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Biomedical subjects

Yoshiaki Hashimoto

Publications and source records attributed to Yoshiaki Hashimoto.

At least 19 recordsLinked to original sources
PubMed2006

Nicotine and cotinine levels in body fluids of smokers who committed suicide.

Cigarette smoking is associated with a higher risk for suicide. The present study was conducted on the hypothesis that suicide smokers show higher nicotine and cotinine levels in blood and urine than non-suicide smokers. We determined nicotine and cotinine levels in blood and urine of 87 deceased individuals (18 suicides and 69 non-suicides) by gas chromatography. The smoking rate was 77.8% for individuals who committed suicide and 42.0% for those who did not commit suicide. Average nicotine and cotinine levels in blood were significantly higher in the suicide smokers than in the non-suicide smokers (nicotine: 93.2+/-46.6 ng/ml versus 25.8+/-14.4 ng/ml, p<0.0001 and cotinine: 378+/-235 ng/ml versus 201+/-137 ng/ml, p<0.005). Average levels of urinary nicotine and cotinine were also significantly higher in the suicide smokers than in the non-suicide smokers (nicotine: 1980+/-2210 ng/ml versus 394+/-376 ng/ml, p<0.005 and cotinine: 1170+/-1330 ng/ml versus 414+/-290 ng/ml, p<0.05). Twenty-six decedents were intoxicated with alcohol, and they included 7 suicides (7 smokers) and 19 non-suicides (15 smokers). Our data suggest that cigarette smokers who commit suicide smoke more heavily than other cigarette smokers.

Adolescent↗
PubMed2006

Effects of drinking and smoking on endogenous levels of urinary gamma-hydroxybutyric acid, a preliminary study.

The aim of this study was to determine if the endogenous levels of gamma-hydroxybutyric acid (GHB) in urine were affected by drinking and smoking. Urine samples were obtained from 20 healthy volunteers (15 males, 21-45 years; 5 females, 22-24 years). This population included four average drinkers (males), 4 average smokers (males), and 12 nonsmokers/nondrinkers (seven males and five females). Urinary levels of GHB were measured by gas chromatography. No gender differences were observed in the urinary levels of endogenous GHB. The urinary levels of GHB in males were 0.52+/-0.37 microg/ml in smokers, 0.28+/-0.21 microg/ml in nonsmokers/nondrinkers, and 0.23+/-0.04 microg/ml in drinkers. Urinary GHB levels were measured three times a day for 5 consecutive days in a male from each group. Large intra-individual differences were observed over the 5-day period in a smoker and a nonsmoker/nondrinker. No significant changes in daily endogenous GHB levels were observed in a drinker during the period. Our preliminary results suggest that stimulatory effects of nicotine on the central nervous system (CNS) may result in an increase in nocturnal formation of GHB and the depressive effects of ethanol on the CNS may not affect, even may inhibit, nocturnal production of GHB.

Adult↗
PubMed2006

Differential effects of apolipoprotein E isoforms on lipolysis of very low-density lipoprotein triglycerides.

Apolipoprotein (apo) E plays a key role in lipoprotein metabolism and has been proposed to modulate triglyceride (TG) lipolysis. However, no systematic investigation on lipolysis using all 3 isoforms of apoE has been performed. To clarify the role of common human apoE isoforms in the lipolysis of very low-density lipoprotein (VLDL) TGs, we overexpressed human apoE isoforms in apoE and low-density lipoprotein receptor-deficient mice using adenoviral-mediated gene transfer and used VLDL particles obtained from these mice for in vitro lipolysis assay. Overexpression of apoE, regardless of its isoforms, increased the TG content of VLDL in mice in vivo. In vitro analysis of the effect of apoE on lipolysis revealed that irrespective of its isoforms, apoE did inhibit TG lipolysis at every concentration of apoE examined, and this inhibitory effect became more pronounced as the apoE content of VLDL increased. No difference was observed in TG lipolysis activity among isoforms at low apoE/TG ratio; however, intermediate ratios of apoE/TG, which reflect physiologic VLDL apoE/TG ratios, demonstrated a significantly greater level of lipolysis inhibition in apoE2, but less so in apoE4 compared with other isoforms. This differential effect by apoE isoforms on lipolysis was attenuated at higher apoE/TG ratios; nevertheless, apoE2 still inhibited lipolysis significantly more than did apoE4. Enrichment of VLDL with apoE decreased both the apoC contents and apoC-II/C-III ratios of VLDL, contributing, at least in part, to the inhibitory function of apoE on lipolysis. The present study clarifies the differential lipolysis-modulating effect of apoE isoforms, which would help explain the difference in pre- and postprandial TG levels among humans carrying different apoE isoforms.

