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Biomedical subjects

T Yokoi

Publications and source records attributed to T Yokoi.

At least 163 records · Page 9Linked to original sources

Giant splenic cyst with high serum concentration of CA 19-9. Failure of treatment with percutaneous transcatheter drainage and injection of tetracycline.

BACKGROUND: Recently, several cases of nonparasitic true splenic cyst with high serum concentration of carbohydrate antigen (CA 19-9) have been reported. CASE: We report a giant splenic cyst presenting with high serum concentration of CA 19-9 in a 21-year-old man without a history of previous trauma. Imaging techniques showed a huge monolocular cyst of the spleen, and laboratory data showed increased serum CA 19-9 levels (326 U/ml; normal, < 37 U/ml). Serologic test was negative for parasitic infection. These findings led us to the diagnosis of epithelial splenic cyst. Percutaneous transcatheter drainage and injection of tetracycline were performed for 2 weeks. The cyst shrank, and the serum CA 19-9 level decreased favorably. However, cystic fluid reaccumulated in a month. CONCLUSIONS: The accumulation of cystic fluid in splenic epithelial cysts may be attributable not only to the secretion of the lining cells but also to influx from the splenic sinuses.

Adult↗

Characterization of CYP2A6 involved in 3'-hydroxylation of cotinine in human liver microsomes.

Nicotine is primarily metabolized to cotinine, and cotinine is further metabolized to trans-3'-hydroxycotinine in human liver, which is a major metabolite of nicotine in humans. We studied the formation of trans-3'-hydroxycotinine from cotinine in human liver microsomes. trans-3'-Hydroxycotinine formation demonstrated single enzyme Michaelis-Menten kinetics (Km, 234.5 +/- 26.8 MicroM; Vmax, 37.2 +/- 2.4 pmol/min/mg protein). Significant correlation (r = .967, P < .001) between cotinine 3'-hydroxylase activities at low (50 microM) and high (1 microM) cotinine concentrations in 20 human liver microsomes suggested the contribution of a single enzyme to cotinine 3'-hydroxylation. The cotinine 3'-hydroxylase activity correlated significantly with immunoreactive cytochrome P450 (CYP)2A6 contents (r = .756, P < .01) and coumarin 7-hydroxylase activity (r = .887, P < .001). The cotinine 3'-hydroxylase activity was inhibited by coumarin, alpha-naphthoflavone, chlorzoxazone and anti-rat CYP2A1 antibodies. Microsomes of B-lymphoblastoid cells expressing human CYP2A6 exhibited cotinine 3'-hydroxylase activity. The Km value of the expressed CYP2A6 (264.7 microM) was almost identical to that of human liver microsomes. In conclusion, cotinine 3'-hydroxylation appears to be catalyzed solely by CYP2A6 in humans. Cotinine is a candidate for a new substrate for CYP2A6 in humans.

Aryl Hydrocarbon Hydroxylases↗

Primary cardiac lymphoma. No evidence for an etiologic association with Epstein-Barr virus.

OBJECTIVES: To report two cases of primary cardiac lymphoma, a rare extranodal lymphoma with an unknown pathogenesis, and to compare them to secondary B-cell cardiac lymphoma. DESIGN: Clinicopathologic features are described, using histologic and immunophenotypic examinations. The Epstein-Barr virus genome is detected by in situ hybridization. PATIENTS: Of 80 autopsied cases of malignant lymphoma identified at Nagoya (Japan) University Hospital, two patients with primary cardiac lymphoma and five patients with secondary cardiac B-cell lymphoma were selected. RESULTS: None of the seven selected cases showed immunodeficiency, autoimmune disorders, or chronic inflammatory processes. Primary cardiac lymphomas had B-cell phenotypes with mu and lambda chain monoclonality. Immunostaining for Epstein-Barr virus (latent membrane protein-1) and Epstein-Barr virus-encoded RNA-1 in situ hybridization did not demonstrate an association of these lymphoma with Epstein-Barr virus infection. The majority of secondary cardiac B-cell lymphomas were extranodal lymphomas and extranodal or serosal involvement was more prominent than nodal involvement. CONCLUSION: These findings suggest that primary cardiac lymphoma, unlike pyothorax-associated pleural lymphoma, appears to have no association with chronic inflammation or Epstein-Barr virus infection.

Aged↗

[Amyloidosis secondary to bronchiectasis].

