Biomedical subjects

M Ichinose

Publications and source records attributed to M Ichinose.

At least 19 recordsLinked to original sources

PubMed2001

Establishment of gene-vaccinated skin grafting against Toxoplasma gondii infection in mice.

Vaccine effects of in vivo gene-vaccinated skin graft were evaluated against Toxoplasma gondii (T. gondii) infection. By using a gene gun, cDNA coding T. gondii SAG1 molecule was intracutaneously vaccinated into C57BL/6 (B6; a susceptible strain), BALB/c (a resistant strain) and (C57BL/6 x BALB/c) F1 (CBF1) mice, and the gene-vaccinated skin of these strains was transplanted to CBF1 mice. Regarding the antibody production against SAG1, CBF1-recipient mice transplanted with the SAG1 gene-vaccinated B6 skin were high responders, whereas CBF1 mice skin grafted with vaccinated skin of both BALB/c and CBF1 mice were low responders. The donor-derived LC/DC migrated to the draining lymph nodes of the recipients from the skin graft within 3 days. The vaccine effect against T. gondii challenge infection was obtained in CBF1 mice which received the skin graft of the SAG1 gene-vaccinated BALB/c mice.

Animals↗

PubMed2001

Mutagenicity of bisphenol A and its suppression by interferon-alpha in human RSa cells.

Bisphenol A is used as a monomer in the production of polycarbonate plastic products. The widespread use of bisphenol A has raised concerns about its effects in humans. Since there is little information on the mutagenic potential of the chemical, the mutagenicity of bisphenol A was tested using human RSa cells, which has been utilized for identification of novel mutagens. In genomic DNA from cells treated with bisphenol A at concentrations ranging from 1x10(-7) to 1x10(-5)M, base substitution mutations at K-ras codon 12 were detected using PCR and differential dot-blot hybridization with mutant probes. Mutations were also detected using the method of peptide nucleic acid (PNA)-mediated PCR clamping. The latter method enabled us to detect the mutation in bisphenol A-treated cells at a dose (1x10(-8)M) equivalent to that typically found in the environment. Induction of ouabain-resistant (Oua(R)) phenotypic mutation was also found in cells treated with 1x10(-7) and 1x10(-5)M of bisphenol A. The induction of K-ras codon 12 mutations and Oua(R) mutations was suppressed by pretreating RSa cells with human interferon (HuIFN)-alpha prior to bisphenol A treatment. The cells treated with bisphenol A at the concentration of 1x10(-6)M elicited unscheduled DNA synthesis (UDS). These findings suggested that bisphenol A has mutagenicity in RSa cells as well as mutagens that have been tested in these cells, and furthermore, that a combination of the PNA-mediated PCR clamping method with the human RSa cell line may be used as an assay system for screening the mutagenic chemicals at very low doses.

Avian Sarcoma Viruses↗

PubMed2001

Adrenocorticotropic hormone activates an outward current in cultured mouse peritoneal macrophages.

To define the effects of adrenocorticotropic hormone (ACTH) in immunocompetent cells, ion channel activities in cultured mouse peritoneal macrophages were analyzed by the perforated patch-clamp method. ACTH induced outward currents at smaller holding potentials than K+ equilibrium potentials. Reversal potentials of ACTH-induced currents were dependent on external K+ concentrations, but not on external Cl- concentration. Quinine potently blocked the outward current and tetraethylammonium (TEA) partially suppressed that current. ACTH did not induce the response in Ca2+ free solution containing EGTA. These results suggest that ACTH can modulate macrophage functions through the activation of Ca2+ dependent K+ channels.

Adrenocorticotropic Hormone↗

PubMed2001

Mesenchymal transcription factor Fkh6 is essential for the development and differentiation of parietal cells.

The role of transcription factor forkhead homologue 6 (Fkh6) gene expressed only in gastrointestinal mesenchymes on the differentiation of gastric epithelia was analyzed by inactivating the gene by targeting disruption. Gastric mucosa exhibited hyperplasias with disordered glandular structures in the absence of gene. Measurement of acid secretion in the isolated whole stomach demonstrated that both basal and stimulated secretions were severely suppressed in the Fkh6-/- stomach, while immunohistochemical studies showed that comparable numbers of parietal cells were differentiated in both wild-type and Fkh6-/- stomachs. Ultrastructurally Fkh6-/- parietal cells were furnished with developed intracellular canaliculi and many mitochondria, but their canaluculi were not enlarged nor fully connected to the luminal surface even when animals were treated with histamine, suggesting that Fkh6-/- parietal cells were far less responsive to acid secretion-inducing stimulations. Some parietal cells contained secretory granules positively stained with anti-pepsinogen antibodies, indicating that they retained characteristics of oxynticopeptic cells found in lower vertebrates. We thus concluded that Fkh6 plays essential roles for the development and differentiation of parietal cells via epithelial-mesenchymal interactions.