Adenoviridae↗
PubMed2005

Adenovirus-mediated gene transfer and lipoprotein-mediated protein delivery of plasma PAF-AH ameliorates proteinuria in rat model of glomerulosclerosis.

Oxidative stress has been proposed to play a crucial role in glomerulosclerosis, although its in vivo demonstration has proved taxing given the difficulty of inducing gene expression in specific renal cells. In this study, we examined whether the liver-directed expression of plasma platelet-activating factor acetylhydrolase (PAF-AH) would affect the glomerular pathophysiology in Imai rats, an animal model for glomerulosclerosis. Adenovirus-mediated liver-directed gene delivery of human PAF-AH resulted in a significant increase in plasma PAF-AH activity, which was detected almost exclusively on HDL. Histological examination of rats overexpressing PAF-AH showed not only the deposition of PAF-AH in mesangial cells, but also a reduction in hydroxynonenal and matrix protein content in the glomeruli. In situ hybridization analysis was negative for human PAF-AH mRNA in the kidney, while injection of HDL abundant in PAF-AH resulted in the deposition of PAF-AH in mesangial cells. Urine protein levels did not increase in rats overexpressing PAF-AH, while those of control rats increased significantly with age. This study provides direct evidence of the in vivo role of an enzyme that degrades lipid peroxides during the progression of glomerulosclerosis. Adenovirus-mediated extrarenal gene expression and lipoprotein-mediated glomeruli-targeted protein delivery promise to be a novel therapeutic approach to glomerulosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

A fatal poisoning caused by methomyl and nicotine.

A 35-year-old male was found lying in a prone position in his room. He was in cardiopulmonary arrest on arrival to hospital and was pronounced dead. There was no attempt at resuscitation. No miosis was observed on admission. At post-mortem his stomach contained 170 g greenish liquid with a small amount of shredded tobacco leaves. The serum cholinesterase activities were 47-90 IU (normal range for male: 200-440 IU). GC and GC-MS analyses showed nicotine (21.8 mg), methomyl (304 mg), and triazolam (1.69 mg) in his stomach. He had consumed tobacco leaves, Lannate containing water soluble methomyl (45%), and Halcion tablets containing 0.25 mg triazolam. Methomyl concentrations in blood were 3-8 ng/ml. Substantial amounts of methomyl (2260-2680 ng/ml) were detected in cerebrospinal fluid and vitreous humor. Nicotine concentrations in blood ranged from 222 to 733 ng/ml. A small amount of triazolam was detected only in bile (176 ng/ml) and liver (23 ng/g). The cause of death was respiratory paralysis produced by the additive effects of methomyl and nicotine shortly after consumption.

Adult↗
PubMed2005

Site-dependent production of gamma-hydroxybutyric acid in the early postmortem period.

This study compared endogenous gamma-hydroxybutyric acid (GHB) concentrations in various postmortem fluid samples of 25 autopsy cases. All bodies were stored between 10-20 degrees C until autopsy, and the intervals between death and autopsy were less than 2 days (6-48 h). GHB concentrations were measured by headspace gas chromatography after GHB was converted to gamma-butyrolactone. Endogenous GHB concentrations were significantly higher in femoral venous blood (4.6+/-3.4 microg/ml, n=23) than in cerebrospinal fluid (1.8+/-1.5 microg/ml, n=9), vitreous humor (0.9+/-1.7 microg/ml, n=8), bile (1.0+/-1.1 microg/ml, n=9) and urine (0.6+/-1.2 microg/ml, n=12). GHB concentrations were similar in blood samples taken from different sites. Cut-off limits of 30 and 10 microg/ml are proposed for blood and urine, respectively, to discriminate between exogenous and endogenous GHB in decedents showing no or little putrefaction (postmortem intervals usually 48 h or less). The criterion established for endogenous GHB in postmortem urine may also be applicable to analytical results in cerebrospinal fluid, vitreous humor and bile from deceased persons.

