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Biomedical subjects

J Adachi

Publications and source records attributed to J Adachi.

At least 37 records · Page 2Linked to original sources

Plastid genome phylogeny and a model of amino acid substitution for proteins encoded by chloroplast DNA.

Maximum likelihood (ML) phylogenies based on 9,957 amino acid (AA) sites of 45 proteins encoded in the plastid genomes of Cyanophora, a diatom, a rhodophyte (red algae), a euglenophyte, and five land plants are compared with respect to several properties of the data, including between-site rate variation and aberrant amino acid composition in individual species. Neighbor-joining trees from AA LogDet distances and ML analyses are seen to be congruent when site rate variability was taken into account. Four feasible trees are identified in these analyses, one of which is preferred, and one of which is almost excluded by statistical criteria. A transition probability matrix for the general reversible Markov model of amino acid substitutions is estimated from the data, assuming each of these four trees. In all cases, the tree with diatom and rhodophyte as sister taxa was clearly favored. The new transition matrix based on the best tree, called cpREV, takes into account distinct substitution patterns in plastid-encoded proteins and should be useful in future ML inferences using such data. A second rate matrix, called cpREV*, based on a weighted sum of rate matrices from different trees, is also considered.

Algal Proteins↗

7-Hydroperoxycholesterol as a marker of oxidative stress in rat kidney induced by paraquat.

The in vivo paraquat-induced oxidative stress in rat tissue was studied by analyzing cholesterol-derived hydroperoxide as an index of lipid peroxidation. Paraquat (10 mg/kg) was administered i.p. to rats. Rats were sacrificed and lung, liver, and kidney were collected 2, 24 h, and 5 d after paraquat injection. Lipids were extracted and analyzed by HPLC with post-column chemiluminescence. We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in lungs of control animals (0.06 and 0.06 nmol/g, respectively), in livers (6.5 and 15.8 nmol/g, respectively) and in kidneys (3.7 and 8.9 nmol/g, respectively). In liver paraquat increased lipid peroxidation approximately by 60% over the levels of control animals only at 2 h after paraquat treatment. In kidney, augmented lipid peroxidation, 7alpha-OOH and 7beta-OOH (by 70% and 147%, respectively) above levels was found at 2 h after paraquat treatment. Interestingly, these increase remained in kidney of rats 5 d after a single dose of paraquat. In contrast, cholesterol-derived hydroperoxides were not affected in lung of paraquat dosed rats. This is the first report on 7alpha-OOH and 7beta-OOH accumulations in rat liver and kidney, and it seems to reflect greater oxidative stress in the pathology of kidney of rats treated with acute paraquat at low dose.

Animals↗

Markers of enteric inflammation in enteroaggregative Escherichia coli diarrhea in travelers.

As part of a traveler's diarrhea study carried out in Guadalajara, Mexico, and Goa, India, we conducted a case control study to evaluate fecal markers of enteric inflammation in three groups. Forty-five cases of enteroaggregative Escherichia coli (EAEC) diarrhea were compared to 56 controls with enterotoxigenic E. coli (ETEC) diarrhea, and 126 controls with diarrhea without identifiable pathogens. For EAEC cases we found fecal leukocytes, occult blood, and lactoferrin in 13 (28.9%), 14 (31.1%), and 27 (60.0%) patients, respectively; for ETEC controls they were 15 (26.8%), 16 (28.6%), and 15 (26.8%) respectively; and for patients without identifiable pathogens 19 (15.1%), 34 (27.0%) and 27 (21.4%) were seen for the presence of a positive fecal lactoferrin test in EAEC cases was statistically significant compared to both control groups. The study provides evidence that EAEC infection is associated with an intestinal inflammatory response.

Adolescent↗

Identification of 7-hydroperoxycholesterol in human liver by liquid chromatography-mass spectrometry.

