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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 271 records · Page 15Linked to original sources

Image feature analysis of false-positive diagnoses produced by automated detection of lung nodules.

RATIONALE AND OBJECTIVES: To reduce the number of false-negative diagnoses by radiologists, the authors are developing a computer-aided diagnosis scheme for detection of lung nodules in digital chest images. In this study, the authors attempted to reduce the number of false-positive diagnoses obtained with a previous computer scheme by incorporating additional knowledge from experienced chest radiologists into the computer scheme. METHODS: The authors applied their previous computer scheme, using less-strict criteria, to 60 clinical chest radiographs; this yielded 735 candidate nodules (23 true nodules and 712 false-positive diagnoses). These candidates were analyzed using region-growing, trend-correction, and edge-gradient techniques to determine measures by which to quantify image features of candidate nodules. RESULTS: The 712 false-positive diagnoses represented various anatomic structures that were located throughout the chest image. From this analysis, we were able to decrease the number of false-positive errors from an average of 12 to approximately 5 per image without eliminating any true nodules. CONCLUSION: Our results show that incorporating knowledge from experienced chest radiologists into the computer algorithm will play an important role in the development of computerized schemes for the detection of pulmonary nodules.

Diagnostic Errors↗

Enhanced elimination of theophylline, phenobarbital and strychnine from the bodies of rats and mice by squalane treatment.

Our previous study suggested that squalane would be a good candidate for an antidote to reduce the toxicity of drug ingested accidentally at a high dose by enhancing the drug elimination from the body. In the present study, we investigated whether squalane given orally could enhance the elimination of theophylline, phenobarbital and strychnine which were administered parenterally to rats or mice. Squalane increased the fecal excretion of theophylline and reduced the serum level of the drug in rats. Squalane accelerated the fecal excretion of strychnine in mice. These results suggest that squalane may stimulate more the elimination of neutral (theophylline) or basic (strychnine) drugs which should be present in unionized form in intestinal lumen, than that of acidic drugs.

Algorithms↗

Mechanism of hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol to 11-oxo-delta 8-tetrahydrocannabinol. Evidence for hydration of the aldehyde formed.

Hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC) to 11-oxo-delta 8-THC was investigated. Hepatic microsomes from mice, rats, guinea pigs and rabbits catalyzed the oxidation of 11-OH-delta 8-THC to 11-oxo-delta 8-THC together with the formation of dihydroxy-delta 8-THCs oxidized at the 7-position or at the pentyl side chain of 11-OH-delta 8-THC. 11-Oxo-delta 8-THC formed under oxygen-18 gas was analyzed by gas chromatography-mass spectrometry (GC-MS) indicating that molecular oxygen was not significantly incorporated into the aldehyde formed. 11-Oxo-delta 8-THC formed from 11-18OH-delta 8-THC (18O/16O = 0.81 - 1.05) was also found to lose oxygen-18 from the molecule. These results suggest that 11-oxo-delta 8-THC is hydrated in the incubation mixture and the aldehyde oxygen is exchangeable with the oxygen atom of water. When 11-oxo-delta 8-THC was incubated with hepatic microsomes and phosphate buffer containing H2 18O (44 atom%), GC-MS analysis indicated the incorporation of oxygen-18 into the aldehyde recovered from the incubation mixture. The results suggest that the hepatic microsomes may facilitate the hydration of 11-oxo-delta 8-THC and exchange an oxygen atom of the aldehyde group with that of water in the incubation mixture.

Aldehydes↗

A new metabolite of 2,4,3',4'-tetrachlorobiphenyl in rat feces.

Metabolism in vivo of 2,4,3',4'-tetrachlorobiphenyl (TCB) was further studied using male Wistar rats. When the extract of feces of rats given TCB with chloroform was methylated and applied to gas chromatography (GC)-mass spectrometry (MS), a new metabolite was detected. The structure of this new metabolite was 4-hydroxy-2,5,3'4'-TCB based on both its retention time in GC and comparison of the mass spectrum with that of the synthetic sample. 4-Hydroxy-2,5,3',4'-TCB was assumed to be formed via a 4,5-oxide intermediate followed by NIH-shift of a chlorine atom at 4-position.

Animals↗

[Comparison of the effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic behavior in male mice].

