Biomedical subjects

Y Harada

Publications and source records attributed to Y Harada.

At least 289 records · Page 16Linked to original sources

PubMed1995

The role of cyclic AMP in the lipopolysaccharide-induced suppression of thymidine kinase activity in macrophage.

We observed that lipopolysaccharide (LPS, 1 micrograms/ml) can suppress [3H]thymidine incorporation into acid-insoluble fraction in a mouse macrophage cell line J774 (over 70% at 6 h) without affecting the uptake of [3H]thymidine or DNA polymerase activity. Paralleling this suppression, a decrease in the thymidine kinase (TK) activity, but not of thymidine monophosphate (TMP) kinase and thymidine diphosphate (TDP) kinase, was observed. LPS dose-dependently increased intracellular cAMP levels to about 3.5-times basal at 6 h, proportionally to the decrease of the TK activity. Elevation of intracellular cAMP by several reagents also decreased TK activity. Apparently LPS treatment elevates cAMP concentration by decreasing the low Km cAMP phosphodiesterase activity (58% at 6 h). The time course of cAMP-dependent protein kinase (PK-A) activity during the first 6 h after LPS treatment correlated with that of cAMP concentration. Treatment with a PK-A inhibitor restored about 63% of LPS-induced reduction of TK activity at 6 h. At longer times, however, there was a discrepancy between the change of cAMP concentration or PK-A activity and the reduction of TK activity. Therefore, protein kinase activation caused by the accumulation of intracellular cAMP probably triggers some mechanism responsible for the reduction of the TK activity.

Cells, Cultured↗

PubMed1995

Evaluation of plasma 11-dehydro-thromboxane B2 as an indicator for thromboxane A2 synthesis in vivo in laboratory animals.

Since thromboxane (TX) B2 is not a reliable indicator of TXA2 generation in vivo, because of artifactual TXA2 generation during blood collection, we tested the feasibility of replacing TXB2 with 11-dehydro (dh)-TXB2 as the indicator. Plasma levels of TXB2 and 11-dh-TXB2 were measured after i.v. administration of TXB2 to rabbits, guinea pigs, rats, dogs and a monkey, and after i.v. infusion of collagen in rabbits. In the rabbits and dogs, 2,3-dinor-TXB2 levels were also measured. After intravenous injection of TXB2 (10 micrograms/kg) in rabbits, the ratio of the area under the curve (AUC) of 11-dh-TXB2 to that of TXB2 (1.94) was far higher than the AUC ratio between 2,3-dinor-TXB2 and TXB2 (0.42). When endogenous TXA2 was generated by infusion of collagen (2 mg/kg/5 min), the plasma level of 11-dh-TXB2 was significantly increased, and had a longer half-life than TXB2. In the guinea pigs, rats and monkey, the peak plasma levels of 11-dh-TXB2 were significantly increased after injection of TXB2 (10 micrograms/kg, i.v.), whereas the AUC ratios of 11-dh-TXB2/TXB2 were less than one fourth of that in rabbits. No significant increase in 11-dh-TXB2 was observed after TXB2 injection (10 micrograms/kg) in dogs, but the 2,3-dinor-TXB2 level rose significantly, its AUC ratio to TXB2 being 0.29, comparable with that in rabbits. The order of the 11-dh-TXB2/TXB2 AUC ratios was: rabbits > guinea pigs > monkey > rats >> dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Population persistence and spatially limited social interaction.

We investigate the persistence of a population composed of socially interacting individuals living in a lattice structured habitat and the effect of spatially limited social interaction, reproduction, and migration. Both cooperative interaction (enhancing the survivorship of neighboring individuals) and competitive interaction (reducing it) are examined. Mathematical analysis based on pair approximation (or doublet decoupling approximation) and computer simulation are used. Results are: If migration rate is not very large, the population tends to form clusters of individuals (clumped distribution) due to spatially limited reproduction. Although cooperative interaction is more effective in a spatially structured population, the population is more difficult to persist than in the corresponding population without spatial structure, because the shortage of nearest neighbor vacant sites reduces reproduction. Migration of individuals reduces the clumping of the spatial pattern. Pair approximation predicts the equilibrium density fairly accurately when the predicted density is sufficiently high (i.e., more than 40% sites are occupied). If the predicted density is low however, the pair approximation overestimates the equilibrium population level. To overcome this disagreement, we examined improved pair approximation.

Bias↗

PubMed1995

Characterization of cell surface antigens expressed in the HMA-1 breast cancer cell line.

