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Biomedical subjects

A Saitoh

Publications and source records attributed to A Saitoh.

At least 19 recordsLinked to original sources
PubMed2002

Long-term effect on optic nerve of silicone oil tamponade in rabbits: histological and EDXA findings.

PURPOSE: Side-effects after intravitreal use of silicone oil (SO) are not well defined and elucidated. The object of this study was to examine the influence and toxicity of SO on the optic nerve after vitrectomy with SO tamponade. METHODS: We injected medical grade SO and emulsified SO into rabbit eyes after gas-mediated vitreous compression and examined the eyes by light microscopy (LM), transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDXA) (point analysis and area analysis) 6 months after injection. We compared the findings in the non-treated eyes and eyes with only gas-mediated vitreous compression with those in SO-injected eyes. RESULTS: Vacuole-like structures were seen in the optic nerve posterior to the lamina cribrosa. In the group treated with only gas-mediated vitreous compression, the myelin structures were shown by TEM to be destroyed and replaced by glial tissue, while in groups injected with medical grade or emulsified SO severe destruction of the myelin sheath (myelinolysis) was observed. Silicone was identified at the electron-dense edges of the vacuoles by EDXA point analysis, but not in the vacuoles without electron-dense deposits. Dots of Si K alpha were not seen in the control groups, and dense dots were observed in SO-injected groups, by EDXA area analysis. CONCLUSIONS: Some of the vacuoles might be artefacts caused by insufficient fixation or the operative procedure, but TEM showed almost no artefacts in the control optic nerve. Thus, most vacuoles may be SO storage sites. SO uptake into the optic nerve might play a role in the pathogenesis of optic nerve atrophy after SO injection.

Animals↗
PubMed2001

[Detection of TDH-producing Vibrio parahaemolyticus O3:K6 from naturally contaminated shellfish using an immunomagnetic separation method and chromogenic agar medium].

We attempted to isolate TDH-producing Vibrio parahaemolyticus O3:K6 from shellfish. Asari samples were incubated with TSB supplemented with 2% (w/v) NaCl for 6 h, and then the 6-h cultures were incubated with salt polymyxin broth for 18 h. After the two-step enrichment, a 1 ml portion of the culture was treated with magnetic beads coated with K6 antibody for immunoconcentration of V. parahaemolyticus O3:K6. The immunoconcentrated and untreated cultures were plated onto a chromogenic agar and TCBS agar media for isolation of V. parahaemolyticus. TDH-producing V. parahaemolyticus O3:K6 was isolated from 3 out of 66 lots (4.5%) of naturally contaminated Asari. Six of 4,265 colonies suspected as V. parahaemolyticus (0.14%) were TDH-producing V. parahaemolyticus O3:K6.

Agar↗
PubMed2001

TRK-820, a selective kappa-opioid agonist, produces potent antinociception in cynomolgus monkeys.

TRK-820 ((-)-17-cyclopropylmethyl-3,14b-dihydroxy-4,5a-epoxy-6b-[N-methyl-trans-3-(3-furyl)acrylamide]morphinan hydrochloride) has been shown to be a potent opioid kappa-receptor agonist with pharmacological properties different from those produced by kappa1-opioid receptor agonists in rodents. To ascertain whether or not these properties of TRK-820 would be extended to primates, the antinociceptive effect of TRK-820 was evaluated in cynomolgus monkeys by the hot-water tail-withdrawal procedure. TRK-820 given intramuscularly (i.m.) produced a potent antinociceptive effect that was 295- and 495-fold more potent than morphine with the 50 degrees C and 55 degrees C hot-water tests, respectively, and 40-fold more potent than U-50,488H and 1,000-fold more potent than pentazocine in the 50 degrees C hot-water test. The duration of antinociceptive effects of TRK-820 treatment (0.01 and 0.03 mg/kg, i.m.) lasted more than 6 h, which was much longer than those of U-50,488H. The antinociception produced by the higher dose (0.03 mg/kg, i.m.) of TRK-820 was not inhibited by nor-binaltorphimine (3.2 and 10 mg/kg, s.c.) or by naloxone (0.1 mg/kg, s.c.), although the antinociception induced by a lower dose of TRK-820 (0.01 mg/kg, i.m.) was inhibited by nor-binaltorphimine (10 mg/kg, s.c.). The same doses of nor-binaltorphimine and naloxone effectively inhibited the antinociception induced by the higher doses of U-50,488H (1.0 mg/kg, i.m.) and morphine (10 mg/kg, i.m.), respectively. These results indicate that the antinociception induced by TRK-820 is less sensitive to nor-binaltorphimine and suggest that it is mediated by the stimulation of a subtype of kappa-opioid receptor different from the kappa-opioid receptor in cynomolgus monkeys.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Characterization of immortalized human chondrocytes originated from osteoarthritis cartilage.