The present study investigated whether there is any difference between the effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic behavior in male mice, using an ethopharmacological technique. Agonistic behavior was evoked using a resident-intruder paradigm. The effects of four doses of the following drugs were assessed in either resident or intruder mice: diazepam (vehicle, 1, 2.5 and 5 mg/kg, p.o.) and tandospirone (vehicle, 2.5, 5 and 10 mg/kg, p.o.). Residents and intruders were drugged on alternate test days, and all animals received different sequences of each of the drug conditions according to a random schedule. The injection-test interval was 30 min. When a resident mice were treated with either diazepam or tandospirone, the frequency of attack bite was suppressed significantly in a dose-dependent manner. When intruder mice were treated with diazepam, attack bites by untreated residents were significantly increased, whereas tandospirone was ineffective. Although diazepam caused a significant decrease in both locomotion and rearing, tandospirone did not cause motor dysfunction. These evidence indicate that tandospirone, a 5-HT1A receptor agonist, has different pharmacological properties from diazepam.

Agonistic Behavior↗

Metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl with liver microsomes of phenobarbital-treated dog; the possible formation of PCB 2,3-arene oxide intermediate.

1. Metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) was investigated in vitro using liver microsomes of one male beagle dog after phenobarbital treatment. 2. Three major metabolites were isolated and identified as 3-hydroxy-2,4,5,2',4',5'-HCB, 2-hydroxy-4,5,2',4',5'-pentachlorobiphenyl (PenCB), and 2-hydroxy-3,4,5,2',4',5'-HCB, by comparison of g.l.c.-mass spectrometry and 1H-n.m.r. data with those of authentic samples. 3. 2-Hydroxy-3,4,5,2',4',5'-HCB was found as a metabolite of 2,4,5,2',4',5'-HCB for the first time using dog liver microsomes. Present result indicate that this metabolite and the dechlorinated PenCB are derived from a metabolic intermediate, namely, 2,3-epoxy-2,4,5,2',4',5'-HCB. 2,3-Epoxide formation is a new metabolic pathway of PCB.

Animals↗

Pulmonary blastoma. Comparison between its epithelial components and fetal bronchial epithelium.

Three cases of pulmonary blastoma exhibiting biphasic epithelial and stromal patterns, and a case of fetal lung-type adenocarcinoma, were examined by immunohistochemistry and electron microscopy (EM) and compared with fetal bronchial epithelium in order to explore the multidirectional differentiation of their epithelial components. The glandular cells of all four tumors resembled fetal bronchial epithelial cells in the pseudoglandular stage. Neuroendocrine (NE) cells were also present; they were argyrophilic and expressed pan-NE markers, neurosecretory granules and peptide hormones. The neural cell adhesion molecule (NCAM) was strongly expressed on the cell membranes of glandular cells, as in the case of proximal bronchial epithelial cells at the pseudoglandular stage in fetal lung. Sialosylated Lewis X was also expressed, indicating that the epithelial cells were possibly of endodermal origin. Two of the four cases showed considerable immunoreactivity for alpha-fetoprotein (AFP). The epithelial cells of pulmonary blastomas may occasionally de-differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP. Tumor examination by immunohistochemistry and EM suggested that the glandular cells of the tumors may differentiate to some extent like those of fetal large bronchi at the pseudoglandular stage, but there was concordance and discordance in the expression of neuroendocrine and oncofetal markers between blastomatous tumors and fetal bronchial epithelium.

Aged↗

Sex difference in hepatic microsomal aldehyde oxygenase activity in different strains of mice.

Hepatic microsomal oxidation of 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC) and 9-anthraldehyde (9-AA) to the corresponding carboxylic acids was investigated using six strains of male and female mice (ddN, ddY, C57BL, DBA, C3H and ICR). No significant sex difference was observed in the activity toward 11-oxo-delta 8-THC except for ICR, whereas the activity toward 9-AA was significantly higher in female than in male of ddN, C57BL, DBA and C3H mice. The present study suggests that female specific form(s) of cytochrome P450 may be responsible at least in part for the microsomal oxidation of 9-AA, but not that of 11-oxo- delta 8-THC.

Aldehyde Oxidase↗

[Studies on cell proliferation activities in acute toxic lesions in the liver and pancreas of hamsters treated with N-nitrosobis(2-oxopropyl)amine].

