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Biomedical subjects

T Yokoi

Publications and source records attributed to T Yokoi.

At least 127 records · Page 7Linked to original sources

Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes.

Mequitazine [10-(3-quinuclidinylmethyl) phenothiazine] is a long-acting and selective histamine H1-receptor antagonist that is mainly biotransformed by human liver microsomes to yield hydroxylated and S-oxidized metabolites. Mequitazine hydroxylase was inhibited by propranolol and quinidine. Lineweaver-Burk plots for the hydroxylation and the S-oxidation indicated that the hydroxylation occurred with a low Km (0.72 +/- .26 microM) in human liver microsomes. Microsomes from genetically engineered human B-lymphoblastoid cells expressing cytochrome P450 2D6 (CYP2D6) efficiently metabolized mequitazine to the hydroxylated and S-oxidized metabolites. The results indicate that CYP2D6 isozyme is a major form of CYP responsible for the metabolism of mequitazine in human liver microsomes. Inhibition of CYP3A-catalyzed midazolam 1'-hydroxylase by various histamine H1 antagonists, including mequitazine, suggested that mequitazine and some other histamine H1 antagonists could also be inhibitors of CYP3A in human liver microsomes.

1-Propanol↗

[Subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with SMANCS].

Recently, subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein has been performed to treat hepatic infarction in subregion hepatocellular carcinoma (HCC). Here, we report subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with styrene maleic acid neocarzinostatin lipiodol (SMANCS) (SMANCS-TAE under balloon occlusion of the corresponding hepatic vein). This study included 9 patients with HCC who underwent SMANCS-TAE under balloon occlusion of the corresponding hepatic vein. In all patients, the therapeutic effects (TE) were evaluated according to the criteria of direct response to liver cancer treatment on abdominal computed tomography (CT) 3 weeks after surgery. In 7 patients who could be followed for more than one year, there was no postoperative relapse at the site of treatment. Furthermore, this procedure facilitated the detection of accumulation of SMANCS not only in the tumor but also in the subregion of the tumor in patients with HCC involving immature arterial tumor neoplastic vessels. In patients with large HCC complicated by severe heart failure showing a poor general condition, this procedure allowed treatment to be completed without complication. SMANCS-TAE under balloon occlusion of the corresponding hepatic vein, which can also embolize the portal vein by applying targeting chemotherapy with SMANCS, may cause necrosis not only in the tumor but also in noncancerous liver tissues. This procedure may be an indication for a larger number of cases than standard TAE, facilitating more complete local treatment.

Antineoplastic Agents↗

[Quality control in aspiration biopsy cytology].

Comparison and quality control of our experience of thyroid cytology (784 samples) and breast cytology (1,202 samples) were reported. False positive rate and other parameters were superior in breast cytology than thyroid. It may be due to the fact that cytological diagnostic criteria for follicular thyroid carcinoma from follicular adenoma is not established yet. More suspicious diagnosis in thyroid than breast also give low incidence of malignancy in thyroid suspicious diagnosis. As recommended by a guideline for both thyroid and breast cytology from the Papanicolaou society et al, conservative handling and protective diagnosis may help to reduce false positive and false negative rates.

Breast Diseases↗

Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors.

Endocrine tumors of the parathyroid and pancreas are encountered either as sporadic type or as part of multiple endocrine neoplasia type 1 (MEN 1). A high frequency of the loss of heterozygosity (LOH) has been observed in tumors of the sporadic type in the locus of the MEN 1 gene, which has recently been cloned and designated the menin gene. It would be of great interest to determine whether somatic mutations in the menin gene are responsible for the sporadic endocrine tumors. For this purpose, we have investigated the menin gene mutations in 21 sporadic parathyroid adenomas, 2 parathyroid carcinomas, 4 sporadic insulinomas, and 1 malignant VIP (vasoactive intestinal polypeptide)oma with WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome, using PCR-single strand conformation polymorphism analysis and DNA sequencing. In none of these cases did the patient have a family history or other possible association with MEN 1. We have discovered somatic point mutations in two parathyroid adenomas (A340T and A541T), in one insulinoma (T429K), and in the malignant VIPoma (W198X). In addition, we have found two polymorphisms (D418D and V367V) in two parathyroid carcinomas and two parathyroid adenomas. Of these mutations and polymorphisms, three (A340T, T429K, and V367V) are first reported here, in the present article. Our results indicate that somatic mutations of the menin gene are responsible for a proportion of the sporadic parathyroid adenomas and pancreatic islet cell tumors.

