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Biomedical subjects

Y Kano

Publications and source records attributed to Y Kano.

At least 145 records · Page 8Linked to original sources

Effects of carboplatin in combination with other anticancer agents on human leukemia cell lines.

In vitro studies with drug combinations of carboplatin and other anticancer agents were carried out in MOLT-3 human lymphoblastic leukemia and HL-60 human promyelocytic leukemia cell lines. Cells were incubated for 3 days in the presence of various concentrations of carboplatin and other drugs and cell growth inhibition was determined by MTT assay. The antitumor effects of the drug combinations at ID50 were analyzed using an improved isobologram. In MOLT-3 cells, supra-additive (synergistic) effects were observed for carboplatin in combination with cytosine arabinoside, mitoxantrone and CPT-11. Additive effects were observed for combinations of carboplatin with bleomycin, daunorubicin, doxorubicin, etoposide, 6-mercaptopurine, and vincristine. Sub-additive and protective (antagonistic) effects were observed with methotrexate. Synergistic or antagonistic effects for combinations of carboplatin and CPT-11, cytosine arabinoside, mitoxantrone and methotrexate were also observed in HL-60 cells. These findings suggest that carboplatin has additive or synergistic cytotoxic effects with most of the agents tested. Determination of the usefulness of these drug combinations awaits appropriate in vivo experiments that should assess both tumorcidal effects and possible increased toxicity. The simultaneous administration of carboplatin and methotrexate would be of little effect. To find optimal schedules for this combination, further pre-clinical studies of various combinations schedule would appear to be warranted.

Antineoplastic Combined Chemotherapy Protocols↗

Distribution of carbonic anhydrase isozyme III (CA-III)-positive cells in duct segments of the bovine submandibular gland.

The distribution of carbonic anhydrase III isozyme (CA-III)-positive cells in bovine submandibular glands was studied by immunohistochemistry. CA-III showed strong immunoreactivity in basal cells and some lining cells of the intercalated ducts as well as in striated and interlobular ducts cells. No significant immunoreactivity could be found in other portions of the glands. Electron microscopically, the immunoreactive basal cells contained scattered tonofibrils in their cytoplasm. The distribution of CA-III suggests that the CA-III-positive basal cells may play a special physiological role, and that they do not only represent undifferentiated lining cells.

Animals↗

Continuous 5-fluorouracil infusion causing acute gastric mucosal lesions.

A 59-year-old woman with advanced gastric cancer was treated with continuous 5-fluorouracil infusion for thirty-five days. Endoscopy of the upper gastrointestinal tract was performed due to continuing nausea seven days after the cessation of 5-fluorouracil infusion and revealed multiple erosions in the antrum which were absent before chemotherapy. Continuous 5-fluorouracil infusion was probably the cause of acute gastric mucosal lesions and should be included in the differential diagnosis of dyspepsia in 5-FU-treated patients.

Adenocarcinoma↗

Properties of DNA-binding of HU heterotypic and homotypic dimers from Escherichia coli.

The interactions of three forms of HU dimer from Escherichia coli with DNA were compared. The complexes formed between HU and short DNA fragments (35 to 132 bp), uncurved oligodeoxyribonucleotide (oligo) with and without 5-bp deoxyriboadenosine (dA) stretches and curved oligo with 5-bp dA stretches, were analyzed by the gel retardation technique. The binding of HU homodimers to the DNA was less efficient than that of HU heterodimer, and the HU-1 homodimer had lower DNA-binding capacity than the HU-2 homodimer. The equilibrium dissociation constant (KD) for DNA of the HU-1 homodimer was 3 times that of the HU heterodimer. The HU dimers had two- to fourfold higher affinity for DNA duplexes containing 5-bp dA stretches, particularly for curved DNA. The binding of HU heterodimer to the DNA was inhibited more by the curved DNA competitor than the uncurved DNA competitor without dA stretches.

Autoradiography↗

Formation of neurons in the sexually dimorphic anteroventral periventricular nucleus of the preoptic area of the rat: effects of prenatal treatment with testosterone propionate.

