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Biomedical subjects

H Tanimoto

Publications and source records attributed to H Tanimoto.

At least 37 records · Page 2Linked to original sources

Hepsin, a cell surface serine protease identified in hepatoma cells, is overexpressed in ovarian cancer.

Extracellular proteases mediate the digestion of neighboring extracellular matrix components in initial tumor growth, allow shedding or desquamation of tumor cells into the surrounding environment, provide the basis for invasion of basement membranes in target metastatic organs, and are required for release and activation of many growth and angiogenic factors. We identified overexpression of the serine protease hepsin gene in ovarian carcinomas and investigated the expression of this gene in 44 ovarian tumors (12 low malignant potential tumors and 32 carcinomas) and 10 normal ovaries. Quantitative PCR was used to determine the relative expression of hepsin compared to that of beta-tubulin. The mRNA expression levels of hepsin were significantly elevated in 7 of 12 low malignant potential tumors and in 27 of 32 carcinomas. On Northern blot analysis, the hepsin transcript was abundant in carcinoma but was almost never expressed in normal adult tissue, including normal ovary. Our results suggest that hepsin is frequently overexpressed in ovarian tumors and therefore may be a candidate protease in the invasive process and growth capacity of ovarian tumor cells.

Carcinoma, Hepatocellular↗

Expression of the farnesyltransferase beta-subunit gene in human ovarian carcinoma: correlation to K-ras mutation.

The ras signaling protein requires a posttranslational modification to localize it to the inner surface of plasma membrane. In this state it can behave as a signal transduction mediator. Farnesyltransferase plays an important role in this posttranslational processing of ras by attaching a farnesyl group to the cysteine of the ras C-terminal tetrapeptide. In this study, we investigated the relationship of K-ras expression and mutation with farnesyltransferase beta-subunit expression in 20 ovarian tumors (17 carcinomas and 3 low malignant potential tumors) and 4 normal ovaries. The expression level of mRNA was determined by using quantitative PCR and mutation analysis was performed by direct cDNA sequencing. K-ras mutations were found in 1 of 3 low malignant potential tumors and in 4 of 17 carcinoma cases. K-ras mRNA overexpression was found in 1 of 3 low malignant potential tumors (one with mutated ras) and in only 1 of 17 carcinoma cases. Farnesyltransferase beta-subunit mRNA overexpression was found in 2 of 3 low malignant potential tumors and in 7 of 17 carcinoma cases. Interestingly, all K-ras mutation cases showed farnesyltransferase beta-subunit overexpression. These findings suggest that there may be a direct relationship between K-ras (ras dysfunction) mutation and expression of farnesyltransferase beta-subunit gene.

Alkyl and Aryl Transferases↗

Renal hemodynamic changes induced by captopril and angiotensin-converting enzyme gene polymorphism.

We studied the relationship between renal hemodynamic changes induced by a single acute administration of captopril (50 mg p.o.) and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in 27 healthy human volunteers, 7 with DD genotype, 10 with ID, and 10 with II genotype. The increase in effective renal plasma flow (p < 0.02) and the fall in renal vascular resistance (p < 0.01) in response to captopril were significantly less in subjects with the DD genotype than in subjects with the other genotypes. These data suggest that intrarenal ACE inhibition by captopril differs according to ACE gene ID polymorphism in healthy humans.

Adult↗

[Multi-drug antiemetic treatment and effect of treatment duration of concurrent steroids--for complete control of chemotherapy-induced nausea/vomiting in gynecological cancer].

Antiemetic effect and safety of concurrent administration of ondansetron and other antiemetics (dexamethasone, domperidone and ethyl loflazepate), given for complete suppression of nausea/vomiting, were examined in 46 patients (109 courses) with gynecological cancer receiving single high-dose of cisplatin or carboplatin. As for the delayed emesis, antiemetic effect depending on the steroid treatment duration, given concurrently to ondansetron, was compared. The results were as follows; 1. In 78 courses, anticancer drugs were given concurrently to cisplatin or carboplatin only on Day 1. In the remaining 31 courses, those drugs were concurrently administered up to Day 6 at the longest. 2. Complete suppression (i.e., no onsets) rate of acute emesis was 64.2% (70/109 courses) for nausea, and 84.4% (92/109 courses) for vomiting. 3. When the complete suppression depending on duration of concomitant steroid was examined mainly in patients receiving CAP (cyclophosphamide, adriamycin and cisplatin), higher antiemetic effect, especially in nausea, was observed in those on concomitant steroids for 3 days compared to that for 1 day. 4. The food intake rate improved along with nausea symptoms. 5. No adverse event or laboratory abnormality due to the multi-antiemetic treatment was observed. Based on the above, the efficacy of the antiemetic treatment in this study was confirmed. In delayed emesis, concurrent steroids given for 3 days after chemotherapy were considered effective and were also regarded to improve food intake.