Immortalized cloned human chondrocytes isolated from a normal (Ch-4, 8, N) and an osteoarthritis patient (Ch-8-OA) were established by introduction of recombinant SV40-adenovirus vector containing SV40 early gene. These cells exhibited continuous proliferative capacity in monolayer culture and showed chondrocytic characteristics in that they were positive for alkaline phosphatase and collagen type II. When cells were treated with IL-1alpha, the growth was inhibited. IL-1alpha induced the production of IL-6, GM-CSF and TNFalpha from immortalized chondrocytes. Significantly high amounts of cytokines including IL-6, GM-CSF and TNFalpha were produced from Ch-8-OA cells, even in the absence of IL-1alpha stimulation. Interestingly, TNFalpha, exogenously added into the culture, inhibited the growth of Ch-8-OA cells. Further studies are required to clarify the different mechanisms on chondrocytes originating from osteoarthritis cartilage underlying the biological reaction to various cytokines and the production of these cytokines as compared with chondrocytes from normal cartilages. However, the novel chondrocyte cell lines established in the present study may provide researchers with a useful model for studying the pathogenesis of osteoarthritis.

Alkaline Phosphatase↗
PubMed2000

DELETEile chiral bidentate ligands derived from alpha-amino acids: synthetic applications and mechanistic considerations in the palladium-mediated asymmetric allylic substitutions.

A new class of chiral amidine-phosphine hybrid ligands 7a,b, which are readily accessible from the corresponding alpha-amino acids, were developed. A versatility for construction of new ligands is desirable, by which a variety of reactions and substrates become applicable. Indeed, a variety of modifications, such as exchange reactions to other amino groups in the amidine skeleton and the production of other types of ligands, are possible using the precursor compounds of 7a. Thus, novel chiral ligands 7c,d, 8, 11, and 13, which provide sterically and electronically different chiral circumstances, were prepared and used for the palladium-mediated asymmetric allylic substitutions of both acyclic and cyclic compounds. In these reactions, high levels of asymmetric induction were achieved for both substrates. A marked advancement of reactivity and enantioselectivity in palladium-catalyzed asymmetric allylations of 1,3-diphenylpropen-2-yl pivalate 14a was attained by examination of electronic substituent effects in a new series of chiral P-N and S-N hybrid ligands 8 and 11. Mechanistic views concerning the enantiodiscriminating step were demonstrated, in which a good correlation between a novel Pr/Mr concept and the absolute configuration of allylation products are discussed for the prediction of enantioselecting direction. The use of ketene silyl acetals as nucleophiles was investigated and compared with the corresponding harder anionic carbon nucleophiles. The former nucleophiles afforded higher enantioselectivity in asymmetric allylic transformations of 14a.

Alkaloids↗
PubMed2000

Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras.

The expression of facilitative glucose transporter isoforms in colon adenocarcinoma and the possible role of k-ras in inducing GLUT (glucose transporter) mRNA were studied. RT-PCR demonstrated GLUT2 and GLUT3 expression in 100% of the ten normal colon mucosa samples but detected no GLUT1 mRNA. By contrast, GLUT1 mRNA was detected in all 20 (100%) colon cancer samples examined. GLUT4 mRNA was not detected in either normal mucosa or colon cancer tissues. Semiquantitative PCR demonstrated equal amounts of GLUT2 and GLUT3 mRNA in both normal mucosa and colon cancer samples. A point mutation in codon 12 of k-ras was detected in only six of the 20 (30%) colon cancer samples. Thus, a major difference between normal colon epithelia and colon cancer was the acquisition of GLUT1 expression, which was unlikely to have been induced by a point mutation in codon 12 of k-ras.

Adenocarcinoma↗
PubMed2000

Selective upregulation of fibroblast Fas ligand expression, and prolongation of Fas/Fas ligand-mediated skin allograft survival, by retinoic acid: the skin as a retinoide-inducible immune privilege site.

