Exanthem subitum and human herpesvirus 7 infection.
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Biomedical subjects
Publications and source records attributed to K Ueda.
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Eighty-one patients with metastatic liver tumors were studied by ultrasound color Doppler flow mapping examination. Primary origins consisted of gastric (19 cases), colorectal (40 cases), breast (7 cases), pancreatic (3 cases), gallbladder (3 cases) cancers and the others (9 cases). Metastatic lesions originated from breast, gastric and colorectal cancers had higher detection rates, however no blood flow could be observed within metastatic liver cancers from pancreatic and gallbladder cancers. There were no differences among the maximum blood flow velocity (Vmax), the resistance index (RI) and the pulsatile index (PI) in various metastatic liver tumors. In case of colorectal cancers, metastatic lesions originated from moderately differentiated adenocarcinoma had significantly lower RI (p < 0.05) and PI (p < 0.01) than that from well differentiated adenocarcinoma. In conclusion, ultrasound color Doppler flow mapping examination is a useful method for evaluation of the blood flow within metastatic liver tumors and could offer the histological differentiation of the primary origins, in case of metastatic liver cancers originated from colorectal cancers.
Multidrug resistance in human cancer is associated with overexpression of the MDR1 gene, which encodes a plasma membrane energy-dependent efflux pump termed P-glycoprotein (or the multidrug transporter), which confers cross-resistance to multiple hydrophobic natural product cytotoxic drugs. We have previously shown in cotransfection experiments that activity of the human MDR1 gene promoter is modulated by Ras and p53, suggesting that expression of the MDR1 gene may be associated with the activation of oncogenes and/or functional loss of tumor suppressor genes during oncogenesis. To further characterize the effects of p53 on the MDR1 promoter, we have shown in the current study that the region of the promoter that is required for transactivation by p53 mutants overlaps with the region that is essential for basal promoter activity. In addition, we also have shown that several different p53 mutants transactivate the MDR1 promoter in several different cell types, including embryo fibroblasts derived from the p53-deficient (p53-l-) mice generated by gene targeting.
Fifty five children diagnosed as having high-risk acute lymphoblastic leukemia (ALL) between 1985 and 1988 were treated with protocol AL851. The agents used in the protocol were as follows: induction therapy: vincristine (VCR), prednisolone, daunorubicin (DNR) and l-asparaginase, consolidation therapy: an intermediate-dose methotrexate (MTX), central nervous system (CNS) leukemia prophylaxis: intrathecal MTX and 24Gy cranial irradiation, reinduction therapy: VCR, adriamycin, dexamethasone and high dose cytarabine (AraC), maintenance therapy: 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR and AraC. Patients received chemotherapy for 3 years after achieving complete remission (CR). CR was obtained in 51 patients (92.7%). Twenty-four of them relapsed after achieving CR (bone marrow 16, CNS 3 and testis 5). At median follow-up of 79 (range 64-102) months, the estimated 8-year disease free survival rate was 49.1 +/- 6.7%. Four patients relapsed at bone marrow during the first 6 months of the treatment, indicating that more intensive combination chemotherapy should be included in earlier stage of the protocol. The high incidence of testicular relapse (14.3% in boys) suggests that high-dose MTX or AraC should be needed for improvement of the prognosis of high-risk ALL patients.
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Clinical chemistry is one of the core subjects required to master for doctors willing to be certified as a specialist in clinical pathology or laboratory medicine. For the past several decades, clinical chemistry has developed so rapidly and widely into many disciplines, such as microchemistry, electrochemistry, immunochemistry, molecular biology and robotics, that it is no more easy even for specialists to understand details in its whole scope nor to utilize the variety of principles, techniques, and equipment. In fact, clinical chemistry today covers such a wide range of laboratory tests as immunoassays, drug monitoring, toxicology, pregnancy tests, and gene diagnosis, in addition to chemical or enzymatic quantification of thousands of substances. Under such enormous circumstances, the program of postgraduate training, particularly in clinical chemistry, should be aimed at raising the capability to fulfill current requirements in medical practice, scientific research, consultative education and laboratory management, as well as to pursue lifelong self-disciplinary education. This capability must be obtained not only in knowledge or skills but also in attitude.
