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Biomedical subjects

K Higashi

Publications and source records attributed to K Higashi.

At least 19 recordsLinked to original sources
PubMed1992

Reduction and inactivation of the sarcoplasmic Ca(2+)-ATPase by 2-mercaptoethanol--contrast to the (Na+,K+) ATPase.

The sarcoplasmic Ca(2+)-ATPase was reduced with 300 mM 2-mercaptoethanol at elevated temperatures (40-45 degrees C) with a concomitant loss of ATPase activity. The reduction and inactivation of the Ca(2+)-ATPase proceeded rapidly in the absence of Ca2+. The Ca(2+)-ATPase was also inactivated with 2-mercaptoethanol in the presence of diluted SDS (0.4 mg/ml) even at 20 degrees C. In contrast to the (Na+, K+) ATPase, the inactivated Ca(2+)-ATPase in the presence of diluted SDS was sedimented by the centrifugation at 100,000 x g for 30 min.

Animals↗
PubMed1992

Ethnic differences of the primary gene defect at the cytochrome P-450 2D6.

The cytochrome P-450-dependent monooxygenase system is involved in the metabolism of both endogenous compounds and xenobiotics. The role of these enzymes in toxicological response is exemplified by an autosomal recessive polymorphism at the cytochrome P-450 2D6 debrisoquine-4-hydroxylase locus, which results in the severely impaired metabolism of many drugs [Gough et al. (1990) Nature 347: 773-776]. The prevalence of this polymorphism (poor metabolizer) differs considerably between ethnic groups. Here we analyzed the P-450 2D6 polymorphism in 25 Japanese and 20 Chinese by DNA-based genetic assay using peripheral leukocyte. Although the phenotype of all the normal metabolizers and 79% of the poor metabolizers could be identified in Caucasians, this DNA-based genomic assay could not predict poor metabolizers in both the Japanese and Chinese. These results indicate that the genetic mechanism of the phenotyped poor metabolizer in Orientals is different from that in Caucasians.

Asian People↗
PubMed1992

The mechanism of the action of IFN-gamma and TPA on the modulation of epidermal growth factor receptors of human amnion cells.

We have examined the mechanism of synergistic action occurring between interferon (IFN)-gamma and 12-0-tetradecanoylphorbol-13-acetate (TPA) with respect to the reduction of 125I-epidermal growth factor (125I-EGF) binding to human amnion (WISH) cells [Karasaki Y et al (1989) J Biol Chem 264: 6158-6163]. The cells were treated with protein kinase C (PKC) inhibitors (H7, staurosporine) to investigate the role of PKC in the synergism between IFN-gamma and TPA, since TPA is a strong activator of PKC. The combined effect of IFN-gamma and TPA was blocked by the PKC inhibitor, suggesting that PKC plays an important role in the synergistic action of TPA and IFN-gamma on the inhibition of EGF binding to the cells. The prolonged incubation (24 h) of the cells with TPA resulted in the restoration of EGF binding to the cells. A 24 h treatment of WISH cells with both IFN-gamma and TPA, however, still exhibited greater than 50% inhibition of EGF binding. No PKC activity, however, was observed in the WISH cells treated with both IFN-gamma and TPA for 24 h as well as with TPA alone for 24 h, indicating that IFN-gamma may synergize with the second mediator induced by PKC rather than PKC itself in the reduction of EGF binding to WISH cells. In addition, IFN-gamma showed the synergistic action with calcium ionophores on the reduction of EGF binding to the cells, suggesting that Ca2+ may be one of the second mediators which was induced by TPA and which cooperated with IFN-gamma.

Amnion↗
PubMed1992

Ontogenetic development, differentiation, and phenotypic expression of macrophages in fetal rat lungs.