Animals↗

PubMed2001

Thymoma. Analysis of prognostic factors.

OBJECTIVE: We evaluated the prognostic factors for thymoma that remain controversial. METHODS: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using log-rank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model. RESULTS: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival. CONCLUSIONS: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.

Adult↗

PubMed2001

Appendectomy protects against the development of ulcerative colitis and reduces its recurrence: results of a multicenter case-controlled study in Japan.

OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent the development of ulcerative colitis, but no detailed study has been conducted in Japan, where ulcerative colitis is uncommon and the population is racially homogeneous. In addition, there has been no detailed analysis of the relationship between appendectomy and the clinical course of ulcerative colitis. In this multicenter clinical study, we evaluated the effects of appendectomy on ulcerative colitis in Japan. METHODS: A case-control study was undertaken in seven medical institutions comparing the incidence of appendectomy and tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were determined in 21 patients with ulcerative colitis who underwent appendectomies and 304 patients with ulcerative colitis who did not undergo appendectomies. RESULTS: Appendectomy was performed in a significantly lower percentage of patients in the ulcerative colitis group (21/325, 6.5%) than in the control group (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208-0.603). In contrast, no significant difference was observed between the groups with respect to tonsillectomy. The mean age (25.7 +/- 10.9 yr) of patients with ulcerative colitis at the time of appendectomy was significantly higher than the mean age (20.1 +/- 8.7 yr) of patients in the control group at the time of appendectomy (p < 0.05). The incidence of proctitis was higher in the appendectomy group than in the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the recurrence rates were significantly lower in the appenectomy group than in the group that did not undergo appendectomies (57. 1% vs 78.6%, p < 0.05), although both groups were similar in composition as to sex, age, duration of disease, smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate that appendectomy has a negative association with and perhaps a preventive effect on the development of ulcerative colitis in the Japanese population. Furthermore, appendectomy also appears to reduce the extent and recurrence of ulcerative colitis.

Adult↗

PubMed2000

Identification of an optimal Ncx binding sequence required for transcriptional activation.

The Ncx gene encodes a homeobox containing transcription factor that belongs to the Hox11 gene family. We determined specific Ncx protein binding consensus DNA sequences. Optimal Ncx binding sequences were 5'-CGGTAATTGG-3' (TAAT core) and 5'-CGGTAAGTGG-3' (TAAG core), which coincided with the Hox11 binding sequence. Both Ncx and Hox11 could bind to the TAAT and the TAAG core oligonucleotide in vitro. However, they could efficiently transactivate the reporter plasmid linked to the TAAT core sequence but not to the TAAG core sequence. Thus, Ncx and Hox11 act as transcriptional activators via their target sequence, 5'-CGGTAATTGG-3'.

Binding Sites↗

PubMed2000

Inhibition of the glutamate-induced K(+) current in identified Onchidium neurons by nitric oxide donors.

Nitric oxide (NO) acts as a neurotransmitter and neuromodulator in the nervous system of many vertebrates and invertebrates. The effects of extracellularly applied sodium nitroprusside (SNP) and diethylamine NO (C(2)H(5))(2)N[N(O)NO]-Na(+) (DEA/NO), NO donors, on a glutamate (Glu)-induced K(+) current in identified Onchidium neurons were investigated using voltage clamp and pressure ejection techniques. Bath-applied SNP (10 microM) and DEA/NO (5-10 microM) reduced the Glu-induced K(+) current without affecting the resting membrane conductance and holding current. The Glu-induced K(+) current also was inhibited by the focal application of SNP to the neuron somata. The suppressing effects of NO donors were concentration-dependent and completely reversible. Pretreatment with hemoglobin (50 microM), a nitric oxide scavenger, and 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microM), a specific inhibitor of NO-stimulated guanylate cyclase, decreased the SNP-induced inhibition of the Glu-induced current. Bath-applied 50 microM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase inhibitor, or intracellular injection of 1 mM guanosine 3',5'-cyclic monophosphate (cGMP) inhibited the Glu-induced current, mimicking the effect of NO donors. These results demonstrate that SNP and DEA/NO inhibit the Glu-induced K(+) current and that the mechanism of NO inhibition of the Glu-induced current involves cGMP-dependent protein kinase.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Molecular cloning of neonate/infant-specific pepsinogens from rat stomach mucosa and their expressional change during development.

