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S Nakajima

Publications and source records attributed to S Nakajima.

At least 55 records · Page 3Linked to original sources
PubMed2001

Dynamic observation of selective accumulation of a photosensitizer and its photodynamic effects in rat experimental choroidal neovascularization.

PURPOSE: The authors investigated the selective accumulation of a photosensitizer, ATX-S10(Na), in experimental choroidal neovascularization (CNV) in rats using a highly sensitive colorchromatic charge coupled device (CCD) camera. METHODS: To detect the development of experimental CNV in 30 rats, the animals were followed weekly with simultaneous fluorescein and indocyanine green angiography. After injecting ATX-S10(Na), the authors detected fluorescence from the photosensitizer using a highly sensitive color CCD camera. The camera was connected to a surgical microscope, under which rat fundi were observed through a coverglass in contact with the cornea. The retinas were excited with 405-435 nm light, and the light emitted from the photosensitizer passed through a 680-nm bandpass filter before being detected by the CCD camera. RESULTS: Immediately after injection, fluorescence appeared in the retinal vessels and then the entire retina. Thirty minutes postinjection, the intensity of the fluorescence was still strong from the whole retina, and the CNV was not detected. One hour after injection, retinal fluorescence was weak but still observable; 1.5 hours postinjection, retinal fluorescence was undetectable but fluorescence was strong from the CNV. Under the optimum therapeutic conditions, CNV was effectively occluded. CONCLUSION: ATX-S10(Na) selectively accumulates in the CNV in rats. The optimum therapeutic timing is approximately 1.5 hours postinjection of the dye in this CNV model.

Animals↗
PubMed2001

Pharmacokinetic study of a gallium-porphyrin photo- and sono-sensitizer, ATX-70, in tumor-bearing mice.

The tissue distribution of a gallium-porphyrin photo- and sono-sensitizer, 7,12-bis(1-decyloxyethyl)-Ga(III)-3,8,13,17-tetramethylporphyrin-2,18-dipropionyldiaspartic acid, ATX-70, was pharmacokinetically examined in tumor-bearing mice. The drug was administered intravenously to CDF(1) mice implanted with Colon 26 carcinoma. Blood and tissue samples were collected for up to 72 h after administration. The drug concentration was determined by high-performance liquid chromatography (HPLC) with fluorescence detection. ATX-70 was found to accumulate in tumors at a relatively high concentration that peaked between 2 h and 6 h after administration. However, modest concentrations of ATX-70 also remained in healthy tissues for up to 6 h. We examined the distribution of ATX-70 in the tumor in comparison with other tissues from the viewpoint of minimizing possible side effects of laser or ultrasound exposure while maintaining the treatment effect. About 24 h after administration, the tumor / plasma concentration ratio peaked, and relatively high tumor / skin and tumor / muscle concentration ratios were seen.

Adenocarcinoma↗
PubMed2001

Role of chemical mediators in airway hyperresponsiveness in an asthmatic model.