Development, differentiation, and distribution of macrophages in fetal rat lungs were investigated immunohistochemically using anti-rat macrophage monoclonal antibodies. In the lung buds, RM-1+ macrophages were first detected on fetal day 13, and some showed reactivity for TRPM-2. They populated in the peribronchial mesenchyme of the lung buds, proliferated in loco, and showed no peroxidase activity in any intracellular organelles. Their immunophenotypic and ultrastructural features were consistent with those of primitive/fetal macrophages. By fetal day 16, some of them expressed ED1, but ED1+ cells were a minor subpopulation throughout the fetal period. On fetal day 18, ED2+ macrophages developed; some also were positive for RM-1, but the others were negative. Both the RM-1+ and ED2+ macrophages were major macrophage subpopulations and expressed Ki-M2R and/or TRPM-3; ED2+ and/or Ki-M2R+ cells are regarded as pulmonary interstitial resident macrophages. In organ culture, a similar expression of differentiation antigens by macrophages was confirmed. None of these macrophages cytochemically showed any peroxidase activity in vivo or in vitro. In the fetal stage, both RM-1+ and ED2+ macrophage subpopulations showed proliferative potential, suggesting their ability to proliferate and survive in vivo.

Animals↗
PubMed1992

Isolation and characterization of a cDNA that encodes ECP31, an embryogenic-cell protein from carrot.

A full-length cDNA for ECP31, an embryogenic cell protein from carrot (Daucus carota L.) with a M(r) of 31,000 (Kiyosue T, Satoh S, Kamada H, Harada H (1991) Plant Physiol 95: 1077-1083), was isolated from a cDNA library prepared from embryogenic cells using PCR-amplified DNA as a probe. The genomic Southern blot analysis revealed that there are two or three genes for ECP31 in the carrot genome. The transcripts of ECP31 accumulated in the peripheral regions of clusters of embryogenic cells and disappeared in the course of somatic embryogenesis that was induced by transfer of the embryogenic cells to auxin-free media. The cDNA encodes a polypeptide of 256 amino acids, and the calculated molecular weight of this polypeptide is 26,111. The deduced amino acid sequence shows a high degree (62.2%) of similarity to that of a protein that is abundant during late embryogenesis of cotton (LEA D34; Baker JC, Steele C, Dure III (1988) Plant Mol Biol 11: 227-291). The mRNAs for ECP31 started to accumulate in zygotic embryos at a late stage of embryogenesis but were undetectable in mature embryos within 24 h after imbibition of seeds. In dry fruits (seeds), the transcripts were detected only in zygotic embryos by in situ hybridization. The level of ECP31 transcripts increased after treatment with abscisic acid (ABA) in torpedo-shaped somatic embryos but not in seven-day-old seedlings. These results suggest that both embryo-specific factor(s) and ABA are involved in the expression of the gene for ECP31.

Abscisic Acid↗
PubMed1992

Differences of L-myc polymorphic patterns of neuroblastoma in patients under 1 year versus older ages: a preliminary report.

The age of the patient at the onset of symptoms or at diagnosis is generally accepted as one of the most important prognostic factors of neuroblastomas (NBs). Children less than 1 year of age have a better survival rate than older patients, but the reason for this is unknown. Forty-eight unselected NB patients were divided into two groups: less than 1 year (younger NB patient) and over 1 year (older NB patient) of age at diagnosis. Two of 12 younger NB patients and 18 of 36 older NB patients had N-myc amplification in their tumors. To elucidate further the possible genetic difference between younger and older NB patients, studies of restriction fragment length polymorphism (RFLP) of the L-myc gene was carried out in these two groups. The L-myc locus showed 2-allele polymorphism, allele L(10 kb) and S (6.6 kb), after digestion with EcoRI. Patients homozygous for L-band have been reported as individuals having less metastatic potential in some cancers. The allele frequencies of L and S in neuroblastomas of younger NB patients were 0.50 and 0.50, while those of older NB patients were 0.35 and 0.65, respectively. Although we did not determine L-myc RFLP in normal tissue of individual patients, we expect that the distribution of allele L and S is partly affected by possible allelic loss involving the L-myc region. However, the L-myc RFLP patterns in younger NB patients were the same as those of normal individuals and significantly differed from those of older NB patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Supernumerary ring marker chromosome as a secondary rearrangement in a parapharyngeal lipoma with t(10;12)(q25;q15) as the primary karyotypic abnormality.