Fas/Fas ligand-mediated lymphocyte apoptosis has been implicated in the suppression of immune responses and may cause immune privilege. Human corneas exhibit immune privilege and can be transplanted across allogeneic barriers without immunosuppressive therapy, perhaps, because corneal keratinocytes express Fas ligand. To characterize Fas and Fas ligand expression in skin, we examined expression by murine keratinocytes, dermal fibroblasts, melanocytes, and human umbilical endothelial cells. We also studied the regulation of Fas and Fas ligand in skin cells by retinoic acid, vitamin D3, and dexamethasone as well as various cytokines. Among the molecules and cells tested, retinoic acid selectively upregulated the expression of Fas ligand molecule by fibroblasts. Retinoic acid-induced Fas ligand+ fibroblasts killed Fas+ target cells, and this killing was blocked by anti-Fas ligand antibody. The function of Fas ligand on dermal fibroblasts in vivo was tested in a cutaneous allograft system. Histoincompatible BALB/C mouse (H-2d) donor skin was grafted on to allogeneic C57BL/6 mice (H-2b). Daily local injection of retinoic acid blocked inflammation and extended graft survival for more than 10 d. Injection of retinoic acid into Fas ligand mutated gld/gld donor skin did not prevent leukocyte infiltration into the allograft or prolong graft survival. These experiments indicate that, in skin, retinoic acid selectively increases Fas ligand expression by fibroblasts and that retinoic acid has potent Fas/Fas ligand-dependent immunosuppressive activity.

Animals↗
PubMed2000

Factors influencing the expression of Fas and Fas ligand on newborn murine keratinocytes and fibroblasts.

OBJECTIVE: To investigate the expression of Fas, FasL mRNA and proteins on keratinocytes and fibroblasts, and the influence by retinoid acid (RA) and dexamethasone (Dex). METHODS: RNase protection assay and flow cytometry were used. RESULTS: Fas mRNA was expressed on neonatal murine keratinocytes and was up-regulated by all-trans retinoid acid and down-regulated by Dex. RA and Dex also increased the Fas protein expression on keratinocytes. Newborn murine keratinocytes express FasL mRNA, which was up-regulated by RA and Dex, while its protein expression was moderately induced by RA. Newborn murine fibroblasts also expressed Fas and FasL mRNA, which were up-regulated by the RA and Dex. CONCLUSIONS: The results indicated that RA and Dex might regulate apoptosis of keratinocytes and fibroblasts via the Fas-FasL system.

Animals↗
PubMed1999

The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice.

To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception.

Analgesics↗
PubMed1999

Pneumonia in HIV-infected patients: a case-control survey of factors involved in risk and prevention.

OBJECTIVE: To assess the factors that increase or decrease the risk of pneumonia with particular attention to immunization with pneumococcal and influenza vaccines in a group of HIV-infected persons. DESIGN: A retrospective, case-control study based on information entered into a standard database and the medical record. SETTING: Patients attending a referral clinic specializing in AIDS/HIV care at a public hospital. PATIENTS: Among over 2000 subjects entered into a database in 8 years, 127 incidents of pneumonia were identified from the record. These cases were matched with 127 CD4 cell count matched, concurrent controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The principal hypothesis was that chart review would find a decreased frequency of pneumococcal immunization in the pneumonia cases compared with matched controls. RESULTS: Pneumococcal immunization was associated with a reduction of the risk of pneumonia by nearly 70%. The effect was seen even when immunization was given with a CD4 cell count of less than 100/mm3. Injection drug users and African-Americans had a twofold increased risk of pneumonia. CONCLUSION: The study provides data to support the current recommendation for pneumococcal immunization of all HIV-infected persons. Although this conclusion could lead to renewed enthusiasm for increasing pneumococcal immunization rates in HIV-infected persons, it must be recognized that the study is observational and ascertainment bias cannot be excluded.

AIDS-Related Opportunistic Infections↗
PubMed1999

Potent antinociceptive effects of TRK-820, a novel kappa-opioid receptor agonist.

TRK-820, a new type of 4,5-epoxymorphinan derivative, was investigated in vivo for antinociceptive activities and its selectivity on various opioid receptors in mice. TRK-820 given s.c. or p.o. was found to be 351- and 796-fold more potent than U50,488H with acetic acid-induced abdominal constriction test. The duration of the antinociceptive effect produced by TRK-820 was longer than that produced by mu-opioid receptor agonist morphine or other kappa-opioid receptor agonists. In addition, with four other antinociceptive assays, low temperature hot plate (51 degrees C), thermal tail flick, mechanical tail pressure and tail pinch tests, TRK-820 was also found to be 68- to 328-fold more potent than U-50488H, and 41- to 349-fold more potent than morphine in producing antinociception, as comparing the weight of the different compound. However, TRK-820 was less active in inhibiting the high temperature (55 degrees C) hot plate response. The antinociceptive effects produced by TRK-820 were inhibited by nor-BNI, but not by naloxone or naltrindole (NTI) with the abdominal constriction test, indicating that the antinociception is selectively mediated by the stimulation of kappa-, but not mu- or delta-opioid receptors. Co-administration of TRK-820 with morphine slightly enhanced the antinociception induced by morphine in the mouse hot plate test. On the other hand, pentazocine significantly reduced the morphine-induced antinociception. TRK-820 produced sedation at doses, which are much higher than the doses for producing antinociception. These results indicate that the potent antinociception induced by TRK-820 is mediated via the stimulation of kappa-, but not mu- or delta-opiod receptors.

