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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 55 records · Page 3Linked to original sources
PubMed2003

Gamma radiation inhibits fibroblast-mediated collagen gel retraction.

Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role in the production and modification of extracellular matrix in wound repair. Since one important aspect of wound repair is the contraction of the wound, this study investigated the effects of radiation on the ability of fibroblasts to mediate collagen gel contraction in an in vitro model of wound retraction. After irradiation, the cells were detached and suspended in a solution of rat tail tendon collagen. Radiation exposure decreased retraction, and this effect was dose dependent. In order to define the mechanism of reduced gel retraction, we investigated alpha2beta1 cell surface integrin and fibronectin, which are thought to mediate contraction, and prostaglandin E2 (PGE2), which is known to inhibit this process. PGE2 release increased dose responsively following radiation. The cyclooxygenase inhibitor indomethacin could partially restore the contractile activity of irradiated fibroblasts. Fibronectin production in gel culture showed a significant decrease. In contrast, there was no decrease in alpha2beta1 integrin expression in radiated cells. In conclusion, radiation decreases fibroblast-mediated gel contraction. Increased PGE2 production and decreased fibronectin production by irradiated fibroblasts may contribute to this effect and may be in part responsible for poor healing of radiated tissue.

Animals↗
PubMed2003

Axonal and demyelinating forms of the MPZ Thr124Met mutation.

OBJECTIVE: We report on a Japanese family with Charcot Marie Tooth disease (CMT) with the Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene. MATERIAL AND METHODS: Based on the clinical study, we investigated MPZ gene by direct sequence analysis and polymerase chain reaction restriction fragment length polymorphism analysis. RESULTS: Genotyping of four symptomatic family members showed that one family member with severe disease symptoms was homozygous, while the other three were heterozygous. The heterozygous cases were clinicopathologically determined to be the axonal type, which is characterized by late-onset and slow progression associated with Adie's pupil and deafness. The homozygous case was the demyelinating type, which showed earlier onset, rapid progression, sural nerve demyelination, and cranial nerve demyelination at autopsy. CONCLUSIONS: We suggest that axonal and demyelinating forms of CMT are not two distinct classes, but rather parts of a spectrum of genotypically related conditions, particularly with some MPZ mutations.

Adult↗
PubMed2003

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma.

Interleukin 4 (IL-4) is essential for the switching of B cells to IgE antibody production and for the maturation of T helper (Th) cells toward the Th2 phenotype. These mechanisms are thought to play a crucial role in the pathogenesis of the allergic airway inflammation observed in asthma. In the present study, we examined the anti-inflammatory effects of DNA administration of murine IL-4 mutant Q116D/Y119D (IL-4 double mutant, IL-4DM), which binds to the IL-4 receptor alpha and is an antagonist for IL-4. Immunization of BALB/c mice with alum-adsorbed ovalbumin (OVA) followed by aspiration with aerosolized OVA resulted in the development of allergic airway inflammation. A single administration of IL-4DM DNA before the aerosolized OVA challenge protected the mice from the subsequent induction of allergic airway inflammation. Serum IgE level and extent of eosinophil infiltration in bronchoalveolar lavage (BAL) from IL-4DM DNA-administered mice were significantly lower than those in BAL from control plasmid-immunized mice. In our study, IL-4 or IL-4 mutants were not detected in sera from mice that had received a single administration of IL-4DM DNA. The results of this study provide evidence for the potential utility of IL-4 mutant antagonist DNA inoculation as an approach to gene therapy for asthma.

Animals↗
PubMed2003

Developmental changes in interleukin-12-producing ability by monocytes and their relevance to allergic diseases.