BACKGROUND: A liquid chromatography-mass spectrometry with an atmospheric chemical ionization interface has been developed to identify simultaneously various oxygenated cholesterols in lipid extracts from alcoholic fatty liver. METHODS: We collected human liver tissues from alcoholic and control subjects at autopsy. We purified the lipid extracts with solid phase extraction and injected them onto a spherisorb ODS column, by using methanol that contained 10 mM ammonium acetate as a mobile phase and a flow rate of 0.7 ml/min. RESULTS: We found the presence of 7-hydroperoxycholesterol and other oxysterols (5-cholesten-3beta-ol-7-one, cholest-5-ene-3beta, 7-diol, and 5, 6beta-epoxy-5beta-cholestan-3beta-ol) in alcoholic fatty liver tissues. CONCLUSIONS: We assume that long-term ethanol ingestion leads to excessive oxidative stress and to the accumulation of cholesterol-derived hydroperoxides and oxysterols in alcoholic fatty liver.

Adult↗

7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol in muscle as indices of oxidative stress: response to ethanol dosage in rats.

BACKGROUND: Alcohol-induced muscle disease (AIMD) encompasses both acute and chronic lesions, and affected patients exhibit concomitant functional and structural lesions. The pathogenic mechanisms are unknown, although it is possible that defects in the membrane-lipid domain are involved. Therefore, the effect of acute ethanol on membrane lipid from rat skeletal muscles (control, n = 7; ethanol, n = 7) was investigated. METHODS: Soleus and plantaris skeletal muscles were collected 24 hr after a single dose of 75 mmol/kg of ethanol. Lipids were analyzed by high-performance liquid chromatography with postcolumn chemiluminescence. RESULTS: We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in soleus muscles of control animals (1.29 nmol/g and 3.20 nmol/g, respectively) and in plantaris (1.83 and 5.18 nmol/g, respectively). These hydroperoxides were significantly elevated by acute ethanol, in not only plantaris but also soleus skeletal muscle of rats. In contrast, protein carbonyl concentration, another indicator of oxidative stress, albeit to proteins, was not significantly affected in either soleus or plantaris muscles of ethanol dosed rats. In addition, gas chromatographic study of fatty acid composition from phospholipid of rat muscle showed a significant increase of 18:2 by ethanol in plantaris as well as soleus. Concomitant decreases occurred in the nonessential/essential fatty acid ratios. CONCLUSIONS: This is the first report on 7alpha-OOH and 7beta-OOH accumulation in rat skeletal muscle, and it seems to reflect greater oxidative stress in the pathology of muscle of rats treated with acute ethanol. Together with the elevation of 18:2, these results signify perturbations in membrane lipids in response to ethanol, which may have important implications for the pathogenesis of alcohol-induced muscle disorders.

Animals↗

[Membrane disorder and free radical].

The aim of this study is to confirm cholesterol-derived hydroperoxides in membrane lipids as indices of free radical or active oxygen-induced membrane disorder or pathological changes at legal medicine. First, 7 alpha- and 7 beta-hydroperoxycholesterol (7 alpha-OOH and 7 beta-OOH) were synthesized. Then, these were identified in lipids from human fatty liver by liquid chromatography-mass spectrometry. Secondly, the method for quantifying 7 alpha-OOH and 7 beta-OOH by high-performance liquid chromatography with chemiluminescent detection (HPLC-CL) was developed. Finally, the following membrane disorders were examined based on lipid peroxidation. Elevated lipid peroxidations were found in erythrocyte membranes of alcoholic patients, in alcoholic fatty liver, and in muscle of alcohol dosed rats. Enhanced lipid peroxidation was induced in rat kidney by paraquat. In addition, lipid peroxidation was increased in brains of senile dementia as well as in atheroscleroic plaque. Thus, we confirm 7-hydroperoxycholesterol as a marker of free radical-induced oxidative stress.

Alcoholism↗

An unusual case of suicide by stabbing with a falling weighted dagger.

An unusual suicide by self-stabbing is presented. A 42-year-old man committed suicide with a dagger weighted with 2.72 kg in total and allowed to fall freely. The blade of the dagger fell from a height of 10 cm above the chest, penetrated the second left intercostal skin and pierced the upper lobe of the left lung. However, the weapon did not penetrate the chest skin from a stationary position in our trial at the autopsy. This finding confirms the results of experiments with stab wound dynamics which demonstrated that the impact velocity of the weapon as well as the sharpness of the tip is important for skin penetration.

Adult↗

Cholesterol-derived hydroperoxides in alcoholic liver disease.