Administration, Oral↗
PubMed1999

Migration of Langerhans cells in an in vitro organ culture system: IL-6 and TNF-alpha are partially responsible for migration into the epidermis.

Although it is well established that epidermal Langerhans cells (LC) originate from bone marrow, little is known about the mechanism of this migration into the epidermis from bone marrow. In order to clarify the mechanism of this migration, we constructed an in vitro model. LC were depleted by daily topical application of clobetazole propionate (CP) solution onto the ear of Balb/c mice. Seven days later, ear skin was cut off, separated and co-cultured dermal-side-up with syngeneic (Balb/c), semisyngeneic ((C3H x Balb/c)F1), or allogeneic (C3H) epidermal cells (EC) for 3 days. We found (1) that a marked migration of donor LC into the recipient epidermis was observed in the LC-depleted skin, (2) that only syngeneic LC actively migrated into the recipient epidermis; however, the migration of semisyngeneic and allogeneic LC was detected at very low levels, (3) that the migratory capacity of donor LC was directly proved by a biolabeling technique using donor EC labeled with PKH-26, and (4) that anti-IL-6 and anti-TNF-alpha antibodies inhibited the migration of donor LC into the recipient epidermis. These data demonstrate that the resident LC have the potential to traffic through the dermis into the epidermis in a highly syngeneic-specific fashion, and that IL-6 and TNF-alpha are partially responsible for promoting this migration.

Animals↗
PubMed1999

Molecular mechanisms involved in the migration of epidermal dendritic cells in the skin.

The murine epidermis contains two types of dendritic cells (DC), Thy-1+ dendritic epidermal T cells (DETC) and Langerhans cells. In this review, we introduce our data obtained using a skin organ culture system to examine the migratory capacity of DETC and Langerhans cells into the epidermis. DETC or Langerhans cells were depleted by topical application ofclobetazole propionate (CP) solution onto the murine ears. CP-treated or untreated ear skin was co-cultured with syngeneic (semi-syngeneic, or allogenic, in experiments with Langerhans cells) epidermal cell suspension. We found (i) that donor DETC or Langerhans cells migrated into the CP-treated epidermis as well as into untreated epidermis, (ii) that leukosialin Ly48 recognized by monoclonal antibody S11 and TNF-alpha strongly inhibited donor Langerhans cell migration into the epidermis. We mention other molecules that may participate in the migration of Langerhans cells such as chemotactic cytokines, monocyte chemoattractant protein (MCP)-1, TGF-beta and skin-homing molecule, cutaneous lymphocyte-associated antigen (CLA) on Langerhans cells.

Animals↗
PubMed1999

Major organ function under mechanical support: comparative studies of pulsatile and nonpulsatile circulation.

We examined a major organ function during 3 h biventricular assisted circulation after acute myocardial infarction model in the pig. In left ventricular circulation, the outflow cannula was placed in the ascending aorta and an inflow cannula through the mitral valve in the left ventricle. A pump (pulsatile group, Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso, Inc., Tokyo, Japan) was connected to each cannula. In right ventricular circulation, the outflow cannula was placed in the pulmonary artery and an inflow cannula in the right ventricle. The right ventricular circulation was supported by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional blood flows of the cortex and medulla in the kidney, white matter and gray mater in brain, and liver; renal arterial flow; carotid arterial flow; portal vein flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow increased, and the medulla blood flow decreased. On the other hand, in the nonpulsatile group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved rather than in the nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and L/P showed significant differences between the pulsatile and nonpulsatile groups. On the other hand, the white matter and gray matter regional blood flows and carotid arterial flow did not show significant differences between the groups. The results of our study indicated that pulsatile circulation produced superior circulation in the kidney and liver, and microcirculation on the cell level was superior as well in early treatment of acute heart failure.

Animals↗
PubMed1999

Conradi-Hünermann syndrome with ocular anomalies.

We report a Japanese girl with the Conradi-Hünermann form of chondrodysplasia punctata and anterior segment malformations characteristic of Axenfeld-Rieger syndrome. The patient also had cataracts and unilateral optic atrophy. A possible role for homeobox-containing genes in the etiology of this type of chondrodysplasia punctata is suggested as an explanation for the coincidence of these two syndromes.

Anterior Eye Segment↗