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Biomedical subjects

Hiromasa Inoue

Publications and source records attributed to Hiromasa Inoue.

At least 19 recordsLinked to original sources
PubMed2006

A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs.

A 43-year-old woman was found dead in a car in the supine position. She had been suffering from depression for 2 years and hesitation wounds on the left forearm and wrist were observed. On microscopic examination, pulmonary congestion and edema were observed with heart failure cells in many alveoli, thereby suggesting not only acute but also chronic heart failure. Drug screening in the blood by gas chromatography-mass spectrometry (GC-MS) revealed the presence of amoxapine and levomepromazine, and their concentrations in tissues were determined by GC-MS with three-step solvent extraction followed by acetylation. The concentration of amoxapine in the blood and liver was 0.86-1.77 and 18.76microg/ml, respectively; the levels were much higher than the therapeutic level but did not reach the lethal level. The concentrations of levomepromazine in tissues were within the therapeutic level. Based on the pathological and toxicological findings, the cause of death was determined to be amoxapine poisoning on the basis of chronic heart failure due to the chronic use of psychotropic drugs.

Adult↗
PubMed2006

A pregnant woman with complications of lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura.

A pregnant 26-year-old woman developed hemosputum, dyspnea and pneumothorax. Lymphangioleiomyomatosis was suspected based on multiple cystic lesions on chest computed tomography. Additionally, moderate thrombocytopenia occurred during the last trimester. Hyperplasia of megakaryocytes in a bone marrow specimen and a high serum titer of platelet-associated IgG led to a diagnosis of idiopathic thrombocytopenic purpura. High-dose intravenous gammaglobulin promptly restored her platelet count, and the patient successfully gave birth to a healthy baby by cesarean section. After delivery, lymphangioleiomyomatosis was diagnosed by lung biopsy that was obtained during a video-assisted thoracoscopic abscission for recurrent pneumothorax. Underlying lymphangioleiomyomatosis and idiopathic thrombocytopenic purpura may be obviated by pregnancy.

Adult↗
PubMed2006

Effects of salmeterol in patients with persistent asthma receiving inhaled corticosteroid plus theophylline.

BACKGROUND: Patients with severe asthma require multiple therapies to improve lung function and reduce symptoms. The use of long-acting inhaled beta(2)-agonists plus theophylline in addition to high doses of inhaled corticosteroids (ICSs) for the treatment of severe asthma has not been extensively studied. OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of salmeterol combined with high-dose ICSs plus theophylline in severe asthma. METHODS: We undertook a randomized, placebo-controlled, crossover study to compare the effect of a single dose of inhaled salmeterol (50 microg) or a placebo in patients with severe asthma whose conditions were not being adequately controlled by therapies with high-dose ICSs plus oral theophylline with or without leukotriene receptor antagonists. RESULTS: Twenty patients took part in the trial. Compared with the placebo, the inhalation of salmeterol significantly increased the FEV(1). Even in the 9 patients treated with high-dose ICSs plus theophylline plus a leukotriene receptor antagonist, the FEV(1) increased significantly more after salmeterol than after the placebo. CONCLUSION: Patients with severe asthma receiving high-dose ICSs plus theophylline may benefit from the addition of salmeterol.

Administration, Inhalation↗
PubMed2006

Relationship between pulmonary fat embolism and core body temperature in rats with a severe fatty liver.

We previously demonstrated that pulmonary fat embolism was induced by elevation of the core body temperature, in rats with a fatty liver. The aim of the present examination was to investigate the core body temperature at which pulmonary fat embolism developed capillaries through exposure to a high temperature, in rats with a fatty liver. Following heat stress, pulmonary fat embolism was observed to a slight degree at a core body temperature of 41 and 42 degrees C, whereas the severity of pulmonary fat embolism was greatly increased and was classified as severe at a core body temperature of 43 degrees C. Moreover, the concentrations of aspartate aminotransferase and alanine aminotransferase within plasma were significantly increased at a core body temperature of 43 degrees C. These results clearly indicate that the development of pulmonary fat embolism could be related to hyperthermia at above 42 degrees C following heat stress, and that fat emboli may be derived from the fatty liver itself. It is thus likely that pulmonary fat embolism can be considered as one form of evidence of hyperthermia in an individual with a fatty liver.

Animals↗
PubMed2006

Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1.

Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator of signal transducer and activator of transcription (STAT)3-activating cytokines. Transgenic mouse studies indicate that high levels of SOCS3 in T cells result in type 2 T helper cell (Th2) skewing and lead to hypersensitivity to allergic diseases. To define the physiological roles of SOCS3 in T cells, we generated T cell-specific SOCS3 conditional knockout mice. We found that the mice lacking SOCS3 in T cells showed reduced immune responses not only to ovalbumin-induced airway hyperresponsiveness but also to Leishmania major infection. In vitro, SOCS3-deficient CD4+ T cells produced more transforming growth factor (TGF)-beta1 and interleukin (IL)-10, but less IL-4 than control T cells, suggesting preferential Th3-like differentiation. We found that STAT3 positively regulates TGF-beta1 promoter activity depending on the potential STAT3 binding sites. Furthermore, chromatin immunoprecipitation assay revealed that more STAT3 was recruited to the TGF-beta1 promoter in SOCS3-deficient T cells than in control T cells. The activated STAT3 enhanced TGF-beta1 and IL-10 expression in T cells, whereas the dominant-negative form of STAT3 suppressed these. From these findings, we propose that SOCS3 regulates the production of the immunoregulatory cytokines TGF-beta1 and IL-10 through modulating STAT3 activation.

Animals↗
PubMed2006

Niflumic acid suppresses interleukin-13-induced asthma phenotypes.

RATIONALE: Chloride channels have been implicated in the regulation of mucus production in epithelial cells. Expression of hCLCA1, a calcium-activated chloride channel, has been reported to be increased in the airway epithelium of patients with asthma. Interleukin (IL)-13 induces the cardinal features of bronchial asthma, and glucocorticoids are not sufficient to suppress IL-13-induced airway hyperresponsiveness or goblet cell hyperplasia. OBJECTIVES: We studied the effects of chloride channel inhibitors in IL-13-induced asthma. METHODS: The effects of niflumic acid (NA), a relatively specific blocker of calcium-activated chloride channel (CLCA), on goblet cell hyperplasia, eosinophil accumulation, and airway hyperresponsiveness were evaluated after IL-13 instillation into the airways. Because IL-13-dependent features rely on JAK/STAT6 signaling, the effect of NA on phosphorylation of JAK2 and STAT6 after IL-13 stimulation was examined in airway epithelial cells in vitro. The expression of the mCLCA family in mouse lung after IL-13 local administration in vivo was analyzed using reverse transcription-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Treatment with NA inhibited not only IL-13-induced goblet cell hyperplasia but also airway hyperresponsiveness and eosinophilic infiltration. NA suppressed the eotaxin levels in bronchoalveolar lavage fluids and overexpression of the MUC5AC gene, a marker of goblet cell hyperplasia, in the lung after IL-13 instillation. NA suppressed JAK2 activation, STAT6 activation, and eotaxin expression in epithelial cells. The expression of mCLCA3 (mouse homolog hCLCA1), but not that of other CLCA family members, was up-regulated by IL-13. CONCLUSIONS: These findings suggest that a chloride channel inhibitor can control IL-13-mediated airway features at least by suppressing JAK/STAT6 activation.

Animals↗
PubMed2006

Methamphetamine-related sudden death with a concentration which was of a 'toxic level'.

We reviewed 32 cases where a forensic autopsy detected methamphetamine in the blood, and all of these autopsies were performed at two institutes between 1991 and 2003. In accordance with several criteria, the blood concentration in 11 cases was classified as above the toxic level, and 10 of these cases were diagnosed as methamphetamine poisoning. In 20 cases (62.5% of total cases), the blood concentration was of a 'toxic level', and 10, 2 and 1 of these cases were diagnosed as methamphetamine poisoning, cardiomyopathy and intracerebral hemorrhage, respectively. Since it is unclear how the effects of methamphetamine may contribute to the death of an individual, a diagnosis of the exact cause of death is often difficult to make in cases where the blood concentration of methamphetamine was of a 'toxic level'. Therefore, a diagnosis has to be carefully made in consideration of the pathological findings, the pharmacological effects of methamphetamine and the process until death in such cases. Additionally, the mechanism of methamphetamine-related death needs to be more fully studied to enable an appropriate diagnosis to be made easily.

Adult↗
PubMed2006

Vulnerability of experimentally induced fatty liver to heat stress in rats.

BACKGROUND: The aim of this study was to confirm the vulnerability of fatty liver to heat stress using fatty liver rats from the viewpoint of the induction of apoptosis. METHODS: We exposed rats with and without a fatty liver to heat stress and then looked for apoptotic cells within the liver tissue using two apoptosis detection kits. We also determined the mRNA expression of heat shock protein (HSP) 70, caspase-3, bcl-2, and bax using a quantitative reverse transcription-polymerase chain reaction method. RESULTS: Following heat stress, apoptosis was strongly visible in the fatty liver comparing with that noted in the normal liver. The expression of HSP70 was increased following heat stress in both livers, but the volume of its expression was significantly less in the fatty liver than in the normal liver. The ratio of bcl-2/bax expression tended to increase in the normal liver but decrease in the fatty liver following heat stress. Caspase-3 demonstrated no significant change following heat stress in both livers. CONCLUSIONS: The detection of apoptosis, together with changes in the mRNA expression of HSP70 and the expression ratio bcl-2/bax mRNA may indicate vulnerability of a fatty liver to heat stress and may support the hypothesis that morphologic change is induced in a fatty liver by exposure to heat stress. These results suggest that fatty liver may be more vulnerable to heat stress than normal liver.

