Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 217 records · Page 12Linked to original sources

PubMed1999

Stimulatory effect of laser irradiation on calcified nodule formation in human dental pulp fibroblasts.

The purpose of the present study was to investigate the effect of laser irradiation on calcified nodule formation in human dental pulp (HDP) cells. HDP cells were irradiated once with a Ga-Al-As laser for 5 and 10 min, and calcified nodule formation was determined by von Kossa staining. The laser irradiation increased the number of calcified nodules in a time-dependent manner. The activity of alkaline phosphatase and production of collagen and osteocalcin in conditioned medium were measured. Both were higher in the irradiated group than in the nonirradiated group. These results suggested that formation of calcified nodules in HDP cells, as well as in alkaline phosphatase activity, the production of collagen and osteocalcin were enhanced by laser irradiation.

Alkaline Phosphatase↗

PubMed1999

Bone reactions to titanium screw implants in ovariectomized animals.

OBJECTIVE: The purpose of this study was to investigate the reactions of bone tissue after the placement of implants into the tibiae of osteopenic model rats. STUDY DESIGN: Commercially pure titanium screw implants were placed in the bilateral proximal tibial metaphyses 168 days after ovariectomy had been performed on 12-week-old female Wistar rats. For control purposes, implants were similarly placed in sham-ovariectomy rats. The healing process was examined histologically by means of undecalcified sections at various intervals from 7 to 168 days after implantation. Through use of an automated imaging analytic system, changes in relative bone mass and implant-bone contact were histomorphometrically evaluated. RESULTS: In the cortical bone area, only a slight difference in bone contact was noted with the implant until 28 days after implantation. However, ovariectomy significantly affected bone contact at 56 days after implantation. The rate of bone contact in the cancellous bone area and the relative bone mass around the implant were significantly lower in the test group than in the control group. CONCLUSIONS: It is considered that a decrease in bone mass causes a reduction in the contact area between implant and bone and may also cause a reduction in the supporting ability of the implant because of thinning of the surrounding bone tissue.

Animals↗

PubMed1999

An unusual autopsy case of a victim stabbed during sadomasochistic prostitution.

A 29-year-old male who lived alone was found dead with his back leaning against the wall of his room. He had been stabbed in his abdomen with a survival-type knife. The victim's mouth was plugged with a pink-colored glove and was sealed with packing tape. His wrists were tightly tied behind his back with the same type of packing tape. The cause of death was diagnosed as hemorrhage from the right common iliac artery and vein. Due to the strange circumstances of the crime scene, the police initially considered the possibility of homicide by a group of assassins. Two months later, the police arrested a male suspect who was a member of a vice racketeer. The victim was characterized as a masochist and bisexual. He often hired the male suspect to perform sadomasochistic activities. On the day of the crime, the victim prepared a survival-type knife and packing tape himself to experience fear and pain more strongly. The victim hoped to use the knife to increase sexual excitement. In this case of sadomasochistic prostitution leading to death, the legal issues of homicide for money, malicious request of injury by the victim and accidental death were involved.

Journal Article↗

PubMed1999

A constitutively expressed Myc-like gene involved in anthocyanin biosynthesis from Perilla frutescens: molecular characterization, heterologous expression in transgenic plants and transactivation in yeast cells.

The coordinate expression of anthocyanin biosynthetic genes in leaves and stems of a red forma of Perilla frutescens is presumably controlled by regulatory gene(s). A Myc-like gene (Myc-rp) was isolated from a cDNA library prepared from the leaves of red P. frutescens, and its deduced amino acid sequence shows 64% identity with that of delila from snapdragon. The Myc-rp gene was expressed in leaves and roots of both red and green P. frutescens equally. Comparison of deduced amino acid sequence of Myc-rp with that of Myc-gp, the second allele isolated from a green forma of P. frutescens, indicates that the 132nd amino acid, alanine, existing in MYC-RP was changed to serine in MYC-GP. The heterologous expression of these two alleles of Myc-like gene in tobacco and tomato resulted in an increase of the anthocyanin contents in flowers of tobacco and vegetative tissues and flowers of tomato. However, the flowers of transgenic tobacco expressing the fragment with a partial deletion (encoding 1-115 amino acids deleted) of Myc(-gp gave no change in anthocyanin accumulation, but some morphological changes of the flower were observed. In yeast, the MYC-RP/GP and Delila protein exhibited transactivation activity on the GAL-1 promoter from yeast and the promoter of dihydroflavonol 4-reductase (DFR) gene from P. frutescens. A transactivation domain of MYC-RP/GP and Delila could be located in the region between the 193rd and the 420th amino acid of MYC-RP/GP proteins. Our data indicate that this Myc-like gene presumably functions in the regulation of anthocyanin biosynthesis similarly in different tissues of dicot plants.