Human liver samples from 33 patients were collected at autopsy (controls, n = 9; fatty liver, n = 12; liver cirrhosis, n = 12), and samples homogenized. Lipids extracted with chloroform and methanol were injected into the octyl column of a high-performance liquid chromatograph with post-column chemiluminescence. Liquid chromatography-mass spectrometry was developed to identify 7-hydroperoxycholest-5-en-3 beta-ol (7-OOH). We found that two cholesterol-derived hydroperoxides, 7 alpha-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH) and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-OOH), are present in significantly elevated amounts (12.4 and 25.0 nmol/g tissue, respectively) in lipid extracts from alcoholic fatty liver, but not in extracts from alcoholic cirrhotic liver. 7 alpha-OOH and 7 beta-OOH are early intermediates produced during free radical-mediated cholesterol oxidation and can serve as molecular indicators of chain peroxidative damage in cell membranes. This is the first demonstration of 7 alpha-OOH and 7 beta-OOH accumulations in human liver, and it is presumed to reflect greater oxidative stress pathology in alcoholic fatty liver.

Adult↗

Objective scratch monitor evaluation of the effect of an antihistamine on nocturnal scratching in atopic dermatitis.

We previously reported a simple and easy-to-use device, Scratch Monitor for evaluation of nocturnal scratching. In the present study, the effect of an antihistamine (azelastine hydrochloride) on atopic dermatitis was investigated using this device. In 40 patients with atopic dermatitis, nocturnal scratching was measured by the monitor, when taking the drug and while off medication. Neither the 'sleeping time' nor the 'pre-asleep time' differed significantly, but there was a significant difference in 'scratch rate', 'minute scratch records', 'hourly awake number' and 'awake rate', which indicated that this drug alleviated nocturnal scratching and sleep disturbance. The difference was most prominent especially in patients with a serum IgE > or = 1000 IU/ml as well as in patients with mild symptoms and normal serum lactate dehydrogenase levels. The drug was more effective for nocturnal scratching in the early period, when the 'sleeping time' was divided into three equal parts (early, mid and late periods) and each period was compared.

Adolescent↗

Review article: travellers' diarrhoea.

In this review we will briefly consider the important aetiological agents and clinical expressions in travellers' diarrhoea, then we will review the prevention and therapy of the illness.

Diarrhea↗

Cholesterol hydroperoxides in erythrocyte membranes of alcoholic patients.

Evidence for the presence of 5alpha-hydroperoxycholest-6-en-3beta-ol (cholesterol 5alpha-hydroperoxide, Ch 5alpha-OOH) and 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ols (cholesterol 7-hydroperoxides: Ch 7alpha-OOH and Ch 7beta-OOH, respectively) in human erythrocyte membrane was found. Blood samples were collected from alcoholic patients and healthy volunteers (controls), and their cholesterol hydroperoxides were analyzed by high-performance liquid chromatography postcolumn chemiluminescence and roughly identified by liquid chromatography-mass spectrometry. Ch 7alpha-OOH and Ch 7beta-OOH were present in each sample, being significantly higher in alcoholic samples than in control samples. Ch 5alpha-OOH was present in some alcoholic samples, but not in the control ones. The accumulation of cholesterol hydroperoxides suggests enhanced lipid peroxidation by active oxygen species and/or a reduced elimination system for lipid peroxide in alcoholic patients.

Adult↗

Cell cycle arrest and astrocytic differentiation resulting from PTEN expression in glioma cells.