An examination was made of neurogenesis in the anteroventral periventricular nucleus (AVPv) of the preoptic area of the rat using bromodeoxyuridine (BrdU), a thymidine analog, and a BrdU-specific antibody. Cells in the AVPv of adult rats were labeled with the antibody when BrdU was injected into pregnant rats once during day 13 to 18 of gestation, but not during day 10 to 12 nor 19 to 20 of gestation nor on postnatal day 1, indicating the neurogenesis of the AVPv occurs during a limited period from day 13 to 18 of gestation. Next, to examine the effects of androgen on neurogenesis, BrdU was injected once on day 15 into pregnant rats that also received injections of testosterone propionate (TP). The number of BrdU-labeled cells in the AVPv was similar in control female and male fetuses and female fetuses from pregnant rats that received daily injections of TP during days 14 to 16, when fetuses were examined on day 17 of gestation. These results suggest that the neurogenesis that was recognized by labeling with BrdU was not affected by the treatment with TP. On day 21 of gestation, BrdU-labeled cells in the AVPv of control male fetuses and female fetuses that received TP during days 14 to 18 were fewer in number than those in female fetuses of the control group, whereas treatments with TP during days 14 to 16 and during days 17 to 18 did not cause any significant decrease in number of BrdU-labeled cells. These findings can support the hypothesis that elimination of a population of cells, for example, by cell death as described previously, is enhanced in male fetuses and in female fetuses treated with TP repetitively.

Animals↗

Branching mode of the middle rectal artery from the prostatic artery in the dog.

The branching mode of the middle rectal artery from the prostatic artery was studied by gross dissection in 50 male dogs. The prostatic artery arose at the level of the 1st-3rd sacral vertebra from the internal pudendal artery, and gave off the ductus deferential and the middle rectal arteries, and supplied the prostate. The middle rectal artery ran caudally along the pelvic peritoneum, and supplied the rectum ampulla. The branching mode of the middle rectal artery could be classified into four types. Nineteen cases on the right side and 22 cases on the left side showed that the middle rectal artery was a first visceral branch of the prostatic artery. Fifteen cases on the right side and 11 cases on the left side showed that it was a second visceral branch of the prostatic artery which gave off the ductus deferential artery as its first visceral branch. Nine cases on the right side and 7 cases on the left side showed that it arose at the prostatic artery ramifying at the surface of the prostate. Seven cases on the right side and 10 cases on the left side showed that it arose at the urethral branch of the prostatic artery.

Animals↗

Enzyme inhibitory activities of acetylene and sesquiterpene compounds in atractylodes rhizome.

In an attempt to elucidate the physiological activities of (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol diacetate (TDEYA), which was detected as a hydrolysis form (TDEY) in the plasma after oral administration of a decoction of Atractylodes rhizome in rats, we examined the inhibitory effects of various enzymes which are considered to participate in the regulation of body fluid levels and inflammatory reactions. TDEY and TDEYA did not show inhibitory effects on carbonic anhydrase (CA) or angiotensin converting enzyme (ACE) at concentrations less than 1.0 x 10(-3) M. However, both acetylene compounds inhibited Na+,K+ adenosine triphosphatase (Na+,K(+)-ATPase) weakly and xanthine oxidase (XO) strongly. From the results of several acetylene compounds examined on XO inhibition, it is clear that the active structure of the compounds is due to the presence of conjugated triple and double bonds. In the in vivo experiment of TDEYA, urine volume, urinary electrolytes and uric acid excretion showed no significant differences from the control. However, the administration of TDEYA to rats tended to increase xanthine excretion.

Acetylene↗

Proton NMR study on a histone-like protein, HU alpha, from Escherichia coli and its complex with oligo DNAs.

It was confirmed that the flexible arm region of HU alpha forms an antiparallel beta-sheet and that all of the residues of phenylalanines, together with some of leucines and/or valines, form a hydrophobic core within the dimer of HU alpha. HU alpha protein alone is thermally labile and melts at 38 degrees C, but it becomes remarkably stabilized and melts at 59 degrees C in the presence of DNA. Several resonances from both HU alpha and DNA perturbed by their complex formation, notably those of His C-2 and C-4 protons, downfield shifted C alpha protons in the antiparallel beta-sheet, as well as Arg C delta and Lys C epsilon protons. The results indicated that a beta-sheet region of HU alpha binds to DNA, and also showed that rapid equilibrium occurs on the NMR time scale between bound and unbound states of HU alpha. A few intermolecular nuclear Overhauser effects (NOEs) were also observed between the protein and H1' protons of DNA in the complex, suggesting that HU alpha binds primarily to the minor groove of DNA.

