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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 217 records · Page 12Linked to original sources
PubMed2000

Design and synthesis of the novel cross-linking reagents triggered by the triple helix formation.

In our attempt to new nucleobase analogs capable of interstrand cross-linking, we developed 2-amino-6-vinyl purine analog (1). The oligonucleotides incorporating 1 showed efficient interstrand cross-linking with selectivity toward cytidine at a target site. In this paper, we describe the design of the new cross-linking reagents (2) bearing 2-amino-6-vinyl purine motif, and triplex-directed alkylation with 2 to double-stranded DNA.

Alkylation↗
PubMed2000

A half-type ABC transporter TAPL is highly conserved between rodent and man, and the human gene is not responsive to interferon-gamma in contrast to TAP1 and TAP2.

TAPL is a half-type ABC transporter with sequence similarity to TAP1 and TAP2 that is transcribed in various rat tissues [Yamaguchi, Y., Kasano, M., Terada, T., Sato, R., and Maeda, M. (1999) FEBS Lett. 457, 231-236]. Primary structures of the human and mouse orthologous counterparts were deduced from cDNAs cloned by means of polymerase chain reaction, and they were compared with that of the rat. The mammalian TAPLs (rat, mouse, and human) are highly conserved, since about 95% of the amino acid residues are identical between rodents and man. Phylogenetic analysis demonstrated that the evolutional rate of TAPL is much slower than those of TAP1 and TAP2, although TAPL could have diverged from an ancestor of TAP1 or that of TAP1 and TAP2. The TAPL-GFP fusion protein transiently expressed in Cos-1 cells was co-localized with PDI, suggesting that TAPL is inserted into endoplasmic reticulum membrane. The conservation of the peptide-binding motifs of TAP proteins in TAPL raises the possibility that the TAPL might be a peptide transporter. The gene for human TAPL is assigned to chromosome 12q24.31-q24.32, while those for TAP1 and TAP2 are located at the MHC locus of chromosome 6p21.!3. Furthermore, the transcription of TAPL gene is not responsive to interferon-gamma, in contrast to TAP1 and TAP2. These results indicate that the gene regulation of TAPL is different from those of TAP1 and TAP2.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Long-term observation after transjugular intrahepatic portosystemic stent-shunt in two patients with hepatocellular carcinoma.

Two patients with hepatocellular carcinoma (HCC) were treated with transjugular intrahepatic portosystemic stent-shunt (TIPS) and followed for 22 and 58 months thereafter. HCC was well controlled by transcatheter arterial chemoembolization. Hepatic failure or metastasis, especially in the lung, was not observed in the long-term observation. TIPS seems to be useful even in patients with HCC, provided HCC is controlled.

Aged↗
PubMed2000

The role of osteopontin in the development of granulomatous lesions in lung.

Osteopontin (OPN) has been shown to be expressed by cells in granulomas of various origins, but whether it plays a functional role in granuloma formation is not known. Here we used a cardiomyopathic hamster (TO2) model, to test the hypothesis that OPN contributes functionally to granuloma development. We immunized cardiomyopathic and normal hamsters by subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, and assessed various tissues for both OPN RNA expression and granuloma formation. Cardiomyopathic hamsters expressed OPN, and formed granulomatous lesions, in heart tissue in both immunized and untreated animals. In addition, immunization induced expression of OPN in lung and lymph nodes of cardiomyopathic (but not normal) hamsters, and also induced granuloma formation in these organs. To test whether OPN expression could play a functional role in inducing granulomas, we produced an adenoviral vector containing the murine OPN gene, and introduced this vector intratracheally into the lungs of normal hamsters. The OPN-containing vector, but not the control vector, induced pulmonary granuloma formation. These studies provided direct in vivo evidence that OPN can contribute functionally to the formation of granulomatous lesions, and suggest that OPN expression may be a common factor involved in formation of granulomas of various origin.

Adenoviridae↗
PubMed2000

Human tissue distribution of TA02, which is homologous with a new type of aspartic proteinase, napsin A.

The N-terminal amino acid sequence of TA02 (molecular weight 35.0 kDa, isoelectric point 5.29), which is associated with primary lung adenocarcinoma, was determined and a fragment peptide was used to generate mouse monoclonal antibodies (mAbs) against TA02. The amino acid sequence suggested that TA02 might be homologous with napsin A, a new type of aspartic proteinase. In this context, we confirmed the expression of napsin A in primary lung adenocarcinoma using reverse-transcription polymerare chain reaction (RT-PCR) and showed that the TA02 mAbs reacted with glutathione-S-transferase (GST)-napsin A fusion protein. We concluded that TA02 is the same molecule as napsin A, and showed immunohistochemically that it is distributed mainly in type II pneumocytes, alveolar macrophages, renal tubules and exocrine glands and ducts in the pancreas. In particular, type II pneumocytes and alveolar macrophages showed high expression of TA02 among human normal tissues. In primary lung adenocarcinoma, 47 out of 58 (81.0%) primary lesions were positive. All well-differentiated adenocarcinomas except those of goblet cell type showed high expression of TA02. In addition, two out of seven (28.6%) large cell carcinomas showed low expression of TA02. The other histopathological types of primary lung cancer did not express TA02 at all. A few cases of renal cell cancer, pancreatic cancer, breast cancer, thyroid cancer, colon cancer and ovarian cancer showed low expression, but the staining patterns were completely different from that of primary lung adenocarcinoma, which showed a granular staining pattern. Our novel mAbs should be valuable for immunochemical detection of TA02/napsin A.