Granisetron (3 mg/body) was administered immediately before single CDDP administration (80 mg/m2 or more) to 53 patients with lung cancer. This chemotherapy was performed a total of 73 times. Concerning Grade 2 or 3 nausea and vomiting, good conditions were observed on day 1 (day of treatment), most marked aggravation on day 2, and initiation of improvement on day 4. Vomiting was slight on day 1, most aggravated on day 2, but began to improve on day 3; good results were generally observed thereafter. Decreased appetite was slight on day 1, but was most aggravated on day 3 and 4; its recovery was delayed even until day 7. In the treatment for delayed emesis, comparison was made among the group treated with granisetron alone who did not require treatment for delayed emesis, the group with delayed emesis treated with granisetron, and the group with delayed emesis treated with drugs other than granisetron. Slightly better results were observed in terms of nausea, vomiting, and the frequency of vomiting in the group treated with granisetron alone on days 2 and 3. However, no significant difference was observed in decreased appetite among the 3 groups. Granisetron had no side effects and was safe. It inhibited vomiting, but measures to improve decreased appetite are needed.
To study the alteration of nuclear DNA content of cancer cells after peplomycin (PEP) treatment, DNA cytofluorometry was performed in combination with 3H-thymidine (3H-TdR) autoradiography using cultured A431 cells. The cells in the logarithmic growth were treated with PEP (1.25 micrograms/ml) for 24 hr, during the first 4 hr of which they were pulse-labeled with 3H-TdR (2.4 x 10(4) Bq/ml). After washing with PBS, the cells were then cultured without both PEP and 3H-TdR, fixed at different times and stained with propidium iodide (PI) for the auto-stage cytofluorometry, which enabled DNA content analysis for labeled and unlabeled cells by repeated scanning of the same cell population. The nuclear DNA content histograms demonstrated that A431 cells were mostly arrested in G2 phase of 4C stem line by treatment with PEP for 24 hr. This G2 block lasted up to 8 hr after removal of the drug, and thereafter, marked polyploidization associated with DNA synthesis occurred, showing almost no mitotic figures, while only a few cells returned to G1 phase via M phase. During the period of 72-120 hr, however, the fractions of advanced polyploid cells (DNA content > or = 8C) gradually decreased and the DNA content distribution pattern became eventually similar to the original one as seen before PEP treatment. From these results we hypothesized as follows: 1) At S-G2 boundary, there is some control mechanism that checks whether the cells, after S phase, can enter the M phase or not. 2) The cells, which are not permitted to enter mitosis by the control mechanism, show marked polyploidization. 3) Only the cells that enter into mitosis can live and proliferate, though the advanced polyploid cells die shortly. 4) This control mechanism might be related to the precision of DNA repair that is checked at the G2-M checkpoint.
A case of Borrmann type 4 gastric cancer responding to sequential methotrexate and 5-fluorouracil combined with cis-diamminedichloroplatinum (CDDP) is reported. A 57-year-old woman was admitted to our hospital complaining of abdominal fullness. Upper gastrointestinal series and gastrofiberscopy revealed almost the entire stomach was involved with Borrmann type 4 cancer. Gastrectomy could not be performed because of peritoneal dissemination. However, the patient responded to sequential methotrexate and 5-fluorouracil therapy and CDDP administration. She enjoyed more than one year of hospital-free survival period and survived for almost two years.
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Alternative splicing of a transcript of amyloid precursor protein (APP) gene generates at least three types of mRNA coding for APP770, APP751, and APP695; the former two harbor, while the latter one lacks a Kunitz-type serine protease inhibitor (KPI). We compared, by using the RNase protection technique, APP mRNAs expression between gray and white matters in the frontal lobe, with special reference to Alzheimer's disease (AD) and aging. The proportions (y) of APP770 plus APP751 mRNAs in the white matter were nearly twice as much as those in the gray matter, both in control (non-AD) and AD brains; the difference between the two matters was statistically significant. Furthermore, in the gray matter of control, there was a positive correlation (y = 1.07 x-57.1, r = 0.899) between the age (x) and the proportion (y), but not in the white matter where the proportion varied markedly among individuals. In AD brains, no significant correlation was found in either of the two matters. These results indicated that the APP mRNAs proportion in the gray matter may serve as a molecular index of the brain aging in non-AD persons.