BACKGROUND: The T helper type-2 (Th2)-dominated situation can be observed in allergic diseases such as asthma or atopic dermatitis. A reduced ability to produce IL-12, which is a key cytokine for the induction of Th1 responses, has been proposed to lead to aberrant Th2 development in these disease conditions. OBJECTIVE: This study was intended to examine how IL-12-producing ability might associate with allergic diseases as a function of age. METHODS: IL-12 production by monocytes at various ages was assessed in patients with bronchial asthma and/or atopic dermatitis (n = 100) in comparison with non-allergic control subjects (n = 144). Whole blood cells were stimulated with lipopolysaccharide (LPS) after priming with IFN-gamma, then intracellular cytokine expression of IL-12 and IL-8 as a control cytokine of CD14-positive cells was assessed by flow cytometric analysis. RESULTS: In the control subjects, the ability of monocytes to produce IL-12 was negligible at birth and gradually increased with advancing age, whereas IL-8 production was intense throughout the human life. At more than 7 years of age, IL-12 production of patients with allergic diseases was significantly lower compared with that of control subjects. The unexpected finding was that infants and children below 6 years of age with allergic diseases tended to produce more IL-12 compared with age-matched controls. In this young group, it was noted that enhanced IL-12 production by monocytes was especially observed in allergic patients with specific IgE antibodies against some food allergens. Significant inverse relationships between serum IgE levels and IL-12-producing ability were found in the teenage and adult groups, but not in the younger children. CONCLUSION: IL-12 appeared to play different roles in the pathogenesis of allergic diseases between younger and older ages.

Adolescent↗
PubMed2003

Less sensitivity for late airway inflammation in males than females in BALB/c mice.

Several studies have investigated allergic airway inflammation, a T helper 2 (Th2)-type immune response, using a mouse model of asthma. At present, however, no reports have described sex differences in the sensitivity of late airway inflammation (LAI). The LAI induced by ovalbumin in adult BALB/c mice was compared in males and females or sham-operated males and castrated males. The males showed less severe bronchial-bronchiolar inflammation with infiltration of eosinophils and lymphocytes and lower content of such cells in bronchoalveolar fluid than the females. Moreover, interleukin-4 (IL-4) mRNA expression levels in splenic cells were lower in the males than in the females. Castrated males performed like the females. Moreover, when compared with the sham-operated males, the castrated males showed lower testosterone levels in the blood. The present results suggest that less sensitivity for LAI in the males may be because of the decreased Th2 cell responses compared with the females. Moreover the testosterone, at least in part, may be responsible for the decreased Th2 cell responses in males in vivo.

Animals↗
PubMed2003

Expression and cytoprotective effect of protease-activated receptor-1 in gastric epithelial cells.

Thrombin is a serine protease involved in many physiological functions and its receptor. the protease-activated receptor-1 (PAR-1), has a wide tissue distribution. We hypothesized that PAR-1 is expressed in gastric epithelial cells and that thrombin can modulate defence mechanisms through PAR-1. The rat gastric epithelial cell line (RMG1) and gastric biopsy specimens from gastritis patients were used in the study. Reverse transcriptase polymerase chain reaction analysis showed that the thrombin receptors PAR-1, PAR3 and PAR-4 are expressed by RGM1 gastric epithelial cell line. Immunohistochemical and electron microspcopic studies also showed PAR-1 expression in human gastric epithelial cells. Thrombin stimulated the secretion of mucin and prostaglandin E2 (PGE2) formation in RGM1 cells in a dose-dependent manner. PAR-1 agonist also stimulated PGE2 formation. In addition, thrombin significantly increases the expression of the PGE2 receptors EP2-R and EP4-R in RGM1 cells. In conclusion, the results of the present study showed for the first time that gastric epithelial cells express thrombin receptors and that these receptors may play a protective role in the gastric mucosa.

Animals↗
PubMed2003

Glutathione S-transferase polymorphisms: susceptibility to migraine without aura.

Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. We investigated glutathione S-transferase (GST) P1 Ile(105)Val, T1 and M1 polymorphisms in 174 Japanese headache sufferers and 372 Japanese controls. The headache group consisted of 38 cases of migraine with aura, 95 migraine without aura (MWOA) and 41 tension-type headache sufferers. The M1 homozygous deletion genotype was significantly higher in MWOA (64%) compared with controls (46%; p < 0.01; odds ratio = 2.18, 95% confidence interval: 1.32-3.61, adjusted for age and gender). In a comparison of the current smokers, the M1 null frequencies in MWOA were further increased. GSTM1 may be one of the genetic risk factors for MWOA in the Japanese population.