Histopathology and cell proliferation activities in acute toxic lesions in the liver and pancreas of female Syrian hamsters given a S.C. injection of N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 100 mg/kg, were investigated. Histologically, at one day after administration, hypertrophy and focal necrosis of the hepatocytes were observed, whereas no remarkable changes were seen in the pancreas. At 7 days after administration, when diffuse hypertrophy, vacuolation and necrosis of the hepatocytes, and atypical hyperplasia of the bile duct were seen in the liver, hyperplasia of the pancreatic duct and focal necrosis and vacuolation of the acinar cells were noticed in the pancreas. Immunohistochemistry for both 5-bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) revealed remarkable increases of cell proliferation activities in the target cells for BOP toxicity, especially at 7 days after BOP treatment. Meanwhile, the number per nucleus of silver-stained proteins related to nucleolar organizer regions (AgNOR) was significantly increased in the target cells at both 1 and 7 days after BOP treatment. Thus, in the present study, it was suggested that acute toxic changes in the liver of hamsters treated with BOP precedes those in the pancreas. The speculation that AgNOR may be an indicator recognizing earlier alterations on acute BOP toxicity remains to be examined.

Animals↗

[A case of hydropneumothorax].

A 19-year-old girl was admitted because of fever, cough and suddenly occurred chest pain. One month earlier she had experienced a fever and cough, then she had felt sudden chest pain 2 weeks prior to the admission. A chest X-ray showed left pneumothorax and massive pleural effusion. A diagnosis of hydropneumothorax was made. In spite of the chest tube drainage, reexpansion of the lung was unsatisfactory. Thoracotomy and decortication of the lung resulted in good reexpansion. Histological finding revealed pleuritis due to bacterial peribronchial infection, which resulted in hydropneumothorax, namely an abscess ruptured to the pleural cavity.

Adult↗

Regiochemical differences in cytochrome P450 isozymes responsible for the oxidation of methylenedioxyphenyl groups by rabbit liver.

The cytochrome P450 isozymes catalyzing the oxidation of the methylenedioxyphenyl compounds methylenedioxybenzene (MDB) and methylenedioxyamphetamine (MDA) have been investigated in rabbit liver preparations. The aromatic ring in MDB undergoes both demethylenation to catechol and aromatic hydroxylation to sesamol, whereas that in MDA undergoes only demethylenation to dihydroxyamphetamine. Formation of catechol and sesamol from MDB in microsomal incubation mixtures was enhanced about 5- and 3-fold, respectively, by pretreatment of the rabbits with phenobarbital, which induced CYP2B4 and CYP4B1. The cytochrome P450 isozyme responsible for aromatic hydroxylation of MDB was induced by beta-naphthoflavone and was inhibited by alpha-naphthoflavone. Microsomal demethylenation of MDA was minimally sensitive to pretreatment of the rabbits with phenobarbital, beta-naphthoflavone, pyrazole, or rifampicin. However, MDA competitively inhibited the N-demethylation of erythromycin. Antibodies against CYP2B4, but not those against CYP4B1, caused a marked inhibition of the demethylenation and aromatic hydroxylation of MDB. Antibodies against CYP2C3 did not inhibit the demethylenation of MDA, nor did substrates or inhibitors of the CYP2D family except for bufuralol. MDB and MDA were both capable of forming metabolic intermediate complexes, and the rate of complex formation was accelerated by phenobarbital induction. Reconstitution experiments with CYP2B4 suggested that phenobarbital-inducible complex formation from MDA was not due to the carbene pathway involving the methylenedioxy group but was due to oxidation of the amino group. These results indicate that CYP2B4 oxidizes different regions of methylenedioxyphenyl compounds depending on their structure. MDB undergoes oxidation at the methylenedioxy group (major) and the benzene ring (minor). MDA is oxidized at the alkylamino side chain at the nitrogen and alpha-carbon. The results suggested that one or more constitutive isoforms (probably unknown) of cytochrome P450 present in rabbit liver microsomes are primarily responsible for MDA demethylenation but that CYP3A6 contributes slightly.

3,4-Methylenedioxyamphetamine↗

[Myocardial infarct size and left ventricular function in diabetic patients].

