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Biomedical subjects

K Hori

Publications and source records attributed to K Hori.

At least 127 records · Page 7Linked to original sources

Adaptive changes in the thermogenesis of rats by cold acclimation and deacclimation.

Male Wistar rats, aged 6 weeks, were maintained at 25 degreesC for 9 to 11 weeks (W group), at 10 degreesC for 9 to 11 weeks (C group), and at 25 degreesC for 2 weeks after exposure to 10 degreesC for 9 weeks (D group). Thermogenesis at 10 degreesC was significantly greater than at 25 degreesC. Thermogenesis per body mass in the C group was greater than in the W and D groups. The RQ value at 10 degreesC was greater than at 25 degreesC in the W group, whereas the opposite was observed in the C and D groups. It is suggested that a large part of enhanced thermogenesis, caused by cold acclimation for 9 weeks, is lost because of a decreased secretion of calorigenic hormones, in spite of a slight decrease in BAT mass, during deacclimation for 2 weeks.

Adaptation, Physiological↗

Hypercoagulable state and disseminated intravascular coagulation following an effective chemotherapy in tumor-bearing rats.

OBJECTIVE: To detect the changes in blood coagulation system and clarify the related mechanisms of chemotherapy-induced disseminated intravascular coagulation. METHODS: Changes in blood coagulation system and immunohistochemistry for fibrinogen were investigated in six groups of rats designed for different purposes. RESULTS: Decreased platelet count, prolonged prothrombin time and active partial thromboplastin time, elevated fibrinogen level, and decreased antithrombin were observed in the rats receiving a newly developed chemotherapy (NDC group), in which mitomycin C was administered intravenously together with angiotensin. Accumulation of fibrinogen and microthrombi in the blood vessels of multiple organs were also found in the NDC group by immunohistochemistry and histopathological examination. CONCLUSIONS: Rapid reduction of tumor mass induced by an effective chemotherapy could cause hypercoagulable state and disseminated intravascular coagulation.

Angiotensins↗

Clinical significance of serum P53 antibody in patients with gastric cancer.

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

Adenoma↗

Molecular evolution of amphioxus fructose-1,6-bisphosphate aldolase.

The cDNA for amphioxus fructose-1,6-bisphosphate (FBP)-aldolase was isolated and its nucleotide sequence was determined. In the cDNA, there existed a probable open reading frame comprising 1080 bp; hence, 359 amino acid residues were deduced. The amino acid sequence indicates the deletion of 4 residues from N-terminus, in comparison with the sequence of FBP-aldolase isozymes from other sources. There was only one FBP-aldolase gene, and one enzyme species corresponding, in the amphioxus; this is the first report of the existence of a single FBP-aldolase species in animals. Enzymatic studies of both native and the recombinant FBP-aldolase suggest that the amphioxus enzyme belongs to an ancestral class I type which is not discovered among vertebrate aldolase isozymes.

Amino Acid Sequence↗

Structure of aldolase A (muscle-type) cDNA and its regulated expression in oocytes, embryos and adult tissues of Xenopus laevis.

We obtained cDNA (XALDA; 1466 bp) for Xenopus laevis aldolase A gene (muscle-type), whose amino acid sequence had 88% similarity to those of mammalian aldolase A genes. XALDA mRNA occurred abundantly in skeletal muscle and at low levels also in other adult tissues, and such mRNA distribution was reflected in zymograms. In oocytes XALDA mRNA occurred at a relatively high level from stage I, and the mRNA level peaked at stage II, then decreased in later stages. XALDA mRNA in the full-grown oocyte was inherited as maternal mRNA throughout maturation and fertilization until midblastula stage, but its level became very low during gastrula and early neurula stages, and then increased greatly in later stages. While maternal XALDA mRNA was distributed uniformly in early embryos, mRNA zygotically expressed after late neurula stage occurred mainly in somites. In blastula animal caps XALDA mRNA occurred at a low level, but the expression was greatly enhanced by activin treatment. Thus, in Xenopus laevis aldolase A gene is actively transcribed in earlier phase of oogenesis, inherited as maternal mRNA in early embryos in a cell-type nonspecific way, then in later phases of embryogenesis, it is strongly expressed in somites with its concomitant ubiquitous expression at low levels in almost all the other cell types.