A 77-year-old woman was hospitalized repeatly due to frequent hemoptysis and production of bloodly sputum for several years. Bronchography in 1989 revealed bronchiectasis. She had complained of abdominal pain and diarrhea since 1991, and her urine was first positive for protein in 1992. She was admitted to our hospital in October 1992 because of edema, anemia, and hypoproteinemia. Despite treatment, renal dysfunction and the gastrointestinal disorder progressed and she died in January 1993. An autopsy revealed diffuse depositions of amyloid in many organs, especially in the kidney and the gastrointestinal tract. This amyloid protein was identified as AA protein, which was suggestive of secondary amyloidosis. Bronchiectasis appears to have been the disease underlying this patient's amyloidosis.

Aged↗

Evaluation of handling methods in the histological diagnosis of Helicobacter pylori: the effect of filter paper.

OBJECTIVES: Few studies have evaluated the handling methods used in the histological diagnosis of Helicobacter pylori. Filter paper has conventionally been used as a receptacle for the biopsy specimen before fixation. The aim of this study was to determine the presence of any effect caused by the use of filter paper. METHODS: The study population consisted of 104 consecutive patients undergoing endoscopic examination. Two antral biopsy specimens from the same area were obtained from each patient. One specimen was put onto a piece of filter paper, and the other into a plastic case. The specimens were fixed overnight in buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin and Giemsa. A direct smear was also prepared from 77 patients by vigorously rubbing the filter paper on a glass slide and staining it with Giemsa. RESULTS: The detection rate of H. pylori was 47.1% (49 of 104) for the filter paper method, 56.7% (59 of 104) for the plastic case method, and 57.7% (60 of 104) for either of the two methods. Of the 60 positive patients, 11 filter paper specimens were negative, whereas only one plastic case specimen was negative. Statistical analysis revealed a significant difference between the two groups (p < 0.01). On the amount of H. pylori, the filter paper method showed a significantly lower grade than the plastic case method (p < 0.05). In the Giemsa-stained smears, H. pylori was identified in 17 (22.1%) of the 77 patients studied. CONCLUSIONS: Use of filter paper may decrease the sensitivity for detection of H. pylori infection. We recommend not using filter paper in the histological diagnosis of H. pylori.

Biopsy↗

Role of human cytochrome P4502A6 in C-oxidation of nicotine.

Nicotine is primarily metabolized to cotinine in humans. In this study, human cytochrome P450 (CYP) isoform involved in cotinine formation was identified. The formation of cotinine in 16 human liver microsomes was determined with a 50 microM nicotine concentration and with a cytosol preparation as a source of aldehyde oxidase. Cotinine formation in human liver microsomes significantly correlated with immunochemically determined CYP2A6 levels (r = 0.663, p < 0.05), coumarin 7-hydroxylase activities (r = 0.831, p < 0.01), and cotinine 3'-hydroxylase activities (r = 0.735, p < 0.01) that are responsible for CYP2A6. In inhibition studies, cotinine formation in human liver microsomes was inhibited by coumarin and rabbit anti-rat CYP2A1 antibody specifically. When the capability of microsomes of B-lymphoblastoid cells expressing human CYPs to perform biotransformation of nicotine to cotinine was determined, cDNA-expressed CYP2A6 exhibited the highest cotinine formation. The KMapp values from microsome expressing CYP2A6 cDNA were similar to the value obtained from human liver microsomes. The large interindividual variabilities in cotinine formation and immunochemically determined CYP2A6 levels were observed in human liver microsomes, suggesting genetic polymorphism of CYP2A6. Nicotine is a new in vivo probe for phenotyping of CYP2A6 in humans.

Aryl Hydrocarbon Hydroxylases↗

[Rapidly progressing BOOP in a patient with positive anti-Jo-1 antibody: response to corticosteroid pulse and immunosuppressant therapy].