Adult↗
PubMed2002

Development of port-site metastasis after pneumoperitoneum.

BACKGROUND: Port-site metastasis is a critical problem in laparoscopic cancer surgery; the pathogenesis and means of prevention are still unclear. The aim of this study was to clarify by scanning electron microscopy the initial morphologic changes in the development of port-site metastasis. METHODS: Fifteen nude mice were injected with human gastric cancer (MKN 45) cells. Mice were killed on days 0, 3, and 8 (n = 5 each day) after intraperitoneal injection of 5 x 105 cancer cells and carbon dioxide (CO2) pneumoperitoneum at 4-6 mmHg for 20 min. The abdominal wall with the port sites was harvested and examined under both light and scanning electron microscopy. RESULTS: Immediately after CO2 pneumoperitoneum (day 0), the abdominal peritoneum was peeled away and the muscular layer was destroyed at the port site in all mice. Several cancer cells were attached to the injured port sites. On day 3, the subperitoneal tissue and muscular layer defects were replaced by granulation tissue, and several cancer cells were observed in the subperitoneal tissue. On day 8, a small nodule was macroscopically visible at the port site; it was completely covered by mesothelial cells and consisted of numerous cancer cells. CONCLUSIONS: Free cancer cells appear to attach to the injured port sites immediately after CO2 pneumoperitoneum, and these are associated with the development of port-site metastasis after laparoscopic cancer surgery.

Animals↗
PubMed2002

Activation of protein C pathway in the airways.

The protein C (PC) pathway plays important roles in the regulation of the coagulation system and inflammatory response. This study evaluated the degree of PC activation in the airway of patients with bronchial asthma (BA), and the expression and regulation of PC and its receptor in airway epithelial cell lines. Thirteen BA patients and 8 healthy volunteers were enrolled in the study. BEAS-2B and A549 epithelial cell lines were used in experimental assays. Expression of anticoagulant factors was evaluated by RT-PCR and Western blotting. The activated protein C (APC)/thrombin (1.65 +/- 0.35 vs 3.34 +/- 0.59) and APC/PC (8.30 +/- 2.26 vs 24.41 +/- 9.88) ratios were significantly decreased and the concentrations of soluble thrombomodulin (TM) were significantly increased in induced sputum from BA patients compared with healthy subjects. Airway epithelial cells express PC, its receptor, and TM. PC antigen prepared from epithelial cells was significantly activated in the presence of thrombin. Thrombin increased the expression of PC antigen from lung epithelial cells. However, tumor necrosis factor-alpha, eotaxin, and RANTES (regulated on activation, normal T-cell expressed and secreted) decreased the expression of PC and its receptor in bronchial epithelial cells. Overall, these results showed for the first time that reduced activation of PC pathway occurs in the airway of BA patients and that TM, PC, and its receptor, are expressed by human airway epithelial cells. The expression of these PC pathway components was found to be downregulated by inflammatory cytokines. The decrease in PC activation may contribute to exacerbation of the inflammatory response in the airway of asthmatic patients.

Asthma↗
PubMed2002

The effect of antibiotics on the production of superantigen from Staphylococcus aureus isolated from atopic dermatitis.

Staphylococcus aureus (S. aureus) often colonizes on the skin of patients with atopic dermatitis. It is known that superantigens which are staphylococcal enterotoxins can activate T cells without processing by antigen presenting cells. It has been suggested that activated T cells release various cytokines which may exacerbate or prolong the cutaneous inflammation associated with atopic dermatitis. Reduction of bacterial colonization from skin lesions has been reported to be effective in the treatment of atopic dermatitis. Therefore, antimicrobial therapy using antibiotics may be a treatment option for atopic dermatitis in selected patients. We examined the effect of antibiotics on the production of superantigen from S. aureus in vitro to determine the action mechanism of antibiotics in the treatment of atopic dermatitis. It was found that antibiotics with inhibitory effect on protein synthesis can suppress the production of superantigen. On the other hand, the superantigen production was not suppressed by antibiotics having either the inhibitory effect on cell wall synthesis or on nucleic acid synthesis. Levels of the suppressive effect on superantigen production by S. aureus varied with strains tested in this study. Moreover, we demonstrated that replication of DNA coding of superantigen produced by S. aureus was suppressed only by roxithromycin (ROX), which is a new macrolide. This finding suggests that ROX may have an effect at the gene level. These results suggested that the suppressive effects of antimicrobial agents that act as inhibitors of protein synthesis on superantigen production from S. aureus may be useful in the treatment of atopic dermatitis.

