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Biomedical subjects

N Seo

Publications and source records attributed to N Seo.

At least 19 recordsLinked to original sources
PubMed2006

Male New Zealand Black/KN mice: a novel model for autoimmune-induced permanent alopecia?

BACKGROUND: Irreversible, permanent and scarring alopecia is associated with several autoimmune diseases, including all autoimmune connective tissue disorders. The pathogenesis of autoimmune-induced permanent alopecia (APA) is still poorly understood, and instructive, simple mouse models for the study of APA are needed urgently. During the course of our studies in a well-established mouse model for chronic rheumatoid arthritis, the New Zealand Black/KN (NZB/KN) mouse, we noticed that ageing male NZB/KN mice developed spontaneous APA. OBJECTIVES: To study whether alopecia seen in ageing male NZB/KN mice displays key features of human APA and may, thus, be a useful new mouse model for clinically relevant APA research. METHODS: NZB/KN, the F1 hybrid of NZW/N Slc x NZB/KN (W/BKN F1), the F1 hybrid of NZB/KN x NZW/N Slc (BKN/W F1), and the F2 hybrid of W/BKN F1 x W/BKN F1 mice were employed in this study, in order to check which strain carries the highest risk of alopecia development. Besides routine histology, CD3, CD4 and CD8 expression as well as immunoglobulin (Ig) G and IgM deposition in hair follicles were investigated by immunohistology/immunofluorescence. Mast cell distribution/degranulation and Ki-67 (proliferation)/TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling) (apoptosis) positive cells were also analysed. RESULTS: Only F2 male NZB/KN mice were prone to develop alopecia, suggesting that Y chromosome-associated gene(s) are involved in the pathogenesis of APA, which incidence rises with increasing age. The lesional alopecia skin in 12-month-old male NZB/KN mice showed a sharp decline in hair follicle density, thus meeting a key criterion of permanent alopecia. Both macroscopically and histologically, the alopecia seen in these mice resembled in many respects different stages of clinical APA, such as alopecia associated with chronic discoid lupus erythematosus (DLE) in humans. Lesional APA hair follicles in mice displayed intrafollicular and perifollicular mononuclear cell infiltrates, as well as an increased number of activated (degranulated) perifollicular mast cells. In the fully developed lesion, many CD4+ cells were seen in perifollicular locations, including the epithelial stem cell region (bulge), and also contained a few CD8+ T cells. IgM deposits were found in the follicular basement membrane zone (BMZ). Both in the bulge and the hair matrix region of the affected anagen hair follicles, there were signs of massive keratinocyte apoptosis. CONCLUSIONS: Our currently available data suggest that male but not female NZB/KN mice may indeed represent a suitable mouse model for APA, with some similarities to the permanent alopecia seen in human DLE patients, although additional and confirmatory investigations are needed before this mouse strain can be accepted as a murine equivalent of APA in humans.

Aging↗
PubMed2006

Genetic background differences between FVB and C57BL/6 mice affect hypnotic susceptibility to pentobarbital, ketamine and nitrous oxide, but not isoflurane.

BACKGROUND: Pharmacogenomics has allowed us to identify the mechanisms underlying much of the inherited variability in drug response. There have been several reports of strain-dependent anesthetic actions in rodents, indicating that significant genetic differences exist in the hypnotic and antinociceptive effects of various anesthetics. METHODS: Loss of righting reflex was used to compare the hypnotic action of pentobarbital, ketamine, nitrous oxide and isoflurane between two genetically different populations of mice, C57BL/6 with black hair and Friends virus B (FVB) with white hair. RESULTS: C57BL/6 mice were more susceptible than FVB mice to the hypnotic effects of ketamine, pentobarbital and nitrous oxide. However, the sensitivity to isoflurane did not differ between C57BL/6 and FVB mice. CONCLUSION: Genetic background affects the hypnotic susceptibility to some anesthetic agents in mice. Our results indicate that there may be a different genetic basis for the operation of hypnosis between isoflurane and other anesthetics, such as pentobarbital, ketamine and nitrous oxide.

Anesthetics, Dissociative↗
PubMed2005

Evaluation of intraoperative infusion solution using a complete anhepatic model in baby pigs.