Human MDR1 cDNA was introduced into the human cultured cells KB-3-1 and Schizosaccharomyces pombe pmd1 null mutant KN3. The drug sensitivity of KB-G2 and KN3/pgp, expressing human P-glycoprotein, was examined. KB-G2 was resistant to the peptide antibiotics valinomycin and gramicidin D as well as having a typical multidrug resistance (MDR) phenotype. KN3/pgp was resistant to valinomycin and actinomycin D, but not to adriamycin. The ATP-hydrolysis-deficient mutant did not confer KN3 resistance to these antibiotics. Human P-glycoprotein expressed in S. pombe seemed to lack N-glycosylation. The N-glycosylation-deficient mutant, however, conferred a typical MDR phenotype on KB-3-1. These results suggest that human P-glycoprotein functions as an efflux pump of valinomycin and actinomycin D in the membrane of S. pombe.
An assay for erythtocyte galactokinase based on high performance liquid chromatographic determination of galactose 1-phosphate (Gal-1-P) is described. The determination of Gal-1-P was applied to a post-column fluorometric detection of reducing sugars using arginine. This method is as sensitive and accurate as conventional radioisotopic methods, but needs no radioisotopic facilities. It requires only a small blood sample and is suitable as a follow-up test in neonatal screening.
Occurrence of the antibodies against human papillomavirus (HPV) 16 proteins E4 and E7 is specifically but independently associated with cervical cancer. To correlate HPV DNA and antibody data, we examined the biopsy specimens and sera, by polymerase chain reaction (PCR) and by ELISA, respectively, from 51 patients with cervical cancer (including 3 recurrent cases) and 22 with cervical intra-epithelial neoplasia. Consensus primers for the L1 region were used for PCR and bacterially expressed, purified fusion protein HPV-16 E4 and non-fusion protein HPV-16 E7 were used for ELISA. HPV-16 DNA and other HPV types were detected in 17 and 25, respectively, out of 51 cases of cervical cancer. Ten out of the 17 HPV-16-DNA-positives were positive either for anti-E4 or for anti-E7: positivities for anti-E4, for anti-E7, and for both were 6/17, 5/17 and 1/17 respectively. Three anti-E7-positives consisted of those for HPV-33, -52 and -58 DNA, suggesting that limited cross-reaction occurred between the HPV types. Among the HPV-16-DNA-positive cases of cancer, lymph-node or distant metastasis was recorded more frequently in the seropositives than in the seronegatives. Our results show that the HPV-16 anti-E4 or anti-E7 occurs in some, but not in all, of the HPV-16-DNA-positive cases, and support the hypothesis that the presence of the HPV-16 antibodies can be used as a marker for possible metastasis.
We established a reversed phase high performance liquid chromatographic (HPLC) method of assaying lymphocyte steroid sulfatase activity using estrone sulfate as the substrate. Application of this method for diagnosis of 8 patients allowed us to clearly distinguish the patients from the normal controls. This method is simpler and less expensive than the method previously reported, since neither radioisotope labeled substrates nor radioisotope facilities are required. We consider it to be easily used and widely available in most clinical laboratories.
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Understanding of the interactions between P-glycoprotein and multidrug resistance (MDR) reversing agents is important in designing more effective MDR modulators. We examined transcellular transport of several MDR modulators by using a drug-sensitive epithelial cell line, LLC-PK1, and its transformant cell line, LLC-GA5-COL300, which expresses human P-glycoprotein on the apical surface. Basal-to-apical transports of azidopine and diltiazem across the LLC-GA5-COL300 monolayer were increased and apical-to-basal transports were decreased compared to those across the LLC-PK1 monolayer, indicating that P-glycoprotein transports azidopine and diltiazem. Movements of nitrendipine and staurosporine across the epithelial monolayer were not affected by P-glycoprotein. These results suggests that some MDR modulators exert their inhibitory effect not only by blocking the initial binding of anticancer drugs but throughout the course of the transport process.