Alcohol Oxidoreductases↗

PubMed1999

Complete cure of established murine hepatocellular carcinoma is achievable by repeated injections of retroviruses carrying the herpes simplex virus thymidine kinase gene.

Although xenotransplantation of retrovirus-producing cells into a tumor has been shown to be effective for the treatment of cancer, injections of recombinant retroviruses are much more feasible for clinical applications. We established a clone producing retroviruses carrying the herpes simplex virus thymidine kinase (HSVtk) gene with titers of up to 4 x 10(7) colony-forming units/ml, and examined the effectiveness of in vivo gene therapy against cancer. Syngeneic mice were inoculated subcutaneously with murine hepatocellular carcinoma (HCC) cells, BNL1ME A.7R.1, and the treatment was initiated after tumors were established. When mice were given an intratumoral injection of HSVtk-carrying retroviruses or their producing cells followed by ganciclovir (GCV) treatment, significantly prolonged survival periods were observed. When mice were treated with repeated intratumoral injections of HSVtk-carrying retrovirus-producing cells, significant antitumor responses and some cures were induced by GCV treatment. Furthermore, repeated intratumoral injections of HSVtk-carrying retroviruses and GCV treatment resulted in complete regression of established HCC tumors in all animals used in the experiment. Mice that completely eradicated tumors exhibited protective immunity against wild-type HCC tumors. These results suggest that repeated injections of HSVtk-carrying retroviruses followed by GCV treatment is a potent modality for the treatment of solid tumors.

Animals↗

PubMed1999

Hair cycle-dependent expression of hepatocyte growth factor (HGF) activator, other proteinases, and proteinase inhibitors correlates with the expression of HGF in rat hair follicles.

We previously reported that hepatocyte growth factor (HGF) had a stimulatory effect on hair growth in vivo and in vitro. The secreted inactive form of HGF is processed into an active form by serine proteinases such as HGF activator and urokinase. The mRNA expressions of various proteinases and their inhibitors in relation to HGF activation in hair growth were examined using animals with a synchronous hair cycle. Total RNA were extracted from the anterior dorsal skin of rats in different hair cycle stages, and mRNA expressions of the specific genes were compared using semiquantitative reverse transcription polymerase chain reaction. The mRNA of HGF, HGF activator, urokinase, plasminogen activator inhibitor (PAI)-1, nexin-1, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-1 were expressed strongly in anagen tissue and slightly in telogen tissue. Moreover, topical application of 1% minoxidil sulfate to the anterior dorsal skin of rats in telogen stimulated hair growth and increased the mRNA expressions of HGF and MMP-2. These findings suggest that some proteinases and their inhibitors, strongly expressed in anagen, may act as hair growth regulatory molecules, and may also be involved in processing the latent form of HGF.

Animals↗

PubMed1999

Direct evidence for anthocyanidin synthase as a 2-oxoglutarate-dependent oxygenase: molecular cloning and functional expression of cDNA from a red forma of Perilla frutescens.