This report describes the characterization of an estrogen receptor-positive breast cancer cell line, HMA-1, established from a breast cancer patient, based on the expression of tumor-associated antigens (TAAs), the HLA-DR antigen, and the c-erbB-2 proto-oncogene product. In flow cytometric and immunohistochemical analyses, HMA-1 was found to express increased levels of several TAAs including MUC1, TAG-72 (sialyl Tn), Tn, T, sialyl Le(a), Le(x), and Le(y). HMA-1 also expressed enhanced levels of the HLA-DR antigen and c-erbB-2 protein. These results indicate that HMA-1 is a unique cell line with abundant TAAs which may serve as an appropriate breast cancer cell line for application in the multidisciplinary research of breast cancer.

Amino Acid Sequence↗

PubMed1995

Carcinoma of the reconstructed stomach tube following esophageal resection for a benign stricture: report of a case and review of the literature.

We report herein the case of a 60-year-old woman who presented with dysphagia and anorexia and was subsequently diagnosed as having gastric cancer of the reconstructed stomach tube 36 years after undergoing surgery for a benign esophageal stricture. Reports on carcinoma of the reconstructed stomach tube are rarely found and interestingly, all of the previous cases, which were documented only in the Japanese literature, corresponded to metachronous double cancers after esophageal malignancies. To our knowledge, this is the first case of carcinoma of the reconstructed stomach tube following esophageal resection for a benign stricture, and it is thought that the carcinoma probably developed at the site of the anastomosis a long time after the first operation. We reviewed 30 cases of carcinoma of the reconstructed stomach tube for which the clinicopathological data was complete, and we believe that this new type of cancer needs more than 10 years to develop and should be defined as "carcinoma of the gastric remnant".

Adenocarcinoma↗

PubMed1995

Inheritance of mitochondrial DNA in sexual crosses and protoplast cell fusions in Lentinula edodes.

By using mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) as genetic markers, the modes of mitochondrial inheritance in sexual crosses and protoplast cell fusions of the higher basidiomycete Lentinula edodes were examined. All newly established dikaryons from reciprocal crosses between compatible monokaryons carrying different mtDNA RFLP phenotypes retained mtDNA genotypes from one of the monokaryons, suggesting that mitochondrial inheritance is principally uniparental. In contrast, it was shown that recombinant mtDNA genomes arose in some dikaryons obtained after protoplast cell fusion. Based on these results, a possible mechanism for mitochondrial inheritance in L. edodes is discussed.

Agaricales↗

PubMed1995

Can concordant criss-cross heart be ameliorated by hemodynamic changes?

A 2-year-old female child with "ameliorated" concordant criss-cross heart, complicated superior-inferior ventricles, complete transposition of great arteries, hypoplastic right ventricle, ventricular septal defect, and aortic coarctation is described. The patient underwent subclavian flap, pulmonary artery banding, and balloon atrioseptostomy at age 1 month. The ameliorated concordant criss-cross anatomy was obtained after 2 years of follow-up. This dynamic morphologic change allowed us to perform a subsequent anatomic correction.

Aortic Coarctation↗

PubMed1995

Role of WDR neurons in a hind limb noxious heat evoked flexion withdrawal reflex.

Behavioral experiments and neurophysiological experiments, the two major types of preclinical studies which have paved the way for the development of spinal analgesia were compared under identical conditions utilizing the same animals. The results demonstrate that the activation of the wide dynamic range (WDR) neurons preceded the behavioral withdrawal reflexes, and that the activation of the WDR neurons occurred at lower stimulus temperature than that for the withdrawal reflex. The results suggest that the neuronal activation began before the behavioral reflex but also that the firing frequency of the WDR neurons at the time of the withdrawal reflex could not distinguish between non-noxious and noxious stimuli. Further study is needed to elucidate the neuronal mechanisms of the activation of the behavioral reflex.

Animals↗

PubMed1995

Nitroxidergic vasodilator nerve in the canine nasal mucosa.

The canine nasal mucosa was studied by in vitro bioassay. Non-adrenergic, non-cholinergic (NANC) vasodilator response to transmural electrical stimulation was observed in the presence of guanethidine and atropine. This vasodilator response was abolished by NG-nitro-L-arginine (L-NA) which is an inhibitor of nitric oxide (NO) formation but not by NG-nitro-D-arginine. The inhibitory effect of L-NA was partially reversed by treatment with L-arginine but not with D-arginine. The vasodilator response was significantly suppressed by tetrodotoxin. The present results indicate that NO may mediate neurogenic vasodilation in the canine nasal mucosa.