Activins↗

Selenium supplementation suppresses tumor necrosis factor alpha-induced human immunodeficiency virus type 1 replication in vitro.

Selenium is a nutritionally essential trace element that is important for optimal function of the immune system. It is incorporated into selenoproteins as the amino acid selenocysteine and it is known to inhibit the expression of some viruses. In this study, we show that selenium supplementation for 3 days prior to exposure to tumor necrosis factor alpha (TNF-alpha) partially suppresses the induction of human immunodeficiency virus type 1 (HIV-1) replication in both chronically infected T lymphocytic and monocytic cell lines. In acute HIV-1 infection of T lymphocytes and monocytes in the absence of exogenous TNF-alpha, the suppressive effect of selenium supplementation was not observed. However, selenium supplementation did suppress the enhancing effect of TNF-alpha on HIV-1 replication in vitro in acutely infected human monocytes, but not in T lymphocytes. Selenium supplementation also increased the activities of the selenoproteins, glutathione peroxidase (GPx) and thioredoxin reductase (TR), which serve as cellular antioxidants. Taken together, these results suggest that selenium supplementation may prove beneficial as an adjuvant therapy for AIDS through reinforcement of endogenous antioxidative systems.

Cells, Cultured↗

Mode of interactions of human aldolase isozymes with cytoskeletons.

Three isoforms of fructose-1,6-bisphosphate aldolase were found to bind specifically to the actin-containing filament of the cytoskeleton and to show tissue-specific binding patterns. Aldolase A (muscle type) bound more tightly to the skeletal muscle cytoskeleton among the three isozymes, while aldolase B (liver type) preferred the liver cytoskeleton to those of other tissues. The specific binding of aldolase A to the skeletal muscle cytoskeleton was inhibited strongly by the substrates fructose 1,6-bisphosphate and fructose 1-phosphate. Several mutant aldolases A were examined to identify the amino acid residues or regions that play a role in specific binding. Among the mutant aldolases tested, A-E34D, A-K41N, and A-Y363S exhibited remarkably reduced binding activities. Experiments using FITC-labeled enzymes and Rh-labeled phalloidin disclosed that aldolase A associated with the cytoskeleton. Specifically, when aldolase A was incubated with human fibroblast MRC-5 permeabilized with Triton X-100, aldolase A bound to the actin filaments in the stress fibers within the cell. Aldolase A reversibly inhibited the contraction of MRC-5 cells which usually occurred in the presence of Mg2(+)-ATP and Ca2+. These results provide direct evidence that aldolase binds specifically to the actin-containing stress fibers and suggest that aldolase may regulate cell contraction through its reversible binding to the filaments in the permeabilized MRC-5 fibroblast.

Actin Cytoskeleton↗

Subfornical organ efferents enhance extracellular noradrenaline concentrations in the median preoptic area in rats.

The present study was carried out to examine whether angiotensinergic pathways from the subfornical organ (SFO) regulate the noradrenergic system in the median preoptic nucleus (MnPO). Intracerebral microdialysis techniques were used to quantify the extracellular concentration of noradrenaline (NA) in the MnPO area. In urethane-anesthetized male rats, electrical stimulation (5-20 Hz, 0.6 mA) of the SFO significantly increased the NA concentration in the MnPO area, and the increase was significantly diminished by pretreatment with the angiotensin II (ANG II) antagonist saralasin (Sar; 5 microg), into the third ventricle (3V). Injections of ANG II (5 microg) into the 3V significantly enhanced NA release in the MnPO area. The data imply that the angiotensinergic pathways from the SFO to the MnPO may act to enhance NA release in the MnPO area.

Angiotensin II↗

Lamprey fructose-1,6-bisphosphate aldolase: characterization of the muscle-type and non-muscle-type isozymes.