Anthocyanidin synthase (ANS), an enzyme of the biosynthetic pathway to anthocyanin, has been postulated to catalyze the reaction(s) from the colorless leucoanthocyanidins to the colored anthocyanidins. Although cDNAs have been isolated that encode putative ANS, which exhibits significant similarities in amino acid sequence with members of a family of 2-oxoglutarate-dependent oxygenases, no biochemical evidence has been presented which identifies the actual reaction that is catalyzed by ANS. Here we show that anthocyanidins are formed in vitro through 2-oxoglutarate-dependent oxidation of leucoanthocyanidins catalyzed by the recombinant ANS and subsequent acid treatment. A cDNA encoding ANS was isolated from red and green formas of Perilla frutescens by differential display of mRNA. Recombinant ANS tagged with maltose-binding-protein (MBP) was purified, and the formation of anthocyanidins from leucoanthocyanidins was detected by the ANS-catalyzed reaction in the presence of ferrous ion, 2-oxoglutarate and ascorbate, being followed by acidification with HCI. Equimolar stoichiometry was confirmed for anthocyanidin formation and liberation of CO2 from 2-oxoglutarate. The presumptive two-copy gene of ANS was expressed in leaves and stems of the red forma of P. frutescens but not in the green forma plant. This corresponds to the accumulation pattern of anthocyanin. The mechanism of the reaction catalyzed by ANS is discussed in relation to the molecular evolution of a family of 2-oxoglutarate-dependent oxygenases.

Amino Acid Sequence↗

PubMed1999

Primary structure and possible functions of a trypsin inhibitor of Bombyx mori.

A protein with a low molecular mass of 6027 was purified from cocoon shell of silkworm, Bombyx mori. Two-dimensional polyacrylamide gel electrophoresis (2D/PAGE) resolved this protein into a single spot with pI 4.3 and Mr 6000. Amino acid sequence analysis revealed that this protein consists of 55 amino acids, six of these being cysteine residues and is highly homologous to bovine pancreatic trypsin inhibitor-type inhibitors. The 6-kDa protein is heat stable and acid stable and inhibits bovine trypsin by forming a low-dissociation complex with trypsin in a 1 : 1 molar ratio (Ki = 2.8 x 10-10), but does not alpha-chymotrypsin. This cocoon shell-associated trypsin inhibitor (CSTI) was thus concluded to belong to the bovine pancreatic trypsin inhibitor class. CSTI was developmentally regulated in the silk gland at the final stage of larval growth, and its specific distribution in the middle silk gland, an organ in which silk proteins are stored during the final larval instar, occurred before the onset of spinning. This inhibitor protects the tryptic degradation of fibroin light (L) chain in vitro. These results suggest that this trypsin inhibitor may play an important part on regulating proteolytic activity in the silk gland or protecting silk proteins from degradation during histolysis.

Amino Acid Sequence↗

PubMed1999

Adenosine, the anxiolytic-like principle of the Arillus of Euphoria longana.

According to traditional usage, the extract of Longan Arillus was tested for its anxiolytic-like effect by application of the Vogel-type anti-conflict method in mice. The extract indicated significant activity at a dose of 2 g/kg, s.c., and results of the bioassay-oriented isolation revealed adenosine to be the active principle. Adenosine produced the anti-conflict effect significantly at a dose of 30 mg/kg, s.c. Adenine, uridine, and 5-methyluridine did not exhibit the effect, although these compounds were isolated from the extract. Some other related compounds such as AMP and c-AMP showed no effect, except for inosine. Adenosine also contributed to the analgesic effect which was observed in the extract by the writhing method.

Adenosine↗

PubMed1999

Comparison of gene therapy with the herpes simplex virus thymidine kinase gene and the bacterial cytosine deaminase gene for the treatment of hepatocellular carcinoma.

BACKGROUND: Bystander effects induced by suicide gene/prodrug systems play an essential role in achieving successful antitumor effects. Although it has been shown in several in vitro studies that the bacterial cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) system is superior to the herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system, we examined here which suicide gene system was more promising in vivo for the treatment of hepatocellular carcinoma (HCC). METHODS: BNL1ME A.7R.1 murine HCC cells were retrovirally transduced with the HSV-TK or CD gene, and bystander effects caused by the appropriate prodrug treatment were examined not only in vitro but also in vivo. RESULTS: The CD/5-FC system was superior to the HSV-TK/GCV system in HCC cell elimination in vitro. The bystander effect of the HSV-TK/GCV was shown to be substantially dependent on cell-to-cell contact, whereas that of the CD/5-FC was not. However, antitumor effects on HCC and tumor immunity to parental HCC induced by the HSV-TK/GCV system were not inferior and even superior to those induced by the CD/5-FC system. Bystander effects induced by the suicide gene/prodrug systems in immunocompetent syngeneic mice were much more profound than those induced in vitro. However, significant bystander effects were not observed in athymic nude mice. CONCLUSIONS: These results suggest that both HSV-TK/GCV and CD/5-FC systems are useful for the treatment of HCC. The results also suggest that T-cell-mediated immune responses elicited by the suicide gene/prodrug systems play a substantial role in antitumor effects in vivo.