We determined the relationship between myocardial infarct size (MIS) estimated by electrocardiographic measurements of infarct size (QRS score) and left ventricular function estimated by angiographically left ventricular ejection fraction (EF). MIS estimated by QRS score were the same in both DM and NDM (5.2 +/- 0.5 vs 4.3 +/- 0.4: p greater than 0.05), but EF in DM was significantly lower than in NDM (43.1 +/- 1.4 vs 51. +/- 1.1%: p less than 0.05). There was clear linear correlation between MIS and EF in NDM (r = -0.71) but not in DM. EF was much lower in DM than in NDM even at the same QRS score level. There were no differences in blood pressure, serum lipid levels, age, and the site of the myocardial infarction. The most likely explanation for this appears to be due to a previous left ventricular disease in DM.

Aged↗

[Metabolite of 15-p-iodophenyl-3(R,S)-pentadecanoic acid (123I) in blood and urine].

We analyzed metabolites of 123I-BMIPP in blood and urine using rats, rabbits and human, while human samples were obtained from normal volunteers of Phase I clinical study. We estimated metabolic pathway of 123I-BMIPP as a myocardial metabolic imaging agent. Radioactivity accumulated in heart after administration gradually decreased and was mainly excreted to bladder via kidneys. The main radioactive component in blood was 123I-PIPA for any species and the urinary components were metabolic conjugates of 123I-PIPA. As results of these studies, we considered that 123I-BMIPP was metabolized to 123I-PIPA by alpha-oxidation process for the first step, follow by beta-oxidation process, then 123I-PIPA was released to blood from tissues. Moreover, 123I-PIPA in blood was conjugated with other compounds and excreted to the bladder.

Animals↗

[Slow releasing anticancer drug containing CDDP for intraoperative use in residual cancer cells].

We have already reported the slow releasing property and anticancer effect of Plachitin, which is reconstituted by combination of CDDP and chitin. This study deals in more detail with the slow releasing property, and the renal complications and the effectiveness for solid tumor were examined. After implantation of Plachitin subcutaneously in the abdominal wall, the platinum concentration in the different organs was measured. In the abdominal muscle around the implanted Plachitin, a high concentration of platinum was maintained until 8 weeks and the peak was 4 weeks after implantation. At the same time, the serum concentration of platinum remained low. In kidney, the platinum concentration resembled the levels in the abdominal muscle, but no renal dysfunction was found serologically or histologically. When Plachitin was implanted around the solid tumor, the survival rates were improved and the gain in tumor weight was suppressed as compared with the controls. From these findings, Plachitin seemed to be effective as a slow releasing anticancer drug for topical application.

Animals↗

[Five cases of Crow-Fukase syndrome].

We presented five cases of Crow-Fukase syndrome. Plasma cell hyperplasia or dyscrasia in bone marrow were recognized in all cases and localized bone lesion was seen in three cases. Thyroid dysfunction was seen in three cases; hyperthyroidism in one case and hypothyroidism in two cases, which was considered to be one of the characteristics though it has seldom been described in this disease. Two of four cases treated with prednisolone had good responses but two cases treated with interferon had no effect.

Adult↗

Lymphocyte-mucosal interaction of the middle ear mucosa.

The middle ear mucosa possesses immunologic features similar to those of the peripheral mucosa sites in the common mucosal immune system and after mucosal immunization, antigenspecific IgA-forming cells appear in the inflamed mucosa of the tympanic cavity. Recent investigations suggest that lymphocyte migration to lymphoid tissues is regulated by lymphocyte-high endothelial venules (HEV) interaction. However, the lymphocyte migration mechanism to the middle ear mucosa is still unclear. We investigated whether or not organ-specific determinants which lymphocytes bind with are present on the middle ear mucosa by in vivo and in vitro lymphocyte adherence assays by using fluorescein-labeled lymphocytes from various lymphoid tissues. Many lymphocytes from Peyer's patches and hilar lymphnodes adhered on the inflamed middle ear mucosa with or without mucosal immunization, while these cells were not found on the normal tympanic mucosa. The number of the cells was smaller than that in the gastrointestinal mucosa. Lymphocyte adherence to the middle ear mucosa was not suppressed by anti-T cell antibody. These findings suggest that the middle ear mucosa possesses organ-specific mucosal determinants which B-lymphocytes selectively bind with, and that those determinants which regulate lymphocyte migration to the middle ear mucosa differ from those of other mucosae in the gastrointestinal tract.

Animals↗