Anti-Bacterial Agents↗
PubMed2002

Decrease in minimum alveolar concentration of sevoflurane during anaesthesia and arthroscopy.

BACKGROUND AND OBJECTIVE: Although the MACtetanus (minimum alveolar concentration that prevents movement in response to electrical tetanus stimulation in 50% of patients) of isoflurane decreases during anaesthesia and surgery, it is not known whether this occurs to the same extent with other inhalational anaesthetics. We determined the MACtetanus of sevoflurane before and after surgery. METHODS: Eleven patients who underwent arthroscopy of the shoulder underwent inhalational induction of anaesthesia with sevoflurane and tracheal intubation by succinylcholine. MACtetanus was determined in each patient by testing the response to a 10 s, 50 Hz, 80 mA transcutaneous tetanic electrical stimulus to the ulnar nerve at varying concentrations of sevoflurane. The end-tidal concentration of sevoflurane was kept constant for 15 min before each stimulus and the concentration of sevoflurane varied in increments of 0.1% until a sequence of three alternate responses (move, not move, move) or (not move, move, not move) was obtained. After arthroscopy of the shoulder, individual MACtetanus were measured as described above. RESULTS: The mean MACtetanus decreased from 2.22 +/- 0.29% before arthroscopy to 1.82 +/- 0.26% after arthroscopy (P < 0.01). CONCLUSIONS: It is concluded that the MACtetanus of sevoflurane decreases during anaesthesia and surgery.

Adult↗
PubMed2002

Oral clonidine premedication reduces the EC50 of propofol concentration for laryngeal mask airway insertion in male patients.

BACKGROUND: Oral clonidine, an alpha2-adrenergic receptor agonist, reduces the dose of propofol required for laryngeal mask airway (LMA) insertion. Target-controlled infusion (TCI) is becoming increasingly popular for propofol infusion. There is no information, however, on the propofol blood concentrations required for LMA insertion and the effect of oral clonidine premedication on these values. METHODS: Propofol at target effect-site concentrations from 4.0 to 12.0 microg/ml were randomly administered using TCI in three groups of healthy male patients (n=35 each) who were undergoing elective orthopedic surgery: control, 2.5 microg/kg clonidine, and 5.0 microg/kg clonidine groups. Nothing was administered to the control group. Clonidine(2.5 microg/kg or 5.0 microg/kg) was administered orally 90 min before arrival at the operating room in the clonidine groups. After equilibration between the blood- and effect-site for 15 min, insertion of the LMA was attempted. The EC50 for LMA insertion (measured propofol serum concentration in equilibrium with the effect-site at which 50% of patients do not respond to the insertion of the LMA) was determined by logistical regression. RESULTS: EC50+/-standard error values in the control, 2.5 microg/kg clonidine, and 5.0 microg/kg clonidine groups were 8.72+/-0.55, 7.76+/-0.60, and 5.84+/-0.58 microg/ml, respectively. The EC50 in the 5.0 microg/kg clonidine group was significantly lower than that in the control group (P < 0.01). CONCLUSIONS: The propofol concentration required for LMA insertion in healthy male patients is reduced by premedication with 5.0 microg/kg oral clonidine.

Adrenergic alpha-Agonists↗
PubMed2002

Evaluation of aviguard, a commercial competitive exclusion product for efficacy and after-effect on the antibody response of chicks to Salmonella.