Animals↗

PubMed1999

Potassium channel-mediated hyperpolarization of mesenteric vascular smooth muscle by isoflurane.

BACKGROUND: A primary source of calcium (Ca2+) necessary for excitation contraction in vascular smooth muscle (VSM) is influx via voltage-dependent Ca2+ channels. Thus, force generation in VSM is coupled closely to resting transmembrane potential, which itself is primarily a function of potassium conductance. Previously, the authors reported that volatile anesthetics hyperpolarize VSM of small mesenteric resistance arteries and capacitance veins. The current study was designed to determine whether isoflurane-mediated hyperpolarization is the result of specific effects on one or more of four types of potassium channels known to exist in VSM. METHODS: Transmembrane potentials (Em) were recorded from in situ mesenteric capacitance and resistance vessels in Sprague-Dawley rats weighing 250-300 g. In separate experiments, selective inhibitors of each of four types of potassium channels known to exist in VSM were administered in the superfusate of the vessel preparations to assess their effects on isoflurane-mediated hyperpolarization. RESULTS: Resting VSM Em ranged from -38 to -43 mV after local sympathetic denervation. Isoflurane produced a significant hyperpolarization (2.7-4.3 mV), whereas each potassium channel inhibitor significantly depolarized (2.8-8.5 mV) the VSM. Both 100 nM iberiotoxin (inhibitor of high conductance calcium-activated potassium channels) and 1 microM glybenclamide (inhibitor of adenosine triphosphatase-sensitive potassium channels) significantly inhibited VSM hyperpolarization induced by 1 MAC (minimum alveolar concentration) levels of inhaled isoflurane (0.1-0.9 mV Em change, which was not significant). In contrast, isoflurane hyperpolarized the VSM significantly despite the presence of 3 mM 4 aminopyridine (inhibitor of voltage-dependent potassium channels) or 10 microM barium chloride (an inhibitor of inward rectifier potassium channels) (3.7-8.2 mV change in VSM Em). CONCLUSIONS: These results suggest that isoflurane-mediated hyperpolarization (and associated relaxation) of VSM can be attributed in part to an enhanced (or maintained) opening of calcium-activated and adenosine triphosphate-sensitive potassium channels but not voltage-dependent or inward rectifier potassium channels.

Anesthetics, Inhalation↗

PubMed1999

Effect of isoflurane on in situ vascular smooth muscle transmembrane potential in spontaneous hypertension.

BACKGROUND: Administration of general anesthetics to patients with chronic hypertension often causes hemodynamic instability that has been attributed in part to a poorly understood increased loss of control of peripheral vascular smooth muscle tone. The purpose of the current study was to determine if such an increased loss occurs in the spontaneously hypertensive (SH) rat neurogenic model of chronic hypertension, as reflected by a greater volatile anesthetic-induced in situ vascular smooth muscle hyperpolarization compared with normotensive Wistar-Kyoto (WKY) rat controls. METHODS: Vascular smooth muscle transmembrane potentials (E(m)s) were measured in situ using glass microelectrodes in externalized small mesenteric resistance- and capacitance-regulating blood vessels in 10- to 12-week-old SH and WKY rats before, during and after administration of 1 minimum alveolar concentration levels (1.5%) of inhaled or 0.60 mM superfused isoflurane. Vascular smooth muscle E(m)s were also measured in vessels after local sympathetic denervation with superfused 6-hydroxydopamine. RESULTS: Local sympathetic denervation caused a significant hyperpolarization of arterial and venous vascular smooth muscle in SH but not WKY rats. Hyperpolarization induced by either inhaled or superfused isoflurane was significantly greater in innervated than in denervated arterial and venous vascular smooth muscle, particularly in SH rats. In addition, for innervated (but not denervated) arterial and venous vascular smooth muscle, hyperpolarization induced by inhaled (but not superfused) isoflurane was significantly greater in SH than in WKY rats. CONCLUSIONS: In the neurogenic SH rat model of human hypertension, a primary mechanism underlying elevated isoflurane-induced vascular smooth muscle hyperpolarization (and reduced vascular smooth muscle tone) in both resistance- and capacitance-regulating blood vessels is a central neural inhibition of excitatory sympathetic input. Peripheral neural and nonneurally mediated hyperpolarization by isoflurane is similar in SH and WKY rat vascular smooth muscles.

