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Biomedical subjects

K Hori

Publications and source records attributed to K Hori.

At least 91 records · Page 5Linked to original sources
PubMed1999

Human NK cells express endothelial nitric oxide synthase, and nitric oxide protects them from activation-induced cell death by regulating expression of TNF-alpha.

Although NO appears important in rodent immune responses, its involvement in the human immune system is unclear. We report that human NK cells express constitutive endothelial NO synthase mRNA and protein, but not detectable levels of inducible NO synthase. They produce NO following activation by coculture with target cells or cross-linking with anti-CD16 mAb, and production is increased in the presence of IL-2. N-monomethyl-L-arginine (L-NMA), a NOS inhibitor, partially inhibited NK cell lysis of four different target cells (<40% inhibition at 500 microM L-NMA), but not granule release following coculture with target cells, or Fas ligand induction following cross-linking with anti-CD16 mAb. However, L-NMA augmented apoptosis of NK cells induced by activation through CD16 ligation or coculture with K562. An NO donor, S-nitroso-N-acetylpenicillamine (SNAP), suppressed apoptosis of NK cells induced by CD16 cross-linking or coculture with target cells, suggesting that endogenous NO production is involved in protection of NK cells from activation-induced apoptosis, thereby maintaining NK activity. SNAP also suppressed, and L-NMA enhanced, expression of TNF-alpha, reported to be involved in activation-induced NK cell death, in response to CD16 cross-linking. Suppression of anti-CD16-induced apoptosis by SNAP was reversed by the addition of rTNF-alpha. DNA-binding activity of the transcription factor, NF-AT, which is involved in TNF-alpha induction upon ligation of CD16, was inhibited by SNAP and enhanced by L-NMA. Our results suggest that down-regulation of TNF-alpha expression, possibly due to suppression of NF-AT activation, is a mechanism by which endogenous NO protects NK cells from activation-induced apoptosis, and maintains lytic capacity.

Adjuvants, Immunologic↗
PubMed1999

Establishment of a simple and practical procedure applicable to therapeutic angiogenesis.

BACKGROUND: Therapeutic angiogenesis is thought to be beneficial for serious ischemic diseases. This investigation was designed to establish a simple and practical procedure applicable to therapeutic angiogenesis. METHODS AND RESULTS: When cultured skeletal muscle cells were electrically stimulated at a voltage that did not cause their contraction, vascular endothelial growth factor (VEGF) mRNA was augmented at an optimal-frequency stimulation. This increase of VEGF mRNA was derived primarily from transcriptional activation. Electrical stimulation increased the secretion of VEGF protein into the medium. This conditioned medium then augmented the growth of endothelial cells. The effect of electrical stimulation was further confirmed in a rat model of hindlimb ischemia. The tibialis anterior muscle in the ischemic limb was electrically stimulated. The frequency of stimulation was 50 Hz and strength was 0.1 V, which was far below the threshold for muscle contraction. After a 5-day stimulation, there was a significant increase in blood flow within the muscle. Immunohistochemical analysis revealed that VEGF protein was synthesized and capillary density was significantly increased in the stimulated muscle. Rats tolerated this procedure very well, and there was no muscle contraction, muscle injury, or restriction in movement. CONCLUSIONS: We propose this procedure as a simple and practical method of therapeutic angiogenesis.

Animals↗
PubMed1999

Human astrocytes inhibit HIV-1 expression in monocyte-derived macrophages by secreted factors.

OBJECTIVE: To determine the effects of primary human fetal and adult astrocytes on HIV-1 replication in monocyte-derived macrophages (MDM). DESIGN: HIV-1 can infect the brain in the early stage of systemic infection. The HIV-1-associated cognitive/motor complex develops later in the course of the disease, suggesting that brain cells may inhibit the early productive infection and the development of neurological disease. In this study, we established an in-vitro coculture system to determine whether astrocytes can modulate HIV-1 replication in MDM. METHODS: Elutriated human monocytes were differentiated in culture, then infected with monocyte tropic HIV-1. One day after infection, MDM were co-cultured with primary astrocytes. Reverse transcriptase (RT) activity was used to monitor virus replication. RT-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and bioassay were used to assess cytokine production. RESULTS: Primary human astrocytes suppressed HIV-1 replication in MDM via the production of soluble factors. Cytokine inhibitors of HIV-1, such as IFN-gamma, IL-4, IL-10 and IL-13, were not detectable, whereas transforming growth factor beta (TGF-beta) was constitutively produced only in its latent form. Paraformaldehyde-fixed astrocytes, unable to secrete cytokines, failed to inhibit HIV-1. These cells caused enhanced virus replication, however, which correlated with an increase in macrophage colony stimulating factor (M-CSF) production. CONCLUSIONS: Human astrocytes can increase and decrease HIV-1 expression in MDM. An imbalance between the positive and negative effects of astrocytes may contribute to the expression of virus in the brain, and the development of HIV-1-associated cognitive/motor complex.