BACKGROUND: Airway hyperresponsiveness (AHR) is one of the characteristic features of human asthma. The presence of AHR and the precise mechanisms immediately after establishment of sensitization in guinea pigs are unclear, although there are many reports showing allergen exposure that causes an increase in bronchial responsiveness associated with eosinophil influx into the airway in sensitized guinea pigs. OBJECTIVE: We investigated the inhibitory effects on AHR to histamine of ONO-1078, a leukotriene antagonist; indomethacin, a cyclooxygenase inhibitor; S-145, a thromboxane A(2) (TXA(2)) antagonist, and Y-24180, a platelet-activating factor (PAF) antagonist, to assess the involvement of chemical mediators in AHR employing ovalbumin (OA) sensitized guinea pig models. METHODS: Male Hartley guinea pigs were used. Each group comprised 4-7 animals. The animals were sensitized to OA, injecting intraperitoneally 30 mg of cyclophosphamide and 2,000 microg of OA together with 100 mg of aluminum hydroxide as the adjuvant. The guinea pigs were artificially ventilated via a cannula using a small-animal respirator after intraperitoneal anesthesia with pentobarbital sodium for tracheotomy. The pressure at the airway opening (PAO) was measured using a differential pressure transducer, and a differential pressure of peak PAO (peak DeltaPAO) at inspiratory phase as an overall index of bronchial response to bronchoactive agents was used. While being artificially ventilated, the animals were exposed to physiological saline solution containing various concentrations of histamine (4.9, 9.8, 20, 39, 78, and 156 microg/ml) by inhalation for 30 s at 3-min intervals. Determinations were made at 1 min after each inhalation. The chemical mediators were each (30 mg/kg of ONO-1078, 3 mg/kg of S-1452, and 1 mg/kg of Y-24180) administered orally to sensitized guinea pigs, and the airway response to histamine was assessed. Each group comprised 4-7 animals. RESULTS: The airway response to histamine was significantly greater in the sensitized group than in the nonsensitized group at histamine concentrations of 36 (p < 0.05), 78, and 156 mg/ml (p < 0.01). Leukotrienes C(4) and D(4): 30 mg/kg of ONO-178 did not show any inhibitory effect on airway response to inhaled histamine. Cyclooxygenase: 5 mg/kg of indomethacin did not show any inhibitory effect on the airway response to inhaled histamine. TXA(2): the AHR to inhaled histamine at doses of 9.8, 39, 78, and 156 microg/ml was significantly inhibited by prior administration of 3 mg/kg of S-1452. PAF: the AHR to inhaled histamine at doses of 9.8, 39, and 78 microg/ml was significantly inhibited by prior administration of 1 mg/kg of Y-24180. CONCLUSIONS: S-1452 (3 mg/kg) and Y-24180 (1 mg/kg) significantly inhibited AHR to histamine, while ONO-108 (30 mg/kg) and indomethacin (5 mg/kg) did not. The results suggest that TXA(2) and PAF are involved in AHR in OA-sensitized guinea pigs.

Airway Resistance↗
PubMed2001

Histopathology of the airway epithelium in an experimental dual-phase model of bronchial asthma.

BACKGROUND: Lesions of trachea cuticles are a pathological histological characteristic of bronchial asthma. Furthermore, collected tracheal cuticles desquamated from the respiratory tract are found in patients' sputum when asthma attacks occur or after the induction of allergen inhalation. From these facts, it is assumed that desquamation of trachea cuticle cells is a pathological symptom of bronchial asthma. However, there has not been any chronological report of desquamation of trachea cuticles through the process of bronchial asthma attacks. OBJECTIVE: For this report, we made an experimental bronchial asthma model using guinea pigs, and conducted chronological examinations of trachea cuticle lesions related to pathological symptoms of bronchial asthma using a transmission electron microscope and a scanning electron microscope. METHODS: The experimental asthma models were made by injection of ovalbumin into the abdominal cavity of guinea pigs. Then the airway responses to inhaled aerosolized ovalbumin were induced. The trachea were enucleated and examined under an optical microscope, a transmission electron microscope (hereafter abbreviated as TEM), and a scanning electron microscope (hereafter abbreviated as SEM) after 1, 2, 4, 8, 12, 24 h and 7 days after the immediate airway responses. RESULTS: Intercellular oedema of ciliated epithelium was observed in the sensitization groups immediately after the immediate airway response. SEM observation revealed increased mucus secretion and shortening of cilium. A slight case of desquamation or deciduation of ciliated epithelium was also beginning to appear. TEM observation revealed a dilation of ciliated epithelium intervals. Infiltration of eosinophilic leucocytes was already detectable beneath the ciliated epithelium. The degree of ciliated epithelium desquamation and infiltration of eosinophilic leucocytes progressed with time. When the late airway response occurred 4 hours later, eosinophilic leucocytes had increased drastically, and ciliate epithelium had desquamated to the extent that basal cells were exposed. Seven days after the immediate airway response, epithelium intercellular oedema had improved, and cilium had been reproduced. CONCLUSION: These results suggest that desquamation of epithelium caused by trachea cuticle lesions appears at an early stage of an asthma attack, owing to the contraction of the trachea, and that the damage is intensified by the infiltration of eosinophilic leucocytes.

Animals↗
PubMed2001

[Anti-bleeding effect of nafamostat mesilate for the surgery of thoracic ascending aorta].