Anesthetics, Inhalation↗

PubMed1999

Prednisolone inhibits endotoxin-induced disseminated intravascular coagulation and improves mortality in rats: importance of inflammatory cytokine suppression.

In order to determine whether prednisolone has a protective effect against the development of disseminated intravascular coagulation (DIC), we measured the effect of prednisolone on changes in hemostatic parameters and plasma levels of inflammatory cytokines in endotoxin-treated rats. Decreases in platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products and levels of thrombin-antithrombin III (TAT) complex following the administration of endotoxin, all of which are associated with DIC, were significantly suppressed by the administration of prednisolone. Heparin administration significantly suppressed changes in all these parameters except for the decrease in platelet count. The combination of prednisolone and heparin was more effective than either treatment alone. In order to determine whether these effects of prednisolone are correlated with the suppression of inflammatory cytokine production, we examined the relationship between changes in plasma levels of cytokine, the hemostatic parameters listed above, and mortality using a number of intervention regimens designed to alter events of the experimentally induced DIC. Changes in hemostatic parameters associated with DIC following 30 mg/kg per 4 h of endotoxin infusion were significantly suppressed by treatment with 1 mg/kg prednisolone 30 min before beginning endotoxin infusion, followed by administration of 250 U/kg heparin 2 h after the start of endotoxin infusion (prednisolone-endotoxin-heparin regimen). The heparin and prednisolone were administrated subcutaneously. The administration of prednisolone and heparin in the reverse order (i.e. heparin first and prednisolone second: heparin-endotoxin-prednisolone regimen) also suppressed changes in hemostatic parameters, albeit to a smaller degree. Cytokine production was also significantly suppressed by the first treatment, but was not affected by the regimen in which heparin was administered first. Administration of prednisolone alone or heparin alone 30 min before endotoxin significantly reduced the number of renal glomeruli with fibrin thrombi. Plasma levels of creatinine and alanine transferase were reduced only by prednisolone. Increased plasma levels of interleukin-1beta, tissue necrosis factor-alpha and interleukin-6 were suppressed by prednisolone but not by heparin, and there were significant correlations between plasma levels of TAT and cytokines. Prednisolone was more effective than heparin in reducing mortality at 24 h after 100 mg/kg over 4 h of endotoxin infusion (four of 20 versus 15 of 20 deaths for prednisolone and heparin, respectively). These findings suggest that prednisolone inhibits the development of endotoxin-induced DIC and reduces mortality by a different mechanism than heparin, possibly through suppressing the production of inflammatory cytokines. Prednisolone may be efficacious in preventing DIC and multiple organ dysfunction caused by endotoxin.

Animals↗

PubMed1999

Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.

Antineoplastic Agents↗

PubMed1999

Effects of propofol on contractile response and electrophysiological properties in single guinea-pig ventricular myocyte.

Effects of propofol on contractile response, action potential, resting membrane potential and L-type voltage-dependent calcium channel current were examined in guinea-pig single cardiac myocyte. Propofol (10(-4) M) inhibited contractile response induced by electrical stimulation (83.6% of control, n = 5), but did not change the resting membrane potential. On the other hand, propofol reduced the overshoot of action potential (10(-4) M), and shortened the duration of action potential (10(-5) and 10(-4) M). Whole-cell voltage clamp experiment showed inhibition of L-type calcium channel current (ICa, 10(-5) M: 90.8+/-1.39, 10(-4) M: 83.4+/-1.53% of control, n = 5). In addition, propofol showed use-dependent block of ICa. It is concluded that negative inotropic effect of propofol is caused by suppression of action potential, and that inhibition of ICa plays a role in shortening of the duration of action potential.

