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Biomedical subjects

Shogo Tokudome

Publications and source records attributed to Shogo Tokudome.

At least 19 recordsLinked to original sources
PubMed2006

Changes in blood viscosity with the recombinant tissue plasminogen activator alteplase.

We measured whole blood viscosity to investigate the time course of the fibrinolytic activity of the recombinant tissue plasminogen activator alteplase. Changes in blood viscosity over time were determined using an oscillation-type viscometer at a shear rate of 400 to 500 per second. Blood viscosity initially increased with alteplase as in untreated blood, but then decreased, reflecting the fibrinolytic activity of generated plasmin. Blood viscosity subsequently stabilized at a level below the initial value owing to the dissolution of both fibrin and fibrinogen by alteplase. To our knowledge, the present study is the first to examine the time course of changes in BV during fibrin formation and degradation. The results indicated that the fibrinolyic agent alteplase might provide the additional benefit of increasing blood flow by lowering blood viscosity.

Blood Viscosity↗
PubMed2006

Fungi can be a useful forensic tool.

We present a practical case in which the fungi have contributed to the estimation of postmortem interval of the cadaver. A 71-year-old man wearing a shirt and pants was found dead at the bottom of an open well about 6m below the ground in his garden. Externally the face was dotted with colonies of white fungi, which was devoid of dipteran larvae and other insects. The fungi were identified as Penicillium sp. and Aspergillus terrous. These fungi, widely inhabit in the life circumstances, can generally colonize 3-7 days after attaching on the subjects. The appearance of the body surface, the state of decomposition of various organs, police information describing that the man had last been seen 12 days before discovery and the fungal evidence indicated that the man had been dead for about 10 days. We suggest that fungi can provide an useful means of estimating the minimum interval since death when forensic entomology is not applicable. Although, no data about growth rates of the fungi on human cadavers have been available, further researches should be needed to clarify the successive colonization of fungi on human cadavers.

Aged↗
PubMed2006

Analysis of fungi detected in human cadavers.

We examined and identified fungi flora found growing on two human cadavers. The main isolate colonized on the surfaces of the skin and bones was morphologically identified as Eurotium repens. The genus Eurotium usually inhabits soil and exhibits osmophilic properties. Because the cadavers contained abundant organic materials, Eurotium species formed ascomata and conidia. To our knowledge, this is the first study to describe in detail the species of fungus obtained from human cadavers. Because the detection of some species of fungus found in human cadavers may reveal the local habits of them, more forensic cases is needed to develop fungi into the forensic tool.

Aged↗
PubMed2006

Isoflavones inhibit nicotine C-oxidation catalyzed by human CYP2A6.

The inhibitory effects of isoflavones (daidzein, genistein, and glycitein) on human cytochrome P450 (CYP) 2A6 activities were investigated. Daidzein, genistein, and glycitein uncompetitively inhibited nicotine C-oxidation catalyzed by recombinant CYP2A6 expressed in baculovirus-infected insect cells with Ki values of 1.3 +/- 0.3 microM, 0.7 +/- 0.2 microM, and 5.2 +/- 0.8 microM, respectively, but not coumarin 7-hydroxylation. Effects of the intake of soy isoflavones on in vivo nicotine metabolism were investigated with 7 healthy Japanese homozygotes of CYP2A6*1. The cotinine/nicotine ratio of the plasma concentrations 2 hours after chewing 1 piece of nicotine gum under the basal condition (after abstaining from soy foods for 1 week) was 8.8 +/- 2.6 (4.4-11.4). The ratio was significantly (P < .05) reduced to 6.7 +/- 1.6 (4.0-8.2) after consumption of a soy isoflavone supplement (60 mg of total isoflavones/d) for 5 days. The authors found that isoflavone contained in soy products significantly decreased nicotine metabolism.

Animals↗
PubMed2006

Accidental strangulation of a mentally retarded patient by a clothing collar: a case report.

A 40-year-old mentally retarded woman died of accidental strangulation in a nursing home. She was found in a kneeling position with her hands on her knees and the collar of her clothing compressing the front and sides of the neck. Before the accident, a nurse had dressed the patient in one-piece overall-style pyjamas put on back to front so that she could not remove the garment herself. The post-mortem findings and reconstruction of the scene of death suggested that the patient had been strangled by the collar of her backward-facing clothing while in a kneeling position. Because patients with psychiatric illnesses may have a limited ability to recognize or communicate symptoms of physical danger, they must be closely monitored by knowledgeable medical and nursing staff. This case highlights the importance of preventing the accidental deaths of mentally retarded patients in nursing homes.