Compared to cadaveric liver transplantation, living-related liver transplantation (LRLT) has the physiological advantage of avoiding hemodynamic changes due to the nonsystemic clamping of the inferior vena cava (IVC). However, metabolic changes in the level of blood glucose and lactate usually occur during the anhepatic phase in LRLT. For pediatric patients, intraoperative infusions have the potential to maintain immature homeostasis during LRLT. In the present study, a complete anhepatic model of baby pigs with nonsystemic clamping of IVC, which mimics the procedure of pediatric LRLT, was established using a heparin-coated tube as an internal shunt lactate Ringer solution (LR, Lactec), acetate Ringer solution (AR, VeenF), and a solution comprising acetate Ringer with 1% glucose (AR-G, Phisio140) were tested using piglets. Hemodynamic and metabolic (blood gas analysis, electrolytes, blood lactate, and glucose) changes were observed during the anhepatic phase. Although no major difference was observed in hemodynamic parameters, arterial blood gas data, or concentration of electrolytes among the three solution groups, significant progressive hyperlactatemia was observed in the LR group. Also, though severe hypoglycemia was found in the LR and AR groups, the AR-G group maintained blood glucose levels throughout the anhepatic phase. To conclude, using the simplified pig anhepatic model, we evaluated various solutions for pediatric LRLT.

Animals↗
PubMed2005

Effect of continuous infusion of propofol on its concentration in blood with and without the liver in pigs.

In living donor liver transplantation, propofol, an intravenous anesthetic drug, has recently been used in both donors and recipients. Propofol is known to have intra- and extrahepatic metabolic pathways, but the effect of its continuous infusion during a long-term anhepatic state is yet to be determined. Recently, we successfully established a simplified pig model of the complete anhepatic state. In this state, we first evaluated hemodynamic parameters relating to the pharmacokinetics of continuously infused propofol (6 mg.kg(-1) x h(-1)). No significant changes in the concentration of hemoglobin or in hemodynamic parameters other than the heart rate were observed during the anhepatic phase when porpofol was continuously infused at the rate that maintains the state. Blood propofol concentrations in the mixed vein, artery, and portal vein were stable during the anhepatic phase. Finally, we confirmed the pharmacokinetics of continuously infused propofol using orthotropic liver transplantation in miniature pigs. The propofol concentration did not change markedly during the transplant procedure. In conclusion, the pharmacokinetics of continuously infused propofol was almost stable with and without the liver in pigs. Extrahepatic metabolism of propofol might help prevent changes in propofol concentrations.

Anesthetics, Intravenous↗
PubMed2004

Lysis of adhesions and epidural injection of steroid/local anaesthetic during epiduroscopy potentially alleviate low back and leg pain in elderly patients with lumbar spinal stenosis.

BACKGROUND: Lumbar spinal stenosis causes various forms of back or leg pain, and is recognized with increasing frequency in elderly patients whose physical status is not always suitable for surgery. Epiduroscopy, a new, minimally invasive diagnostic and therapeutic technique, may be useful for pain relief in such patients. We investigated the epiduroscopic findings and immediate and long-term changes in back and leg pain after epiduroscopy in elderly patients with spinal stenosis. METHODS: Patients with degenerative lumbar spinal stenosis (n=58, median age 71 yr) were divided into two groups based on presenting symptoms: a monosegmental group (n=34) and a multisegmental group (n=24). Each patient underwent epiduroscopy, and the findings were evaluated using visual analogue scales for low back and leg symptoms. Epiduroscopy included breaking down adhesions in the epidural space by injections of saline, and injection of steroids/local anaesthetic. RESULTS: Epiduroscopy showed that the amount of fatty tissue and the degree of vascularity were greater in the monosegmental group than in the multisegmental group. Relief of low back pain was observed up to 12 months after epiduroscopy in both groups. Relief of leg pain was evident up to 12 months after epiduroscopy in the monosegmental group, and up to 3 months after epiduroscopy in the multisegmental group. None of the patients showed deterioration of motor or sensory deficits during follow-up. One patient was excluded from analysis because of accidental dural puncture during the procedure. CONCLUSIONS: The findings of epiduroscopy corresponded to the symptoms. Epiduroscopy may reduce low back and leg pain in elderly patients with degenerative lumbar spinal stenosis, particularly those with radiculopathy.