Adult↗
PubMed1999

Human immunodeficiency virus-1-infected macrophages induce inducible nitric oxide synthase and nitric oxide (NO) production in astrocytes: astrocytic NO as a possible mediator of neural damage in acquired immunodeficiency syndrome.

Nitric oxide (NO) plays an important role in normal neural cell function. Dysregulated or overexpression of NO contributes to neurologic damage associated with various pathologies, including human immunodeficiency virus (HIV)-associated neurological disease. Previous studies suggest that HIV-infected monocyte-derived macrophages (MDM) produce low levels of NO in vitro and that inducible nitric oxide synthase (iNOS) is expressed in the brain of patients with neurologic disease. However, the levels of NO could not account for the degree of neural toxicity observed. In this study, we found that induction of iNOS with concomitant production of NO occurred in primary human astrocytes, but not in MDM, when astrocytes were cocultured with HIV-1-infected MDM. This coincided with decreased HIV replication in infected MDM. Supernatants from cocultures of infected MDM and astrocytes also stimulated iNOS/NO expression in astrocytes, but cytokines known to induce iNOS expression (interferon-gamma, interleukin-1beta, and tumor necrosis factor-alpha) were not detected. In addition, the recombinant HIV-1 envelope protein gp41, but not rgp120, induced iNOS in cocultures of uninfected MDM and astrocytes. This suggests that astrocytes may be an important source of NO production due to dysregulated iNOS expression and may constitute one arm of the host response resulting in suppression of HIV-1 replication in the brain. It also leads us to speculate that neurologic damage observed in HIV disease may ensue from prolonged, high level production of NO.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue.

To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy.

Animals↗
PubMed1999

A fibrinolytic enzyme from a marine green alga, Codium latum.

A fibrinolytic enzyme was isolated from a marine green alga, Codium latum, and designated C. latum protease (CLP). It also had fibrinogenolytic activity, hydrolyzing A alpha, B beta and gamma chains with preference in this order. As CLP hydrolyzed oxidized insulin B chain at position Arg22-Gly23, and the peptide map of lysozyme digested with CLP was similar to that with trypsin, CLP would be expected to have a high substrate specificity, similar to that of trypsin. Protease activity peaked at pH 10, and was completely inhibited by diisopropyl fluorophosphate (DFP). Therefore, we conclude that CLP is a trypsin-like serine protease.

Animals↗
PubMed1999

Structural analysis of a biofilm which enhances carbon steel corrosion in nutritionally poor aquatic environments.

Carbon steel coupons were exposed to nutritionally-poor synthetic wastewater inoculated with activated sludge from a municipal waste water plant. Biofilm formation was observed after one day incubation, and the thickness of the film increased proportionally with the incubation period. Mass loss of the coupons was also proportional to the incubation time, and reached 70.4 (mg/cm2) after incubation for 140 d. The observed mass loss was 5 times as much as that under sterile conditions. To characterize the microbiologically influenced corrosion (MIC) of carbon steel, structural analysis of the biofilm was performed. Rapid decrease in the dissolved oxygen (DO) concentration in the zone near the surface of the biofilm was observed by a microelectrode mounted on a micromanipulator. Heterogeneous distribution of the DO concentration on the surface of the steel plate was observed after multiple analyses. The heterogeneous structure of the biofilm composed of viable cells, inanimate objects, voids and pores was elucidated by confocal scanning laser microscopy. Concentrations of both aerobic bacteria and sulphur-reducing bacteria in the biofilm decreased with the incubation time, indicating that the increase in the biofilm thickness reflected an increase in the density of dead microbial cells or in extracellular polymer accumulation by the microbes. The average roughness of the metal surface observed after 112 d of incubation was +/-7.14 microm, which was 14.1% of the average thickness of the coupons. These observations indicated that uneven distribution of the DO profile and the cell concentration were critical for MIC of the carbon steel.