Adult↗
PubMed2005

Effects of perimortem physical factors associated with death on exogenous ethanol concentrations in cardiac blood.

The purpose of this study was to determine whether perimortem physical factors associated with death affect exogenous ethanol concentrations in cardiac blood. Forty-one autopsies of alcohol-intoxicated decedents with no or little putrefaction were involved. Postmortem intervals ranged from 6 to 96 h at the time of autopsy. Our 41 cases consisted of 17 fire victims, 8 drowned persons, 3 blood-loss patients who underwent unsuccessful cardiopulmonary resuscitation (CPR) for 30-50 min, 3 blood-loss persons without CPR, three non-blood-loss patients who underwent unsuccessful CPR for 5-60 min, and seven people who died of other causes. Ethanol concentrations in right cardiac chamber blood ranged from 0.12 to 4.40 mg/g (mean 1.39 mg/g) in all cases. An excellent correlation was observed between ethanol concentrations in right cardiac chamber blood and femoral venous blood (y=1.01x-0.087, n=38, r2=0.990). The ratios of blood ethanol concentrations in the left to right cardiac chambers were significantly lower in blood-loss decedents with CPR (0.71+/-0.13) than other decedents (0.92+/-0.07-1.06+/-0.06). Two factors, blood-loss and prolonged chest compression under ventilation, might have caused a decrease in blood ethanol concentration in the left cardiac chambers. Postmortem cardiac blood ethanol concentration as well as postmortem femoral venous blood ethanol concentration may usually reflect blood ethanol levels at the time of death when putrefaction is not evident. However, special attention is required for cases that received CPR after massive bleeding.

Adult↗
PubMed2004

Endogenous gamma-hydroxybutyric acid levels in postmortem blood.

The goal of this study was to determine how the postmortem interval and duration of storage of blood at 4 degrees C affect endogenous gamma-hydroxybutyric acid (GHB) levels in blood. Forty-three autopsy cases of non-users of GHB were involved. The postmortem interval ranged from 8 to 132 h. Blood samples were collected and stored without any preservatives at 4 degrees C for 1 day up to 15 months until analysis. In some cases, samples were also stored at -20 degrees C for 10 days to 7 months to determine GHB levels at autopsy. Blood GHB concentrations were measured by headspace gas chromatography after GHB was converted to gamma-butyrolactone. Blood GHB concentrations ranged from 0 to 43.0 microg/ml and averaged 9.80 microg/ml. A positive correlation was observed between concentration and postmortem interval (r = 0.571) but no correlation was found between concentration and storage interval at 4 degrees C. In 14 blood samples stored at -20 and 4 degrees C for 10 days, GHB concentrations were 4.55+/-3.88 and 6.06+/-4.27 microg/ml, respectively. In another eight blood samples stored at -20 and 4 degrees C for 1-7 months, GHB concentrations were 3.77+/-2.76 and 5.49+/-2.97 microg/ml, respectively. A large portion of endogenous GHB detected in blood of corpses may be produced during the interval between death and autopsy, rather than during storage of blood at 4 degrees C until analysis. In an additional experiment, it was suggested that glycolysis by bacteria may enhance endogenous GHB production.

Adolescent↗
PubMed2004

Nicotine and cotinine levels in blood and urine from forensic autopsy cases.

