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Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 1,171 records · Page 65Linked to original sources

Transcatheter hepatic arterial embolization with Avitene in dogs.

The hepatic arteries in 36 dogs were embolized with microfibrillar collagen (Avitene) to evaluate the effects on the liver parenchyma. Serial examinations were then conducted over 4 weeks. The dogs were divided into 3 groups: Group 1 received Avitene soaked in saline, Group 2 received decanted Avitene, and Group 3 received Avitene decanted and filtered through gauze. Coagulation necrosis and degeneration of the liver parenchyma was noted in all 3 groups, but was least in Group 3. These results in dogs suggest that gauze filtration of Avitene prior to arterial embolization may also reduce damage to liver parenchyma.

Animals↗

Necrotizing fasciitis caused by Vibrio vulnificus: first published infection acquired in Turkey is the second time a strain is isolated in Germany.

Vibrio vulnificus, a marine vibrio, has recently been recognized as a potential human pathogen. It causes human infections with mortality rates up to 60%. Until 1991, most human isolations were reported from the USA, Japan and Taiwan. The second strain isolated in Germany is documented and a significant case of V. vulnificus infection acquired in Turkey is published for the first time.

Aged↗

Left atrial thrombus formation immediately after cardioversion of atrial fibrillation despite adequate anticoagulant therapy.

We observed a patient who exhibited de novo left atrial thrombus formation after cardioversion, despite administration of adequate anticoagulant therapy. Preexisting atrial thrombus was excluded by transesophageal echocardiography. Preexisting severe left atrial mechanical dysfunction may be considered as a risk factor for de novo thrombus formation after cardioversion, as well as the poor outcome of cardioversion.

Adult↗

Comparison of rates of enzymatic oxidation of aflatoxin B1, aflatoxin G1, and sterigmatocystin and activities of the epoxides in forming guanyl-N7 adducts and inducing different genetic responses.

The genotoxicity of the dihydrofurans aflatoxin B1 (AFB1), aflatoxin G1 (AFG1), and sterigmatocystin (STG) was examined in a bacterial system in which the induction of SOS repair is monitored with the umuC gene linked to a lacZ reporter gene in plasmid pSK1002. Human liver microsomal cytochrome P-450NF oxidized the dihydrofurans (in the presence of calf thymus DNA) to give guanyl-N7 adducts in the order AFB1 greater than STG greater than AFG1. The order of the umu response seen was STG greater than AFB1 greater than AFG1, when either the dihydrofurans were activated enzymatically or the synthetic epoxides of the dihydrofurans were added directly to the bacteria. Thus, the umu response per molecule of guanyl-N7 DNA adduct follows the order STG greater than AFB1 greater than AFG1. A similar pattern has been reported in the literature for Salmonella typhimurium base substitution dependent his reversions, but the pattern AFB1 greater than STG greater than AFG1 has been found for bacterial frame-shift-dependent mutagenesis and hepatocarcinogenesis. The guanyl-N7 adduct derived from AFG1 has considerably less of all of these biological activities per molecule. Neither guanine imidazole ring opening nor apurinic site formation appears to be a factor involved in the differential biological responses seen with the three guanyl-N7 adducts. These findings indicate that these structurally related guanyl-N7 DNA adducts have intrinsic differences which give rise to divergent biological responses.

Aflatoxin B1↗

Oxidation of aflatoxins and sterigmatocystin by human liver microsomes: significance of aflatoxin Q1 as a detoxication product of aflatoxin B1.

Aflatoxin Q1 8,9-oxide was synthesized and found to yield lower levels of N7-guanyl adducts than obtained from aflatoxin B1 8,9-oxide when mixed with calf thymus DNA or Salmonella typhimurium TA 98 cells. However, when S. typhimurium TA 98 was treated with the (analogous) epoxides of aflatoxin B1, aflatoxin G1, aflatoxin Q1, or sterigmatocystin, the ratios of revertants to N7-guanyl DNA adducts were similar. Aflatoxin Q1 and aflatoxin B1 8,9-oxide (trapped here as the glutathione conjugate) are the major oxidative products formed from aflatoxin B1 at all substrate concentrations in human liver microsomes, and cytochrome P-450 (P-450) 3A4 appears to be the dominant enzyme involved in both oxidations, as judged by studies involving correlation of activities in different liver samples, chemical inhibition, immunoinhibition, and reconstitution with purified hepatic and yeast recombinant P-450 3A4. Aflatoxin Q1 is not appreciably oxidized in human liver microsomes and is not very genotoxic. The postulated formation of both aflatoxin Q1 and aflatoxin 8,9-oxide from aflatoxin B1 can be rationalized by a model in which P-450 3A4 binds the substrate in either of two different configurations. This is further demonstrated by the dichotomous effect of 7,8-benzoflavone--this flavone stimulates 8,9-epoxidation while inhibiting the 3 alpha-hydroxylation reaction to form aflatoxin Q1. Thus, the 3 alpha-hydroxylation of aflatoxin B1 to aflatoxin Q1 is viewed as a potentially significant detoxication pathway.