Base Sequence↗

Pharmacological properties of galenical preparation. XVI. Pharmacokinetics of evodiamine and the metabolite in rats.

In an attempt to evaluate its pharmacokinetics, [3H]evodiamine, which is one of the characteristic alkaloids of Evodia fruit was synthesized. The pharmacokinetics of [3H]evodiamine were investigated in rats. In plasma, the main source of radioactivity was a metabolite of d-evodiamine (EM). One hour after oral administration of 200 micrograms/kg of [3H]evodiamine, the radioactivity level in the plasma was maximal. The radioactivity declined in a biphasic manner with half-life times of 1.6 and 78.4 h. The distribution volume was 560 ml/kg. Radioactivity in tissues was higher in the liver, kidney, heart, lung, and adipose tissue than in plasma, but radioactivity in other tissues it was lower than that in plasma. In all tissues the radioactivity proportionally decreased to the level of that in plasma. At 24h after administration, 19% and 63% of orally administered radioactivity was excreted in urine and bile, respectively.

Adipose Tissue↗

Cholesterol biosynthesis inhibitory component from Zingiber officinale Roscoe.

We previously reported on the isolation and identification of (E)-8 beta,17-epoxylabd-12-ene-15,16-dial (ZT) from ginger (rhizome of Zingiber officinale Roscoe, Zingiberaceae). In this paper, the pharmacological effects of ZT are reported. The experimental mouse hypercholesterolemia induced by Triton WR-1339 was treated after oral administration of ZT. In homogenated rat liver with ZT, cholesterol biosynthesis was decreased. In addition, the same activity was observed in the homogenated rat liver which was resected after the oral administration of ZT. According to the results of general pharmacological screening, no remarkable activity of ZT was observed except for an inhibitory effect on the cholesterol biosynthesis.

Animals↗

Peritoneal dialysis using a recycling system in dogs.

In this study, Recirculation Peritoneal Dialysis (RPD) apparatus using a pump to circulate the dialysate was devised and its dialysis efficiency was investigated. In the experiment, 15 mongrel dogs with body weights of 6.6 +/- 0.7 kg were used. The surgery to induce azotemia was performed on the dogs, a disk catheter for drainage was placed between the liver and diaphragm, and a straight catheter for infusion was placed on the abdominal side of the bladder. RPD was conducted using 2 l of dialysate containing 1.3% glucose, and the dialysate was circulated by a pump through the peritoneal cavity and the dialysate chamber at the circulation rates of 30, 60, 90 and 120 ml/min. RPD was conducted for 3 hr and the clearances of urea nitrogen, creatinine, inorganic phosphorus and potassium were recorded every hour. The clearances in RPD became higher with an increase in the circulation rate. Although RPD requires two catheters in the peritoneal cavity, it has no appreciable technical difficulty in handling and is considered to be easier than hemodialysis. RPD enabled higher dialysis efficiency to be achieved in a short time compared with conventional peritoneal dialysis. It seems reasonable to conclude that RPD is a useful new dialysis technique for animals.

Animals↗

[Etoposide, doxorubicin, cisplatin and 5-FU (EAP-F) therapy of advanced gastric cancer--its antitumor effect and evaluation of quality of life].

Fourteen patients with advanced gastric cancer were treated with EAP-F therapy. The regimen was CD DP 40 mg/m2 day 1 and 6, 5-FU 600 mg/m2 day 2 and 4, leucovorin 20 mg/m2 day 2 and 4, etoposide 60 mg/m2 day 3 and 5, and doxorubicin 20 mg/m2 day 7, with repetition every 28 days. Thirteen patients were evaluable; one patient was CR, four were PR, five were NC and three were PD. The response rate was 38.5% and median survival was 7 months. Hematologic toxicities were moderate to severe but tolerable, gastrointestinal toxicities were mild and renal toxicity was absent. Quality of life (QOL) of the patients was evaluated by means of symptom-free ratio (duration of symptom-free to survival time) and outpatient ratio (duration at home in relation to survival time). Patients with lymph node metastasis showed a higher symptom-free ratio and outpatient ratio than those with liver metastasis or peritoneal dissemination. All high-QOL patients were chemotherapy responders. In conclusion, EAP-F therapy is effective for advanced gastric cancer and its side effects are tolerable. CR or PR is necessary to achieve a high QOL.

