Very fast flagellar rotation.
Explore the source record for details and available documents.
Flagella↗
Biomedical subjects
S Kudo
Publications and source records attributed to S Kudo.
Contribution of gene conversion to the retention of the sequence for M blood group type determinant in glycophorin E gene.
M and N blood group antigens are presented by glycophorins A (GPA) and B (GPB) of the erythrocyte membrane. GPA expresses M or N blood group antigen depending on the allelic gene (GPAM gene or GPAN gene), while GPB expresses only the N antigen. M or N blood group antigen is specified by the first and fifth NH2-terminal amino acid residues in the mature proteins, encoded by the second exon of these genes. Glycophorin E (GPE) gene, another member of this gene family, has a genomic structure very similar to that of GPB. However, a predicted product of GPE gene carries M blood group antigen. To delineate evolutionary events leading to the formation of the sequences for M or N blood group type determinant in the members of human glycophorin gene family, the nucleotide sequences of a 1.45-kilobase pair region including the 3' part of intron 1, exon 2, and the entire intron 2 were compared for GPAM, GPAN, GPB, and GPE genes. Encompassing exon 2, there were identical sequences stretches of 139 and 138 base pairs between GPAM and GPE genes and between GPAN and GPB genes, respectively. The data of the entire sequences in this region revealed that the divergence of the sequence between GPE and GPA genes (2.14-2.49%) is less than that of the sequence between GPE and GPB genes (3.10%). The higher rate of divergence in this region was observed between GPA and GPB genes (3.79-3.86%). These results strongly suggest that GPE gene acquired the sequence for M blood group type determinant from GPAM gene through gene conversion after duplication of a progenitor gene common to GPB and GPE genes.
Alleles↗
Transcriptional activation of human leukosialin (CD43) gene by Sp1 through binding to a GGGTGG motif.
Human leukosialin (CD43) is expressed on the surface of hematopoietic cells in cell-type specific and differentiation-stage-specific manners. Previously we found that the sequence from -53 to -40 was critically involved in the promoter function [Kudo, S. & Fukuda, M. (1991) J. Biol. Chem. 266, 8483-8489]. A transient-expression assay using a chloramphenicol acetyltransferase reporter gene revealed that the promoter could confer a high basal transcriptional activity in both leukosialin-producing and non-producing cells. The transcription factor interacting with the promoter sequence was determined by DNase I footprinting and gel-mobility-shift assays. The nuclear extracts from both leukosialin-producing Jurkat cells and non-producing Hela cells showed a footprint on the 5' flanking region from -58 to -34. Gel-mobility-shift assays revealed that DNA-protein complexes were formed with both nuclear extracts, and these complex formations were inhibited by an oligonucleotide containing the Sp1-binding consensus sequence. Prior incubation of anti-Sp1 antibody with nuclear extracts in this assay resulted in the supershift of the band for the DNA-protein complex. In addition, the footprint produced by the purified Sp1 transcription factor was identical to those produced by nuclear extracts of Jurkat and Hela cells. The mutational analyses revealed that the binding affinities of Sp1 to mutated promoter sequences were parallel to the transcriptional activity of these promoter sequences. Transient expression analyses in Drosophila Schneider cells demonstrated that cotransfection with Sp1 expression plasmid increased the transcriptional activity. These results establish that Sp1 can bind to the promoter and positively regulates the expression of the leukosialin gene. Even the stable expression of CAT constructs in non-producing Hela cells showed high transcriptional activity. The leukosialin expression thus appears to be regulated by the unique mechanism, that is the repression of high basal transcriptional activity rather than the activation of the basal transcriptional level. Tissue-specific expression is probably achieved by suppression of the basal transcriptional activity in non-producing cells.
Animals↗
[Clinical study of drug-induced pneumonitis].
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Genomic organization of glycophorin A gene family revealed by yeast artificial chromosomes containing human genomic DNA.