Aged↗
PubMed2004

Chronopharmacological studies of ketamine in normal and NMDA epsilon1 receptor knockout mice.

BACKGROUND: The effectiveness and toxicity of many drugs depends on the dosing-time schedule, relative to the circadian rhythms of biochemical, physiological, and behavioural processes. Previous studies have found chronopharmacology of ketamine, which is a N-methyl-d-aspartate (NMDA) receptor antagonist. The in vivo contribution of the NMDA receptor epsilon1 subunit (NR2A) in this effect is unclear. METHODS: In the present study, daily variations in the hypnotic effect of ketamine were determined in wild-type mice and NMDA epsilon1 knockout (KO) mice. RESULTS: The effect of ketamine had a definite daily variation in wild-type mice. No significant difference in blood concentration was observed at different dosing times (10:00 and 22:00). In NMDA receptor epsilon1 KO mice, the hypnotic effect of ketamine was weaker than in wild-type mice and there was no dependence on the time of administration. Significant pharmacokinetic differences were not observed between wild-type and KO mice. CONCLUSIONS: The enhanced hypnotic effect in the active phase of the circadian cycle is likely a result of changes with the time of day in the susceptibility of the central nervous system to ketamine. Knockout of the NMDA receptor epsilon1 subunit gene markedly reduced the effect of ketamine, and eliminated the time-dependent sensitivity to ketamine.

Anesthetics, Dissociative↗
PubMed2004

Susceptibility of T cell receptor-alpha chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus.

The anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-alpha(-/-) mice and B6 TCR-delta(-/-) mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-alpha(-/-) mice with low FU (0.2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2.0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-delta(-/-) mice at a very low incidence. Specifically, the skin lesions of TCR-alpha(-/-) mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE.

Animals↗
PubMed2003

Anesthesia-related mortality and morbidity over a 5-year period in 2,363,038 patients in Japan.

BACKGROUND: Statistical data of mortality and morbidity related to anesthesia have not been reported in Japan since World War II. The need to comprehensively examine the events of cardiac arrest as well as mortality prompted the first national study in Japan. METHODS: Confidential questionnaires were sent to all Japan Society of Anesthesiologists Certified Training Hospitals every year from 1994 through 1998. Collected data were analyzed for incidence of cardiac arrest and other critical events during anesthesia and surgery, and their outcomes within 7 postoperative days. The principal causes of the critical incidents were also analyzed. RESULTS: With an average response rate of 39.9%, a total of 2,363,038 cases were documented over 5 years. The average incidence per year of cardiac arrest during surgery due to all etiologies and that totally attributable to anesthesia was 7.12 [95%CI: 6.30,7.94] and 1.00 [0.88, 1.12]) per 10,000 cases, respectively. The average mortality per year in the operating room or within 7 postoperative days due to all etiologies and that totally attributable to anesthesia was 7.18 [6.22, 8.13] and 0.21 [0.15, 0.27] per 10,000 cases, respectively. The two principal causes of cardiac arrest during anesthesia and surgery due to all etiologies were massive hemorrhage (31.9%) and surgery (30.2%), and those totally attributable to anesthesia were drug overdose or selection error (15.3%) and serious arrhythmia (13.9%). Preventable human errors caused 53.2% of cardiac arrest and 22.2% of deaths in the operating room totally attributable to anesthesia. CONCLUSIONS: The rates in Japan of cardiac arrest and death during anesthesia and surgery due to all etiologies as well as those totally attributable to anesthesia are comparable to those of other developed countries.

Anesthesia↗
PubMed2002

An anaphylactic reaction to blood supplied from patient's mother.

We present the case of a 4-year-old girl who developed anaphylactic shock during general anesthesia. Symptoms appeared 80 min into the operation and may have been an immediate allergic reaction to the transfused blood supplied from the child's mother based on the clinical signs, the decrease of components of complements and the elevated concentrations of histamine and tryptase. The blood type was the same and antibody screening test and crossmatch was negative. The blood was irradiated and we used a white cell-reduction filter. This patient possibly has antibodies to her mother's plasma and this type of reaction cannot be prevented by these routine methods. It is reported that the risk of transfusion associated graft-vs.-host disease is high when a patient receives blood from a closely related donor. However, there are, no reports of anaphylactic reactions to blood supplied from mother to child. We suggest that there is a potential for anaphylactic reaction as well as transfusion associated graft-vs.-host disease when a child patient receives blood from the mother.