To study evolutionary aspects of fructose-1,6-bisphosphate (Fru-1,6-P2) aldolase during deuterostomian evolution, we have purified and characterized aldolases from the muscle and liver of lamprey (Entosphenus japonicus). Aldolase from the skeletal muscle and liver was identified to be the muscle-type isozyme and the non-muscle-type isozyme that was encoded by cDNAs M8 and L3, respectively, as described previously (Zhang, R., Yatsuki, H., Kusakabe, T., Iwabe, Miyata, T., Imai, T., Yoshida, M., and Hori, K., J. Biochem. 117, 545-553, 1995). The muscle-type isozyme has properties similar to vertebrate aldolase A, while the non-muscle-type isozyme shows a similarity to bacterial class I aldolase and vertebrate aldolase C but not to aldolase B, the liver-type aldolase, in terms of kinetic parameters: the Kcat values toward Fru-1,6-P2 and Fru-1-P, the Fru-1,6-P2/Fru-1-P activity ratio, and the Km values toward these substrates. The two enzymes have tetrameric forms with a molecular mass of approximately 160,000 and have similar pH optimum. The muscle-type and non-muscle-type isozymes from the tissues show different electrophoretic mobility; the muscle-type isozyme moves much faster than the non-muscle-type isozyme toward anodic side. The recombinant muscle-type and non-muscle-type aldolases gave similar characteristics as those from the tissues. The results presented in this paper, together with the data presented in the previous paper, strongly suggest that in lamprey it is possible to have two types of aldolase isozymes rather than one or three isozymes.

Amino Acid Sequence↗

Effects of discrimination learning on the rat striatal dopaminergic activity: a microdialysis study.

The prefrontal cortex (PFC) has anatomical and functional relationships with the striatum. In a previous study we showed that dopamine (DA) turnover in the PFC of rats is enhanced during the performance of a discrimination task. In the present study, we used an in vivo microdialysis method to examine whether DAergic activity in the striatum could also be altered by the discrimination task. The results showed a substantial and sustained suppression of DAergic activity during and after the discriminative behaviour. The fact that the discriminative performance induced opposite changes in DAergic activity in the striatum and the PFC is consistent with the results of biochemical studies, suggesting that the suppressed DA turnover in the striatum may be induced by the enhanced DAergic activity in the PFC during the discrimination task.

3,4-Dihydroxyphenylacetic Acid↗

Caenorhabditis elegans has two isozymic forms, CE-1 and CE-2, of fructose-1,6-bisphosphate aldolase which are encoded by different genes.

Two distinct types of cDNAs for fructose-1,6-bisphosphate (FBP) aldolase, Ce-1 and Ce-2, have been isolated from nematode Caenorhabditis elegans, and the respective recombinant aldolase isozymes, CE-1 and CE-2, have been purified and characterized. The Ce-1 and Ce-2 are 1282 and 1248 bp in total length, respectively, and both have an open reading frame of 1098 bp, which encodes 366 amino acid residues. The entire amino acid sequences deduced from Ce-1 and Ce-2 show a high degree of identity to one another and to those of vertebrate and invertebrate aldolases. The highest sequence diversity was found in the carboxyl-terminal region that corresponds to one of the isozyme group-specific sequences of vertebrate aldolase isozymes that play a role in determining isozyme-specific functions. Southern blot analysis suggests that CE-1 and CE-2 are encoded by different genes. Concerning general or kinetic properties, CE-2 is quite different from CE-1. CE-1 exhibits unique characteristics which are not identical to any aldolase isozymes previously reported, whereas CE-2 is similar to vertebrate aldolase C. These results suggest that CE-2 might preserve the properties of a progenitor aldolase with a moderate preference for FBP over fructose 1-phosphate (F1P) as a substrate, whereas CE-1 evolved to act as an intrinsic enzyme that exhibits a much broader substrate specificity than dose CE-2.

Amino Acid Sequence↗

Squamous cell carcinoma of the endometrium with human papillomavirus type 31 and without tumor suppressor gene p53 mutation.