To clarify the nature of rat neonate/infant-specific pepsinogens, we carried out their purification and molecular cloning. Prochymosin was found to be the major neonatal pepsinogen. The general proteolytic activity of its active form, chymosin, was, however, lower than those of pepsins A and C which are predominant in adult animals. Molecular cloning of rat prochymosin cDNA was achieved along with cDNA for another neonate-specific pepsinogen, pepsinogen F, although determination of pepsinogen F in neonatal gastric mucosa was unsuccessful, presumably due to its lack of proteolytic activity or different proteolytic specificity. Northern blot analysis confirmed that genes for prochymosin and pepsinogen F are expressed only at neonatal/infant stages and the switching of gene expression to that of pepsinogen C occurred at late infant stages. A phylogenetic tree based on nucleotide sequences showed clearly that pepsinogens fall into four major groups, namely prochymosin and pepsinogen F of the neonate/infant and pepsinogens A and C of adult animals. Although, to date, prochymosin and pepsinogen F were believed to be expressed in only a limited number of mammals, the present results suggest that they might be expressed at the neonatal/infant stage in a variety of mammals.

Aging↗

PubMed2000

Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor.

The contribution of the aryl hydrocarbon receptor (AhR) in induction of a battery of xenobiotic-metabolizing enzymes has been studied extensively. However, no direct proof has been obtained that it plays a role in modulating carcinogenesis. To address the question of whether AhR is required for tumor induction, we have investigated the response of AhR-deficient mice to benzo[a]pyrene (B[a]P), a widely distributed environmental carcinogen. B[a]P treatment induced expression of the cytochrome P450 gene Cyp1a1 in the skin and liver of AhR-positive mice bearing +/+ and +/- genotypes and did not induce expression of the cytochrome P450 gene Cyp1a1 in AhR-null mice in either skin or liver. In contrast, Cyp1a2 gene expression was positive in liver irrespective of the presence or absence of the AhR gene, or B[a]P treatment, although its inducibility was lost in the AhR(-/-) mouse. All AhR-positive male mice of both +/+ and +/- genotypes that received subcutaneous injection of B[a]P (2 mg) on the first and the eighth days had developed subcutaneous tumors at the site of injection at the end of the 18-week experiment. In contrast, no tumors were apparent in any of the AhR-deficient mice. Likewise, topical application of B[a]P (200 microg) at weekly intervals to the skin of female mice for 25 weeks produced skin tumors only in the AhR-positive mice. Thus the carcinogenic action of B[a]P may be determined primarily by AhR, a transcriptional regulator of the gene for CYP1A1. The results of the present study provide direct evidence that AhR is involved in carcinogenesis.

Animals↗

PubMed2000

Establishment of a parabiotic rat model by anastomosis of common carotid artery.

A cross circulation model was established by replacing mutual blood between two rats by anastomoses of each common carotid artery. In this model, parabiotic rats were shown to replace their mutual blood completely without any artificial materials or instruments, such as silicon tubes or pumps. The rate of blood exchange was measured by intravenous injection of Evans blue dye without the use of the radioactive materials that were so far commonly used. The partial alteration of blood circulation through microvascular surgery may reveal the mechanisms of organ tropism of bacteria, protozoa, and parasites. Microvascular surgery is available for reconstruction and analysis of organ functions as well as for clinical use in organplasty.

Anastomosis, Surgical↗

PubMed2000

Effect of a calcium sensitization modulator, Y-27632, on isolated human bronchus and pulmonary artery.