UNLABELLED: During extracorporeal cardiopulmonary bypass (ECB), the activated coagulation and fibrinogenolysis system causes bleeding and postoperative multiple organ failures. We studied the effect of an anti-bleeding agent, nafamostat mesilate (NM) during the surgery of thoracic ascending aorta to decrease a side effect of bleeding. From March 1980 to January 1998, for thoracic ascending aorta operations in our department (true aneurysm, 16-, psudoaneurysm, 2-, and dissection, 11 cases, in 29 cases, respectively), age from 16 to 79 (mean 62.9 +/- 9.5 year of age), we classified the objects in two groups, NM group (intraoperative infusion with NM of 60 mg/hr and with heparin 300 IU/kg) and C group (only with heparin treated, 500 IU/kg). We investigated the preoperative factors (age and aneurysmal diameter), the intraoperative factors (ACT, hematcrit, platelet, aorta clamping time, operative time, ECB time, bleeding volume, and blood transfusion), and the postoperative factors (bleeding and blood transfusion) after the administration of NM. RESULTS: There was no significance for the protection effect of NM infusion on the preoperative and the postoperative factors. However, intraoperative bleeding and blood transfusion volume in NM group were significantly lesser than those in group C. CONCLUSIONS: It might be useful for NM infusion during the surgery of thoracic ascending aorta due to the decrease of volume of intraoperative bleeding and blood transfusion amount with the remarkable anti-bleeding effect.

Adolescent↗
PubMed2001

PDT to monkey CNV with ATX-S10(Na): inappropriateness of early laser irradiation for selective occlusion.

PURPOSE: There is controversy about which mode of laser irradiation, early irradiation with low-dose photosensitizer or late irradiation with high-dose, benefits the selective occlusion of choroidal neovascularization (CNV) in photodynamic therapy (PDT). In this study, using an amphiphilic photosensitizer, 13,17-bis (1-carboxypropionyl) carbamoylethyl-8-etheny-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetraethyl porphyrin sodium (ATX-S10(Na); Photochemical Inc., Okayama, Japan), photodynamic and adverse effects of early irradiation on CNV-bearing monkey eyes were investigated. METHODS: Experimentally induced CNV lesions and normal retina were irradiated with a diode laser (670-nm wavelength) at a dose of 1 to 90 J/cm(2) at 1 to 19 minutes after intravenous injection of 2 mg/kg body weight of ATX-S10(Na). Vascular occlusion and CNV recurrence were evaluated by fluorescein and indocyanine green angiography and histologic analysis, until 4 weeks after irradiation. RESULTS: Of 45 different conditions, 23 did not induce CNV closure, 20 provided both CNV occlusion and retinal vessel damage, and 2 achieved selective CNV occlusion without retinal vascular injury. Recurrence of CNV was induced in 19 of 22 CNV-occluding conditions. ATX-S10(Na) angiography showed that dyes were similarly distributed between normal vessels and CNV at early time periods after injection, whereas they were preferentially accumulated in CNV after 30 minutes. CONCLUSIONS: In PDT with ATX-S10(Na), irradiation within 20 minutes of dye injection failed to induce selective CNV occlusion, probably because there is no significant difference in the biodistribution of dye between CNV and retinal vessels. It also caused frequent CNV recurrence after extensive inflammation in the irradiated retina.

Animals↗
PubMed2001

[Tarantulas bite: two case reports of finger bite from Haplopelma lividum].

The risk of envenomations by venomous exotic spiders have not been well recognized in Japan. Two cases of finger bite from Asian pet tarantula, Haplopelma lividum (Cobalt blue), are reported. In both cases, initial severe pain and inflammatory signs were completely healed with only symptomatic treatments within several hours. In one case, arthritic stiffness lasted for a few weeks following bite but resulted no permanent deficit. Bites from Haplopelma lividum seemed relatively harmless like other various tarantulas, although the composition of the venom has been unknown.

Adolescent↗
PubMed2001

Expression of METH-1 and METH-2 in pancreatic cancer.