We measured nicotine and cotinine levels in blood and urine from 31 forensic autopsy cases. Initially, we developed a sensitive and reproducible gas chromatographic method with a minimum limit of detection of 2.1 ng/ml for both nicotine and cotinine. Calibration curves for nicotine and cotinine were linear in the ranges of 2.1-1030 ng/ml (r2=0.994-0.999) and 2.1-1380 ng/ml (r2=0.998-0.999) respectively. Our population included 13 smokers and eight of these smokers committed suicide. They showed high levels of nicotine and cotinine at 65.1-205 ng/ml (mean: 115 ng/ml) and 31.3-938 ng/ml (mean: 405 ng/ml) in blood, respectively, and 234-7290 ng/ml (mean: 1940 ng/ml) and 143-4620 ng/ml (mean: 1170 ng/ml) in urine, respectively. None of these individuals consumed nicotine preparations or tobacco leaves. In five smokers who did not commit suicide, nicotine and cotinine levels were 4.4-62.1 ng/ml (mean: 33.2 ng/ml) and 49.9-217 ng/ml (mean: 140 ng/ml) in blood, respectively, and 158-314 ng/ml (mean: 246 ng/ml) and 68.9-300 ng/ml (mean: 179 ng/ml) in urine, respectively. Our results suggest that there may be a marked increase in consumption of cigarettes in smokers with suicidal thoughts.

Adult↗
PubMed2004

Postmortem production of ethanol and n-propanol in the brain of drowned persons.

We examined endogenous ethanol and n-propanol levels in the brain in 29 drowning cases in which ethanol consumption was excluded. Based on the stage of putrefaction of the brain, our cases were classified into 4 groups: pulpified brain (PB, n = 11), softened brain (SB, n = 6), discolored brain (DB, n = 2), and normal brain (NB, n = 10). The endogenous ethanol and n-propanol levels (mg/g), respectively, in the brains from these groups were 1.06 +/- 0.401 and 0.076 +/- 0.032 in PB, 0.195 +/- 0.136 and 0.012 +/- 0.009 in SB, and 0.053 +/- 0.032 and 0.001 +/- 0.001 in DB. Ethanol and n-propanol were not detected in NB. The concentration ratios of ethanol to n-propanol were 16.2 +/- 7.1 in specimens with ethanol levels > or = 0.50 mg/g (n = 10), and 17.6 +/- 13.5 in specimens with ethanol levels of 0.10 to 0.49 mg/g (n = 9). Drinking may strongly be suspected when (1) ethanol concentration in the brain is > or = 0.50 mg/g and cerebral ethanol to n-propanol ratio is > or = 40; and (2) the concentration of ethanol is 0.10 to 0.49 mg/g and the ethanol to n-propanol ratio is > or = 60.

1-Propanol↗
PubMed2004

Tissue distribution of intubation-related lidocaine in brain-dead patients.

Tissue distribution of lidocaine that was used for endotracheal intubation during cardiopulmonary resuscitation (CPR) was measured in 3 patients who were brain-dead or near brain death. Case 1 was a 69-year-old female whose heartbeat was restored by CPR but stopped 10 hours later. The lidocaine ratios of cerebrum to blood (2.04) and diencephalon to blood (1.01) were within ranges of those found in non-brain-dead patients. Case 2 was a 77-year-old female whose heart resumed beating after CPR but stopped 66 hours later. The lidocaine ratios of cerebrum to blood (5.69), diencephalon to blood (18.7), and cerebellum to blood (11.3) were much higher than those in non-brain-dead patients. Case 3 was a 48-year-old male who had cardiopulmonary arrest following an acute subarachnoid hemorrhage. His heart resumed beating after resuscitation but ceased beating 114 hours after admission. Lidocaine was detected only from the cerebrum, cerebellum, and blood clots in the superior sagittal sinus at levels of 0.028, 0.024, and 0.007 mug/g, respectively. Tissue distribution of intubation-related lidocaine in brain-dead patients is useful as supplementary data for reviewing hemodynamic changes in their brains during medical treatment.

Aged↗
PubMed2003

Tissue distribution of lidocaine in critical care patients after intubation.

