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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 811 records · Page 45Linked to original sources
PubMed1994

Comparative studies on Borrelia afzelii isolated from a patient of Lyme disease, Ixodes persulcatus ticks, and Apodemus speciosus rodents in Japan.

The genospecies Borrelia afzelii was isolated from a patient of Lyme disease in Hokkaido, Japan, for the first time, by culturing the minced erythema lesion in BSK II medium. Two analytical methods, rRNA gene restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) using the specific primer set to amplify the 16S rRNA gene, revealed that this clinical isolate belongs to the group of B. afzelii. In our culture collection of spirochetes, part of the isolates from Ixodes persulcatus ticks, and from Apodemus speciosus rodents, were also classified as B. afzelii. These results strongly suggest that the agent pathogenic to humans is maintained in "rodent-tick" transmission cycle.

Adult↗
PubMed1994

Analysis of AP-1 function in cellular transformation pathways.

To understand the role of endogenous AP-1 activity in cellular transformation induced by oncogenes, we have made use of a fos mutant (supfos-1) and a jun mutant (supjun-1), either of which can function as a transdominant inhibitor of AP-1-mediated transcriptional regulation. Chicken embryo fibroblasts (CEF) infected with a series of transforming retroviruses were doubly infected with retrovirus carrying supfos-1 or supjun-1, and suppression of cellular transformation was monitored in terms of reversion to normal cellular morphology or acquisition of anchorage-dependent growth. Cellular transformation induced by several exogenously expressed transforming genes of the fos or jun family was efficiently suppressed, as expected. CEF transformed by v-src, v-yes, v-fps, c-Ha-ras, and N-terminally truncated c-raf were also induced to revert to the normal phenotype by these transdominant mutants, suggesting that functional transcription factor AP-1 activity is essential for the cellular transformation induced by these oncogenes. The suppression is not attributable to nonspecific inhibition of cellular proliferation, because CEF transformed by v-ros or v-myc were not induced to revert to the normal phenotype. We next analyzed changes in all known components of chicken AP-1 induced by v-src, c-Ha-ras, or activated c-raf transformation. The levels of both Fra-2 and c-Jun expression were elevated two- to fourfold, and hyperphosphorylation of Fra-2 was also observed. We further showed that Fra-2-c-Jun heterodimer is mainly responsible for the elevated AP-1 DNA-binding activity in these transformed cells, and we propose that this heterodimer play a crucial role in the transformation induced by these oncogenes.

Animals↗
PubMed1994

CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of Ras in PC12 cells.

It has been reported that growth factors activate Ras through a complex of an adaptor type SH2-containing molecule, Grb2, and a Ras guanine nucleotide-releasing protein (GNRP), mSos. We report on the involvement of another adaptor molecule, CRK, in the activation of Ras. Overexpression of wild-type CRK proteins CRK-I and CRK-II enhanced the nerve growth factor (NGF)-induced activation of Ras in PC12 cells, although the basal level of GTP-bound active Ras was not altered. In contrast, mutants with a single amino acid substitution in either the SH2 or SH3 domain of the CRK-I protein inhibited the NGF-induced activation of Ras. Two GNRPs for the Ras family, mSos and C3G, were coimmunoprecipitated with the endogenous Crk proteins in PC12 cells. The association between C3G and the CRK mutants was dependent upon the presence of intact SH3. The SH2 domain of CRK bound to the SHC protein phosphorylated on tyrosine residues by NGF stimulation. The results demonstrate that, in addition to Grb2, CRK participates in signaling from the NGF receptor and that two GNRPs appear to transmit signals from these adaptor molecules to Ras.

Animals↗
PubMed1994

Ossification of the Achilles tendon: a case report.

Ossification of the Achilles tendon is a rare condition. We recently treated a patient with ossification of bilateral Achilles tendons. The patient was a 50 year old male whose chief complaint was discomfort around the Achilles tendon. He had a previous history of treatment of bilateral club feet. On the roentgenograms, the length of the bony mass in the Achilles tendon was 5.5 cm on the right side and 1.5 cm on the left side. The left side was treated by surgical removal of a bony mass and suture of the tendon. Microscopic examination of the extirpated specimen revealed bone formation through enchondral and intramembranous ossification in the Achilles tendon.

Achilles Tendon↗
PubMed1994

Novel actin rods appeared in spores of Dictyostelium discoideum.