Journal Article↗
PubMed1999

The effects of several nucleotides on the molecular state and catalytic activity of Thiobacillus novellus cytochrome c oxidase. ATP affects the oxidase uniquely.

The catalytic activity and molecular aspects of Thiobacillus novellus cytpchrome c oxidase were affected by ATP. The steady-state kinetics in the oxidation of ferrocytochrome c by the oxidase varied with the presence or absence of ATP; the [S]-v curve of the reaction was sigmoid in the absence of ATP whereas it was a Michaelis-Menten-type hyperbola in the presence of 700 microM ATP. The oxidase was a dimer of the minimal structural subunit consisting of one molecule each of two subunits in the presence of Tween 20 and in the absence of ATP. The dimer dissociated into monomers in the presence of 700 microM ATP. The trough at 452 nm seen in the second derivative absorption spectrum of the CO compound of the oxidase in the absence of ATP, a characteristic of the cytochrome a component of cytochrome aa3, dissappeared in the presence of 700 microM ATP. However, ADP, AMP, GTP, CTP and UTP had little affect on both the [S]-v curve and the molecular mass of the oxidase when used in place of ATP.

Adenosine Triphosphate↗
PubMed1999

A dose-finding study of nedaplatin and cyclophosphamide for patients with gynecological malignancies.

BACKGROUND: Nedaplatin is a new analogue of cisplatin with similar efficacy but less renal toxicity. We investigated the appropriate dose of nedaplatin in combination with cyclophosphamide for patients with gynecological malignancies. METHODS: Nine patients (five with ovarian cancer and four with uterine cervical cancer) were studied. Three patients received 60 mg/m2 of nedaplatin combined with 500 mg/m2 of cyclophosphamide every 4 weeks. Another three patients were each administered 80 or 100 mg/m2 of nedaplatin with the same dose of cyclophosphamide. A total of 27 courses was given. RESULTS: No patient needed dose reduction due to myelosuppression and no severe adverse events were observed. CONCLUSIONS: Treatment with 100 mg/m2 of nedaplatin and 500 mg/m2 of cyclophosphamide is feasible for patients with gynecological malignancies. However, phase II studies are needed to clarify the efficacy of this combination chemotherapy.

Adult↗
PubMed1999

Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy.

Tubulin binding agents (TBAs) reduce tumor perfusion and inhibit mitosis of tumor cells in solid tumors, but it is not clear which effects contribute to the suppression of solid tumor growth. We evaluated the antivascular and antimitotic effects of several TBAs, combretastatin A-4 (CS A-4) phosphate, AC-7700, a novel CS A-4 derivative, colchicine, E7010, and vinblastine, on subcutaneous (s.c.) murine colon26 adenocarcinoma (c26). Tolerable doses of vinblastine and E7010) strongly inhibited tumor growth and induced mitotic arrest of tumor cells without affecting tumor perfusion. Colchicine had no effect on tumor growth and perfusion. When the injected dose was increased to the lethal range, however, these drugs markedly reduced tumor perfusion and caused necrosis of tumor tissue. Within the tolerable dose range, AC-7700 both strongly suppressed tumor growth and reduced tumor perfusion, and CS A-4 phosphate also exhibited a moderate antivascular effect. To evaluate the contribution of antivascular activity of TBAs to tumor growth suppression, excluding their direct cytotoxic effect on tumor cells, we established c26/acr, which is resistant to TBAs in vitro. Although E7010 showed a reduced suppressive effect on s.c. c26/acr tumor growth as compared with its effect on wild-type c26, AC-7700 remained potent against both cell lines. These results indicate that TBAs exert antivascular and antimitotic effects on solid tumors with marked differently effective dose ranges from agent to agent, and that the antivascular effect of TBAs inhibits solid tumor growth independently of the direct cytotoxic effect on tumor cells.