Human glycophorins A, B, and E are members of the glycophorin gene family located at chromosome 4, band q31. These genes were apparently generated by two successive gene duplications, and the following evolutionary pathway was proposed based on the genomic sequences. First, the ancestral gene was duplicated, and one of the duplicated genes evolved directly into the GPA gene. Another duplicated gene acquired a 3' sequence from the precursor genomic segment and was then duplicated to yield glycophorin B and E genes (Onda, M., Kudo, S., Rearden, A., Mattei, M.-G. and Fukuda, M. (1993) Proc. Natl. Acad. Sci. USA 90, 7220-7224). Although the above hypothesis was proposed, it has been difficult to provide solid evidence for this, because no genomic clones studied encompass two members of the gene family. In this study we isolated several yeast artificial chromosome (YAC) clones encoding the entire region or a portion of this gene locus. The physical gene mapping was carried out by testing the presence of specific sequences using a polymerase chain reaction. Moreover, the YAC clones were digested by rare cutting restriction enzymes, and the resultant large DNA fragments were separated by pulse-field electrophoresis. Southern blot analyses of those DNA fragments were carried out using various probes encoding specific portions of glycophorin genes. The results obtained revealed that the distance between glycophorin A and B genes is almost the same as that between glycophorin B and E genes. Moreover, it was shown that no precursor genomic sequence was present in the sequences downstream from the GPB or GPE gene, suggesting that the duplication of glycophorin B/E progenitor gene was made through unequal crossing over homologous recombination. These combined results suggest that two duplication events took place tandemly to produce these three members of the glycophorin gene family.
Chromosomes, Artificial, Yeast↗
A novel ex vivo method for assaying adhesion of cancer cells to the peritoneum.
A novel ex vivo method to determine the cell adhesion of cancer cells to the peritoneum was described. The wells of a microtiter plate were filled with cell suspension and sealed using mouse peritoneum. The peritoneum was fixed using a plastic cover and the plate was turned upside down and incubated for cell adhesion. After incubation for 80 min, the plate was centrifuged and non-adherent cells were assayed by MTT assay. Human cancer cells (MKN28, MKN45, MKN74, KM12C and KM12SM) adhered to the mouse peritoneum as well as cells from mouse (Colon26) and the ratio of cells attached to the peritoneum was estimated to be between 12.8 and 66.4%. This simple method could be useful to investigate the adhesion molecule associated with peritoneal dissemination.
Animals↗
Photodynamic therapy and/or external beam radiation therapy for roentgenologically occult lung cancer.
BACKGROUND AND METHODS: Thirty-nine roentgenologically occult lung cancers in 29 patients were treated using photodynamic therapy (PDT) and/or thoracic radiotherapy (TRT) from January 1986 to March 1992. With the exception of one mixed-tumor case, all were squamous cell carcinomas. RESULTS: Initial PDT achieved complete responses in 25 of 39 (64%) of the cancers. Of the remaining 14 cancers that showed less than complete response (CR), 10 of the 14 (71.4%) showed a CR when subsequently treated with TRT, yielding an overall CR rate of 89.7% for cancers treated. Although nine patients experienced recurrences, six of these had CR when treated with PDT and/or TRT. To date, 22 patients are alive. Causes of death in the patients enrolled in this study are as follows: pyothorax (2); heart failure due to pulmonary hypertension (1); chronic respiratory insufficiency (1); subsequent primary brain cancer (1); and subsequent primary lung cancer (1). Only one died of primary lung cancer. CONCLUSIONS: These findings suggest that PDT and/or TRT may be used as an alternative to surgery in the treatment of selected patients with roentgenologically occult lung cancer.
Adult↗
Differentiation of Clara cells and pneumocytes of the rat by means of enzyme- and immunohistochemistry.