Adenoma↗

Pulmonary hypertension associated with systemic lupus erythematosus: predominantly thrombotic arteriopathy accompanied by plexiform lesions.

We report an autopsy case of pulmonary hypertension associated with systemic lupus erythematosus in a 48-year-old woman. After 8-year follow-up under a definite diagnosis of systemic lupus erythematosus, she experienced gradually developing exertional dyspnea with palpitation. Her chest x-ray showed clear lung fields with marked cardiac enlargement. A right cardiac catheterization revealed a pulmonary arterial pressure of 74/30 mm Hg (mean: 47). She was treated with repeated plasmapheresis, oral corticosteroid, and immunosuppressant without improvement, and she died suddenly, 23 days after admission. Pathological examination revealed that small pulmonary arteries and arterioles were diffusely involved by florid thrombotic lesions, which were characterized by intimal eccentric fibrous thickening, luminal occlusion with recanalization, and occasional fresh thrombi. In addition, some arteries showed plexiform lesions coexistent with intimal thrombotic lesions. Concentric laminar intimal fibrosis was not seen. No significant parenchymal change was seen. Our study not only adds a rare case of thrombotic pulmonary hypertension associated with systemic lupus erythematosus, but also suggests that plexiform lesions can occur in association with thrombotic arteriopathy.

Fatal Outcome↗

[A study on accuracy of rCBF measurements loaded with acetazolamide based on the microsphere model using iodine-123-IMP SPECT].

We studied the accuracy of the method for measuring regional cerebral blood flow (rCBF) loaded with acetazolamide based on the microsphere model using iodine-123-IMP (IMP) SPECT. Two methods were examined, the super-early microsphere method with continuous withdrawal of arterial blood using the SPECT image obtained 5 min after tracer injection and the early microsphere method with one-point arterial sampling using the SPECT image obtained 30 min postinjection. On five subjects, after acetazolamide administration we measured rCBF by the analysis based on the two-compartment model using the data derived from dynamic SPECT scans and the sequential arterial blood sampling after IMP injection. Values of rCBF obtained by both super-early microsphere method and early microsphere method were significantly correlated with those obtained by the two-compartment model analysis (r = 0.982, 0.930, respectively). We conclude that it is possible to use the method based on the microsphere model in measuring rCBF loaded with acetazolamide. The early microsphere method with one-point sampling should be used clinically because of its simplicity and less-invasiveness.

Acetazolamide↗

[Anaphylactic shock associated with a central venous catheter impregnated with chlorhexidine and silver sulfadiazine].

A 28 year-old male patient developed anaphylactic shock on separate occasions, possibly due to the contact with a central venous catheter impregnated with chlorhexidine and silver sulfadiazine. He was successfully resuscitated. On the second operation, blood basophils disappeared and plasma histamine level increased extremely up to 80 ng.ml-1 soon after anaphylactic shock. One year after the first shock, he did not develop anaphylactic shock following the insertion of a central venous catheter without the impregnation. Pin prick test and scratch test showed positive reactions only to chlorhexidine. Latex-specific anti-IgE antibody was not detected. Therefore, chlorhexidine was confirmed as the causative agent of anaphylactic shock. Because chlorhexidine is extensively used as an antiseptic drug in emergency rooms and intensive care units, we should be aware of the possibility of chlorhexidine induced anaphylactic reactions.

Adult↗

[A case of fibromatosis needed reconstruction of the chest wall for postoperative local recurrence].

The case was a sixty-four-year-old female with a history of fibrous tumor in the right supraclavicular and neck region thirty years ago. A fibrous tumor developed in the right pleural cavity and was surgically resected. Since local recurrence occurred, the chest wall was partially resected including the tumor followed by reconstruction with a composite graft. This graft was made of hydroxyapatite filler wrapped with two sheets of Dacron fabric. A diagnosis of fibromatosis was made according to the study of the resected specimen, which showed unclear borders, homogenisity, poor evidence of nuclear atypia and mitosis in histological examination as well as negative finding of CD 34 in immunohistochemical examination.

Female↗

[Combined scatter and attenuation correction for 201Tl myocardial perfusion SPECT using OS-EM algorithm].