Aflatoxin B1↗

Activation and inactivation of carcinogenic dihaloalkanes and other compounds by glutathione S-transferase 5-5 in Salmonella typhimurium tester strain NM5004.

A newly developed tester Salmonella typhimurium NM5004 strain was constructed by introducing a plasmid containing both rat GSH S-transferase (GST) 5-5 cDNA and the umuC"lacZ operon into the host strain Salmonella typhimurium TA1535 and used to examine whether or not GST modified the genotoxic activities of several dihaloalkanes and other compounds. Twenty-nine chemicals that were suggested to be conjugated by GST were compared with regard to their abilities to induce umu gene expression and cause cytotoxicity responses in both the NM5004 strain and the original tester strain (S. typhimurium TA1535/pSK1002, which is devoid of GST activity toward 1,2-epoxy-3-(4'-nitrophenoxy)propane). Ten chemicals--1,2-dibromoethane,N-(2,3-epoxypropyl)phthalimide, 1,3-dichloroacetone, CH2I2, 1,2-epoxy-3-phenoxypropane, 2,3-epoxypropyl p-methoxyphenyl ether, 1-bromo-2-chloroethane, 1-bromo-2,3-dichloropropane, CH2BrCl, and CH2Br2--were found to enhance induction of umu gene expression in the NM5004 strain as compared with the TA1535/pSK1002 strain. 1,2-Epoxy-3-(4'-nitrophenoxy)propane and 2,3-dibromo-1-chloropropane were inactivated by GST 5-5 in the NM5004 tester strain, although these chemicals were cytotoxic in both tester strains. Roles of GST 5-5 were also examined for the inactivation of reactive metabolites of several procarcinogens that were formed through oxidation by liver microsomes of polychlorinated biphenyl-treated rats. The results suggest that reactive metabolites (possibly epoxides) of aflatoxin B1, sterigmatocystin, 1,2-dihydro-1,2-dihydroxy-6-aminochrysene, and (+)- and (-)-enantiomers of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene could be trapped as inactivated GSH conjugates in the NM5004 strain. High-performance liquid chromatographic analysis suggested that exo-aflatoxin B1-8,9-oxide--GSH conjugate was formed during the oxidation of aflatoxin B1 by rat and human liver microsomes in the presence of GSH and several GST enzymes including purified rat theta class GST Yrs-Yrs and rat liver GST (a mixture of alpha and mu class enzymes). Thus, the present results support the view that the theta class rat GST 5-5 enzyme participates in the activation and inactivation of potential environmental carcinogenic chemicals. This newly developed NM5004 tester strain is of use in the elucidation of roles of GST 5-5 in transformations.

Aflatoxin B1↗

Sublingual nifedipine in elderly patients: even a low dose induces myocardial ischaemia.

1. Low doses of sublingual nifedipine are still used for the treatment of hypertensive crises, although recent studies have raised concerns that sublingual nifedipine may cause serious dose-dependent adverse effects. The present study was performed to test the safety of low-dose sublingual nifedipine administered to elderly hypertensive patients. 2. Systemic blood pressure measurements and electrocardiographic (ECG) examinations were performed before and 45-60 min after a 5 mg dose of sublingual nifedipine in 93 consecutive hypertensive patients, 65 years of age or older, who were without coronary artery disease. In 33 patients, the effects of nifedipine on myocardial lactate metabolism were studied during cardiac catheterization. 3. In all patients, following nifedipine administration, blood pressure (BP) decreased significantly, while heart rate (HR) increased, and symptoms associated with elevated BP disappeared. However, changes consistent with myocardial ischaemia appeared on the ECG in six of 55 patients with left ventricular hypertrophy (LVH) and in one of 38 patients without LVH, although only two of these seven patients experienced angina-like precordial tightness. Sublingual nifedipine decreased myocardial lactate extraction from 52 +/- 13 to 38 +/- 19% in 20 patients with LVH (P = 0.02), but myocardial lactate extraction remained stable in 13 patients without LVH (49 +/- 7 to 50 +/- 5%; NS). The change in lactate extraction was significantly correlated with the percentage change in diastolic arterial pressure (r = 0.77, P < 0.001). 4. These results suggest that sublingual nifedipine, even at the low dose of 5 mg, may cause myocardial ischaemia in some elderly patients with LVH that is associated with a marked reduction in coronary perfusion pressure.