Animals↗
PubMed2006

Suppressor of cytokine signaling 3 (SOCS3) in Th2 cells evokes Th2 cytokines, IgE, and eosinophilia.

Atopic dermatitis, allergic rhinitis, and bronchial asthma are allergic immune disorders characterized by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-specific immunoglobulin E (IgE), and mast cell- and eosinophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determines the direction of helper T-cell differentiation into Th1 or Th2 cells. Therefore, negative regulators of cytokine signaling, suppressors of cytokine signaling (SOCS) proteins, play an important role in Th2-mediated allergic responses through the control of the balance between Th1 and Th2 cells. SOCS3 and SOCS5 are predominantly expressed in Th2 and Th1 cells, respectively, and they reciprocally inhibit the Th1 and Th2 differentiation processes. In this article, we discuss the role of SOCS3 and SOCS5 proteins in atopic asthma and allergic conjunctivitis and explore the potential of SOCS proteins as targets for therapeutic strategies in allergic disorders.

Animals↗
PubMed2006

The interleukin-4 enhancer CNS-2 is regulated by Notch signals and controls initial expression in NKT cells and memory-type CD4 T cells.

Epigenetic changes in chromatin structure at the T helper (Th2) locus correlate with interukin-4 (IL-4) and IL-13 expression during Th2 differentiation. By using a transgenic green fluorescence protein (GFP) reporter system, we show that conserved noncoding sequence-2 (CNS-2), located downstream of the Il4 locus, is a constitutively active enhancer in NKT cells as well as in a subset of CD44(hi) memory phenotype CD4+ T cells. CNS-2 enhancer activity and initial IL-4 expression in CD44(hi) CD4+ T cells were abolished in mice with a CD4-specific deletion of the transcriptional mediator of Notch signaling, Rbp-j. Depletion of CNS-2 active CD4+ T cells markedly decreased Th2 differentiation from naive CD4 T cells and antigen-specific IgE production after in vivo priming. These findings indicate that Notch-regulated CNS-2 enhancer controls initial IL-4 expression in NKT and memory phenotype CD4+ T cells and that CNS-2 active CD44(hi) memory phenotype T cells are important in facilitating Th2 differentiation of naive CD4+ T cells in allergic responses.

Animals↗
PubMed2006

Rapid screening for and simultaneous semiquantitative analysis of thirty abused drugs in human urine samples using gas chromatography-mass spectrometry.

In Japan, a wide variety of designer drugs became popular among juveniles because of their availability via the Internet and mobile phones. Hence, it is necessary to develop simple and rapid screening method for these drugs. We devised a rapid screening method for and simultaneous semiquantitative analysis of 30 abused drugs, including amphetamines, amphetamine-, piperazine-, tryptamine-, and phenethylamine-derived designer drugs and opiates in human urine. The urine sample was digested with urease, and the drugs were analyzed by gas chromatography-mass spectrometry in the scan mode after solid-phase extraction with a Focus column and acetylation. The retention time obtained with the use of a retention time locking technique and three qualifier ions were used to obtain positive results. As the Focus column requires only simple extraction steps and can retain various drugs of a wide range of polarity, screening of 30 abused drugs was feasible within 3 h. The calibration curves were linear in the concentration range of 100-5,000 ng/mL in most drugs with correlation coefficients exceeding 0.99. The absolute recoveries for all drugs in urine samples were 6.9-125.4% at the concentration 1,000 ng/mL. This method will be most useful to confirm the presence of many abused drugs in urine in clinical and forensic cases.

Amphetamines↗
PubMed2006

Induction of salivary antibodies to inhibit Candida albicans adherence to human epithelial cells by tonsillar immunization in rabbits.

To examine the possibility of a vaccine for Candida albicans infection in the oral cavity, we induced salivary antibodies by immunization of killed-C. albicans ATCC 18804 on the palatine tonsils of rabbits. The enzyme-linked immunosorbent assay reaction of salivary antibodies was high against C. albicans serotype A. The saliva antibodies greatly inhibited C. albicans adherence to cloned epithelial cells from human gingiva. Tonsillar immunizations of C. albicans ATCC 18804 induce salivary antibodies that prevent C. albicans adherence to epithelial cells, and thus should prove useful in the prevention of oral candidiasis caused by C. albicans serotype A.

Animals↗
PubMed2006

Homicidal sharp force injuries inflicted by family members or relatives.