Animals↗

PubMed1995

Effect of troglitazone (CS-045) and bezafibrate on glucose tolerance, liver glycogen synthase activity, and beta-oxidation in fructose-fed rats.

To clarify the relationship between lipid and glucose metabolism abnormalities in fructose-fed rats, we examined whether an improvement of insulin sensitivity by troglitazone (CS-045) or a decrease in plasma lipids by bezafibrate affects the relationship between serum levels of lipid and glucose. In addition, we also examined changes in liver glycogen metabolism and beta-oxidation in fructose-fed rats. Troglitazone ameliorated fasting hyperlipidemia, hyperglycemia, and hyperinsulinemia. In addition, it augmented glycogen synthase activity by 53%, and decreased the mitochondrial palmitic acid beta-oxidation rate and ketone body production rate by 27% and 55%, respectively. However, hyperglycemia and liver glycogen synthase activity were not improved by bezafibrate treatment despite a marked reduction of serum triglyceride (TG) levels resulting from a 1.76-fold increase in mitochondrial oxidation and a 2.04-fold increase in hepatic ketone body production. These results suggest that abnormalities in glucose and lipid metabolism in fructose-fed rats, which are ameliorated by troglitazone, may be closely linked to reduced glycogen synthase activity in the liver.

Animals↗

PubMed1995

Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer.

To investigate possible relationships between genetic alterations and hormonal deregulation during breast cancer development and/or progression, we examined 616 primary breast cancers for loss of heterozygosity (LOH) at chromosomal regions 16q24, 17p13.3 and 17q21, and for amplifications of the ERBB2 and c-MYC loci. A comparison of oestrogen receptor (ER) and progesterone receptor (PgR) status in tumour cells with data concerning these genetic alterations revealed that LOH at 17q21 was significantly correlated with absence of oestrogen receptors (ER) (P < 0.0003) or progesterone receptors (PgR) (P < 0.0001), and with the absence of both (P < 0.0001). Similarly, a significant association was observed between amplification of ERBB2 and the absence of either ER or PgR. LOH at 17p13.3 was associated with the absence of PgR (P < 0.01). These data suggest a possible relationship between specific genetic changes on chromosome 17 and hormonal deregulation in the progression of breast cancer.

Breast Neoplasms↗

PubMed1995

Correlation between the induction of a gene for delta 1-pyrroline-5-carboxylate synthetase and the accumulation of proline in Arabidopsis thaliana under osmotic stress.

The isolation and characterization is reported of a cDNA for delta 1-pyrroline-5-carboxylate (P5C) synthetase (cAtP5CS), an enzyme involved in the biosynthesis of proline, from a cDNA library prepared from a dehydrated rosette plant of Arabidopsis thaliana. Southern blot analysis suggested that only one copy of the corresponding gene (AtP5CS) is present in A. thaliana. The deduced amino acid sequence of the P5CS protein (AtP5CS) from A. thaliana exhibited 74% homology to that of the P5CS from Vigna aconitifolia. Northern blot analysis revealed that the gene for P5CS was induced by dehydration, high salt and treatment with ABA, while it was not induced by heat or cold treatment. Moreover, the simultaneous accumulation of proline was observed as a result of the former treatments in A. thaliana. A cDNA for P5C reductase (cAtP5CR) was also isolated from A. thaliana and Northern blot analysis was performed. The AtP5CR gene was not induced to a significant extent by dehydration or high-salt stress. These observations suggest that the AtP5CS gene plays a principal role in the biosynthesis of proline in A. thaliana under osmotic stress.

1-Pyrroline-5-Carboxylate Dehydrogenase↗

PubMed1995

Temporally distinctive changes of alternative splicing patterns during myogenic differentiation of C2C12 cells.

It is well known that skeletal muscle differentiation is accompanied by the appearance of many muscle-specific components and that some of these components are generated through muscle-specific alternative splicing. It is not clear, however, in what manner, including timing, the system that regulates the muscle-specific splicing reactions is constructed during the process of myogenic differentiation. We simultaneously examined the changes in several splicing patterns for the neural cell adhesion molecule (NCAM), beta-tropomyosin, and M-type pyruvate kinase genes during myogenic differentiation of cultured myoblasts using the reverse transcription-polymerase chain reaction method. The NCAM glycosylphosphatidylinositol anchor form increased in preference to the transmembrane form immediately after the induction of differentiation, while the selection of NCAM MSD1 (muscle-specific domain 1) exons started and abruptly increased at about the time when cell-fusion appeared. M2-type pyruvate kinase was gradually substituted for the M1-type molecule. Skeletal muscle-type beta-tropomyosin was predominantly selected even in myoblasts in the growth medium. As a result, each transcript of these genes independently showed a temporally distinctive pattern of change in isoform selecting during the myogenic differentiation of C2C12 cells. These observations suggest that some independent regulation of alternative splicing reactions should occur during myogenic differentiation.