Administration, Sublingual↗

Troponin T in the coronary sinus and percutaneous transluminal coronary angioplasty related myocardial injury.

1. Myocardial injury has been shown to be associated with successful percutaneous transluminal coronary angioplasty (PTCA). The present study was designed to determine whether uncomplicated successful PTCA results in myocardial injury by measuring coronary sinus (CS) cardiac troponin T (cTnT). 2. We measured cTnT in the CS and the femoral vein (FV) in 16 patients with stable angina pectoris who underwent uncomplicated PTCA for stenotic lesions of the left anterior descending artery. Blood samples were drawn from both the CS and FV before and immediately after PTCA and every 4 h for the next 12 h. 3. All patients had chest pain and electrocardiographic ST segment elevation or depression during balloon inflation and higher peak elevation of cTnT in the CS than in the FV (0.054 +/- 0.059 vs 0.036 +/- 0.022 ng/mL; P < 0.05). However, all CS cTnT levels were within the normal range over the 12 h period. 4. The fact that CS cTnT measurements showed no evidence of uncomplicated PTCA-related myocardial injury led us to conclude that uncomplicated successful PTCA does not cause myocardial injury.

Aged↗

Hypoxia and induced mutations in Syrian (golden) hamsters. The origin and perpetuation of a species.

We were able to identify anomalous chromosome patterns-monosomy, trisomy, and polyploidy-in metaphase plates prepared from embryos of Syrian hamsters (Mesocricetus auratus) whose mothers had been exposed to low-pressure hypoxia during the hours after copulation. These females were exposed in a low-pressure chamber for 4 hours at pressures equivalent to 30,000 feet of altitude before (estimated) ovulation to create acid shifts of pH equilibrium in the milieu of newly released eggs during passage of sperm upward, during fertilization itself, and during early cleavage stages. The D group chromosomes were most frequently involved in both monosomy and hyperdiploidy. The easily identifiable X chromosome also appeared to be susceptible to aneuploid formation. Chromosomally abnormal patterns most frequently among sibling embryos conceived by aging mothers exposed to low-pressure hypoxia. The significance of induced mutations is discussed.

Animals↗

Trisomies and triploidies in hamster embryos: induction by low-pressure hypoxia and pH imbalances.

The authors produced trisomic and triploid embryos by mating hamster females approximately 1 hr before estimated ovulation and subsequently submitting them to low-pressure atmospheres equivalent to those found at mountain altitudes for 6 hr. During hypoxic exposures in the low-pressure chamber, the continuous monitoring of pH levels--both subcutaneously and intramuscularly--registered pH decreases from inital values as high as 7.6 to below 6.9. These findings indicate that trisomies in some embryos and triploidies in others have their origin in different, but related mechanisms involving maternal pH imbalances between ovulation and fertilization.

Acid-Base Imbalance↗

Lack of teratogenic and mutagenic effects of nitrite on mouse fetuses.

To assess embryotoxic effects of sodium nitrite, pregnant ICR mice were given drinking water containing sodium nitrite at a concentration of either 100 or 1000 mg/L on days 7-18 of gestation. There were no significant differences between treated and control groups in measures of developmental toxicity, e.g., litter size, fetal weight, and number of resorbed or dead fetuses. The incidences of external and skeletal malformations in fetuses of treated groups were not significantly different from those in the controls. No significant increase was observed in the frequency of gaps and breaks of liver cell chromosomes in fetuses exposed in utero to sodium nitrite. Teratogenic and mutagenic effects of sodium nitrite were absent in mice at the doses used.

Animals↗

Degeneration of the posterior columns of the spinal cord: postmortem MRI and histopathology.

Postmortem MR images of two cases of posterior column degeneration were correlated with histopathological findings. The abnormal MR findings were volume loss and high signal intensity of the posterior columns associated with mild deformity of the dorsal surface of the spinal cord, corresponding to tract degeneration on histopathological examination. These results strongly suggest that further development of MR technique will permit in vivo detection of posterior column degeneration.

Adult↗

Protective immunity of gene-deleted SHIVs having an HIV-1 Env against challenge infection with a gene-intact SHIV.

We constructed three simian-human immunodeficiency viruses (SHIVs) lacking regulatory gene(s) and analyzed their induction of protective immunity against challenge infection with gene-intact SHIV in rhesus macaques. Inoculation of SHIV-dn lacking nef and SHIV-drn lacking nef and vpr induced transient viremia, while that of SHIV-dxrn lacking nef, vpr, and vpx induced no viremia. The SHIVs with fewer deletions were more effective in inducing neutralizing antibodies and cytotoxic T lymphocyte responses. When these macaques were challenged with parental gene-intact SHIV-NM-3rN, all the SHIV-dn-vaccinated macaques and two of the four SHIV-drn-vaccinated macaques showed complete resistance. The other two SHIV-drn-vaccinated macaques and all SHIV-dxrn-vaccinated macaques did not show complete resistance, but they did show suppression of replication of the challenge virus. These results suggested that as more genes were deleted, protective immunity was decreased.