Administration, Oral↗

Efficient promoter cassettes for enhanced expression of foreign genes in dicotyledonous and monocotyledonous plants.

A series of chimeric promoters for higher-level expression of foreign genes in plants was constructed as fusions of a gene for beta-glucuronidase (GUS) with the terminator of a gene for nopaline synthase (nos) or of the cauliflower mosaic virus (CaMV) 35S transcript, and the strength of these promoters was assayed in transient and stable expression systems in tobacco and rice. As parts of these promoters, the CaMV 35S core promoter, three different 5'-upstream sequences of the 35S promoter, the first intron of a gene for phaseolin, and a 5'-untranslated sequence (omega sequence) of tobacco mosaic virus were used in various combinations. In tobacco and rice protoplasts, all three fragments of the 35S promoter (-419 to -90, -390 to -90 and -290 to -90, relative to the site of initiation of transcription), the intron, and the omega sequence effectively enhanced GUS activity. Some chimeric promoters allowed levels of GUS activity that were 20- to 70-fold higher than those obtained with the 35S promoter in pBI221. In tobacco protoplasts, the two longer fragments of the 35S promoter were more effective than the shortest fragment. In rice cells, by contrast, the shortest fragment was as effective as the two longer ones. The terminator of the 35S transcript was more effective than that of the nos gene for gene expression. In transgenic tobacco plants, a representative powerful promoter, as compared to the 35S promoter, allowed 10- and 50-fold higher levels of expression on average and at most, respectively, with no clear qualitative differences in tissue- and organ-specific patterns of expression. When the representative promoter was introduced into tobacco with a gene for luciferase, the autofluorescence of detached leaves after a supply of luciferin to petioles was great and was easily detectable by the naked eye in a dark room.

Amino Acid Oxidoreductases↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1993)].

Bacteria isolated from respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981, and the Ikemotor et al. have been investigating susceptibilities of the isolates of various antibacterial agents and antibiotics, and the relationships between the isolates and backgrounds of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1993 to September 1994, 584 strains of bacteria were isolated mainly from sputa of 473 patients with respiratory tract infections and presumed to be the etiological agents. MICs of various antibacterial agents and antibiotics were determined against 91 strains of Staphylococcus aureus, 98 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 91 strains of Pseudomonas aeruginosa (non-mucoid), 34 strains of Pseudomonas aeruginosa (mucoid), 42 strains of Moraxella subgenus Branhamella catarrhalis, 25 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strain sfor which MICs of methicillin was higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 56.0%, but this frequency of the drug resistant bacteria was lower than the previous year's 61.4%. Arbekacin and vancomycin showed the highest activities against MRSA and MIC80s were 1 microgram/ml. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC90 was 0.063 microgram/ml. 3. H. influenzae All the drugs tested were quite active against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime among the cephems showed the most potent activities, and MIC90 were 0.063 microgram/ml against H. influenzae. Ofloxacin also showed MIC90 of 0.063 microgram/ml. 4. P. aeruginosa (mucoid) Tobramycin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Ceftazidime, cefsulodin, imipenem, aztreonam, gentamicin and ciprofloxacin showed potent activities with MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin showed the highest activity against P. aeruginosa (non-mucoid), and MIC80 was 1 microgram/ml, followed by ciprofloxacin with MIC80 of 2 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested had relatively low activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae. The activities of all drugs except ampicillin and minocycline were high against K. pneumoniae. Cefozopran, imipenem and carumonam showed the highest activities and MIC80s were 0.125 microgram/ml. Flomoxef showed the next highest activities with an MIC80 of 0.25 microgram/ml. 7. M.(B.) catarrhalis Imipenem showed the most potent activity against M.(B.) catarrhalis, with an MIC80 of 0.063 microgram/ml, followed minocycline and ofloxacin with their MIC80s of 0.125 microgram/ml. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological agents. As for patients background, there were many infectious diseases found among patients a high age bracket, and the patients over age 60 accounted for 61.3% of the diseases. The distribution by respiratory tract infections was as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest numbers of cases with 31.1% and 26.0%, respectively, followed by bronchiectasis with 10.4%. In this year chronic bronchitis under age 29 were 41.7%, thus was much higher than 12.5% in previous year. This marked change was first noted in your research during the recent 5 years. As for frequencies of etiologic bacteria by respiratory tract infections, S. pneumoniae (ABSTRACT TRUNCATED)