PURPOSE: METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified genes that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows metalloproteinase function. Because the significance of METH-1 and METH-2 has not been determined in solid tumors, we examined the mRNA expressions of these molecules in pancreatic cancer and hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: METH-1 and METH-2 mRNA expressions were identified in six pancreatic cancer cell lines and were quantified by TaqMan reverse transcription-PCR in 18 paired samples of pancreatic cancer and surrounding noncancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA expression was also examined in 16 pairs of HCC and cirrhotic liver. Vascularity was estimated by CD34 staining. The correlation between clinicopathological factors and METH-1 expression was additionally analyzed. RESULTS: Four of six pancreatic cancer cell lines expressed METH-1, and 1/6 expressed METH-2. METH-1 was substantially expressed in both pancreatic cancer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pancreatic cancer tissue was significantly lower than that in noncancerous pancreas (P = 0.002), and a similar result was obtained between HCC and cirrhotic liver (P = 0.003). METH-1 expression did not show a significant correlation with vascularity in pancreatic cancer or in HCC. However, pancreatic cancer with higher expression of METH-1 showed significantly severe lymph node metastasis or retroperitoneal invasion (P = 0.033 and P = 0.018, respectively) and worse prognosis (P = 0.038). CONCLUSIONS: METH-1, which was initially reported to have a potent antiangiogenic effect, does not seem to be a predominant determinant of tumor vascularity in pancreatic cancer. Rather, METH-1 seems to be involved in progression of pancreatic cancer through local invasion and lymph node metastasis.

ADAM Proteins↗
PubMed2000

Investigation of the release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing for intravenous administration.

The release behavior of diethylhexyl phthalate (DEHP) from a polyvinyl-chloride (PVC) tube, which is part of an intravenous administration set, was investigated with the coexistence of polysorbate 80 (Tween 80) in various solutions such as physiological saline (PS), distilled water for injection (DWI) and glucose solution (TZ). The cumulative amount of DEHP released after 5 h was in the following order; PS, DWI > 50% TZ. From a comparison of the amount of released DEHP and the critical micelle concentration (CMC) of various solutions, the lower the CMC of the solution, the higher the amount of DEHP released from the PVC tubing. When the concentration of Tween 80 was kept constant at 1 mg/ml, the cumulative amount of DEHP released with a flow rate 90 ml/h was higher than that at 60 ml/h. These results suggest that the release of DEHP from the PVC tubing is closely correlated with the interaction of Tween 80 and DEHP such as the formation of micelles, the collision of micelles against the surface of the PVC tubing and the diffusion properties of DEHP and or Tween 80 in the liquid medium.

Diethylhexyl Phthalate↗
PubMed2000

Cellular responses and repair of single-strand breaks introduced by UV damage endonuclease in mammalian cells.

Although single-strand breaks (SSBs) occur frequently, the cellular responses and repair of SSB are not well understood. To address this, we established mammalian cell lines expressing Neurospora crassa UV damage endonuclease (UVDE), which introduces a SSB with a 3'-OH immediately 5' to UV-induced cyclobutane pyrimidine dimers or 6-4 photoproducts and initiates an alternative excision repair process. Xeroderma pigmentosum group A cells expressing UVDE show UV resistance of almost the wild-type level. In these cells SSBs are produced upon UV irradiation and then efficiently repaired. The repair patch size is about seven nucleotides, and repair synthesis is decreased to 30% by aphidicolin, suggesting the involvement of a DNA polymerase delta/epsilon-dependent long-patch repair. Immediately after UV irradiation, cellular proteins are poly(ADP-ribosyl)ated. The UV resistance of the cells is decreased in the presence of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. Expression of UVDE in XRCC1-defective EM9, a Chinese hamster ovary cell line, greatly sensitizes the host cells to UV, and addition of 3-aminobenzamide results in almost no further sensitization of the cells to UV. Thus, we show that XRCC1 and PARP are involved in the same pathway for the repair of SSBs.

Animals↗
PubMed2000

Variation in response among individuals to antigenic sites on the HA protein of human influenza virus may be responsible for the emergence of drift strains in the human population.