Cytogenetic analysis of a large parapharyngeal lipoma, a rare tumor at this site, showed the karyotype 46,XY,t(10;12)(q25;q15)/47,XY,t(10;12)(q25;q15),+r. The primary abnormality must have been t(10;12), whereas the +r developed secondarily as an additional aberration. Although a similar translocation between chromosomes 10 and 12 has not been described previously, that the tumor had a rearrangement of the 12q13-15 region, the most frequently involved genomic region in lipogenic tumors, indicates that the tumorigenetic mechanisms are identical in parapharyngeal lipomas and lipomas of other locations. Supernumerary ring markers are not usually detected in lipomas with 12q rearrangements but are common in atypical lipomas and well-differentiated liposarcomas. The parapharyngeal lipoma we describe recurred after initial resection, and we hypothesize that the more aggressive tumor phenotype thus demonstrated may be causally related to the clonal evolution it had undergone.

Chromosomes, Human, Pair 10↗
PubMed1992

Differential responsiveness of normal and simian virus 40-transformed human fibroblast cells to interferon-gamma.

The effect of interferon-gamma (IFN-gamma) on epidermal growth factor (EGF) receptor binding and the proliferation of normal and simian virus 40 (SV40)-transformed human fibroblast cells was compared under identical culture conditions. IFN-gamma induced an enhancement of EGF binding to normal cells, whereas it decreased the EGF binding to SV40-transformed cells. Half-maximal enhancement occurred at 72 h after the normal cells were exposed to 10 U/ml of IFN-gamma, and maximal stimulation was obtained at about 10(2) U/ml of IFN-gamma at 72 h. On the other hand, half-maximal reduction was observed for SV40-transformed cells at less than 10 U/ml of IFN-gamma at 72 h, and maximal reduction was obtained at around 10(3) U/ml of IFN-gamma at 72 h. Scatchard analysis indicated that the number of EGF binding sites of normal and SV40-transformed cells was calculated to be 1.6 x 10(5) and 0.88 x 10(5) per cell, respectively, and was little altered by IFN-gamma treatment. The dissociation constant (Kd) of normal cells, however, decreased from 4.5 nM (control) to 2.0 nM (IFN-gamma-treated), while the Kd of SV40-transformed cells increased from 3.6 nM (control) to 17.0 nM (IFN-gamma-treated). The immunoprecipitation of 125I-labeled EGF-bound EGF receptors with anti-receptor antiserum indicated that a 72-h IFN-gamma treatment did not induce a conformational alteration in the EGF receptors of both normal and transformed cells. The DNA synthesis of normal cells was enhanced by EGF, and IFN-gamma treatment potentiated the effect of EGF on DNA synthesis, probably due to the increased binding affinity of EGF to the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Viral↗
PubMed1992

Comparison of Ki-ras gene mutation among simultaneously occurring multiple urethan-induced lung tumors in individual mice.

Mouse lung tumors were induced in C57BL/6J(female) x A/J(male) F1 mice by a single s.c. injection of urethan. About 6 months later, multiple small-sized lung tumors were detectable in almost all mice. After a further 6 months, some of these tumors became larger than the rest. We examined whether there were any mutational differences among multiple lung tumors in a single mouse. Direct DNA sequencing of a separately amplified Ki-ras gene by polymerase chain reaction (PCR) was carried out with 25 DNA samples from multiple tumors in four mice. Twenty-four of 25 tumors (96%) had mutations at the codon 61 of the Ki-ras gene. The major mutations involved were either AT to GC transition (44%) or AT to TA transversion (44%) at the second base of codon 61. We compared the types of these gene mutations among the tumors from each of two mice from two different groups of siblings and then compared the two groups. Interestingly, in the first group of siblings, we detected CTA in 5/6 tumors in the first mouse and again CTA in 4/6 tumors in the second one. In the second group of siblings, we detected CGA in 5/7 tumors in one mouse and CGA again in 3/5 tumors in the second mouse. These results show that the pattern of Ki-ras codon 61 mutations in urethan-induced lung tumors is similar in tumors developing in siblings, suggesting that host factors have an effect on the carcinogen-induced mutational pattern. There was no major mutational difference between small and large tumors. The results suggested that other event(s) in addition to the mutation of the Ki-ras gene might play a role during the development of large-sized tumors.