A 61-year-old woman was admitted to our hospital with a two week history of knee-joint pain, dry coughing and dyspnea on exertion. A chest roentgenogram revealed bilateral patchy and infiltrative shadows. Laboratory examination revealed high CK and aldolase levels. Although myositic symptoms were absent, the respiratory symptoms rapidly worsened and respiratory failure developed. An open-lung biopsy and a muscle biopsy were done. The open-lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP), but the muscle biopsy specimen revealed non-specific findings. After 4 weeks of intravenous intermittent high-dose corticosteroid therapy, 50mg of cyclophosphamide was given daily, along with 20mg of prednisolone on alternate days. There were marked clinical, physiological and roentgenographic improvements. A test for anti-Jo-1 antibody was positive, which suggested that this patients had pulmonary manifestations of polymyositis/dermatomyositis. Although BOOP can have an indolent course and a good prognosis, it may rapidly worsen and respiratory failure may develop, in which case it should be treated aggressively with a combination of intravenous high-dose corticosteroids and immunosuppressants.

Antibodies, Antinuclear↗

Random errors in anthropometry.

In order to present basic information on the magnitude of and variance due to the random error in anthropometry, 219 measurement items were taken on 12 subjects twice by the same observer. The precision (i.e., consistency between the repeated measurements) was investigated for these measurement items. The reliability was quantified using mean absolute difference (MAD), technical error of measurement (TEM), and reliability coefficient (R). MAD and TEM are highly correlated with each other and both represent the magnitude of error. They are not correlated with R, which represents the proportion of error-free variance. Larger measurements tend to have absolutely larger but relatively smaller random errors and higher reliability in the size range of 1-10 cm. Imprecision is inherent in anthropometry of the living because of the fact that the human body is not rigid. This may be responsible for the above tendency. Relatively large MAD and low R may be due to small absolute size, landmarks difficult to locate precisely, soft tissue deformation, and the inconsistency of the posture of the subject.

Adult↗

Establishment of immortal hepatocytes from a CYP3A7-transgenic/p53-knockout mouse.

Immortal hepatocytes were established from a CYP3A7-transgenic/p53-knockout mouse. The cells could be maintained with shorter doubling time after culture for 1 month. Detectable amounts of CYP3A7 mRNA and the activity of 7-propoxycoumarin O-depropylase, one of the representative CYP3A activities, were present in the immortal hepatocytes. Albumin mRNA, which is specifically expressed in the liver, remained in these cells.

7-Alkoxycoumarin O-Dealkylase↗

Isolation and characterization of a new cDNA clone belonging to the cytochrome P450 2C gene subfamily in hamsters.

Cytochrome P450s are heme-containing proteins which evolved from an ancestral gene to form a large superfamily of enzymes. We previously isolated three distinct CYP2C cDNAs, namely CYP2C25, 2C26, and 2C27, from liver cDNA libraries of male and female Syrian hamsters. In the present study, we isolated another cDNA clone, assigned as CYP2C28, from the same male cDNA library. This cDNA consisted of 1556 nucleotides and encoded a polypeptide of 490 amino acids. CYP2C28 showed relatively low identities to other hamster CYP2C forms (71.4-72.6% in amino acid sequences) and showed the highest similarity to rat CYP2C24 (88.7%), while the other hamster CYP2C forms showed high similarities among themselves (> 90.2%). CYP2C28 protein expressed in yeast catalyzed the N-demethylation of aminopyrine and benzphetamine, but did not catalyze the hydroxylation of tolbutamide, testosterone, and progesterone. Northern blot analysis demonstrated that CYP2C28 mRNA was expressed in hamster livers 1 week after birth, when the other hamster CYP2C forms were not detectable. The level of CYP2C28 mRNA increased to 3 weeks and then decreased with time in males. The level in females was lower than that in males. In adult hamsters, CYP2C28 was induced almost threefold by administration of phenobarbital but not affected by 3-methycholanthrene. On the other hand, administration of pregnenolone 16 alpha-carbonitrile induced CYP2C28 in females but not in males. These results indicate that CYP2C28 is a unique form in the hamster CYP2C subfamily.

Amino Acid Sequence↗

Fetus-specific CYP3A7 and adult-specific CYP3A4 expressed in Chinese hamster CHL cells have similar capacity to activate carcinogenic mycotoxins.