When spores of Dictyostelium discoideum matured through normal development were stained with rhodamine-phalloidin, rod-shaped fluorescence was found across the nucleus and in the cytoplasm. Electron micrographs of the rod shape showed that it consisted of long and straight fibers 12 nm in diameter. In contrast, a conventional actin rod, which usually is formed under stress conditions, is composed of short filaments 6 nm in diameter, and cannot be stained with fluorescent phalloidin. Hence it can be inferred that the structure appeared in Dictyostelium spores under no stress conditions is a novel actin rod.

Actins↗
PubMed1994

Specific binding of 12-O-tetradecanoylphorbol-13-acetate to histone H1.

12-O-Tetradecanoylphorbol-13-acetate (TPA) binds specifically to histone H1 prepared from HeLa cells and to calf histone H1 with dissociation constants of 4.3 x 10(-7) and 9.3 x 10(-7) M, respectively. The TPA-binding to histone H1 was confirmed immunologically using a monoclonal antibody directed against an evolutionally conserved epitope of histone H1. This binding would influence DNA structure and the basal level of transcription, and may, in turn, account for the cell growth-regulatory activity of TPA.

Amino Acid Sequence↗
PubMed1994

Enhancement of human papillomavirus type 18 gene expression in HeLa cells by 12-O-tetradecanoylphorbol-13-acetate, 3 beta,5 alpha-dihydroxycholestan-6-one, and cholesterol.

Human papillomavirus type 18 (HPV18) is involved in the genesis of cervical cancer through expression of its viral oncoprotein in infected cells. A tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), was found to increase the level of HPV18 transcripts in an HPV18-harboring cervical cancer cell line, HeLa. A similar increase in HPV18 expression was also observed on treatment of the cells with an oxygenated cholesterol, 3 beta,5 alpha-dihydroxycholestan-6-one (yakkasterone). The effects on HPV18 expression elicited by TPA and yakkasterone were repressed by a protein kinase inhibitor, staurosporine. Treatment of the cells with cholesterol under serum-free conditions also resulted in an apparent increase of HPV18 expression.

Alkaloids↗
PubMed1994

Enhancement of phorbol ester-induced production of tumor necrosis factor-alpha by 2,6-dimethylphenylphthalimide.

The effect of phenyl- and benzylphthalimide analogs on tumor necrosis factor (TNF)-alpha production by a human leukemia cell line, HL-60, stimulated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was investigated. Though non-substituted phenyl- and benzyl-phthalimide had no effect on TNF-alpha production after TPA-induction, introduction of methyl group(s) onto the phenyl group resulted in the appearance of potent enhancing activity on TNF-alpha production.

Cell Division↗
PubMed1994

Population analysis of the dose-dependent pharmacokinetics of zonisamide in epileptic patients.

The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (Vmax) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 micrograms/ml, respectively. The parameter of a power function of weight to adjust V and Vmax was estimated to be 0.741. In addition, Vmax for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. The population pharmacokinetic parameters of zonisamide will be useful for designing dosage regimens in epileptic patients.

Administration, Oral↗
PubMed1994

Increase in the chemically-induced differentiation of human leukemia cell lines by tubulin disruptors.

The effect of various structural/functional tubulin disruptors (including colchicine-type disruptors, vinblastine, rhizoxin, maytansine, peptide-type disruptors, and taxol) on the chemically induced differentiation of human leukemia cell lines (HL-60 and K562) was examined. As differentiation-inducing agents, 12-O-tetradecanoylphorbol-13-acetate (TPA) was used for the differentiation of both HL-60 and K562 to monocyte/macrophages, retinoids were used for the differentiation of HL-60 to mature granulocytes, and hemin was used for the erythroid differentiation of K562. All the tubulin disruptors investigated increased the chemically-induced differentiation of HL-60 and K562 cell lines to the cognate mature cell types, regardless of the nature of the differentiation.

Cell Differentiation↗
PubMed1994

Alterations of specific and nonspecific binding of monoclonal antibody by introduction of acidic and hydrophobic groups.

AB-6 monoclonal antibody (mAb) against bovine serum albumin (BSA) was coupled with beta-alanine or n-propylamine using a heterobifunctional cross-linking reagent, N-(epsilon-maleimidocaproyloxy)succinimide (EMCS) and a linker, poly-L-cysteine to introduce acidic or hydrophobic groups into the mAb. The mAb molecules coupled with beta-alanine at lower than 1:16 molar ratios and those coupled with n-propylamine at 1:14 retained the original reactivity to BSA but modification with higher amounts of beta-alanine or n-propylamine decreased the reactivity. In contrast, nonspecific bindings of AB-6 mAb to a plastic culture plate and tumor (MDA-MB-453) cells were decreased by modification with beta-alanine and increased by n-propylamine. These results suggested that introduction of acidic groups, and hydrophobic groups to antibody leads to fluctuations in the non-specific binding of antibody.