There are two possible ways to obtain scatter-corrected images with the ML-EM (maximum likelihood expectation maximization) algorithm: one is the subtraction of scatter estimate si from projection data pi, and then (pi-si) is used for scatter-corrected projection data (denoted as SC(T)); the other method is the addition of scatter estimate si to the projections calculated from the reconstructed image without performing data subtraction (SC(E)). This paper investigated these two ML-EM algorithms of combined scatter and attenuation correction on 201Tl myocardial perfusion SPECT imaging. Scatter windows were placed one full width at half maximum (FWHM) below and above the photopeak centerline. The scatter fraction in the primary peak was estimated using trapezoidal approximation by the triple energy window method. Phantom and clinical images were reconstructed using 6 iterations of ordered subsets EM algorithm (OS-EM). A cylindrical phantom with a cold-rod insert and a heart/thorax phantom with liver insert were used to evaluate scatter and the attenuation compensation technique. A cylindrical phantom filled with uniform 201Tl solution was used to evaluate statistical noise. The percent root-mean-square uncertainty (%RMSU) was used as a quantitative measure of noise amplification. %RMSU showed that the SC(E) method amplified noise less in comparison with the SC(T) method, however, no significant difference in image quality was observed between the two methods. In conclusion, both the SC(T) and SC(E) methods provided significant and similar improvement in the removal of scatter in 201Tl myocardial perfusion SPECT imaging.

Absorption↗

[Development of a high-resolution pinhole SPECT system using dual-head gamma camera for small animal studies].

We developed a high-resolution pinhole SPECT system using dual-head gamma camera (PRISM-2000XP) for small animal, and evaluated the performance of this system. Two pinhole-inserts (Pb) were mounted on the same unit, and it was not attached to the detector but the gantry of gamma camera. We designed two kinds of pinhole collimators with different rotating radii, 40 mm (Type-I) and 50 mm (Type-II). The diameter of the pinhole is 1 mm for both types. The field of view (FOV) and magnification were 45.8 mm phi and 4.25 for Type-I, 57.4 mm phi and 3.40 for Type-II, respectively. We measured full width at half maximum (FWHM) of line spread function using a 99mTc line source. Measured FWHM values were 1.65 mm using Type-I and 1.91 mm using Type-II at the center of FOV in the center slice. The volume sensitivity of this system was 8.54 kcps/MBq/ml (Type-I) and 5.68 kcps/MBq/ml (Type-II). We could observed 1.2 mm phi cold spot in the resolution phantom using Type-I. In conclusion, this system is available for SPECT measurement of small animal studies.

Animals↗

In vivo activation of aflatoxin B1 in C57BL/6N mice carrying a human fetus-specific CYP3A7 gene.

The in vivo activation of aflatoxin B1 (AFB1) was assessed by using two transgenic mouse lines, M2 and M10, in which the human fetus-specific CYP3A7 was expressed in the kidney (M2) and the liver (M10), respectively. Male mice of 8 weeks old from these two lines were treated with a single i.p. injection of AFB1 (4 mg/kg body weight). AFB1-N7-guanine adduct was quantified by high-performance liquid chromatography. DNA damage was measured using the alkaline elution technique 2 and 6 h after AFB1 treatment. Administration of AFB1 resulted in a significantly higher level of AFB1-N7-guanine in the livers of M10 transgenic mice compared with their nontransgenic littermates (16.5 +/- 4.2 versus 10.4 +/- 1.2 ng/mg DNA, P < 0.01). The level of this biomarker was also significantly higher in the kidney of the M2 mice compared with control mice (73.0 +/- 6.3 versus 50.2 +/- 9.5 ng/mg DNA, P < 0.01). Similar results were also observed with DNA damage expressed as normalized area above curve (NAAC) in the two transgenic lineages, e.g., NAAC values were significantly higher in the livers of M10 and the kidneys of M2 mice. A dose-response relationship of NAAC values was observed in the livers of M10 mice when treated with AFB1 at different doses ranging from 1 to 16 mg/kg body weight, whereas in nontransgenic mice, only slight but not statistically significant increases of NAAC values were observed. Both the mouse CYP3A11 and GST-Yc subunit were expressed at identical levels in these transgenic lines. The results of this study present further evidence that human fetuses are also under the carcinogenic attack of AFB1 as adults if exposed to this potent carcinogen.

Aflatoxin B1↗

Comparative analysis of clonality and pathology in primary and secondary hyperparathyroidism.