We retrospectively reviewed 35 autopsy cases where death had resulted from homicidal sharp force injuries and compared cases where the injuries had been inflicted by family members or relatives (relative group) with cases where the injuries had been inflicted by an unrelated person (stranger group). We reviewed the age and sex of the victims, the number of stab wounds, the site of the stab wounds, the presence of defence wounds, the detection of alcohol and other drugs and the mental status of the victims and perpetrators. We found the following tendencies: (a) a female victim was more frequently killed by a relative than by a stranger; (b) the percentage of cases receiving a single stab wound and the percentage of cases receiving more than ten stab wounds were both unexpectedly higher in the relative group than in the stranger group, and (c) in the stranger group, when there were no defence wounds, the victim had usually consumed alcohol, whereas when there were neither defence wounds nor alcohol intake, the case usually fell into the relative group. These tendencies will contribute towards our forensic appraisement in autopsy cases resulting from sharp force injuries.

Adult↗
PubMed2006

[Allergic asthma and intrinsic inhibitors of cytokine signaling].

T helper 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, play an important role in allergic asthma. These cytokines transmit signals through the JAK/STAT and the Ras/ERK signaling pathways, and SOCS family proteins and SPRED family proteins regulate these pathways. SOCS3 controls IL-12-dependent STAT4 activation and Th2 differentiation process. SPRED-1 modulates IL-5-dependent ERK activation and eosinophilia. SOCS3 and SPRED-1 may be targets for therapeutic strategies in allergic asthma.

Animals↗
PubMed2005

The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia.

Neuromedin U (NMU) is a neuropeptide expressed not only in the central nervous system but also in various organs, including the gastrointestinal tract and lungs. NMU interacts with two G protein-coupled receptors, NMU-R1 and NMU-R2. Although NMU-R2 is expressed in a specific region of the brain, NMU-R1 is expressed in various peripheral tissues, including immune and hematopoietic cells. Our recent study demonstrated an important role of NMU in mast cell-mediated inflammation. In this study, we showed that airway eosinophilia was reduced in NMU-deficient mice in an allergen-induced asthma model. There were no differences in the antigen-induced Th2 responses between wild-type and NMU knockout mice. NMU-R1 was highly expressed in the eosinophil cell line, and NMU directly induced Ca(2+) mobilization and extracellular/signal-regulated kinase phosphorylation. NMU also induced cell adhesion to components of the extracellular matrix (fibronectin and collagen type I), and chemotaxis in vitro. Furthermore, NMU-R1 was also expressed in human peripheral blood eosinophils, and NMU induced cell adhesion in a dose-dependent manner. These data indicate that NMU promotes eosinophil infiltration into inflammatory sites by directly activating eosinophils. Our study suggests that NMU receptor antagonists could be novel targets for pharmacological inhibition of allergic inflammatory diseases, including asthma.

Allergens↗
PubMed2005

Simple and sensitive determination of free and total morphine in human liver and kidney using gas chromatography-mass spectrometry.

We developed a reliable, simple and sensitive method to determine free and total morphine in human liver and kidney, using gas chromatography-mass spectrometry (GC-MS). Free morphine or total morphine obtained by acid hydrolysis from 0.2g tissue sample was extracted using an Extrelut NT column with an internal standard, dihydrocodeine, followed by trimethylsilylation. The derivatized extract was submitted to GC-MS analysis of EI-SIM mode. The calibration curves of morphine in both liver and kidney samples were linear in the concentration range from 0.005 to 5 microg/g. The lower limits of detection of morphine were 0.005 microg/g. This method proved successful when we determined free and total morphine in liver and kidney obtained from an autopsied man who was mis-ingested morphine compound in the hospital, which resulted in the cause of death being morphine intoxication.

Analgesics, Opioid↗
PubMed2005

Analysis of mutation of the plasma cholinesterase gene in a man who had died following a traffic accident.

We analyzed mutation of the butyrylcholinesterase (BCHE) gene in a 69-year-old man on whom a forensic autopsy had been performed after he had died following a traffic accident. Extremely low plasma cholinesterase activity had been pointed out by the emergency doctor at the hospital prior to his death and based on this, organophosphorus poisoning had been suspected. However, no pesticides, which could have reduced the plasma cholinesterase activity, were detected by toxicological analysis using GC/MS. Subsequently, one base insertion was found in exon 2. The frame shift mutation had occurred because a homozygous extra T had been inserted between nucleotides 1343 and 1344, resulting in the appearance of a stop codon in codon 454 (AGA454TAA, Arg454stop). This heterozygous frame shift mutation at this point was identified in the man's son. It is likely that there may be many such latent patients with abnormal plasma cholinesterase activity, and accordingly we should always bear this fact in mind and should carry out molecular genetic testing for an accurate diagnosis of this deficiency.

Accidents, Traffic↗