Alternative Splicing↗

PubMed1995

Contrasting actions of intrathecal U50,488H, morphine, or [D-Pen2, D-Pen5] enkephalin or intravenous U50,488H on the visceromotor response to colorectal distension in the rat.

BACKGROUND: Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model. METHODS: The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously. RESULTS: Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg. CONCLUSIONS: The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1995

Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H.

BACKGROUND: Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H). METHODS: Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined. RESULTS: Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine. CONCLUSIONS: Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1995

A specific chromosome abnormality of t(4;12)(q11-12;p13) in CD7+ acute leukaemia.

Three cases of acute leukaemia with t(4;12) (q11-12;p13) karyotypic abnormalities were analysed. They had the following common clinical and biological characteristics: (1) dysplasia of three haemopoietic lineages: (2) absent or low myeloperoxidase activity: and (3) retention of platelets in the peripheral blood and megakaryocytes in the bone marrow. There were increased numbers of basophils in the bone marrow and peripheral blood in two of the cases. In all, the blast cells displayed the unique immunophenotype CD7+CD13+CD34+HLA-DR+. The blasts analysed in one case expressed c-kit on the membrane surface. These findings suggest that the t(4;12) (q11-12;p13) abnormality is associated with a particular type of acute leukaemia, one in which the morphology and immunophenotype suggest that the translocation may have occurred at an early stage of haemopoiesis.

Acute Disease↗

PubMed1995

Human metalloprotease/disintegrin-like (MDC) gene: exon-intron organization and alternative splicing.

A recently identified gene encoding a metalloprotease-like, disintegrin-like, cysteine-rich protein (MDC) represents a candidate tumor suppressor gene for human breast cancer based on its location within a minimal region of chromosome 17q21 previously defined by tumor deletion mapping. The work reported here has shown that the MDC gene consists of 28 exons interrupted by relatively short introns, most of them 67 bp to 5 kb in length. We have identified two forms of transcripts generated by alternative splicing. The more abundant form encodes a protein of 769 amino acids; the other, a previously described cDNA, encodes 524 amino acids. Exons 1a, 1b, 1c, 1d, and 2-7 encode a proprotein domain; exons 7-13, a metalloprotease-like domain; exons 14-17, a disintegrin domain; exons 18-22, a cysteine-rich domain, including an epidermal growth factor (EGF)-like repeat domain within exons 21 and 22; exon 23, a transmembrane domain; and exons 24 and 25, a short cytoplasmic domain. These results show that human MDC contains a mosaic of exons capable of encoding several functional domains.

ADAM Proteins↗

PubMed1995

A sea urchin homologue of the chordate Brachyury (T) gene is expressed in the secondary mesenchyme founder cells.

Chordates are thought to have emerged from some common ancestor of deuterostomes by organizing shared anatomical and embryological features including a notochord, a dorsal nerve cord and pharyngeal gill slits. Because the notochord is the most prominent feature of chordates and because the Brachyury (T) gene is essential for notochord formation, the T gene is a key molecular probe with which to explore the origin and evolution of chordates. We investigated whether the sea urchin (echinoderm) conserves the T gene and, if so, where the sea urchin T gene is expressed. A cDNA clone for the sea urchin T (HpTa) gene contained a long open reading frame that encodes a polypeptide of 434 amino acids. Although the overall degree of amino acid identity was not very high (52%, sea urchin/mouse), in the T domain of the N terminus the amino acid identity was 73% (sea urchin/mouse). The HpTa gene is present as a single copy per haploid genome. As with the chordate T gene, the expression of HpTa is transient, being first detected in the swimming blastula, maximally transcribed in the gastrula, decreasing at the prism larval stage and barely detectable at the pluteus larval stage. HpTa transcripts were found in the secondary mesenchyme founder cells, vegetal plate of the mesenchyme blastula, extending tip of the invaginating archenteron and, finally, the secondary mesenchyme cells at the late-gastrula stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