Adenocarcinoma↗
PubMed1999

A novel combretastatin A-4 derivative, AC-7700, shows marked antitumor activity against advanced solid tumors and orthotopically transplanted tumors.

AC-7700, a novel combretastatin A-4 derivative, suppresses the growth of solid tumors by inhibiting tumor perfusion. We evaluated the antitumor activity of AC-7700 on solid tumors in two experimental models, an advanced tumor model (murine colon 26 (c26) adenocarcinoma, colon 38 (c38) adenocarcinoma, MethA fibrosarcoma, Sarcoma 180 (S180), Lewis lung carcinoma (3LL), human LS180 adenocarcinoma) and an orthotopically transplanted tumor model (c26), compared with that of cisplatin (CDDP). The maximum tolerable dose (MTD) of CDDP suppressed early-stage c26 and c38 tumor growth when treatment was started after the tumor volume (TV) reached 0.2-0.5 cm3, but it showed reduced activity against the same tumors at an advanced growth stage when TV exceeded 2 cm3. At its MTD, AC-7700 was active against all tumors tested except 3LL in both early and advanced growth stages, reducing the tumor mass and having a curative effect in advanced c38 tumors. AC-7700 was also effective on orthotopically transplanted c26 tumors, showing a comparable activity to that on subcutaneous tumors. Unlike flavon acetic acid, which damages tumor vasculature by inducing endogenous tumor necrosis factor-alpha production, AC-7700 potently suppressed the growth of advanced c26 tumors in athymic as well as euthymic mice. These results suggest that AC-7700 is a novel antivascular agent that may have potent activity against advanced-stage cancer in the clinical setting.

Animals↗
PubMed1999

Antitumor effects due to irreversible stoppage of tumor tissue blood flow: evaluation of a novel combretastatin A-4 derivative, AC7700.

The relation between tumor tissue blood flow (tBF) reduction and antitumor effects was investigated. Changes in tBF of normal tissues (liver, kidney cortex, bone marrow and brain cortex) and tumors (Yoshida sarcoma subline, LY80 and Sato lung carcinoma, SLC) due to i.v. administration of AC7700 (1, 3, 10 mg/kg), one of the combretastatin A-4 derivatives, were measured with the hydrogen clearance method. The change in blood flow in tumor microfoci was also observed directly using a rat transparent chamber. Chemotherapy against the solid tumors (LY80, SLC) was performed by administering AC7700 7 times at intervals of 3 days and the effect on the tumor growth, the histological effect, the effect on lymph node metastasis and the survival rate were investigated. Tumor tBF showed a dose-dependent response to AC7700. Although tumor tBF decreased markedly at a dose of 1 mg/kg, it tended to recover partly within several hours. At 10 mg/kg, however, tumor tBF completely stopped within approximately 30 min and never recovered in many regions. The irreversible stoppage of tumor tBF was observed in large s.c. tumors and in microfoci as well. On the other hand, in normal tissues, tBF changes due to AC7700 were not uniform. In the liver, although tBF decreased by approximately 50% at 10 mg/kg AC7700, it recovered within 8 h. In the brain, although the mean maximum reduction was 35%, the blood flow recovered to the original level within 24 h. The blood flow in the kidney cortex did not change at all. In the bone marrow, tBF decreased by approximately 80%. Generally, the blood flow reduction in normal tissues tended to be reversible. The effect on tumor growth and the histological effect were also dependent on the dose of AC7700. The tumor growth was markedly inhibited by 10 mg/ kg AC7700 and extensive necrosis was induced. Lymph node metastases were significantly inhibited and survival was prolonged significantly. In the control group, all 8 SLC tumor-bearing rats died of cancer, the presence of which was verified by gross and microscopic evaluation, within 45 days after tumor implantation. On the other hand, in the treated group, 2 of 8 rats recovered completely and survived. No obvious side effects such as body weight loss, anemia or diarrhea were observed at the dose used in this experiment. From these results, we conclude that strong antitumor effects are obtained by stopping tumor tBF irreversibly and by shutting off the nutritional supply into tumor tissue. AC7700 has been demonstrated to be a promising anticancer compound which has such an action.

Animals↗
PubMed1999

[Variation of chemical constituents in processed licorice roots: quantitative determination of saponin and flavonoid constituents in bark removed and roasted licorice roots].