Accidents, Home↗
PubMed2005

A newly derived protein from Bacillus subtilis natto with both antithrombotic and fibrinolytic effects.

Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intra-duodenum administration of NKCP. Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use.

Amino Acid Sequence↗
PubMed2005

Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction.

Troglitazone is a thiazolidinedione antidiabetic agent with insulin-sensitizing activities that was withdrawn from the market in 2000 due to its association with idiosyncratic hepatotoxicity. To address the suspected autoantibody production associated with troglitazone, we investigated autoantibodies in sera from patients with type II diabetes mellitus with troglitazone-induced liver dysfunction. Two female patients (47- and 70-year-old) ceased taking troglitazone (400 mg/day) after 23.5 and 16 weeks, respectively, due to increased serum ALT. Using two-dimensional electrophoresis and amino acid sequence analyses, aldolase B was identified as an autoantigen that reacted with antibodies in sera from both patients. The titer of anti-aldolase B remained high for several weeks after stopping troglitazone administration. The mean reactivity of autoantibodies to aldolase B determined by ELISA with sera of patients with chronic hepatitis (n = 40) and liver cirrhosis (n = 40) was significantly higher (p < 0.05 and p < 0.001, respectively) than with sera of healthy subjects (n = 80). These findings suggest that liver injury may cause the appearance of autoantibodies to aldolase B which may then aggravate the hepatitis. In addition, the anti-aldolase B titer might indicate the severity of liver dysfunction.

Aged↗
PubMed2005

Accidental choking in a patient with Treacher Collins syndrome.

A 3-year-old boy with Treacher Collins syndrome had undergone tracheostomy and placement of a secured cannula at the age of 4 months. When he was 3 years old, he manually extracted the secured cannula by himself and choked to death. Autopsy revealed upper airway obstruction with posterior deviation and mucosal hyperplasia of the radix linguae, mandibular hyperplasia, and occlusion of the artifical airway owing to intratracheal granuloma due to the long-standing tracheotomy. For safe, long-term use of a tracheostomy to maintain the airway, children with craniofacial abnormalities should be carefully supervised by their families to prevent accidental decannulation.

Accidents↗
PubMed2005

Traffic injuries of the pregnant women and fetal or neonatal outcomes.

OBJECTIVE: To investigate the relationship between pregnancy outcome and injury severity of pregnant woman in traffic accidents. METHOD: We reviewed insurance reports of traffic accidents and collected data on injuries of pregnant women and outcomes of their pregnancies. RESULT: A total of 135 pregnant women, with a mean injury severity score of 1.8+/-4.0, were involved in traffic accidents from 1994 through 2003. Injury severity score, abdominal abbreviated injury scale score were significantly higher in women whose neonates died than in women with healthy newborns. However, neither the likelihood of having been subjected to direct external forces during the accident nor injury severity differed between women with spontaneous abortions and woman with healthy newborns. CONCLUSION: Predicting abortion on the basis of maternal injury severity is difficult. Because unknown variables may contribute to fetal loss, further studies of traffic injuries are needed.

Abortion, Spontaneous↗
PubMed2005

3. Sudden death due to pulmonary thromboembolism after car driving: a case report.

An autopsy case of sudden death due to pulmonary thromboembolism after a car trip is reported. A 56-year-old Japanese man with hypertension and atrial fibrillation suddenly died immediately after having driven for two and a half hours. At autopsy, the pulmonary arteries were found to be filled with dark-red, coiling thrombi consisting of fibrin and red blood cells. In the dilated right popliteal vein, a thrombus consisting of fibroblasts, a large number of collagen fibres, and newly formed capillaries was attached to the vessel wall. The cause of death was determined to be pulmonary embolism due to the thrombus of the right popliteal vein. Two and a half hours of prolonged sitting while driving a car encouraged thrombus formation. We believe that this case, the first autopsy case of fatal pulmonary thromboembolism after a car trip to be reported, highlights the importance of predicting venous thrombosis of the leg or fatal venous thromboembolism after a car trip.