Eight convalescent human sera obtained from patients aged 3 to 14 years old, who were infected with influenza A(H3N2) virus during the 1990/1991 influenza season, were characterized by a binding assay with chimeric hemagglutinin (HA) proteins between influenza virus A/Aichi/2/68 and A/Kamata/14/91(H3N2) strains. These sera did not recognize the HA protein of the A/Aichi/2/68 strain but recognized that of the A/Kamata/14/91 strain. The binding assay revealed that these sera recognized only the HA1 domain of A/Kamata/14/91 HA protein. A further assay of the binding of these sera to the chimeric proteins of the HA1 domain revealed that three sera (A-1, A-2, and A-3) from very young patients bound only to region 150-170 (site B1) and one serum (Y-1) bound to regions 96-150 (site A) and 96-170 (sites A and B1). These four sera showed reduced hemagglutination inhibition (HI) activity with the 203v2 strain, a monoclonal variant of the A/Kamata/14/91 strain with two amino acid changes in the HA protein at antigenic sites A and B1. The other four sera (Y-2, G-1, G-2, and A-4) bound to regions 1-96 (site C/E), 96-150 (site A), 96-170 (sites A and B1), and 170-200 (site B2), two of which further bound to region 240-306 (site C); these sera were all fully reactive with the 203v2 strain. All eight sera showed reduced HI reactivity to a drift strain A/Aichi/4/93. Amino acid changes of the A/Aichi/4/93 strain from the A/Kamata/14/91 strain were located at antigenic sites A, B1, B2, and C. We propose a possible model for the emergence of a drift strain A/Aichi/4/93 from an A/Kamata/14/91-like strain by sequential changes during reinfections of individuals starting from A-1-like, next to Y-1-like, and then to Y-2-like populations.

Adolescent↗
PubMed2000

Taste aversion induced by confinement in a running wheel.

Opportunities of spontaneous wheel running induced aversion in rats to the taste consumed before the running. Eight thirsty rats of Wistar strain were daily allowed to drink one of two taste solutions (sucrose or sodium chloride, say A) followed by confinement in a wheel or another taste solution (say B) followed by confinement in a Skinner box. Repeated training with Tastes A and B made the rats drink Taste A less than Taste B. Post-training two-bottle choice tests also showed clear demonstration of wheel-running-induced aversion to Taste A. These results confirmed those from Lett's laboratory and expanded the generality of the phenomenon in respect to strain of rats, deprivation conditions of the subjects, tastes, and other details. Furthermore, our procedure rejected three accounts alternative to wheel-induced aversion to Taste A.

Journal Article↗
PubMed2000

Hemopexin as a carrier protein of tumor-localizing Ga-metalloporphyrin-ATN-2.

During size exclusion HPLC, ATN-2 binding protein separated from human and mouse sera, SCCVII and colon 26 tumor tissues were found in fraction 13 (A: estimated molecular weight 70,000). Fraction 13(A) of human sera was exclusively reactive to the human hemopexin antibody. During two-dimensional electrophoresis and amino acid sequence analysis, Fraction 13(A) of C3H/He mouse sera was found to have partial homology with the mouse hemopexin precursor. Glycoprotein with the same domain structure of hemopexin has been proposed to be an important carrier protein that forms the tumor-localizing activity of water-soluble porphyrin.

Animals↗
PubMed2000

Effect of cyclic adenosine 3',5'-monophosphate and protein kinase A on ligand-dependent transactivation via the vitamin D receptor.

We examined the effects of cyclic adenosine 3',5'-monophosphate (cAMP) and protein kinase A (PKA) on the ligand-dependent transactivation mediated via the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptor (VDR). A human VDR expression plasmid was transfected into HeLa, Saos-2 and MG63 cells with a luciferase reporter gene construct containing the vitamin D responsive element. With the addition of 0.5 mM 8 bromo-cAMP, the response to 1,25(OH)2D3 was suppressed to 61 and 78% in the HeLa and Saos-2 cells, respectively. The suppressive effect of 8 bromo-cAMP was observed without the introduction of the VDR expression plasmid in the MG63 cells. In the HeLa cells the co-expression of PKA reduced the ligand-inducible transactivation to 61% and the fold induction by 1,25(OH)2D3 to 89% of that without PKA. The CREB binding protein (CBP) was recently reported to integrate the intracellular signals via the cAMP/PKA cascade and nuclear hormone receptors. However, the suppressive effect of cAMP was not influenced by the co-expression of CBP. Lastly, we introduced point mutations at possible PKA phosphorylation sites into the VDR expression vector at serine-172 and threonine-175, but both mutant receptors still exhibited reduced transactivation with the co-expression of PKA. These results indicate that the phosphorylation of proteins other than the VDR may also be involved in the inhibitory effect mediated by the cAMP/PKA cascade.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Selective photodynamic effects of the new photosensitizer ATX-S10(Na) on choroidal neovascularization in monkeys.