Aged↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1994)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981. IKEMOTO et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 23 institutions around the entire Japan, 492 strains of presumably etiological bacteria were isolated mainly from the sputum of 421 patients with lower respiratory tract infections from October 1994 to September 1995. MICs of various antibacterial agents and antibiotics were determined against 70 strains of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1. S. aureus. S. aureus strains for which MICs of oxacillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the highest activity against S. aureus with MIC80 of 0.5 microgram/ml. 2. S. pneumoniae. Most of the drugs tested showed potent activities against S. pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC80 was 0.063 microgram/ml. Erythromycin and clindamycin showed low activities with MIC80s > or = 256 micrograms/ml. Among these strains, however, 46.5% and 68.3% of strains, were quite sensitive toward these agents, respectively, with MICs of 0.063 microgram/ml. 3. H. influenzae. The activities of all drugs were potent against H. influenzae tested. Cefmenoxime a cephem, showed the most potent activity, the MICs of this drug against all of the 92 strains were 0.063 microgram/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of strains with MIC of 0.063 microgram/ml. 4. P. aeruginosa (mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 0.5 microgram/ml. Gentamicin, arbekacin and ciprofloxacin showed next potent activities, and their MIC80s were 2 micrograms/ml. 5. P. aeruginosa (non-mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (non-mucoid strains) with MIC80 of 2 micrograms/ml. Comparing to the activities against P. aeruginosa (mucoid strains), the activities of all the drugs tested were lower against P. aeruginosa (non-mucoid strains). 6. K. pneumoniae. Carumonam showed the most potent activity against K. pneumoniae with MIC80 of 0.063 microgram/ml. Cefozopran showed the next most potent activity with MIC80 of 0.125 microgram/ml. Ampicillin and cephems except cefpodoxime, cefozopran and cefditoren showed low activities and their MIC80s were > or = 16 micrograms/ml, and their MICs were all higher than > or = 4 micrograms/ml. 7. M. (B.) catarrhalis. Imipenem and ofloxacin showed the most potent activities against M. (B.) catarrhalis, their MIC80s were 0.063 microgram/ml. Erythromycin and minocycline showed the next highest activities with their MIC80s at 0.25 microgram/ml. Also, we investigated year to year changes in the background of patients, the respiratory infectious diseases, and the etiology of bacteria. Patients characteristics, in this period of investigation showed varieties of infectious diseases found in patients in a high age bracket, and the patients over age 60 accounted for 62.0% of all the cases. Different lower respiratory tract infectious were distributed as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest number of cases with 35.6%, 27.1%, respectively, followed by