Action Potentials↗

PubMed1999

[Use of a rapid detection assay for influenza virus, on nasal aspirate specimens].

We investigated the usefulness of a rapid antigen detection kit using optical immunoassay for influenza virus (FLU OIA, BioStar, USA). Nasal aspirates were taken from 92 influenza suspected outpatients between March to April of 1999. Compared with virus isolation and PCR, the sensitivity of FLU OIA was 88.5% and 81.6%, and the specificity was 65.2% and 72.2%. All isolated viruses were influenza type B virus. It was difficult to differentiate the weak-positive and negative cases, leading to the rather low specificity, although the assay procedure was easy and quick. FLU OIA may be a useful rapid diagnosis kit for influenza in pediatric outpatient clinics and wards, because it can detect both influenza type A and type B viruses.

Antigens, Viral↗

PubMed1999

The effects of interleukin (IL)-4 and IL-10 on macrophage growth-stimulating activities of oxidized low density lipoprotein (LDL), acetylated LDL and macrophage colony-stimulating factor: the activity of oxidized LDL is refractory to the inhibitory cytokines.

We have previously reported that ligands of scavenger receptor such as acetylated low density lipoprotein (acetyl-LDL) and oxidized LDL induced growth of peripheral macrophages in vitro. This suggests the possibility that in addition to foam cell formation, modified or oxidized LDLs induce macrophage proliferation in atherosclerotic lesions. To learn further the physiological regulation of macrophage growth, we comparatively examined the effect of interleukin (IL)-4 and IL-10 which have been reported to be suppressive to various macrophage functions on macrophage growth-stimulating activities of the acetyl-LDL, oxidized LDL and macrophage colony-stimulating factor (M-CSF). An in vitro study showed that the activity of M-CSF-containing L-cell-conditioned medium was the most sensitive to the suppressive effects of these cytokines. The growth-inducing activity of acetyl-LDL was significantly inhibited by both IL-4 and IL-10. On the other hand, the activity of oxidized LDL was not attenuated by IL-4 or IL-10. These data indicate that macrophage growth-stimulating activity of oxidized LDL, in contrast to that of M-CSF or acetyl-LDL, is refractory to these suppressive cytokines. Oxidized LDL may act as a potent macrophage growth-stimulating factor in atherosclerotic or other inflammatory sites, even when these cytokines are produced by inflammatory and immunological reactions in situ.

Animals↗

PubMed1999

Suppressive activity of lycoricidinol (narciclasine) against cytotoxicity of neutrophil-derived calprotectin, and its suppressive effect on rat adjuvant arthritis model.

Calprotectin is a calcium- and zinc-binding protein complex that is abundant in cytosol of neutrophils. The concentration of calprotectin in extracellular fluids is greatly increased under various inflammatory conditions in vivo. We recently demonstrated that calprotectin inhibited cell growth and induced apoptosis of various cell types including tumor cells and normal fibroblasts; therefore, extracellular calprotectin might cause tissue destruction in severe inflammatory diseases. We previously found that an alkaloid, lycorine inhibits induction of apoptosis by calprotectin. In this paper, we examined the inhibitory activities of other Amaryllidaceae alkaloids, namely, lycoricidinol, hippeastrine and ungerine against the cytotoxicity of calprotectin. Lycoricidinol (narciclasine) inhibited calprotectin-induced cytotoxicity at more than 10-fold lower concentration (IC50=0.001-0.01 microg/ml) than lycorine, while the effects of the latter two alkaloids were very weak. Therefore, we next checked the prophylactic effect of lycorine and lycoricidinol on the adjuvant arthritis model in rats. Lycoricidinol, but not lycorine, significantly suppressed the degree of swelling of adjuvant-treated as well as untreated feet, suggesting that lycoricidinol might be a candidate as a the drug having marked suppressive activity for inflammation which might be influenced by calprotectin.

Alkaloids↗