We investigated tissue distribution of lidocaine in 33 patients after endotracheal intubation with Xylocaine jelly that contains 2% lidocaine hydrochloride. Blood levels of monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, were also determined. Five patients (Group A) were alive on arrival and six patients (Group B) resumed heartbeats after cardiopulmonary resuscitation (CPR). The survival times for Groups A and B ranged from 3 to 72 h. The remaining 22 patients (Group C) did not survive cardiopulmonary arrest on arrival (CPAOA). Systemic distribution of lidocaine was measured in nine patients from Group C. The liver-to-kidney lidocaine ratios and cerebrum-to-cerebrospinal fluid lidocaine ratios were: Group A, 0.1-0.7 and 1.4-3.6, respectively; Group B, 0.2-0.8 and 1.2-2.3, respectively; Group C, 0.1-17 and 0.2-1.0, respectively. MEGX was detected in all blood samples from Group A and only two samples from Group B. No MEGX was detected in samples from Group C. Our results indicate that the absorption of tracheal lidocaine during natural circulation results in a cerebrum-to-cerebrospinal fluid lidocaine ratio of 1.2 or more, whereas absorption during artificial circulation by cardiac massage gives a ratio of 1.0 or less. The cerebrum-to-cerebrospinal fluid lidocaine ratio may be a more useful index to estimate circulatory dynamics of patients during CPR than the liver-to-kidney lidocaine ratio. MEGX was not a useful parameter for monitoring circulatory changes during cardiac massage.

Adult↗
PubMed2003

Human plasma platelet-activating factor acetylhydrolase binds to all the murine lipoproteins, conferring protection against oxidative stress.

OBJECTIVE: Plasma platelet-activating factor (PAF) acetylhydrolase (AH) is an enzyme bound with lipoproteins that degrades not only PAF but also PAF-like oxidized phospholipids that are proposed to promote atherosclerosis. In this study, we investigated the distribution of PAF-AH protein among lipoprotein classes by using adenovirus-mediated gene transfer in mice, and we examined its effects on lipoprotein oxidation and foam cell formation of macrophages. METHODS AND RESULTS: Adenovirus-mediated overexpression of PAF-AH in mice resulted in a 76- to 140-fold increase in plasma PAF-AH activity. Contrary to the previous report, overexpressed human PAF-AH protein was bound to very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and high density lipoprotein (HDL). All the lipoproteins with overexpressed human PAF-AH revealed more resistance against oxidative stress, which was associated with lower levels in autoantibody against oxidized low density lipoprotein in the plasma. In addition, HDL with human PAF-AH inhibited foam cell formation and facilitated cholesterol efflux in macrophages. CONCLUSIONS: These results suggest that human plasma PAF-AH exerts an antiatherogenic effect by binding to all the lipoproteins and thereby protecting them from oxidation, producing less proatherogenic lipoproteins and preserving HDL functions.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2003

Isoform-dependent cholesterol efflux from macrophages by apolipoprotein E is modulated by cell surface proteoglycans.

OBJECTIVE: Apolipoprotein E (apoE) mediates cellular cholesterol efflux and plays a crucial role in the inhibition of atherogenesis. We investigated whether there is an isoform-specific difference in its function for cholesterol efflux from cholesterol-loaded RAW264.7 cells, a murine macrophage cell line that lacks endogenous apoE expression. METHODS AND RESULTS: When human apoE was expressed in RAW264.7 cells, apoE2 reduced cellular total cholesterol (TC) and esterified cholesterol (EC) levels significantly, whereas apoE3 and apoE4 had no effect. However, treatment of cells with 4-methylumbelliferyl-7-beta-D-xyloside (beta-DX) resulted in all 3 isoforms' reducing cellular TC and EC contents significantly. We also investigated the effect of exogenously derived apoE on cholesterol efflux by utilizing the medium harvested from HeLa cells expressing apoE. ApoE2 and E3 reduced both cellular TC and EC contents significantly, whereas apoE4 did not. However, treatment of the cells with beta-DX resulted in all 3 exogenously derived apoE isoforms' reducing TC and EC contents significantly. The binding ability of apoE to heparan sulfate proteoglycans examined by heparinase I treatment revealed less binding ability of apoE2 compared with that of apoE3 or apoE4. CONCLUSIONS: The present study clarified the differential cellular cholesterol-modulating effect of apoE isoforms in macrophages, which would be due to the difference in their binding to proteoglycans.

Adenoviridae↗
PubMed2003

Tissue distribution of nitrazepam and 7-aminonitrazepam in a case of nitrazepam intoxication.