Adult↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1992)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan since 1981, and Ikemoto et al. have been investigating susceptibilities of the isolates to various antibacterial agents and antibiotics, and the relationships between the isolates and characteristics of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1992 to September 1993, 690 strains of bacteria were isolated mainly from sputa of 549 patients with lower respiratory tract infections and presumed to be the etiological bacteria. MICs of various antibacterial agents and antibiotics were determined against 101 strains of Staphylococcus aureus, 121 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 92 strains of Pseudomonas aeruginosa (non-mucoid), 32 strains of Pseudomonas aeruginosa (mucoid), 52 strains of Moraxella subgenus Branhamella catarrhalis, 28 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strains for which MICs of methicillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 61.4% and the frequency of the drug resistant bacteria was higher than the previous year's 58.3%. MICs values indicated that arbekacin was as active as vancomycin against all the strains on S. aureus. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefazolin, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC80 was 0.015 microgram/ml. 3. H. influenzae All the drugs tested were potent against H. influenzae. Ampicillin among the penicillins showed MIC80 1 microgram/ml against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime showed the most potent activities, and MIC80s were 0.063 microgram/ml. The antimicrobial activity of ofloxacin was equivalent to those of cephems. 4. P. aeruginosa (mucoid) Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Cefsulodin, aztreonam, carumonam and tobramycin showed the next most potent activities with an MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin and ciprofloxacin showed the highest activities against P. aeruginosa (non-mucoid) with an MIC80s of 2 micrograms/ml. Norfloxacin also showed some activity, and MIC80 was 4 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested showed lower activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae The activities of all drugs except penicillins were high activities against K. pneumoniae. Carumonam showed the most potent activity with an MIC80 of 0.063 microgram/ml, followed by flomoxef, cefixime and cefozopran with their MIC80s of 0.125 microgram/ml. 7. M.(B.) catarrhalis Imipenem; carbapenems, showed the most potent activity against M.(B.) catarrhalis with an MIC80 0.063 microgram/ml. Minocycline and ofloxacin showed MIC80s 0.125 microgram/ml, respectively. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological bacteria. As for patients backgrounds, there were many infectious diseases found among patients in a high age bracket, and the patients over age 60 accounted for 60.8% of the diseases. The distribution by lower respiratory tract infections was as follows: bacterial pneumonia and chronic bronchitis accounted for the greatest numbers of cases with 30.4%, 29.5%, respectively, followed by bronchiectasis with 12.2%. As for frequencies of etiologic bacteria for respiratory tract infections, H. influenzae: 22.2%, and S. pneumoniae: 15.1% in chronic bronchitis; S. pneumoniae: 2

Anti-Bacterial Agents↗

[Effect of intravaginal administration of cisplatin (CDDP) suppositories to uterine cervical cancer--blood and tissue concentrations and the therapeutic effects].

Four patients with cervical cancer (squamous cell carcinoma: two cases of stage Ib, one of stage IIa, adenocarcinoma: one of stage Ib), were treated preoperatively by intravaginal administration of CDDP (20 mg) suppositories with pessary 7 times every other day. The uptake, distribution and antitumor effect of CDDP were investigated. Results were as follows. 1) Serum total platinum (Pt) concentration varied between individual patients. Cmax profile (0.17-0.57 micrograms/ml) of Pt was observed at 12 hours after the total dose of 140 mg administration in all patients. 2) The tissue Pt concentration showed high values in the cervix (average 55.4 micrograms/g), followed by the vagina (13.13), endometrium (3.17), uterine wall (0.64), ovary (0.57), lymph node group: parametrial (1.14), obturator (0.34), inguinal (0.28), external iliac (0.51), internal iliac (0.42) and common iliac (0.54). Para-aortic node value was too low to detect. 3) Colposcopic findings were disappearance of bleeding and reduction of tumor outgrowth. Microscopic findings were degeneration and necrosis of cancer nest from the surface to about 2 mm depth of the cervix. In conclusion, it may be necessary to improve CDDP penetration from the tumor surface for effective local chemotherapy.

Adenocarcinoma↗

Characterization of the currents induced by sigma ligands in NCB20 neuroblastoma cells.

Electrical and pharmacological properties of currents induced by compounds having affinities for putative sigma receptors were investigated with NCB20 cells by use of the whole-cell patch-clamp technique. Antipsychotics and naloxone induced inward currents with a decrease in membrane conductance at a holding potential of -60 mV. The rank order of potency for compounds inducing these currents was bromperidol > haloperidol > mosapramine = clocapramine > carpipramine > chlorpromazine > remoxipride > naloxone. Sulpiride, which does not have affinity for sigma receptors, induced inward currents only slightly. Haloperidol-induced currents were not affected by the pretreatments with 10 microM of sulpiride, dopamine, atropine, N-methyl-D-aspartate, 2-amino-7-phosphonoheptanoic acid, morphine or A23187, 100 nM of ICS 205-930, 100 microM of forskolin, 1 microM of phorbol-12,13-dibutyrate, or 100 ng/ml of cholera or pertussis toxins. The reversal potential of the currents induced by haloperidol, naloxone or remoxipride was dependent on the concentration of external or internal potassium. These results indicate that the currents induced by the tested compounds are due to blockade of tonic, outward potassium currents and suggest that these agents act on putative sigma receptors and that the second messenger systems within the cell are not essential for the coupling between the receptors and the channels.