Localization of non-specific esterases, Cu-Zn superoxide dismutase and dehydropeptidase-I, in rat lung was investigated enzyme-cytochemically or immunohistochemically. Esterase was demonstrated in Clara cells, type II pneumocytes, and septal cells (or vitamin A-storing lung cells), to a somewhat lesser extent in type I pneumocytes and ciliated epithelial cells of the bronchioles, and to a minor extent in interstitial fibroblasts of the alveolar septum. Large amounts of esterase reaction product were deposited in the rough endoplasmic reticulum and the nuclear envelope in Clara cells, type II pneumocytes, and septal cells, in addition to smaller amounts in other organelles. No reaction product was found in macrophages (histiocytes) in alveolar septi and alveolar macrophages, except for the primary lysosomes or phagolysosomes and trace amounts in the Golgi vesicles, and none in endothelial cells of alveolar blood capillaries, except for primary lysosomes. Immunolocalization of Cu-Zn superoxide dismutase was generally limited to a particular area of Clara cells. A constriction occurred in the apical cytoplasm of Clara cells between an immunoreactive dome-like protrusion and the non-immunoreactive cytoplasm of the supranuclear area, and the dome-like protrusion appeared to be pinched off in a ball-like or oval form. Immunolocalization of dehydropeptidase-I was demonstrated in a dome-like protrusion or supranuclear area of Clara cells or throughout the cytoplasm and in the surface plasma membrane of mesothelial cells. The presence of these enzymes in Clara cells suggests a contribution to the detoxification system of the lung, together with cytochrome p-450-dependent monooxygenase systems.
Animals↗
APC and p53 mutations in de novo colorectal adenocarcinomas.
To investigate genetic features in small and flat colorectal carcinomas that arise de novo, we searched for genetic alterations in six sporadic tumors by examining their APC, K-ras, and p53 genes. Two of the six tumors carried detectable mutations within the mutation cluster region (MCR) of the APC gene; both mutations were predicted to cause truncation of the gene product. Four tumors carried mutations of the p53 gene; three were missense mutations in exon 5, and the other was a 3-bp deletion in exon 6. However, neither codon 12 nor codon 13 of K-ras contained detectable mutation in any tumors. Hence, as "adenoma-carcinoma sequence" model of development of colorectal carcinoma, inactivation of the APC and p53 genes appear to be involved in development of the de novo type of colorectal carcinoma even though the adenoma stage is not observed.
Adenocarcinoma↗
Efficacy of recombinant human granulocyte-macrophage colony-stimulating factor for chemotherapy-induced leukopenia in patients with non-small-cell lung cancer.
To assess the feasibility and efficacy of rhGM-CSF in ameliorating chemotherapy-induced leukopenia in patients with advanced non-small-cell lung cancer, we conducted a double-blind placebo controlled phase III study in a multicenter setting. Patients were eligible if they had cytologically or histologically proven cancer, no prior chemotherapy, stage IIIB or IV disease, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, an age of less than 76 years, and no symptomatic brain metastasis, disseminated bone metastasis, or previous vertebral/pelvic irradiation. The chemotherapy regimen consisted of mitomycin given at 8 mg/m2 on day 1, cisplatin given at 100 mg/m2 on day 1, and vindesine given at 3 mg/m2 i.v. on days 1 and 8 (MVP). If the granulocyte nadir count recorded after the first cycle of MVP was less than 1,000/mm3, patients were randomly assigned to receive recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo during the second cycle of MVP. The dose of rhGM-CSF was 125 micrograms/m2 given daily s.c. for 14 consecutive days starting on day 2. Of the 52 patients enrolled, 45 were evaluable. The nadir of granulocytes was significantly lower in the placebo group (P = 0.007). The period during which the granulocyte count was less than 1,000/mm3 was significantly longer in the placebo group (median, 6 vs 10 days; P = 0.04). The incidence of adverse effects related to rhGM-CSF, such as fever (> or = 38 degrees C) and skin rash, was significantly higher in the rhGM-CSF group (P = 0.011). The rate of response to chemotherapy did not significantly differ between the two groups. In conclusion, rhGM-CSF reduced the duration of chemotherapy-induced granulocytopenia. The clinical usefulness of this agent may be deminished because of the adverse effects encountered when it is used in combination with a moderately myelotoxic chemotherapy regimen.
