forms of p85.

Animals↗

Morphology of ras-transformed cells becomes apparently normal again with tyrosine kinase inhibitors without a decrease in the ras-GTP complex.

Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause morphological reversion of v-Ha-ras-transformed NIH3T3 fibroblasts and T24 human urinary bladder carcinoma cells that contain an activated ras mutation. The network of actin stress fibers was restored during the treatment with radicicol. A similar morphological change was observed with another protein-tyrosine kinase inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of the active GTP binding form of p21ras or its subcellular localization. These results rule out the possibility that the morphological reversion by radicicol is due to direct or indirect inhibition of the p21ras function. Cycloheximide and actinomycin D inhibited the morphological change by radicicol, suggesting that the induced transcription of a gene(s) followed by de novo protein synthesis is required for suppression of the transformed phenotype in ras-transformed cells by tyrosine kinase inhibitors.

Animals↗