We report a case of nitrazepam poisoning in which the distribution of nitrazepam and 7-aminonitrazepam was determined in body fluids and tissues. A 52-year-old woman was found dead in a shallow ditch (approximately 5 cm in depth), in the winter. Ambient temperature was 2-8 degrees C. The postmortem interval was estimated to be approximately 1 day and no putrefaction was observed. The cause of death was thought to be drowning due to nitrazepam overdose and cold exposure. Blood concentrations of nitrazepam and 7-aminonitrazepam were very site dependent (0.400-0.973 microg/ml and 0.418-1.82 microg/ml). In addition, the concentration of the same analytes in the bile were 4.08 and 1.67 microg/ml, respectively, and in the urine: 0.580 and 1.09 microg/ml, respectively. A high accumulation of both substances was observed in various types of brain tissue (2.17-6.22 microg/g and 2.49-5.11 microg/g). Only small amounts of nitrazepam and 7-aminonitrazepam were detected in the liver (0.059 and 0.113 microg/g, respectively). Large differences in the observed concentrations of nitrazepam and 7-aminonitrazepam among arterial and venous blood samples were thought to be mainly due to dilution of arterial blood by water entering the circulation through lungs at the time of death. Bacterial metabolism of nitrazepam may also have contributed to the observed differences.

Anti-Anxiety Agents↗
PubMed2003

Modulation of HDL metabolism by probucol in complete cholesteryl ester transfer protein deficiency.

Probucol, an antioxidative and hypolipidemic agent, has been postulated to increase reverse cholesterol transport by enhancing cholesteryl ester transfer protein (CETP) activity. However, its clinical implication in CETP deficient patients has not been fully defined. To characterize the effects of probucol in the absence of CETP, we evaluated the changes in lipid profile, lipid peroxidation, and paraoxonase 1 (PON1) activity in two complete CETP deficient patients, caused by treatment with probucol. When the patients were not receiving probucol, low-density lipoprotein (LDL) particles were smaller and high-density lipoprotein (HDL) particles were larger in these patients than in controls. Treatment with probucol (500 mg/day) resulted in the decrease in the levels of HDL-C and apolipoprotein (apo) A-I up to 22%. The size of HDL particles became smaller. LDL cholesterol concentration did not change in one patient, while it decreased by 47% in the other. PON1 activity/HDL-C, which was about 40% lower in the patients before treatment than in controls with the matching PON1 genotype, increased by 30% during the treatment. Lag time for LDL and HDL in both cases became prolonged more than 1.8 times after administration of probucol. This study demonstrated for the first time that probucol reduces HDL-C even in humans with complete CETP deficiency. Probucol treatment in these patients was also associated with protection of lipoproteins against oxidative stress, suggesting a clinical benefit of this drug even in such a state.

Aged↗
PubMed2003

A case of fatal triazolam overdose.

A 57-year-old man was found dead lying down in a bamboo thicket. Moderate to severe petechiae were present on his conjunctivae, buccal mucosa, and laryngeal mucosa at autopsy. Cardiac chambers contained a normal volume of fluid blood. Moderate atherosclerosis and fatty liver were observed. No remarkable changes, other than congestion in other organs, were observed. Gas chromatographic screening of the stomach contents, blood and urine was positive for triazolam and alpha-hydroxytriazolam that were confirmed by gas chromatography-mass spectrometry. Blood concentrations of triazolam and free alpha-hydroxytriazolam were 62-251 and 10-66 ng/ml, respectively. A substantial amount of triazolam was detected in bile (1130 ng/ml), but not in urine. Free and total alpha-hydroxytriazolam concentrations were 3920 and 7050 ng/ml, respectively, in the bile and 3710 and 9670 ng/ml, respectively, in urine. Organs contained 216-583 ng/g triazolam. The concentration of free alpha-hydroxytriazolam in the kidney (246 ng/g) was higher than in any other organ. Free alpha-hydroxytriazolam was not detected in the liver. The concentrations of total alpha-hydroxytriazolam in the liver and kidney were 784 and 381 ng/g, respectively. Free to total ratios of alpha-hydroxytriazolam were 0.14-0.56 in fluid samples and 0.56-0.92 in tissue samples, except for the liver. A large quantity of triazolam (8.4 mg) remained in the stomach. The victim probably died of postural asphyxia caused by triazolam poisoning.

Anti-Anxiety Agents↗