Adenocarcinoma↗
PubMed2000

Interleukin-8 levels and granulocyte counts in cervical mucus during pregnancy.

PROBLEM: We measured interleukin-8 (IL-8) and granulocyte counts in cervical mucus to assess local immunity and parturition. METHOD OF STUDY: We detected IL-8 by enzyme linked immunosorbent assay (ELISA) and Western blotting. Granulocytes were counted on a slide glass containing mucus from the external cervical os. RESULTS: ELISA and Western blotting revealed IL-8 in cervical mucus from both nonpregnant and pregnant women. There were no significant differences in cervical mucus IL-8 levels or granulocyte counts between follicular, ovulatory, and luteal phases. However, IL-8 and granulocyte counts were significantly decreased after menopause. IL-8 and granulocyte counts were increased significantly during pregnancy, and were further increased after 38 weeks of gestation and at labor. IL-8 levels were significantly correlated with granulocyte counts, based on the study of 678 samples (P <0.0001). CONCLUSION: IL-8 is involved in the increase of cervical granulocytes and in the process of parturition.

Adolescent↗
PubMed2000

Reduction of carotid arterial blood flow in ventricular septal defect associated with severe congestive heart failure.

After diagnosing abnormality of cardiac and carotid-cerebral circulation in an infant with isolated ventricular septal defect (VSD) associated with severe congestive heart failure, the authors measured the carotid arterial blood flow volume (CABF). At 3 months, the patient was not thriving and had dyspnea because of severe congestive heart failure. The authors measured the VSD size/body surface area (BSA) ratio relative to the predicted value of the left ventricular end-diastolic dimension (%LVEDd), left-to-right shunt ratio (Qp/Qs), and the small stroke volume (SV)/BSA using echocardiography and cardiac catheterization. The mean, maximum, and minimum CABF (mean CABF, maxCABF, and minCABF) among R-R intervals on electrocardiogram were measured by Doppler flowmetry in this patient and 5 healthy age-matched control children. The patient had a large VSD size/BSA ratio (37.9 mm/m2), %LVEDd (164%), and Qp/Qs (3.8), and a small SV/BSA ratio (18 mL/m2). The mean CABF, maxCABF, and minCABF were significantly lower than those of control children (VSD patient vs. controls; 2.7 +/- 0.4 vs. 4.5 +/- 0.6, 6.1 +/- 0.9 vs. 12.0 +/- 2.1, 1.2 +/- 0.2 vs. 1.7 +/- 0.4 mL/sec (mean +/- S.D.)), respectively (p < 0.01). The authors' results showed abnormal cardiac and carotid-cerebral circulation in an infant with large VSD associated with severe congestive heart failure.

Blood Volume↗
PubMed2000

Vascular permeability: quantitative measurement with double-echo dynamic MR imaging--theory and clinical application.

Double-echo dynamic magnetic resonance (MR) imaging was used to evaluate both vascularity and permeability of tissues simultaneously. Vascularity was evaluated on the basis of the T2*-shortening effect due to the intravascular fraction of the contrast agent and permeability on the basis of the T1-shortening effect due to the extravascular fraction. Meningioma was characterized on the basis of higher vascularity and neurinoma on the basis of higher permeability. The proposed method enables better tissue characterization.

Adult↗
PubMed2000

Diffusional anisotropy in cranial nerves with maturation: quantitative evaluation with diffusion MR imaging in rats.

PURPOSE: To investigate the correlation between diffusional anisotropy and developmental changes in anatomy, which include myelination, in central and peripheral nerves in an animal model by using quantitative diffusion magnetic resonance (MR) imaging and electron microscopy. MATERIALS AND METHODS: In vivo transverse and longitudinal apparent diffusion coefficients (ADCs) of the optic and trigeminal nerves in 2-10-week-old rats were measured with MR imaging. Then the animals were sacrificed at each time point, and transverse and longitudinal sections of optic and trigeminal nerves were studied with electron microscopy. RESULTS: In the optic nerve, the ADC parallel to the neurofibers increased with development and increased contemporaneously with myelination, while the ADC perpendicular to the nerve did not change. This resulted in a significant increase in diffusional anisotropy. There were no significant changes in ADCs in either direction in the trigeminal nerve. Longitudinal sections of optic nerve showed a marked change in the orientation of each fiber. As development proceeded, the axons, which initially followed tortuous courses, assumed straighter and more parallel orientations. Trigeminal nerves displayed straight parallel courses at 2 weeks that did not change over the study period. CONCLUSION: Changes in fiber anatomy in maturation from tortuous to straighter and more parallel orientation can account for changes in longitudinal ADC and in diffusional anisotropy.