Adult↗
Characterization of glycophorin A transcripts: control by the common erythroid-specific promoter and alternative usage of different polyadenylation signals.
Glycophorins A (GPA) and B (GPB) are specifically expressed in human erythrocytes and express MN and Ss blood group antigens. While the GPB gene produces one transcript, the GPA gene produces three or four transcripts of different sizes. To understand the mechanisms of production of the different transcripts and erythroid-specific expression, we characterized the transcripts and the transcriptional regulatory regions of the glycophorin A gene. The transcriptional start site was determined by primer extension and S1 nuclease protection analysis, and it was found that all of the transcripts start at one major site. The nucleotide sequence of the newly isolated longest GPA cDNA revealed several polyadenylation signal sequences. To determine which polyadenylation signals are utilized, cDNA clones encoding GPA were isolated from a cDNA library of human erythroleukemia cell line K562 and the 3'-regions of the cDNAs were specifically amplified by the polymerase chain reaction. These results showed that five different polyadenylation signals of the GPA gene are utilized and the size and abundance of the transcripts are consistent with those detected by Northern blot analysis of K562 mRNAs. The 5'-flanking sequence was found to contain several binding motifs for the transcription factors, which were also found in other erythroid-specific genes. These motifs include the binding sites for the GATA-1 and NF-E2 erythroid-specific transcription factors, in addition to Sp1 transcription factor. The 5'-sequence from -750 to +36 relative to the transcriptional start site could confer only a low basal transcriptional activity in K562 cells and Friend erythroleukemia cells. This activity was significantly increased after Friend erythroleukemia cells were differentiated by dimethylsulfoxide. These results suggest that the 5' region regulates the glycophorin gene expression in erythroid-specific fashion.
Amino Acid Sequence↗
Colorectal tumours and pit pattern.
AIMS: To investigate the morphological and histopathological associations between an individual pit seen on stereomicroscopy or magnifying colonoscopy and an individual crypt seen in histological sections; and to examine these associations in colorectal tumours. METHODS: Fourteen thousand and twenty three cases were examined by colonoscope at Akita Red Cross Hospital. The surface mucosal pits of the lesions were observed using a magnifying endoscope in vivo and the pits of the extracted specimens were observed in vitro using a stereo microscope. Histological diagnoses were determined by light microscopy: the pit patterns in 100 glands were analysed. RESULTS: Pit pattern was classified into seven principal types: (1) normal round pit; (2) small round pit; (3) small asteroid pit; (4) large asteroid pit; (5) oval pit; (6) gyrus-like pit; and (7) non-pit. There was a correlation between pit pattern and the structure of the underlying crypt or gland. Furthermore, there was an association between pit pattern and the histology of the cells in the gland. Macroscopically, types 3, 4, 5, and 6 were common in protruding lesions. Type 2 was common in depressed lesions. The non-pit pattern was recognised in both. The depressed lesions had invaded the deeper layers more rapidly than protruding lesions. CONCLUSIONS: There were associations between individual pits and crypts. The branching carcinoma gland is thought to be the result of malignant transformation of the adenoma gland. The straight carcinoma gland is thought to result from the normal gland becoming malignant. The gland of the small round pit is thought to change from normal to the straight carcinoma gland via malignant transformation.
Adolescent↗
Purification and characterization of cytochrome P450 3A enzyme from hepatic microsomes of untreated doguera baboons.
We isolated a form of cytochrome P450 (P450) from hepatic microsomes of untreated doguera baboons. The final preparation (referred to as P450 BLa) was apparently homogenous, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The estimated minimum molecular weight of P450 BLa was 50 kDa. The N-terminal amino acid sequence of P450 BLa (identified 10 residues) was identical with that of P450 3A8 purified from cynomolgus monkeys. This protein was cross-reactive with antibodies raised against P450 3A4 and P450 CMLc which were P450 3A enzymes purified from hepatic microsomes of humans and cynomolgus monkeys, respectively. P450 BLa was capable of catalyzing testosterone 6 beta-hydroxylation and zonisamide reduction. P450 BLa antibody inhibited the activity of testosterone 6 beta-hydroxylase, but not the activities of testosterone 16 alpha- and 16 beta-hydroxylases in liver microsomes of doguera baboons. From these lines of evidence we conclude that P450 BLa can be classified as part of the P450 3A subfamily and acts as a constitutive testosterone 6 beta-hydroxylase in hepatic microsomes of doguera baboons.