Antineoplastic Combined Chemotherapy Protocols↗

Histone-like proteins are required for cell growth and constraint of supercoils in DNA.

The gene hns of Escherichia coli K-12, which encodes the histone-like protein H-NS, was inactivated by insertion of a DNA (gene hph) encoding hygromycin phosphotransferase. The growth rates of two mutants lacking either one or the other of the histone-like proteins, HU and IHF, were not affected by introduction of the hns mutation. However, cells depleted of HU, IHF and H-NS simultaneously, could not be constructed by P1 phage-mediated transduction. These results, together with our previous finding that cells deficient in both HU and IHF are viable at 30-37 degrees C [Kano and Imamoto, Gene 89 (1990) 133-137] showed that E. coli cells deficient in any two of these three histone-like proteins are viable at 30-37 degrees C, and suggested that simultaneous deficiency of all three of the proteins is lethal. There were no detectable differences in the levels of superhelicity of the reporter plasmids isolated from cells deficient in either IHF or H-NS, or from wild-type cells, but about 15% decrease in negative superhelicity was detected for the reporter plasmid isolated from cells lacking HU and lacking both HU and H-NS. However, the cryptic bgl operon, whose expression was reported to be regulated through topological changes of cellular DNA, could not be activated in cells depleted of HU or IHF. The bgl operon was expressed in cells depleted of both HU and H-NS as well as in cells depleted of H-NS.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Outer Membrane Proteins↗

Amino acid substitution in the C-terminal arm domain of HU-2 results in an enhanced affinity for DNA.

Three mutants of the Escherichia coli hupA gene, encoding the HU-2 protein, were constructed by synthetic oligodeoxyribonucleotide-directed, site-specific mutagenesis on M13mp18 vectors. The resulting HupAN10, HupAN11 and HupAN12 proteins contained Thr59-->Lys, Gln64-->Lys and Asn53-->Arg substitutions, respectively. These amino acid (aa) changes increased the positive charge of the N-terminal half of the two-strand, antiparallel beta-ribbon of the arm structure, which is believed to be a domain for DNA binding. The three mutant proteins bound to DNA more tightly than wild-type HU-2, and their affinities for DNA increased in the order of HupAN10, HupAN11, HupAN12. The mutant proteins showed a slightly increased HU activity for supporting Mu phage development. A mutant HU-2 protein with increased basicity, but with an altered aa sequence in the arm region due to a frameshift mutation, was also constructed. This mutant protein showed a reduced affinity to DNA and was unable to support Mu growth, suggesting that a unique aa sequence of the arm domain, rather than mere basicity of this domain, is required for efficient binding to DNA.

Amino Acid Sequence↗

Chimeric HU-IHF proteins that alter DNA-binding ability.

Chimeric proteins between Escherichia coli histone-like HU and IHF were constructed by genetic engineering, in which part of the arm region was replaced by the corresponding region of IHF alpha (designated as HupANhimA) or IHF beta (HupANhimD); alternatively, an alpha-helix 2-beta 1 region was replaced by the corresponding region of IHF alpha (HupAXhimA) or IHF beta (HupAXhimD) (symbols N and X indicate NotI and XhoI junctions). These proteins were synthesized in a hupA-hupB double-deletion mutant. HupANhimA exhibited marked reduction in nonspecific DNA binding in vitro, and a drastic loss of HU activity in replicative transposition of Mu phage in vivo. HupANhimD also showed a significant reduction in the ability for DNA binding, though this protein supported Mu phage development. In contrast, the other two chimeric HU proteins showed only slight changes in nonspecific DNA-binding ability: they retained activities for transposition of Mu phage in vivo. These observations confirm that the flexible arm of HU-2, a domain proposed for DNA binding [Tanaka et al., Nature 310 (1984) 376-381; Goshima et al., Gene 96 (1990) 141-145], plays an important role in the physiological function of this protein. The results indicate that a unique conformation of the arm structure of HU protein, particularly the N-terminal half of a two-strand antiparallel beta-ribbon of the structure, is important for the DNA-binding ability of this protein.

Amino Acid Sequence↗