Primary squamous cell carcinoma of the endometrium (ESCC) is extremely rare. There has been no report of human papillomavirus (HPV) detected in ESCC. A 64-year-old Japanese female underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and dissection of the pelvic, para-aortic, and bilateral inguinal lymph nodes. The tumor was confined to the endometrium, without invasion of myometrium or cervix. The endometrium was seen to be replaced by moderately differentiated squamous cell carcinoma, without any adenocarcinomatous element. Polymerase chain reaction amplification produced a 244- to 256-bp DNA fragment from the L1 region of the HPV genome. The amplification products were restricted, and the restricted fragment length polymorphism patterns were analyzed. The squamous cell carcinoma DNA was amplified for each exon, 5 through 8, of the p53 gene. The amplification products were used in single-stranded conformation polymorphism analysis. The tumor described showed the presence of HPV DNA. This amplified fragment was further purified by extraction from agarose gel, and the DNA was sequenced. Comparison of the fragment DNA sequence with known PV sequences showed that it had been amplified from HPV type 31. This is the first detection of HPV DNA in ESCC. Despite previous reports, HPV cannot not be excluded as a possible factor in the development of the malignancy.

Carcinoma, Squamous Cell↗

A comparison of physical properties, oxalate-oxalic acid soluble substances, protein content, and in vitro protein digestibility of the blue-green alga Nostoc commune Vauch. from the Philippines and Japan.

The physical properties, amount of oxalate-oxalic acid soluble substances (OOSS), protein and in vitro protein digestibility of Nostoc commune from the Philippines and Japan were determined. The samples were the spherical type from the Philippines (PS), the dry field discoid type from the Philippines (PD), and the dry field discoid type from Japan (JD). The discoid types, PD and JD, regardless of origin showed higher settling volume in water (SV) and bulk density than PS. The OOSS values obtained for all samples were directly related to SV and bulk density. The WHC level was highest in PS. This desirable characteristic makes PS a technologically potential sample for large-scale food production applications in the future. Protein and in vitro protein digestibility varied significantly among all samples. In general, the algal samples examined possess desirable physical properties which are expected to be related to physiological functions.

Chemical Phenomena↗

An estimate of divergence time of Parazoa and Eumetazoa and that of Cephalochordata and Vertebrata by aldolase and triose phosphate isomerase clocks.

Previously we suggested that four proteins including aldolase and triose phosphate isomerase (TPI) evolved with approximately constant rates over long periods covering the whole animal phyla. The constant rates of aldolase and TPI evolution were reexamined based on three different models for estimating evolutionary distances. It was shown that the evolutionary rates remain essentially unchanged in comparisons not only between different classes of vertebrates but also between vertebrates and arthropods and even between animals and plants, irrespective of the models used. Thus these enzymes might be useful molecular clocks for inferring divergence times of animal phyla. To know the divergence time of Parazoa and Eumetazoa and that of Cephalochordata and Vertebrata, the aldolase cDNAs from Ephydatia fluviatilis, a freshwater sponge, and the TPI cDNAs from Ephydatia fluviatilis and Branchiostoma belcheri, an amphioxus, have been cloned and sequenced. Comparisons of the deduced amino acid sequences of aldolase and TPI from the freshwater sponge with known sequences revealed that the Parazoa-Eumetazoa split occurred about 940 million years ago (Ma) as determined by the average of two proteins and three models. Similarly, the aldolase and TPI clocks suggest that vertebrates and amphioxus last shared a common ancestor around 700 Ma and they possibly diverged shortly after the divergence of deuterostomes and protostomes.