Animals↗
PubMed2000

CT-guided needle biopsy of small pulmonary nodules: value of respiratory gating.

A respiratory gating technique was developed to allow computed tomography-guided needle biopsy of small pulmonary nodules. Twenty-three pulmonary nodules less than 15 mm in diameter underwent biopsy with the use of this technique. There were 14 true-positive, eight true-negative, and one false-negative result (diagnostic accuracy, 96%). The diagnostic accuracy for small nodules without this technique in a historical control was 69% (P: <.05).

Adult↗
PubMed2000

Effect of SOD-mimetic Fe-chlorine e6-Na on the level of brain lipid peroxide of rat fetal brains exposed to reactive oxygen species leading to intrauterine growth retardation.

The influence of oxidative stress in rat brain and liver on intrauterine growth retardation (IUGR) in rat fetuses was examined. Twenty pregnant Wistar rats were used. On the 15th day of pregnancy, uterine artery and vein were ligated bilaterally using a modified Wigglesworth method. On the 21st day of pregnancy, the fetuses were delivered by hysterotomy. Fetal blood was collected by cardiac puncture. Fetal brain and liver were removed for the analysis of lipid peroxide. Sham surgical operations were performed in the control rats. Within the ligated group, a superoxide dismutase mimicking substance, Fe-chlorine e6-Na (FeCNa), was injected intraperitoneally once a day from day 15 of gestation to day 20. Fetal blood, brain, and liver were stored at -70 degrees C until analysis. Control rats received an equivalent volume of saline. In growth-retarded fetuses, both superoxide released from erythrocytes and brain lipid peroxide showed significantly higher levels, but not superoxide dismutase in erythrocytes and liver lipid peroxide. These changes were alleviated by injection of superoxide dismutase-mimicking substance, FeCNa. Rat fetuses with intrauterine growth retardation suffered from a significant oxidative stress in utero. The increase in reactive oxygen species was alleviated by an injection of FeCNa.

Animals↗
PubMed2000

Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells.

Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.

Adipocytes↗
PubMed2000

Aortic stent-grafting with transrenal fixation: use of newly designed spiral Z-stent endograft.

PURPOSE: To evaluate the feasibility and efficacy of a newly designed stent-graft placed across the renal arteries for exclusion of abdominal aortic aneurysms (AAAs) with short or tortuous proximal necks. METHODS: Among a group of AAA patients treated with endovascular grafting, 5 had tortuous proximal necks and 13 had necks <20 mm (mean 13 mm). In these 18 cases, a 2- to 3-cm uncovered segment of the stent-graft was placed transrenally using a catheter inserted into the renal artery as a guide for graft margin positioning. A newly designed stent-graft was constructed from a custom-made spiral Z-stent covered with a thin-walled Dacron material; the endografts were deployed through 16-F (aortoaortic model) or 18-F sheaths (bifurcated devices). Renal function was assessed by preoperative and postoperative measurement of urea nitrogen and creatinine. Aneurysm exclusion and renal artery patency were evaluated during follow-up using spiral computed tomography and angiography. RESULTS: The stent-grafts were correctly placed at the intended site in all 18 patients. Renal function was not affected except transiently in 1 patient who developed bilateral renal artery stenoses 24 hours after the procedure; Palmaz stents were deployed in each renal artery to reestablish satisfactory blood flow. Of the 33 renal arteries crossed by the bare stent-graft segment, all were patent over a mean 14-month follow-up (range 7-24), including the patient with Palmaz stents implanted for postprocedural renal stenosis. Complete aneurysm exclusion was maintained in 15 (83%) of 18 patients; proximal leaks persisted in 3 patients, including 2 with severely angled proximal necks. CONCLUSIONS: Transrenal placement of the uncovered leading edge of custom-made spiral Z-stent-based endografts appears feasible and clinically effective in the treatment of AAAs with short or tortuous proximal necks.

Aged↗
PubMed2000

Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood.

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.

Adolescent↗
PubMed2000

Epoxide hydrolase affects estrogen production in the human ovary.