The competitive exclusion (CE) action of Aviguard (AG) and its effects on the antibody response of chicks were evaluated in this study. We observed that AG protected the chicks from overwhelming colonization. Fourteen days after infection, fewer AG-pretreated than nonpretreated chicks shed salmonellae from their coloaca in both infected groups, although much less from SE-infected chicks. Antibody titers of sera produced to Salmonella typhimurium (ST) and SE in pretreated and non-pretreated chicks were not significantly different. Immunoblotting showed that these antibodies reacted with SDS-PAGE-separated 71.4, 67.7, 44.0, and 30.3 kDa proteins detectable in the test strains. Few weak bands of doubtful significance were observed in the cross-reaction between the sera of ST- and SE-infected chicks with ST and SE antigens, respectively. Our study showed that AG protected chicks from overwhelming colonization by salmonellae, and neither altered the antigenic proteins of infecting salmonellae nor their recognition by specific antibodies produced in response to the infection.

Animals↗
PubMed2001

The role of Kupffer cell oxidant production in early ethanol-induced liver disease.

Considerable evidence for a role of Kupffer cells in alcoholic liver disease has accumulated and they have recently been shown to be a predominant source of free radicals. Several approaches including pharmacological agents, knockout mice, and viral gene transfer have been used to fill critical gaps in understanding key mechanisms by which Kupffer cell activation, oxidant formation, and cytokine production lead to liver damage and subsequent pathogenesis. This review highlights new data in support of the hypothesis that Kupffer cells play a pivotal role in hepatotoxicity due to ethanol by producing oxidants via NADPH oxidase.

Adenoviridae↗
PubMed2001

A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging.

The treatment of advanced neuroblastoma (NB) or Ewing's sarcoma (ES) is one of the major challenges in pediatric oncology. Both malignancies are refractory to conventional therapies and have an extremely poor prognosis. High-dose myeloablative radiochemotherapy with autologous bone marrow or peripheral blood stem cell rescue is one of the most aggressive treatments attempted for these diseases but is often undermined by residual tumor cells contaminating the graft. Thus, in this approach, purging of tumor cells from the graft is key to the prevention of relapse after transplantation. We investigated a novel approach to eliminate tumor cells from the bone marrow or peripheral blood stem cell graft without causing stem cell damage through the use of a conditionally replicative adenovirus (Ad). ES and NB are sensitive to Ad infection, and advanced NBs express a high level of the growth/differentiation factor midkine (MK). We confirmed in this study that ES cell lines (SK-ES-1 and RD-ES) are also sensitive to Ad infection and express high levels of MK. In contrast, CD34+ stem cells are refractory to Ad infection and express very little MK. A conditionally replicative Ad in which the expression of E1 is controlled by the MK promoter achieved good levels of viral replication in NB or ES and induced remarkable tumor cell killing. On the other hand, this virus caused no damage to CD34+ cells even after 3 h of infection at a dose of 1000 multiplicity of infection. We concluded that application of this replication-competent Ad to hematopoietic grafts could be a simple but effective procedure to achieve complete tumor cell purging.

Adenoviridae↗
PubMed2001

Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes.

Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.

Adenoviridae↗
PubMed2001

Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers.

Matrix metalloproteinases (MMPs) have been implicated in tumor progression. Matrilysin, one of the matrix metalloproteinases, is frequently overexpressed in gastrointestinal cancers. The aim of our study was to assess the validity of matrilysin as a prognostic marker of colorectal cancers. Matrilysin expression was immunohistochemically analyzed using formalin-fixed, paraffin-embedded specimens from 113 colorectal cancer patients who had undergone curative surgery. The lumenal surface of neoplastic glands in the superficial layer was apically stained, while the cytoplasm of cancer cells at the invasive front was diffusely stained for matrilysin. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 47 (42%) cases, were judged as being positive for matrilysin. Matrilysin positivity was significantly correlated with the depth of invasion, lymph node metastasis, lymphatic invasion, advanced Dukes' stage and poor outcome. Patients with matrilysin-positive cancer had a significantly shorter overall survival time than those with matrilysin-negative cancer. For patients with intermediate invasive tumor (T2 or T3), only matrilysin was a significant prognostic variable for predicting overall survival in multivariate analysis. Matrilysin expression at the invasive front could be an important marker, predicting an unfavorable prognosis after surgical treatment in patients with colorectal cancer.

Biomarkers, Tumor↗