Anaphylaxis↗
PubMed2002

Augmentation of monocyte interleukin-8 production by psoralen/UVA-treated CD4+ T cells.

Treatment of cells with psoralen and ultraviolet A light (UVA) modulates their cytokine production. As extracorporeal photochemotherapy has been reported to induce cytokine production by monocytes, we quantified interleukin-8 (IL-8), a representative chemokine produced by monocytes, in culture supernatants from human peripheral blood mononuclear cells (PBMC) treated with 8-methoxypsoralen (8-MOP) and UVA. Lipopolysaccharide stimulated IL-8 production in 8-MOP-phototreated PBMC more efficiently than those untreated or treated with 8-MOP or UVA. More interestingly, when cultured with T-cell-stimulating anti-CD3 and anti-CD28 antibodies, 8-MOP/UVA-treated PBMC produced enhanced amounts of IL-8 with an increased level of IL-8 mRNA expression. Depletion of CD4 but not CD8 T cells from PBMC abrogated this augmented IL-8 elaboration, and CD4 T cells per se secreted no substantial amount of IL-8 even upon CD3/CD28 stimulation. Thus, 8-MOP/UVA-treated CD4 T cells stimulated monocytes to secrete IL-8. The IL-8 overproduction was induced by direct contact of monocytes with 8-MOP/UVA-treated CD4 T cells but not by cytokines from the treated CD4 T cells. These findings imply that in extracorporeal photochemotherapy, monocytes effectively produce IL-8 by cell-to-cell contact with 8-MOP/UVA-treated malignant CD4 T cells. The augmentation of monocyte cytokine/chemokine production by 8-MOP/UVA may be one of the mechanisms underlying the therapeutic efficacy of extracorporeal photochemotherapy.

Adult↗
PubMed2001

Regulation of acute nociceptive responses by the NMDA receptor GluRepsilon2 subunit.

Heterozygous mice mutant for the NMDA-type glutamate receptor (GluR) epsilon2 subunit with a highly homogeneous genetic background showed exaggerated responses to various acute noxious stimuli in the footshock, tail-flick, hot-plate and tail-pinch tests. Because the noxious stimuli in these behavioral tests were electrical, thermal and mechanical, the reduction of GluRepsilon2 proteins exerted stimulatory effects on acute nociceptive responses across modalities. Previous studies showed that GluRepsilon1 and GluRepsilon4 subunit mutant mice exhibited no alteration in the responses to acute noxious stimuli. Thus, among NMDA receptor subunits, the GluRepsilon2 subunit specifically plays an important role in the regulation of the acute nociceptive responses.

Acute Disease↗
PubMed2001

Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy.

Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy.

Amino Acid Sequence↗
PubMed2001

Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity.

We investigated the relationship between transforming growth factor-beta (TGF-beta)-secreting T-regulatory (Tr) cells and anti-B16 melanoma immunity, and studied the association of early cytokines expressed at tumour sites with the generation of Tr cells. A large number of CD4(+) Tr cells producing interleukin (IL)-4, IL-10 and TGF-beta accumulated with functionally depressed CD8(+) cytotoxic T lymphocytes (CTLs) at tumour sites on day 20 after subcutaneous (s.c.) inoculation of B16 tumour cells. Tr cells consisted of two populations, which were termed T helper 3 (Th3) and Tr1 cells. B16-infiltrating Tr cells strongly inhibited the generation of B16-specific T helper 1 (Th1) cells in a TGF-beta-dependent manner and were assumed to suppress effective generation of CTLs. In addition, B16 cells markedly progressed in mice transferred adoptively by the cultured B16-infiltrating Tr cells compared with untreated mice. The capacity of these Tr cells to produce TGF-beta was hampered by neutralizing anti-IL-10 and partly anti-IL-4 monoclonal antibodies (mAbs) injected intralesionally during the early development of B16 tumours, and this treatment markedly attenuated B16 growth. Furthermore, a lesional injection of recombinant mouse IL-10 at an early tumour site resulted in the vigorous progression of B16 tumours. These results provide evidence that Tr cells, belonging to the T helper 3/T-regulatory 1 (Th3/Tr1) type, are activated in B16-bearing hosts under the influence of T helper 2 (Th2) cytokines, mainly IL-10 (produced at early tumour lesions), and that this regulatory T-cell population functions as a suppressor of anti-B16 immunity.