Animals↗
PubMed1994

(S)-form of alpha-methyl-N(alpha)-phthalimidoglutarimide, but not its (R)-form, enhanced phorbol ester-induced tumor necrosis factor-alpha production by human leukemia cell HL-60: implication of optical resolution of thalidomidal effects.

The rate of racemization of N(alpha)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37 degrees C. This fast racemization of thalidomide resulted in no apparent difference between (S)- and (R)-forms of the compound on enhancing activity of phorbol ester-induced tumor necrosis factor (TNF)-alpha production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-alpha-methyl-N(alpha)-phthalimidoglutarimides (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-alpha production-enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.

Cell Division↗
PubMed1994

Synthesis and biological activity of carboxyphenylquinolines and related compounds as new potent retinoids. Retinobenzoic acids. VII.

A series of new quinoline, quinolone, and quinazolinedione derivatives was synthesized and tested for retinoid activity in the human promyelocytic cell line HL-60 differentiation assay. All the quinoline compounds exhibited significant activity, depending on the substituent on the heterocycle. However, the quinolone and quinazolinedione derivatives were poor inducers of the differentiation of the HL-60 cells, the activity depending strongly on the polarity of the molecule.

Benzoates↗
PubMed1994

Synthesis of oxygenated cholesterols as structural mimics of phorbol ester-type tumor promoters.

We designed several oxygenated steroids in which functional groups including a hydrophobic group are arranged analogously to those of phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA), with the aim of finding compounds with TPA-like activity, but having a different skeleton and a rigid conformation. The designed steroids, 1 beta,5 alpha-dihydroxy-3 beta-hydroxymethylcholestan-6-one (4), 3 beta,5 alpha-dihydroxycholestan-6-one (5), 3 beta-hydroxymethylcholestan-5 alpha-ol-6-one (6) and 1 beta,3 beta,5 alpha-trihydroxycholestan-6-one (7), were synthesized. A related oxygenated steroid isolated from soft coral, cholestane-1 beta,3 beta-5 alpha,6 beta-tetrol (8), was also synthesized. Among these analogs, compound 7 showed weak TPA-like activities in three biological tests: inhibition to protein kinase C and to cytosolic-nuclear tumor promoter-binding protein (CN-TPBP), and induction of differentiation of human promyelocytic leukemia cells (HL-60) to monocyte-like cells. On the other hand, compound 5 was found to be a specific ligand for CN-TPBP, but lacked the other TPA-like activities.

Animals↗
PubMed1994

[Chemical control of gene expression].

Expression of specific genes can be controlled by some compounds (gene expression modifiers) which can be divided into two categories, i.e.; (a) compounds which directly bind to nucleic acids having specific sequences and (b) compounds which bind specific transcription factors (including nuclear receptors) or related factors. Recent results on the structural development and mechanistic studies into the gene expression modifiers, mainly retinoids, phorbol ester, hemin, antisense molecules, and thalidomide analogs, have been reviewed. Some of these gene expression modifiers elicit cell differentiation inducing, tumor promoting, and biological response modifying activities. Development of more potent and/or more specific gene expression modifiers might be useful in cancer chemotherapy.

Animals↗
PubMed1994

[Studies on angiotensin I converting enzyme (ACE): inhibitory effect of imidapril, a novel ACE inhibitor (II). Inhibition of various tissue ACEs ex vivo].

The antihypertensive mechanism of imidapril was investigated in relation to its inhibition of ACE activities in the serum, thoracic-abdominal aorta, lung, kidney, heart and brain from adult spontaneously hypertensive rats (SHRs). In comparison with normotensive rats (NTRs), the ACE activities in the aorta, heart, brain and lung were higher, while those in the serum and kidney were considerably lower. Imidapril (2 mg/kg) showed remarkable inhibitions within 6 hr in all tissues, except for the brain, after a single oral administration. Consecutive administration of imidapril (2 mg/kg/day) for 30 days produced inhibitions in all tissues. The inhibitions in the serum, aorta and lung were greater, and the duration of inhibition in the aorta, brain and lung were longer. Blood pressure declined gradually until 6 hr, and the reductions were significant at 24 hr after the single and chronic administrations. Imidapril (0.5 mg/kg, ineffective on normal blood pressure) inhibited ACE activities in NTRs similarly. Enalapril at the same dose exhibited less ACE inhibition and antihypertension. These results suggest that the ACE inhibition in the serum, lung and aorta by imidapril correlate with the antihypertension in SHRs; especially, the lung and vascular ACE inhibitions play an important role in the duration of antihypertension in SHRs.

Administration, Oral↗