Parathyroid adenoma and hyperplasia are the most common causes for hyperparathyroidism, and distinction between them is controversial based on the current criteria for pathological diagnosis. We studied the clonality of hyperparathyroidism and its correlation with the pathological features, analysing 39 female patients with hyperparathyroidism. Clonality was successfully detected in 12 heterozygous cases by PCR amplification of PGK-1 gene. The 12 cases yielded 14 hypercellular glands, 8 affected by primary and 6 by secondary hyperparathyroidism. The results revealed that 7 of the 8 glands with primary hyperparathyroidism showed monoclonal proliferation. Only 1 gland pathologically diagnosed as adenoma showed a polyclonal pattern. In the 4 cases with secondary hyperparathyroidism, at least one monoclonal tumour was detected in each case. Our data indicate that monoclonal tumours are more common than expected in both primary and secondary hyperparathyroidism. Monoclonal tumours and polyclonal hyperplasia can co-exist in the same patient. Comparative study of the clonality and the pathological features showed that the clonality was consistent with the diagnosis of parathyroid adenoma, whereas it was in conflict with the diagnosis of hyperplasia with multigland involvement. One of the reasons for this is that we are ignorant of the true natures of hyperparathyroidism with multigland involvement.

Cell Line↗

Regression of superficial gastric MALT lymphoma with unsuccessful eradication therapy for Helicobacter pylori infection.

A 51-year-old man had a reddish flat granular lesion in the stomach on endoscopic examination. Histology of biopsied specimen confirmed the diagnosis of low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) and simultaneous infection with Helicobacter pylori. He was given antibiotic treatment. Five weeks later, endoscopy and histology of biopsied specimen showed eradication of H. pylori, and the tumor had regressed. Six months later, H. pylori reemerged, but the tumor had not recurred. After the second antibiotic therapy, H. pylori has been eradicated. The lymphoma has been in remission for 14 months.

Anti-Bacterial Agents↗

Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases. Nagoya BMT Group.

We identified eight patients with bronchiolitis obliterans (BO) in the autopsies of 81 bone marrow transplant (BMT) recipients. Rapidly progressive dyspnoea and cough were the main presenting symptoms in all eight patients, associated with overinflation and/or infiltrative opacity seen on chest X-ray and obstructive disorder revealed by pulmonary function tests. Early lesions were characterized by epithelial loss and an inflammatory infiltrate containing foamy histiocytes with mild luminal narrowing. Partial or total occlusion of the bronchiolar lumina by fibrous connective tissue was the feature of late lesions. Both changes were coexistent in all cases. In one case, small bronchi with cartilage were also affected by the obstructive process, showing bronchitis obliterans. All eight patients showed non-obstructive broncho-bronchiolitis characterized by denuding of respiratory epithelium, mural oedema and an inflammatory infiltrate in addition to BO, and these changes were also seen in 18 patients without BO. The submucosal glands of large bronchi and the trachea showed mucous retention and a mild inflammatory infiltrate in four of the eight patients. Coexistent infectious processes were seen in all cases, cytomegalovirus and Aspergillus being the most frequent organisms. BO probably develops as an immunopathological event related to graft-versus-host disease (GVHD) during the impaired immune status phase of the post-BMT period, possibly initiated by infection. Bronchial gland involvement in chronic GVHD is one of the factors responsible for this abnormal immune status.

Adolescent↗

Allelic variants of human calcitonin receptor in the Japanese population.

Evidence from cDNA cloning has shown that calcitonin receptors (CTRs) have seven potential transmembrane domains. In this study, structural analysis of CTRs from ten cultured human tumor cell lines and 117 human blood samples demonstrated allelic variants at the 1377th nucleotide in intracellular domain 4, expressing either proline or leucine as the 463rd amino acid. It was found that the variant with proline at this site was the more prevalent type of CTR among the Japanese population.

Alleles↗

Detection of Epstein-Barr virus DNA in gastric carcinoma with lymphoid stroma.

Gastric carcinoma with lymphoid stroma (GCLS) was considered to be one of the virus-associated neoplasms. However, the precise mechanism of Epstein-Barr virus (EBV) oncogenesis for GCLS remains unclear. We used polymerase chain reaction (PCR) and DNA in situ hybridization (ISH) methods to detect the presence of EBV DNA in 14 cases of gastric carcinoma, including 8 cases of GCLS. Epstein-Barr virus DNA was detected by both PCR and ISH in 3 of the 8 GCLS cases (37.5%) and was negative in the other 6 cases of non-GCLS. In situ DNA hybridization showed that the EBV DNA was in the carcinoma cells in all cases that were positive by PCR. Among the positive cases, one early gastric carcinoma showed that EBV DNA was not only in the carcinoma cells, but also in the normal epithelium. This study provides the interpretation of the finding of EBV DNA in nonneoplastic gastric epithelium. Some genetic changes may be initiated in the EBV-infected nonneoplastic cells, which would lead to oncogenesis.

DNA, Viral↗