To investigate the mechanisms of ovarian cell differentiation, we raised a new monoclonal antibody, HCL-3, which reacted with human luteal cells. It also reacted with human and porcine hepatocytes. The immunoaffinity-purified HCL-3 antigen from human corpora lutea (CL) was shown to be a 46-kDa protein. The N-terminal 22 amino acids of the 46-kDa protein from porcine liver exhibited high homology (82%) to human microsomal epoxide hydrolase (mEH). The purified HCL-3 antigen from human CL or porcine liver showed EH enzyme activity, confirming that HCL-3 antigen is identical to mEH, which is reported to detoxify the toxic substrates in the liver. In human follicles, mEH was immunohistochemically detected on granulosa and theca interna cells. In the menstrual and pregnant CL, mEH was also expressed on large and small luteal cells. A competitive inhibitor of EH, 1,2-epoxy-3,3,3-trichloropropane, inhibited the conversion of estradiol from testosterone by granulosa cells cultured in vitro, indicating the involvement of mEH in ovarian estrogen production. Because anticonvulsant sodium valproate and its analogues were reported to inhibit EH enzyme activity, these findings provide a new insight into the etiology of endocrine disorders that are frequently observed among epileptic patients taking anticonvulsant drugs.

Adolescent↗
PubMed2000

Facile synthesis of a chitosan hybrid of a laminin-related peptide and its antimetastatic effect in mice.

Laminin, a cell adhesion protein, consists of three peptide chains (alpha-1, beta-1 and gamma-1). The beta-1 chain contains a Tyr-Ile-Gly-Ser-Arg (YIGSR) sequence that has been found to inhibit experimental metastasis in mice. We have prepared a hybrid of a water-soluble chitosan and a laminin-related peptide, and have examined its inhibitory effect on experimental metastasis in mice. A laminin-related peptide, acetyl-Tyr-Ile-Gly-Ser-Arg-betaAla-OH (Ac-YIGSRbetaA-OH), was prepared by a solid-phase method. Ac-YIGSRbetaA-OH was then reacted with a water-soluble chitosan. BetaAla is a spacer and was placed to avoid racemization of the Arg residue when the peptide was coupled with chitosan. Although chitosan has amino groups, they did not react with the peptide. Four methods were tried to achieve a coupling reaction, the diphenylphosphoryl azide method, the diisopropylcarbodiimide/1-hydroxybenzotriazole method, the water-soluble carbodiimide (WSC), and the 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) method, but all four methods were unsuccessful. Therefore, a small spacer, tert-butyloxycarbonyl-Gly, was intercalated in chitosan, by the TBTU method, to facilitate its coupling with the peptide. After removal of the protecting group, the Gly-chitosan was coupled with Ac-YIGSRbetaA-OH by the water-soluble carbodiimide method to give Ac-YIGSRbetaAG-chitosan. Conjugation of the peptide with the larger chitosan molecule did not reduce the inhibitory effect of the peptide on experimental metastasis in mice, it actually potentiated the antimetastatic effect, demonstrating that chitosan may be effective as a drug carrier for peptides.

Animals↗
PubMed2000

Amino acids and peptides. XXXV. Facile preparation of p-nitroanilide analogs by the solid-phase method.

p-Nitroanilides of amino acids and peptides are widely used as the chromogenic substrates for the determination of the activity of proteolytic enzymes. However, the preparation of a p-nitroanilide is not easy, in part due to the low nucleophilicity of the amino group of p-nitroaniline. A facile preparation of p-nitroanilide analog by the solid-phase method was investigated. 5-Amino-2-nitrobenzoic acid (Anb5,2) was used instead of p-nitroaniline (pNA) for preparation of p-nitroanilide analogs. Anb5,2 was introduced on a p-methylbenzhydrylamine resin without protection of the amino group of Anb5,2 by the 2-(H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) method in the presence of p-dimethylaminopyridine. The coupling reaction of a Nalpha-,NG-protected arginine with a Anb5,2-resin was difficult to achieve by common coupling methods (such as the carbodiimide and diphenylphosphoryl azide methods), but the phosphoryl chloride method was relatively successful. Synthetic benzoyl-Arg-Anb5,2-NH2 and benzoyl-Arg-pNA were hydrolyzed by trypsin and the both reaction mixtures exhibited same spectroscopic characteristics. H-D-Val-Leu-Arg-Anb5,2-NH2, an analog of human urine kallikrein substrate, was readily prepared by the solid-phase method. H-Arg-Anb5,2-OH and H-D-Val-Leu-Arg-Anb5,2-OH were also synthesized on a Wang resin by the solid-phase method. The aqueous solubility of these free-carboxyl materials was better than those of the corresponding amide analogs. 4-Amino-3-nitrobenzoic acid (Anb4,3) was also introduced on the p-methybenzhydrylamine resin, but the resulting H-Anb4,3-resin did not react with Nalpha,NG-protected arginine by any of the coupling methods.

Amino Acids↗