Animals↗
PubMed2001

Hypersensitivity to mosquito bites as the primary clinical manifestation of a juvenile type of Epstein-Barr virus-associated natural killer cell leukemia/lymphoma.

Hypersensitivity to mosquito bites or mosquito allergy is a mysterious disorder that has been reported mainly in Japanese patients (at least 58 patients) in the first two decades of life. The skin lesion at bite sites is typically a bulla that develops into necrosis. Patients simultaneously exhibit a high temperature and general malaise and subsequently may experience lymphadenopathy and hepatosplenomegaly. Recent studies have revealed that this mosquito hypersensitivity is associated with chronic Epstein-Barr virus infection and natural killer cell leukemia/lymphoma. The natural killer cell, infected with monoclonal (or oligoclonal) Epstein-Barr virus, seems to be involved in the pathogenesis of the hypersensitivity. Half of the patients reported died of hemophagocytic syndrome (or malignant histiocytosis), granular lymphocyte proliferative disorder, or lymphomas. We propose that this disease, defined as the triad of hypersensitivity to mosquito bites, chronic Epstein-Barr virus infection, and natural killer cell leukemia/lymphoma, is a clinical entity mostly seen in Asians.

Adolescent↗
PubMed2001

Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis.

Percutaneous peptide immunization is a method in which tumor-specific cytotoxic T lymphocytes (CTL) are primed in the lymph nodes and spleen following application of tumor peptides to corneum barrier-disrupted murine skin. Immunized mice are protected against subsequent challenge with corresponding tumors and suppress the growth of established tumors. CTL expansion after peptide application seems to be mediated by epidermal Langerhans' cells. In the human, disruption of permeability barrier by tape stripping also induces activation of epidermal Langerhans' cells. Thus, percutaneous peptide immunization provides a simple and noninvasive means of inducing potent antitumor immunity that may be exploited for cancer immunotherapy in the human.

Administration, Cutaneous↗
PubMed2001

Photoactivational cytokine-modulatory action of 8-methoxypsoralen plus ultraviolet A in lymphocytes, monocytes, and cutaneous T cell lymphoma cells.

Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) has been reported to modulate cytokine production in various cells. Our study was conducted to see the effects of 8-MOP/UVA on the expression/production of cytokines in peripheral blood lymphocytes and monocytes in relation to the therapeutic mechanisms of extracorporeal photochemotherapy. 8-MOP/UVA augmented the expression of mRNAs for interferon-gamma (IFN-gamma) and interleukin (IL)-2 and reduced those for IL-4 and IL-10 in peripheral blood mononuclear cells (PBMCs) from normal subjects and Sézary syndrome patients. This enhancement of Th1 cytokines was caused by increment of cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1 cytokines. The number of IFN-gamma-secreting lymphocytes was markedly increased in 8-MOP/UVA-treated PBMCs 20 h after treatment, and its amount was elevated in culture supernatants. However, this enhanced production of IFN-gamma was found only until three days after 8-MOP phototreatment, and its level was rapidly declined by five days after treatment. In addition to this Th1-polarized action, 8-MOP/UVA-treated PBMCs produced enhanced amounts of IL-8 upon stimulation with anti-CD3/CD28 antibodies. Phototreated CD4+ but not CD8+ cells provided excellent T cell help for monocytes to produce IL-8 via a direct cell-to-cell contact mechanism. These findings suggest that 8-MOP/UVA has a transient but biologically active Th1-skewing action in T cells, and the phototreated T cells simultaneously stimulate monocytes to produce IL-8. It is suggested that 8-MOP/UVA exerts a beneficial therapeutic effect on malignant Th2 neoplasms as a Th1-skewing cytokine modifier and that 8-MOP-phototreated CD4+ T cells allow monocytes to become effective tumor antigen-presenting cells for tumor-specific cytotoxic T cells.

Cytokines↗