To assess whether CYP3A4 and CYP3A7 have a similar capacity to activate carcinogenic mycotoxins, we established cell lines stably expressing human CYP3A4 and CYP3A7, which are adult- and fetal-specific forms of cytochrome P450 in human livers, respectively. Each cDNA was introduced into CR-119 cells which had been established by introducing guinea pig NADPH-cytochrome P450 reductase cDNA into Chinese hamster lung cells. The cell lines (4-line and 7-line) stably expressed the mRNA and the protein corresponding to CYP3A4 and CYP3A7, respectively. The concentration-response for aflatoxin B1 (AFB1) cytotoxicity in 4-line and 7-line, respectively, was compared. 4-10 and 7-40 cells were approximately 17- and 20 times more sensitive to AFB1 than the parental CR-119 cells, respectively. In addition, the sensitivities to AFB1 of both 4-10 and 7-40 cells were enhanced approximately seven times by the addition of 10 microM alpha-naphthoflavone, a known activator of CYP3A enzyme, while the sensitivities were suppressed approximately four times by the addition of 100 microM troleandomycin, which forms a metabolite intermediate complex with CYP3A enzyme. Moreover, both cell lines showed approximately 10 and 2 times higher sensitivity to sterigmatocystin and aflatoxin G1 than CR-119 cells, respectively. These results indicate that CYP3A4 and CYP3A7 have essentially similar capacities to activate AFB1, sterigmatocystin, and aflatoxin G1 to produce toxic metabolites.

Adult↗

A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody.

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.

Antibodies, Monoclonal↗

Occurrence of autoimmune antibodies to liver microsomal proteins associated with lethal hepatitis in LEC rats: effects of TJN-101 ((+)-(6S,7S,R-biar)- 5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy-6,7-dimethyl-10,11- methylenedioxy-6-dibenzo[a,c]cyclooctenol) on the development of hepatitis and the autoantibodies.

Long Evans Cinnamon (LEC) rats, that spontaneously develop hepatitis, were found to possess autoantibodies to liver microsomal proteins (anti-LM) before the development of hepatitis. Anti-LM antibody was assumed to appear in association with the lethal hepatitis in the LEC rats. Thus, the purpose of this study was to investigate the effects of an anti-hepatitis drug on the development of hepatitis and the occurrence of the antibody in LEC rats. Mortality, blood biochemical parameters and the titer of serum anti-LM antibody were measured. In control LEC rats, 4 of 8 rats died before 20 weeks of age. In rats treated with TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11 - methylenedioxy-6-dibenzo[a,c]cyclooctenol), 4 of 7 rats died of hepatitis, but the time of death was delayed by 7-10 weeks compared to the control rats. The titer of the anti-LM antibody increased 3-7 weeks before death in the non-survivors in control and TJN-101-treated rats, supporting the idea that anti-LM antibody occurs in association with acute lethal hepatitis.

Animals↗

Expression of CYP3A7, a human fetus-specific cytochrome P450, in cultured cells and in the hepatocytes of p53-knockout mice.

CYP3A7 is a major form of cytochrome P450 in human fetal livers. To elucidate toxicological significance of CYP3A7 in fetal livers, CYP3A7 cDNA was introduced into Chinese hamster lung (CHL) cells. Transformants carrying the CYP3A7 gene were more sensitive to mycotoxins than parental CHL cells. In additional studies, we established a hepatocyte cell line from CYP3A7-transgenic/p53-knockout mice. In hepatocyte cells from CYP3A7-transgenic/p53-knockout mice, CYP3A7 mRNA was expressed and the catalytic activity of CYP3A7 protein was detected. The cells are expected to show cytotoxicity to mycotoxins and teratogens. These cell lines provide a valuable panel for studying the fetal toxicities of chemicals in humans.

Animals↗

Hormonal regulation of the mRNA level of male-dominant cytochrome P450 (CYP2C27) in hamster livers.

Hormonal regulation in the expression of CYP2C27, a male-predominant form of cytochrome P450 in the hamster, was investigated. The mRNA level of CYP2C27 was five-fold higher in male than in female livers. The mRNA level was suppressed by both gonadectomy and hypophysectomy in male, while the mRNA level was increased by the same treatment in female, resulting in the disappearance of sex difference. In both sexes, treatment of the gonadectomized animals with testosterone induced the cytochrome over the level of sham- operated males. Treatment of the hypophysectomized animals with testosterone elevated the level in females. On the other hand, oestradiol did not show any effects on either the gonadectomized or the hypophysectomized animals of both sexes. Twice-daily injection of growth hormone to hypophysectomized animals restored the level in males. Continuous infusion of growth hormone to hypophysectomized animals suppressed the level in both sexes. These results indicate that the expression of CYP2C27 in hamsters is under the control of endocrine factors and suggest that the gonadal-pituitary axis pathway is a control mechanism as proposed in rats and mice.

Androgens↗