OBJECT: Genetic alterations of the PTEN gene (also known as MMAC1 or TEP1) have frequently been identified in high-grade gliomas, indicating that inactivation of PTEN plays a crucial role in human glioma progression. The aim of this study was to assess the biological significance of PTEN inactivation in the development of glioma. METHODS: The authors introduced wild-type PTEN complementary DNA into four human glioma cell lines (T98G, U-251MG, U-87MG, and A172) containing endogenous aberrant PTEN alleles. The number of colonies transfected with the wild-type PTEN was reduced to 15 to 32% of those found after transfection of a control vector, suggesting growth suppression by the exogenous PTEN. To analyze phenotypic alterations produced by PTEN expression, T98G-derived clones with inducible PTEN expression were further established using a tetracycline-regulated inducible gene expression system. Induction of PTEN expression suppressed the in vitro growth of T98G cells with accumulation of G1 phase cells. Furthermore, when cells were cultured in the presence of the extracellular matrix (ECM), PTEN expression caused distinct morphological changes, with multiple and elongated cytoplasmic processes similar to those of normal astrocytes. The level of glial fibrillary acidic protein, an intermediate protein specifically expressed in differentiated astrocytes, was upregulated concomitantly. CONCLUSIONS: These findings strongly indicate that exogenous PTEN expression inhibits the proliferation of glioma cells by inducing G1 arrest and elicits astrocytic differentiation in the presence of the ECM. Inactivation of PTEN would play an important role in the enhancement of unregulated growth of undifferentiated glioma cells.

Astrocytes↗

Prognostic significance of allelic imbalances on chromosome 9p in stage I non-small cell lung carcinoma.

Loss of heterozygosity (LOH) on chromosomes 2q, 9p, 18q, and 22q frequently occurs in advanced non-small cell lung carcinoma (NSCLC). The association of p53 mutations with prognosis is still unclear in NSCLC. Therefore, we investigated the prognostic significance of allelic imbalances (AI) on these chromosomes and p53 mutations in 108 cases of stage I NSCLC by PCR amplification of polymorphic dinucleotide repeat-containing sequences and PCR-single strand conformation polymorphism analysis. AI on 2q, 9p, 18q, and 22q was detected in 22, 38, 29, and 15% of cases, respectively, whereas p53 was mutated in 41% of stage I NSCLC. AI on 9p and 22q and p53 mutations were significantly associated with shortened survival of the patients (P = 0.010, 0.024, and 0.022, respectively). Although gender and smoking history showed more significant associations with prognosis than other clinicopathological and molecular parameters, independent prognostic significance for AI on 9p was observed (P = 0.002) in male patients with a positive smoking history. These results indicate that clinical aggressiveness of early-stage NSCLC can be partly defined by the presence of AI on chromosome 9p in cancer cells, and that AI on 9p could be a clinically useful prognostic indicator for early-stage NSCLC patients.

Adult↗

[An autopsy case of pulmonary thromboembolism associated with chlorine gas poisoning].

We report a rare case of sudden death of a patient with acute pulmonary thromboembolism associated with chlorine gas poisoning. A 21-year-old man in a water-filtration plant accidentally inhaled highly concentrated chlorine gas. He was immediately brought to a hospital after exposure. On admission, the patient had clouding of consciousness, dyspnea, and deep cyanosis. Arterial blood gas values indicated severe hypoxemia; PaO2 was 35.9 mmHg and PaCO2 was 42.4 mmHg. The clinical course was uneventful and he was satisfactorily recovering. However, ten days after admission he became sick and markedly cyanotic. He lost consciousness and then he went into cardiopulmonary arrest. Despite efforts at resuscitation, he died. An autopsy revealed bilateral pulmonary thromboembolism, although he apparently did not have any risk factor for embolism. The toxicity of chlorine gas may be related to the pulmonary thromboembolism, but the mechanisms leading to his death are unclear.

Accidents, Occupational↗

The p16 (CDKN2A) gene is involved in the growth of neuroblastoma cells and its expression is associated with prognosis of neuroblastoma patients.

We previously reported that loss of heterozygosity (LOH) on chromosome 9p21 correlates with poor prognosis of neuroblastoma and the p16 gene is not expressed in approximately two thirds of neuroblastoma cell lines. Here we demonstrated that p16 expression was induced by 5-aza-2-deoxycytidine treatment in cell lines with 5' CpG island methylation but not in cell lines without methylation. Furthermore, the cell cycle of neuroblastoma cell lines significantly delayed with accumulation of cells in G1 phase by transfection of a wild-type p16 expression vector. These results indicate that p16 is inactivated in part by DNA methylation and its expression is involved in the growth of neuroblastoma cells in vitro. To assess the biological and clinical significance of p16 expression in primary tumors, we undertook immunohistochemical analysis in 74 paraffin sections of neuroblastomas. p16 protein was undetectable in 45 of 74 cases (61%) and lack of p16 expression significantly correlated with poor prognosis of patients and advanced stage of the disease. There was no correlation between loss of p16 expression and N-myc amplification in these tumors. These results indicate that inactivation of the p16 gene is involved in the progression of neuroblastoma independently of N-myc amplification.