Animals↗

[Antiemetic efficacy of the repeated use of granisetron in multiple cycles of anti-cancer chemotherapy].

Twenty-three patients with gynecological cancer who were treated with 85 cycles of cytotoxic chemotherapy containing platinum received intravenous granisetron repeatedly. Granisetron (3 mg/body) was drip-infused twice for each cycle at a 24-hour interval. The antiemetic efficacy was evaluated and compared for each day and each cycle, and analysed using the chi-square and H tests. There were no significant differences between the first cycle and the subsequent second through fifth cycles in the severity of nausea and the frequency of vomiting. The latter tended to increase in the second day of each cycle. These results indicated that granisetron does not decrease in antiemetic efficacy by repeated administration during multiple cycles of anti-cancer chemotherapy.

Carboplatin↗

Invasive human T lymphoma cells produce a novel factor that upregulates expression of adhesion molecules on endothelial cells.

The interaction between lymphoma cells and vascular endothelial cells (EC) is the first critical step in the invasion of lymphoma cells. We found that invasive human CCRF-CEM T lymphoma cells (CEM) released a factor that upregulates the expression of adhesion molecules on vascular EC. The supernatant of CEM (CEM-SUP) increased the expression of both ICAM-1 and ELAM-1 in time- and dose-dependent manners as shown by cell enzyme-linked immunoabsorbent assay (ELISA). In contrast, the induction of VCAM-1 on EC with CEM-SUP was relatively weak. No activity for interleukin-1 alpha (IL-1 alpha), IL-1 beta, interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha), which are known to augment ICAM-1 expression, was detected in CEM-SUP by ELISA. In reverse transcriptase polymerase chain reaction (RT-PCR) assay, CEM expressed a minimum amount of TNF-alpha mRNA, but absolutely no IL-1 beta or IFN-gamma mRNA. In addition, antibodies for cytokines did not inhibit the upregulatory effect of CEM-SUP. Semipurified CEM-SUP further increased the cellular binding between CEM cells and EC in vitro. This factor was stable to heat (65 degrees C, 30 minutes) and labile to acid (pH 2.0). Gel filtration and chromatofocusing estimated its molecular weight at 50 kd, with an isoelectric point of pH 7.2. Production of this factor might contribute to the invasive character of CEM through upregulation of adhesion molecules on EC.

Base Sequence↗

Mechanism of nasal secretion mediated via nerve reflex in guinea pigs and evaluation of antiallergic drugs.

In order to confirm the mechanism of nasal secretion mediated via a nerve reflex in guinea pigs, the secretory response from the contralateral side was studied which was induced by local application of various stimulators. There was no difference in the nasal secretion between the contralateral and the stimulated sides when the secretion was induced by allergen, histamine, and capsaicin at lower doses. Methacholine caused a nasal secretion only on the stimulated side. Pretreatment with local anesthetic and ganglionic blockers blocked the secretory response bilaterally which was induced by allergen, histamine, and capsaicin. Antihistaminics also blocked the secretory response induced by allergen and histamine on both sides, but not the capsaicin-induced nasal secretion. Unilateral pretreatment with local anticholinergics prevented all secretory responses only on the stimulated side. Thus, exogenous and endogenous histamine released by the allergen-antibody reaction may stimulate histamine H1 receptors located in the sensory nerve endings as trigger, resulting in the secretory response mediated via a nerve reflex, while methacholine may act directly on nasal glands. Ketotifen and azelastine, which are chemical mediators releasing inhibitor with antihistaminergic activity, prevented the nasal secretion induced by histamine and allergen. On the other hand, disodium cromoglycate, amlexanox, and tranilast had only a slight effect on the allergen-induced nasal secretion. The secretory response on the contralateral side induced by various stimulators would be useful in the in vivo evaluation of anti-allergic drugs to demonstrate the difference in their modes of action.

Allergens↗