Amino Acid Sequence↗
PubMed1992

Responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in multiple myeloma.

The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was investigated in vitro in 21 patients with multiple myeloma to assess the clinical usefulness of rh-Ep in this disease. CFU-E and BFU-E assays were performed by methylcellulose culture methods. The myeloma patients were divided into two groups according to the percentage of plasma cells in the bone marrow (over 50% and under 50%). Among the patients with few plasma cells, some revealed normal CFU-E and BFU-E growth at 2 units of rh-Ep, and no further increase was observed even with an increasing dose of rh-Ep. Among the other patients, more than half demonstrated a good response to rh-Ep. Among the patients with a high percentage of plasma cells, some revealed no response to rh-Ep, but there were patients with a high percentage of plasma cells in the bone marrow who had a good response to rh-Ep. High doses of rh-Ep may be clinically effective in some patients with multiple myeloma independently of the level of plasma cells in the bone marrow.

Aged↗
PubMed1992

Effects of isoflavone compounds on the activation of phospholipase C.

The effect of isoflavone compounds, genistein and daidzein, on the breakdown of inositol phospholipids in 3T3 cells was studied. Genistein (100 micrograms/ml) inhibited the stimulation of the production of inositol phosphates by bombesin. The stimulated production of inositol phosphates by AlF-4 was also inhibited by genistein (IC50 = 0.6 micrograms/ml) and daidzein (IC50 = 2 micrograms/ml). However, the catalytic activity of phospholipase-C (PLC) in 3T3 cell extracts was not inhibited by these isoflavones. These results suggest that the isoflavones inhibited the activation of PLC at the G-protein or downstream of the sequences in signal transduction. In permeabilized 3T3 cells, the inhibition of AlF-4 plus adenosine triphosphate (ATP)-dependent PLC was recovered by increasing ATP but not AlF-4. Genistein also inhibited the activity of adenosine 5'-[3-O-thiotriphosphate] (ATP[S])-dependent PLC. The effect of genistein and other inhibitors of protein tyrosine kinases and phosphatases suggests that protein tyrosine phosphorylation is not involved in the activation of PLC in 3T3 cells and that AlF-4- and ATP[S]-mediated activation of PLC involves a different mechanism from the tyrosine kinase-mediated activation of PLC. Daidzein and genistein seem to interrupt the ATP-dependent step of PLC activation by a putative G-protein.

Animals↗
PubMed1992

Syntheses of 2-(3,4-dimethoxyphenyl)ethylamine derivatives and their antiulcer activities.

A series of acyl derivatives of 2-(3,4-dimethoxyphenyl)ethylamine (4) were synthesized and evaluated for their effectiveness to prevent water-immersion stress-induced gastric ulceration when given intraperitoneally to rats. Among them N-[2-(3,4-dimethoxyphenyl)ethyl]-2-phenylaminoacetamide hydrochloride (15) had significant antiulcer activity. Further modification of the four parts of 15 revealed that only the introduction of a carbamoyl group into 2- or 3-position of the phenylamino part gave compounds (49-51, 54 and 55) which retained antiulcer activity comparable to the lead compound. However, the compounds (49-51 and 54) did not exert a prophylactic effect when administered orally except for the 3-substituted bezamide derivative 55. Alkyl substitution on the nitrogen of benzamide gave 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide (66, DQ-2511) and the related compounds (67, 70, 74 and 77) which all had potent antiulcer activities at oral doses of 50-400 mg/kg.