Azacitidine↗

Women's decisions about hormone replacement therapy after education and bone densitometry.

BACKGROUND: The decisions that postmenopausal women make about whether to start hormone replacement therapy may depend on the potential risks and benefits of such therapy as well as their risk for osteoporosis-related fractures. This study examined the decisions made by women at risk for osteoporosis-related fractures who were educated about hormone replacement therapy and who were given information about their bone mineral density. METHODS: The study employed a prospective cohort design. Thirty-seven post--menopausal women with risk factors for osteoporosis-related fractures were recruited from an orthopedic clinic at a teaching hospital in Hamilton, Ont. The women were given an education kit (consisting of an audio tape and a work-book) to clarify the benefits and risks of hormone replacement therapy. Two to 4 weeks later, densitometry of the hip and the lumbar spine was performed. A summary of the risks, the densitometry findings and decisions about hormone replacement therapy were given to the women's family physicians for follow-up. Outcome measures included decisions about hormone replacement therapy, as well as use of such therapy and other medications at 12 months. RESULTS: After the education component alone, 10 (27%) of the women requested hormone replacement therapy. After densitometry testing, 4 more requested hormone replacement therapy (for a total of 14 women [38%]). At 12 months, 2 (5%) of the women had been lost to follow-up. Of the remaining 35, 6 (17%) were receiving hormone replacement therapy, 7 (20%) were using bisphosphonates, and 24 (68%) were taking calcium supplements. INTERPRETATION: These preliminary findings suggest that the combination of education about hormone therapy and feedback about bone density is associated with an increase in the use of hormone replacement therapy and other preventive medications by women at risk for osteoporosis-related fractures. However, the observed increase was small and so the clinical significance must be confirmed and clarified.

Absorptiometry, Photon↗

Elevated plasma nitrate in patients with crush syndrome caused by the Kobe earthquake.

We investigated the nitric oxide profile in the plasma of ten healthy controls and 29 patients hurt by the Kobe Earthquake. The levels of nitrite (NO2-) and nitrate (NO3-) were measured simultaneously by high-performance liquid chromatography (HPLC) with UV detection using the Griess reaction after the reduction of nitrate to nitrite. Arginine consumed in food or diet-derived nitrite had no effect on the plasma nitrite and nitrate contents of the healthy volunteers. Plasma nitrate was elevated in the crush syndrome patients; whereas neither nitrite nor nitrate was increased in patients with normal renal function. This finding suggests increased nitric oxide synthesis, decreased excretion of nitric oxide in the crush syndrome or both.

Adult↗

Chemiluminescent determination of cholesterol hydroperoxides in human erythrocyte membrane.

A method for separating, detecting, and quantifying cholesterol hydroperoxide (Ch-OOH) based on extraction, purification by solid-phase extraction cartridge, high-performance liquid chromatography with chemiluminescent detection (HPLC-CL), and liquid chromatography-mass spectrometry has been developed for human erythrocyte membrane. We prepared standard compounds of the cholesterol 5alpha-, 7alpha-, and 7beta-hydroperoxides (Ch 5alpha-OOH, Ch 7alpha-OOH, and Ch 7beta-OOH). An octyl silica column with methanol/water/acetonitrile 89:9:2 (by vol) as eluent was used to determine Ch-OOH. HPLC-CL that incorporated cytochrome c and luminol as the post-column luminescent reagent was used. We also investigated the optimal assay conditions and how to prevent formation of artifact Ch-OOH. Analysis of erythrocyte membranes from seven healthy volunteers identified Ch 7alpha-OOH and Ch 7beta-OOH, but not Ch 5alpha-OOH, as commonly occurring components. The respective mean concentrations of Ch 7alpha-OOH and Ch 7beta-OOH were 2.5+/-1.6 and 5.4+/-3.5 pmol/mL blood.

Antioxidants↗