A recently developed pyridine derivative, Y-27632, has been reported to inhibit smooth muscle contraction by inhibiting Ca(2+)sensitization in animal experiments. However, the effect of this compound in human tissues has not yet been elucidated. The aim of the present study was to evaluate the effect of Y-27632 on human bronchi and pulmonary arteries. The tissues were obtained from lung cancer patients undergoing lung resection. Tissue responses were assessed by isometric tension measurement. Y-27632 relaxed the bronchi at basal tone with an IC(50)(concentration causing 50% relaxation of the maximal response) of 2.0+/-0.3x10(-6)M. Y-27632 also dose-dependently relaxed the bronchi precontracted by acetylcholine (ACh), histamine and neurokinin A, and the IC(50)was 3.0+/-0.4x10(-6), 2.5+/-0.5x10(-6)and 1.8 +/-0.3x10(-6)M, respectively. The dilatory effect of Y-27632 was significantly smaller in ACh-precontracted tissues compared with those of basal or histamine- and neurokinin A-induced precontracted bronchi (P<0.05). Further, Y-27632 showed an inhibitory effect on cholinergic nerve stimulation- and ACh-induced bronchial contraction to the same degree, suggesting that a modulatory effect of this compound on ACh release from nerve terminals was unlikely. Y-27632 also dilated the pulmonary arteries precontracted by phenylephrine (IC(50)= 1.6+/-0.1x10(-6)M). These data suggest that Y-27632 has a dilatory capacity on human bronchi as well as on pulmonary arteries.

Amides↗

PubMed2000

Allergic airway hyperresponsiveness and eosinophil infiltration is reduced by a selective iNOS inhibitor, 1400W, in mice.

Nitric oxide (NO) hyperproduction has been reported in asthmatic airways and may contribute to airway inflammatory responses. The purpose of this study was to examine the role of NO via inducible NO synthase (iNOS) in allergic airway inflammation using a selective iNOS inhibitor, N-[3-(aminomethyl)benzyl] acetamidine (1400W), in ovalbumin (OVA)-sensitized Balb/c mice. Sensitized animals were challenged with aerosolized 0.5% OVA for 1 h on two occasions 4 h apart. 1400W or the vehicle was administered by osmotic mini-pump from 2 h before to 24 h after OVA challenge. Twenty-four hours after OVA challenge, the vehicle-treated mice showed a significant airway hyperresponsiveness to intravenous methacholine (P<0.05) as well as an influx of eosinophils into the airways (P<0.05). iNOS immunoreactivity was obvious in the epithelial and, to a lesser extent, the infiltrated inflammatory cells. iNOS protein in the airway assessed by Western blotting also increased. Pretreatment with 1400W almost completely abolished the OVA-induced airway hyperresponsiveness and to a lesser extent eosinophil accumulation into the airways. These results suggest that NO synthesized by iNOS may participate in airway hyperresponsiveness and eosinophil infiltration into the airways after allergic reaction.

Amidines↗

PubMed2000

Reexpansion pulmonary edema due to high-frequency jet ventilation: report of a case.

Barotrauma is well known to be a relatively common complication of high-frequency jet ventilation (HFJV); however, the occurrence of reexpansion pulmonary edema (REPE) is extremely rare. We report herein a case of REPE caused by difficulties encountered with anesthesia using HFJV during video-assisted thoracic surgery (VATS) for a spontaneous pneumothorax. We believe the rapid increase in pressure in the lung after degassing for VATS resulted in REPE as well as typical barotrauma.

Adolescent↗

PubMed2000

Encapsulated pericardial fat necrosis treated by video-assisted thoracic surgery: report of a case.

A 55-year-old moderately obese man who was admitted to a local hospital following a traffic accident reported having experienced an episode of sharp and sudden pleuritic pain in the left anterior lower chest 2 days earlier. A computed tomographic scan on admission demonstrated a nonhomogeneous mass in the anterior left side of the chest, abutting the left cardiac margin, and a left-sided pleural effusion. As a mediastinal tumor was suspected, he was referred to our hospital for investigation and treatment. An exploratory thoracotomy was performed by video-assisted thoracic surgery (VATS) about 3 weeks later, which revealed a firm, yellowish mass on the oral side of the pericardial fat pad, adhering to the anterior chest wall. The mass was easily removed. The resected specimen consisted of a lobulated fragment of adipose tissue measuring 5.0 x 3.5 x 2.0 cm, and the final pathologic diagnosis was pericardial fat necrosis. The patient had an uneventful postoperative recovery and has remained free of symptoms for 10 months since his operation. Pericardial fat necrosis remains a rare clinical entity. Surgical excision by VATS achieves symptomatic cure and probably continues to be the treatment of choice because of the need to exclude a neoplasm in the differential diagnosis.