OBJECTIVE: To determine the optimal treatment variables for photodynamic therapy (PDT) with new photosensitizer ATX-S10(Na) (13,17-bis[1-carboxypropionyl] carbamoylethyl-8-etheny-2-hydroxy-3-hydroxyiminoethyliden e-2,7,12,18-tetranethyl 6 porphyrin sodium) to induce selective occlusion of choroidal neovascularization (CNV) in nonhuman primate eyes. METHODS: Experimental CNV was induced in monkey eyes by laser photocoagulation, and PDT was performed in neovascularized and healthy eyes with different treatment variables. At 0 to 150 minutes after 4-, 8-, and 12-mg/kg of body weight intravenous injections of ATX-S10(Na), a diode laser was irradiated at the dose of 1 to 127 J/cm2 (wavelength, 670 nm). Vascular occlusion induced by PDT was evaluated using fluorescein angiography, indocyanine green angiography, and histological examination at 1 day to 4 weeks after irradiation. RESULTS: Selective occlusion of CNV without damage to healthy retinal and choroidal capillaries was achieved in the following conditions: 30 to 74 J/cm2 irradiation at 30 to 74 minutes after the 8-mg/kg injection, and 1 to 29 J/cm2 irradiation at 30 to 74 minutes or 30 to 74 J/cm2 irradiation at 75 to 150 minutes after the 12-mg/kg dye injection. Regrowth of CNV often occurred when the retina was heavily injured by excessive PDT. CONCLUSION: By using optimal treatment variables, PDT using ATX-S10(Na) induces selective occlusion of CNV in nonhuman primate eyes, providing the possibility of therapeutic application to the clinical practice. CLINICAL RELEVANCE: Occlusion of CNV without direct damage to the sensory retina is useful to preserve visual acuity in patients with exudative age-related macular degeneration. A clinical trial of PDT using ATX-S10(Na) is desirable.

Animals↗
PubMed2000

Long-term effectiveness of photodynamic therapy by using a hydrophilic photosensitizer ATX-S10(Na) against experimental choroidal neovascularization in rats.

BACKGROUND AND OBJECTIVE: We previously demonstrated that a hydrophilic photosensitizer ATX-S10 had a potent photodynamic effect. This study was designed to reveal the long-term effectiveness of photodynamic therapy (PDT) with this agent in occluding choroidal neovascularization (CNV) and its selectivity in the neovascular tissue. STUDY DESIGN/MATERIALS AND METHODS: Experimental CNV was induced by intense photocoagulation in rat eyes. Immediately or 2 hours after intravenous injection of 8 mg/kg body weight of ATX-S10(Na), a cis isomer of ATX-S10, eyes were irradiated by a diode laser at the radiance of 3.25-65.3 J/cm(2) Vascular occlusion was identified by fundus photography, fluorescein angiography, and histology at 1, 3, 7, 14, and 28 days after PDT. As controls, non-neovascular eyes were subjected to PDT and similarly analyzed. RESULTS: By using the following treatment parameters, PDT with ATX-S10(Na) successfully occluded CNV without causing occlusion of retinal capillaries for 28 days; 7.4 and 19.6 J/cm(2) immediately after dye injection and 36.7 and 65.3 J/cm(2) 2 hours after injection. Although these conditions also caused occlusion of normal choriocapillaries and mild injuries of retinal vessels, retinal pigment epithelium, and photoreceptors at 1 day, retinal vessels and pigment epithelial cells recovered from damages by 28 days. No injuries were found in the inner retina. CONCLUSION: In optimal treatment conditions, PDT with ATX-S10(Na) can induce long-term, selective occlusion of CNV without causing irreversible damages in the inner retina.

Animals↗