Amino Acid Sequence↗
[The importance of pain control with morphine for terminally ill patient care for at home].
From April 1987 to June 1994, 81 patients of terminally ill had been care at home. In these home care, 38 patients received pain control with morphine. In 29 patients, pain control had been started before home care but in 9 patients pain control had been started under home care. Routes of morphine administration were oral in 24 cases and rectal in 14 cases. In cases of oral routes, finally 2 cases converted to rectal routes and 2 cases converted to subcutaneous routes. Duration of treatment were from 2 days to 741 days (average 72 days). Dosage of morphine were 7.5 mg to 480 mg (average 116 mg). Two patients lived but 24 patients died at home and 12 patients died at hospital. We concluded that palliative care especially pain control with morphine was very important care for patients of terminally ill who wanted care at home and ultimately die at home. We had to make ourself master of method pain control with morphine.
Administration, Oral↗
[Flat & depressed type tumor].
Explore the source record for details and available documents.
Colonic Neoplasms↗
[Flat & depressed type tumors].
Explore the source record for details and available documents.
Colonic Neoplasms↗
Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. First communication: plasma concentration, distribution, metabolism and excretion of the new monoclonal antibody, regavirumab after intravenous administration in rats and rabbits.
TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was investigated in rats and rabbits. Plasma concentrations of radioactivity were shown to increase dose-dependently after 2, 10 or 50 mg/kg of 125I-labeled TI-23 was administered intravenously to rats. Their elimination of half-lives from plasma were 11-13 days. The radioactivity in plasma corresponded with the idiotype activity (antigenicity against idiotype antibody) of the monoclonal antibody. No significant difference was detected in plasma concentration and half-lives between male and female rats. Quantitative and qualitative distribution studies demonstrated that high radioactivity was distributed predominantly to the blood and blood-rich organs. The idiotype activity which remained in those tissues was attributable to the blood in the tissues. The radioactivity was mainly excreted in the urine as free iodine, and about 40% of the dose remained in the body. After the rabbits received 2 mg/kg of 125I-TI-23, the initial radioactivity in plasma was higher than in rats, and a larger distribution volume and shorter elimination half-lives of radioactivity in plasma were observed.
Animals↗
Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Second communication: distribution and elimination of the new monoclonal antibody, regavirumab after repeated administration in rats, and placental transfer and milk-passage study after single administration to pregnant and lactating rats.
TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The tissue distribution or pharmacokinetics of MCA C23 was investigated after repeated administration in male rats and single administration in pregnant and lactating rats. Radioactivity and MCA C23 idiotype activity (antigenicity against idiotype antibody) in plasma increased with weekly injections during repeated administration of 125I-labeled TI-23 (2 mg/kg/week). After the fourth injection, the plasma radioactivity concentration reached a steady state and the elimination half-life was determined to be 11.2 days. No significant difference was observed between the radioactivity and the idiotype activity in plasma, indicating that MCA C23 was stable in vivo. The plasma concentration curve after repeated administration corresponded with that simulated by the pharmacokinetic parameters obtained previously and the minimum steady state concentration (Css-min) at 168 h after repeated administration was about 33 micrograms eq. of MCA C23/ml. Trans-placental tissue distribution of radioactivity was investigated after single administration of 125I-TI-23 to 19-day pregnant rats. About 12% of the dose was transferred to the fetus and the idiotype activity remained in fetal tissues at 24 h after injection. In lactating rats, some radioactivity was secreted into the milk and the ratio of milk to plasma radioactivity reached 0.28 after a single administration of 125I-TI-23. Some MCA C23 idiotype activity was observed in the milk.
Animals↗