Diagnosis, Differential↗

PubMed2000

Psoas abscess complicating Crohn's disease: report of a case.

We describe herein the case of a psoas abscess complicating Crohn's disease, and present a review of the literature on this unusual disease entity. A 22-year-old Japanese man with a 5-year history of Crohn's ileocolitis presented with right lower abdominal and hip pain, and a diagnosis of right psoas abscess was subsequently made by abdominal computed tomography (CT). Following the administration of antibiotics and CT-guided percutaneous drainage of the abscess, the patient's symptoms temporarily improved; however, 2 weeks later, the abscess cavity was found to have extended around the periarticular tissue of the right hip joint. To prevent the development of septic arthritis of the hip joint, surgical drainage of the abscess cavity and ileocecal resection were immediately performed, after which the patient's condition greatly improved. The resected specimen showed Crohn's ileocolitis with an external fistula in the terminal ileum which was considered to have caused the psoas abscess. Since psoas abscess in Crohn's disease can result in serious complications such as septic arthritis of the hip joint if left untreated, aggressive treatment should be initiated without delay.

Adult↗

PubMed2000

Analysis of risk factors in bronchopleural fistula after pulmonary resection for primary lung cancer.

OBJECTIVES: Despite the advances in surgical technology, bronchopleural fistulas (BPFs) still occur and are often fatal. We studied the risk factors for BPF formation after lung cancer operation to clarify the indication of preventive bronchial stump coverage. In addition, the reliability of our methods of bronchial closure was evaluated. METHODS: We reviewed 557 consecutive bronchial stumps, corresponding to 547 patients without any coverage in pulmonary resection for lung cancer between 1989 and 1998. According to nine variables, stumps that made dehiscence were compared with uneventful ones using contingency table analysis. The incidence of BPFs according to each method of bronchial closure was calculated. RESULTS: BPFs developed in ten patients (1.8%). Compared with the lobar bronchus (LB), the main bronchus (MB; P<0.01; odds ratio, 23.0) and the intermediate bronchus (IB; P=0.03; odds ratio, 10.7) carried a high risk. Previous ipsilateral thoracotomy (P<0.01; odds ratio, 37.9) and preoperative chemotherapy and/or radiotherapy (P=0.02; odds ratio, 13.2) increased the risk. The incidence of BPFs with manual suture, stapling devices only, reinforcement suture at the distal side of staplers, or reinforcement suture at the proximal side of staplers was 1.8, 5.0, 1.9 and 1.0%, respectively. CONCLUSIONS: The main and intermediate bronchial stumps, and the stumps in cases with previous ipsilateral thoracotomy or receiving induction therapy are prone to BPFs. Preventive coverage should be considered for these stumps. Our methods for reinforcement of stapled stumps are thought to be reliable.

Adenocarcinoma↗

PubMed2000

Baseline airway hyperresponsiveness and its reversible component: role of airway inflammation and airway calibre.

Airway hyperresponsiveness (AHR), in which airway inflammation has been reported to be a key factor, is an important component of asthma. However the precise role of inflammation in AHR is still unclear. In this report, airway inflammatory changes were assessed using hypertonic saline-induced sputum examination and exhaled nitric oxide analysis, and the relation between AHR to methacholine, airway calibre forced expiratory volume in one second (FEV1) and airway inflammatory indices examined. Furthermore, the changes in these variables were also examined by means of 8 weeks' open uncontrolled inhaled steroid administration (800 microg x beclomethasone x day(-1)). Asthmatic subjects had higher eosinophil counts and bradykinin concentration in induced sputum and higher exhaled NO levels, and showed AHR to methacholine. Baseline AHR significantly correlated with FEV1 but not with indices of inflammation in sputum or exhaled air. Steroid inhalation therapy was associated with a reduction in eosinophil and bradykinin concentration in sputum and NO levels in exhaled air and an improvement in FEV1 and AHR. The changes in FEV1 and AHR were significantly related to changes in markers in sputum and exhaled air (p<0.01 for each). These results suggest that baseline airway hyperresponsiveness can be predicted from the airway calibre but not from inflammatory parameters in sputum or exhaled air. In contrast, the reversible component of airway hyperresponsiveness appeared to be associated with the reduction in airway inflammation.

Administration, Inhalation↗