AIDS Vaccines↗

The influence of node-fibril morphology on healing of high-porosity expanded polytetrafluoroethylene grafts.

PURPOSE: To manufacture high-porosity expanded polytetrafluoroethylene (ePTFE) vascular grafts with the same internodal distance but different node-fibril morphology, and to evaluate their biologic behaviors in a canine carotid artery implantation model. MATERIALS AND METHODS: Several types of high-porosity ePTFE vascular grafts with the same inside diameter (4 mm) and wall thickness (650 microm) were manufactured under different heating, stretching conditions. The luminal surface and cross section of the grafts were photographed by scanning electron microscopy and the node-fibril structure was examined. Two typical types of high-porosity ePTFE vascular grafts were then selected and proceeded to an animal study. The test grafts were explanted after an interval of 12 weeks and subjected to histomorphometric analyses. RESULTS: The following two types of high-porosity ePTFE vascular grafts were selected; one had a through-pore structure extending from the outer to the inner surface and the other had a random-node architecture with tortuous path channels extending from the outer to the inner surface. The histomorphometric analyses of thrombus-free surface, thickness of pseudointima, cellular ingrowth, capillary ingrowth, and cellular proliferation revealed no significant differences between the grafts. CONCLUSION: In high-porosity ePTFE vascular grafts, graft healing enhanced by transmural tissue ingrowth may be not largely dependent on node-fibril morphology. This knowledge will be helpful to design a new type of high-porosity ePTFE vascular grafts available for clinical use.

Animals↗

Epidemiologic studies of stroke in Shibata, a Japanese provincial city: preliminary report on risk factors for cerebral infarction.

A 6.5-year prospective study of cerebral infarction among residents 40 years and older was conducted at the Akadani-Ijimino district in Shibata City, Niigata Prefecture, Japan. The response rate for the initial examination was 85% of 1,182 males and 93% of 1,469 females. Nine hundred and sixty males and 1,339 females who were initially free of stroke were followed up from July 1977 through December 1983. Statistically significant risk factors for cerebral infarction appeared to be age, elevated blood pressure, high R, ST-T changes and atrial fibrillation on ECG, and albuminuria. The ECG abnormalities and albuminuria were due to the high blood pressure persisted over a long period of time. The strength of association of blood pressure with cerebral infarction got weak in comparison with other factors, and funduscopic changes which had been regarded as a risk factor for stroke in 1965-1974 did not reach statistical significance because of the spread of the community-based hypertension control. Even in 1977-1983 when Japanese dietary habits were westernized, neither hyperlipidemia nor obesity appeared to be related to the development of cerebral infarction.

Adult↗

Neuronal and muscular inclusions in rats with hindlimb dysfunction after treating with difluorobenzhydrylpiperadine.

Rats showing an ataxic gait induced by 20 wk of treatment with 0, 30, or 60 mg/kg of difluorobenzhydrylpiperadine (DFBP), a detriazinyl metabolic of almitrine, were examined by light microscopy and transmission electron microscopy. Vacuolar degeneration associated with lamellar inclusions was observed in musculus soleus and m. interossei of the hindlimbs in DFBP-treated rats. The inclusions were also produced within sensory neurons, satellite and Schwann cells, and vascular endothelial cells of thoracic and lumbar dorsal root ganglia as well as muscle spindles of affected muscles. Membrane-bound vacuoles containing electron-dense granules were seen in the peripheral nerves. This study demonstrated neuronal and muscular toxicity of DFBP in rats.

Almitrine↗

Immunogenetical penetrance in patients with primary biliary cirrhosis.

Two family cases of primary biliary cirrhosis (PBC) followed by the existence of autoantibodies such as anti-mitochondrial antibody, anti-nuclear antibody and anti-thyroid antibody are reported. Case O M has typical PBC, however, case H E is complicated by asymptomatic polymyositis. Common haplotypes of human leukocyte antigen (HLA) were observed as A24-Bw61 in the family members of case O M who had autoantibodies. Only the mother of case H E had identical HLA haplotypes such as A2, Aw31, Bw46, Bw61, DRw8, DRw52 and DQw1. From these results, it can be suggested that immunogenetic penetrance might be associated with the occurrence of familial PBC.

Autoantibodies↗