Animals↗
PubMed1992

Zinc triflate-promoted glycosidation: synthesis of lipid A disaccharide intermediates.

Zinc triflate was found to be superior to the heavy metal salts as a promoter in the Koenigs-Knorr type glycosidation reaction in the synthesis of lipid A disaccharide intermediates. It readily promoted the reaction of a complex glycosyl bromide with a reducing sugar moiety and gave the disaccharide with beta-selectivity in good yield. This method would be suitable for the bulk preparation of lipid A disaccharide intermediates.

Carbohydrate Sequence↗
PubMed1992

A case of primary hyperparathyroidism due to an oxyphil cell adenoma.

A 59-year-old woman with primary hyperparathyroidism was found to have a parathyroid adenoma behind the left clavicle. Preoperatively, it appeared as a hypoechoic mass on ultrasonography, as a hot nodule on thallium scintigraphy, and as a high signal on T2-weighted magnetic resonance imaging. Histological, immunohistochemical and ultrastructural studies of the surgically resected tumor revealed a parathyroid adenoma composed mainly of oxyphil cells with production of a parathyroid hormone. Moreover, a multilocular lesion of lymphangiectasia was contained. Hypercalcemia was alleviated postoperatively. These observations corroborated a functioning parathyroid oxyphil cell adenoma. This is the first case report of functioning oxyphil cell adenoma of the parathyroid gland with lymphangiectasia in Japan.

Adenoma↗
PubMed1992

Aneurysm arising at the triplicate anterior communicating artery--case report.

A very rare case of triplicate anterior communicating artery associated with ruptured aneurysm in a 21-year-old female is reported. The triplicate configuration was not predicted by preoperative cerebral angiography, but found intraoperatively. The aneurysm was trapped successfully, and she recovered with no neurological deficit.

Adult↗
PubMed1992

Expression and assembly of Torpedo californica (Na,K)ATPase alpha-subunit truncated at N-terminal end in Xenopus oocytes.

cDNAs for mutant alpha-subunits of Torpedo californica (Na,K)ATPase variously truncated at the N-terminal end were constructed and transcribed in vitro. Each of the mRNAs thus synthesized was co-injected into Xenopus oocytes together with mRNA for wild-type beta-subunit. Truncation of the alpha-subunit at trypsin accessible site T2(removal of the N-terminal 36 residues, alpha delta K37) led to a decrease in ouabain-sensitive ATPase activity and ouabain-binding capacity, leaving the amount of immunoprecipitable alpha-subunit unchanged. The Km values for Na+ and K+ of alpha delta K37 were about 10mM and 2mM, respectively, and fall in the same range for the wild-type ATPase. Truncation of the alpha-subunit leaving lysine-54(alpha delta K54) or alanine-79(alpha delta A79) resulted in the loss of the ATPase activity as well as a substantial decrease in the amount of immunoprecipitable alpha-subunit. Since the beta-subunit assembles with and thereby stabilizes the alpha-subunit, which is otherwise degraded rapidly, these results suggest that the segment of the alpha-subunit between lysine-37 and lysine-54 is involved in the assembly with the beta-subunit leading to the formation of the stable and active alpha beta complex.

Animals↗
PubMed1992

[Clinical significance of the measurement of serum pepsinogen group I and II by enzyme-linked immunosorbent assay].

We have developed enzyme-linked immunosorbent assay (ELISA) for pepsinogen group I and II (PG I.II) in human serum, and clinical significance of serum pepsinogen measurement was evaluated. Serum PG I.II levels in patients with gastric and duodenal ulcer were higher than those in normal healthy subjects. On the other hand, serum PG I levels in patients with pernicious anemia were significantly low levels. In both gastric ulcer and duodenal ulcer, serum PG I.II levels at active stage were higher than healing stage. These results suggested that the measurement of PG I.II levels was useful for screening or monitoring test for the injury of gastric and duodenal mucosa.

Adolescent↗