Amino Acid Sequence↗

Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Abnormalities of the p53 gene can lead to the production of anti-p53 antibody in the serum of cancer patients. We evaluated the prognostic significance of anti-p53 antibody in 86 patients with hepatocellular carcinoma (HCC) in comparison with clinicopathological factors: age, sex, etiology, smoking and drinking habits, history of blood transfusion, presence of encephalopathy and ascites, Child classification, Pugh score, bilirubin, albumin, prothrombin time, indocyanine green retention time at 15 min (ICG), underlying liver disease, alpha-fetoprotein (AFP), tumor size, number of tumors, differentiation degree of HCC, presence of extrahepatic metastasis and therapy for HCC. METHODS: The serum anti-p53 antibody in 86 patients with HCC, 20 with chronic hepatitis (CH) and 20 with liver cirrhosis (LC) was measured by an enzyme-linked immunosorbent assay (ELISA). A single-strand conformation polymorphism-polymerase chain reaction (SSCP-PCR) analysis and loss of heterozygosity (LOH) study of the p53 gene were performed using 8 tissue samples of 8 HCC from four antibody-positive and four antibody-negative patients. The survival probabilities were assessed by the Kaplan-Meier technique, and a Cox regression analysis was used to identify the independent factors for prognosis. RESULTS: Anti-p53 antibody was positive in 32% (28 of 86) of the sera from patients with HCC, but in none of the 20 with CH and 20 with LC. p53 antibody positivity was associated with bilirubin and the number of tumors (p=0.027 and p=0.018, respectively). Overall survival was shorter in the HCC patients with p53 antibody than in those without p53 antibody (p<0.02). Bilirubin, p53 antibody, AFP and ICG were found to be significant prognostic factors by univariate analysis. A Cox multivariate analysis showed that bilirubin and p53 antibody were independent prognostic variables (p<0.0001 and p=0.003, respectively). In four antibody-positive patients, mutation and LOH of the p53 gene were detected in one patient and two patients, respectively. In contrast, only one of four antibody-negative patients exhibited LOH of the p53 gene. CONCLUSIONS: Serum anti-p53 antibody could be a useful prognostic factor in patients with HCC.

Adult↗

Increased growth and incidence of lymph node metastases due to the angiogenesis inhibitor AGM-1470.

Using the rat tumour cell line LY80, a subline of Yoshida sarcoma, the effects of AGM-1470 on the growth of primary tumour and the incidence of regional lymph node metastasis were evaluated. AGM-1470 (30 mg kg(-1)) was administered subcutaneously or intravenously. Subcutaneous (s.c.) and intravenous (i.v.) injections were repeated for 8 days and 7 days respectively. Tumour growth of a primary region tended to be suppressed by AGM-1470. The s.c. tumours after sacrifice were much smaller in the AGM-1470-treated group (s.c. injection) than in the control groups. However, the growth of metastatic foci in the lymph nodes was prompted markedly by AGM-1470. All six of the AGM-1470-treated rats had developed swollen axillary lymph nodes and/or brachial lymph nodes on day 19 after tumour implantation (the 7th day after the last treatment) compared with one of six saline-injected rats and three of six vehicle-alone treated rats with swollen axillary lymph nodes. The weight of lymph nodes after sacrifice in the AGM-1470-treated rats was much heavier than that of the other two groups. Histological examination showed that in the AGM-1470-treated group, the cortex and the medulla of the axillary lymph nodes were almost entirely replaced by tumour cells while, in the vehicle alone group, a notable hyperplasia of the lymph nodes due to BT cell proliferation tended to be induced. In the saline group, although a slight hyperplasia of lymph nodes was observed, there were only a few lymph node metastases. In the case of i.v. injection of AGM-1470, similar results were obtained. It is thought that LY80 cells spread to regional lymph nodes at a comparatively early stage by some change or other in which AGM-1470 participated. From the present experiment, it is concluded that application of AGM-1470 alone to patients should be carried out with great caution.

Animals↗

Characterization of gramicidin S synthetase aggregation substance: control of gramicidin S synthesis by its product, gramicidin S.

An aggregation substance of gramicidin S synthetases was found and purified by DEAE-cellulose chromatography and CM-chromatography from cell debris of Bacillus brevis Nagano. It specifically aggregated and inactivated gramicidin S synthetases 1 (GS1) and 2 (GS2). On the basis of amino acid composition analysis, reversed-phase HPLC, FAB mass spectrometry, amino acid sequence analysis, and antibacterial activity, this substance (GrS-aggregation substance) was identified as gramicidin S. A gramicidin S derivative bearing a lysine residue in place of one ornithine residue was also detected as a minor component of GrS-aggregation substance. The extent of the aggregation was dependent on the concentration and relative amount of gramicidin S. The inhibition of the enzyme activities was irreversible and the inhibition was proportional to the amount of gramicidin S, like the aggregation of the enzymes. The degree of GS2 inhibition in the amino acid-dependent ATP-PPi exchange reaction varied with the amino acids of gramicidin S and increased in order of the amino acid sequence of gramicidin S. The degree of inhibition of the overall synthesis of gramicidin S was the same as that in the leucine-dependent exchange reaction.

Amino Acid Isomerases↗