As a continuing study of chemical characterization of crude drug processing, we have been analyzing the chemical constituents in licorice roots before and after processing. At first, we analyzed chemical constituents in licorice roots of various origins. Next, we have developed the HPLC analytical method, by which saponins and flavonoids, major constituents in various licorice roots, were determined simultaneously in a quantitative manner. In this paper, by means of the HPLC analytical method, chemical constituents in licorice roots, processed and unprocessed, were determined. It was found that nonglycosidic flavonoid constituents were mostly lost while root bark removing, whereas, in roasted licorice roots, sugar chains in the saponin and glycosidic flavonoid constituents were hydrolyzed stepwise during roasting through hydrothermolysis.

Chromatography, High Pressure Liquid↗
PubMed1999

Geographical features of estuaries for neritid gastropods including Clithon retropictus to preserve thermostable direct hemolysin-producing Vibrio parahaemolyticus.

Thermostable direct hemolysin-producing strain of Vibrio parahaemolyticus was not detected from the alimentary tract of 7 neritid gastropods including Clithon retropictus at 9 estuaries of Southwest Islands in Japan in the present study. The strain has been detected from C. retropictus at 2 estuaries facing The Sea of Japan but not at 2 estuaries facing The Seto Inland Sea and The Pacific Ocean in Western Japan in our previous studies. In comparison with geographical features of the estuaries where the strain was detected and not, thick accumulation of muddy sediments at the riverbed and stagnation of brackish water at low tide seem to be essential for the strain to survive in neritid gastropods including C. retropictus.

Animals↗
PubMed1999

Identification of epi-1 locus as a laminin alpha chain gene in the nematode Caenorhabditis elegans and characterization of epi-1 mutant alleles.

A new genetic locus, epi-1, has been identified and mapped, which affects epithelialization of various tissues in the nematode, Caenorhabditis elegans. Seven independent epi-1 mutant alleles have been obtained. These mutants have a wide spectrum of abnormalities, all seem to be caused by a primary defect of basement membrane. We have identified the epi-1 gene as a structural gene of laminin alpha chain. The sequence analyses of the gene and cDNAs revealed that the gene consists of 15 exons and encodes a protein of 3704 amino acids in an open reading frame of 11115 base pairs. The nematode alpha chain is similar to its vertebrate and fly orthologs in the domain structure. The mRNA is trans-spliced to SL1 leader RNA as many of the nematode mRNAs. Mutation sites have been identified in four alleles. Two alleles have nonsense mutations and produce truncated proteins lacking the domain necessary for the formation of a heterotrimeric laminin molecule. The other two alleles have missense mutations in domains VI and IIIb, respectively.

Alleles↗
PubMed1999

The features of psychological problems and their significance in patients on hemodialysis--with reference to social and somatic factors.

AIM: For the purpose of identifying the features of psychological problems and their significance in patients on hemodialysis, we analyzed how psychological problems are affected by social and somatic factors. SUBJECTS AND METHODS: The subjects all consisted of patients on hemodialysis at the Kidney Center of Fukuoka Red Cross Hospital between December 1994 and December 1996. We used the Cornell medical index health questionnaire on neurosis and the "easily upset or irritated", State-trait anxiety inventory to determine both state and trait anxiety, the Self rating Depression Scale on depression and divided into the patients who demonstrated each psychological problem and those who did not, and then analyzed the psychological problems between the two groups with reference to somatic and social factors which may have led the patients to develop their respective psychological problems. RESULTS: According to a chi-square analysis, neurosis, clinical trait anxiety and clinical state anxiety were all more closely related to somatic factors than to social factors. In contrast to neurosis and anxiety, more social factors than somatic factors were related with "easily upset or factors were related with" easily upset or irritated". "Easily upset or irritated" was significantly related to living with a spouse or with children. In addition, depression was related to various factors including both somatic and social factors. In a stepwise multiple logistic regression analysis, the presence of restless legs also correlated with all the psychological symptoms investigated in this study. The prevalence of depression was also related to the degree of awareness regarding the cause of renal failure (p < 0.01). CONCLUSION: Our results thus revealed the features of the psychological problems and their significance in patients on hemodialysis.

Anxiety↗