Automobile Driving↗
PubMed2005

An autopsy case of sudden death in a boy with primary pulmonary hypertension: a case report.

We report a rare autopsy case of sudden death due to primary pulmonary hypertension. A seven-year-old boy, who had been diagnosed with primary pulmonary hypertension at the age of four years, died suddenly. Forensic autopsy and histopathologic examination revealed extensive obstruction of small muscular pulmonary arteries by plexiform lesions and concentric intimal thickenings, compatible with primary pulmonary hypertension. We concluded that plexiform lesions of pulmonary arteries produced right ventricular hypertrophy and dilatation, decreased the preload of the left ventricle and subsequently led to biventricular failure. This autopsy and histopathologic examination suggested a possible pathophysiologic mechanism of sudden death due to primary pulmonary hypertension in a child.

Autopsy↗
PubMed2005

[Sudden death while bathing].

We describe the epidemiologic and pathophysiologic features of sudden death while bathing. The leading cause of death is cardiovascular disease (60.4%), followed by cerebrovascular disease (18.7%) and drowning (11.2%). Because hydrostatic pressure, autonomic nervous reflexes or endocrine system reflect on hemodynamic changes while bathing, the elderly persons or patients with cardiovascular disease are often suffered from fatal cardiac events. To find the detail pathophysiologic changes while bathing, exact cause of death should be examined by autopsies. Furthermore, elderly or handicapped persons should be supervised by their families for preventing drowning.

Baths↗
PubMed2004

Identification of the cytosolic carboxylesterase catalyzing the 5'-deoxy-5-fluorocytidine formation from capecitabine in human liver.

Capecitabine, a prodrug of 5-fluorouracil, is first metabolized to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase (CES), which is mainly expressed in microsomes. Recently, we clarified that 5'-DFCR formation was catalyzed by the enzyme in cytosol as well as microsomes in human liver. In the present study, the cytosolic enzyme involved in 5'-DFCR formation from capecitabine was identified. This enzyme was purified in the cytosolic preparation by ammonium sulfate precipitation, Sephacryl S-300 gel filtration, Mono P chromatofocusing, and Superdex 200 gel filtration. The purified enzyme was identified by the amino acid sequence analysis to be CES1A1 or a CES1A1 precursor. Based on the result of the N-terminal amino acid sequence analysis, the purified enzyme has no putative signal peptide, indicating that it was CES1A1. The apparent Km and Vmax values of 5'-DFCR formation were 19.2 mM and 88.3 nmol/min/mg protein, respectively. The 5'-DFCR formation catalyzed by the purified enzyme was inhibited by both diisopropylfluorophosphate and bis(p-nitrophenyl)phosphate in a concentration-dependent manner. 7-Ethyl-10-hydroxycamptothecin (SN-38) formation from irinotecan also occurred in the purified enzyme, cytosol, and microsomes. In conclusion, the cytosolic enzyme involved in 5'-DFCR formation from capecitabine would be CES1A1. It is suggested that the cytosolic CES has significant hydrolysis activity and plays an important role as the microsomal CES in drug metabolism. It is worthy to investigate the metabolic enzyme in cytosol involved in the activation of ester-type prodrugs such as capecitabine.

Amino Acid Sequence↗
PubMed2004

Fibrinolytic and anti-thrombotic effect of NKCP, the protein layer from Bacillus subtilis (natto).

NKCP is the completely refined protein layer from cultured Bacillus subtilis (natto) and is supplied in tablet form. It lacks the distinctive fermented odor and bacteria associated with fresh natto. Almost all vitamin K is removed during the manufacturing process. The main component of NKCP is the active fragment of Bacillopeptidase F, which is a serine protease secreted by Bacillus subtilis. In in vivo studies, NKCP shows fibrinolytic and amidolytic activity on plasmin specific synthetic substrate. Daily oral administration of NKCP in 28 volunteers for two weeks and then in 23 volunteers for several months, was examined. The fibrinolytic effect was demonstrated by a shortened euglobulin lysis time in both trials. Furthermore, we observed an improvement in shoulder stiffness. These results suggest that the oral administration of NKCP can be expected to have a fibrinolytic effect and cause positive changes in local blood flow. Further investigations may demonstrate NKCP to be useful in the prevention of thrombosis.

Administration, Oral↗