The major histocompatibility complex (MHC) is known to have a role in the development of non-melanoma skin cancer (NMSC), although the genes and mechanisms involved have yet to be determined. To identify the susceptibility locus for NMSC within the MHC, we used a collection of well-defined polymorphic microsatellite markers from the Human leucocyte antigen (HLA) region for an association analysis of 150 cases with NMSC and 200 healthy controls selected from the Busselton population in Western Australia. High-resolution mapping was undertaken using a total of 40 highly polymorphic markers located at regular intervals across the HLA region (3.
View Article and Find Full Text PDFCCAAT/enhancer binding protein alpha (C/EBP alpha) and C/EBP beta, liver specific transcription factors, are involved in hepatocyte proliferation and differentiation. The expression level of the C/EBP alpha and C/EBP beta genes were examined between tumor and non-tumorous tissues of the same hepatocellular carcinoma patients with quantitative real-time polymerase chain reactions. The expression of both the C/EBP alpha and C/EBP beta genes was down-regulated in the majority of the tumor specimens compared with corresponding non-tumorous tissues.
View Article and Find Full Text PDFRacemic 5-azidoepibatidine [(+/-)-1] was synthesized via 5-aminoepibatidine as a candidate photoaffinity ligand with exceptionally high affinity at the mammalian neuronal nicotinic receptors (K(i) values of 0.027 nM for alpha 4 beta 2 and 9.7 nM for alpha 7) and excellent photoreactivity.
View Article and Find Full Text PDFBackground: Recent studies have shown that cyclooxygenase-2 (COX-2) inhibitors may participate in the proliferation of cancer cells. Because the cadherin-catenin complex is not only a key component of the adherens junction but also has been suggested to regulate cell proliferation, modulation of these molecules may be a mechanism by which COX-2 activity affects cell proliferation. In this study, we evaluated the effect of a COX-2 inhibitor on the proliferation and expression of E-cadherin-complexes in gastrointestinal cancer cell lines.
View Article and Find Full Text PDFImidacloprid (IMI) is the principal neonicotinoid (the only major new class of synthetic insecticides of the past three decades). The excellent safety profile of IMI is not shared with a metabolite, desnitro-IMI (DNIMI), which displays high toxicity to mammals associated with agonist action at the alpha4beta2 nicotinic acetylcholine receptor (nAChR) in brain. This study examines the hypothesis that IMI, DNIMI, and (-)-nicotine activate the extracellular signal-regulated kinase (ERK) cascade via primary interaction with the alpha4beta2 nAChR in mouse neuroblastoma N1E-115 cells.
View Article and Find Full Text PDFWe report a Sendai virus (SeV) vector system for expression of major histocompatibility complex (MHC) class I/peptide complexes. We cloned the extracellular domain of a human MHC class I heavy chain, HLA-A*2402, and human beta-2 microglobulin (beta2m) fused with HLA-A*2402-restricted human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte (CTL) epitopes (e-beta2m) in separate SeV vectors. When we coinfected nonhuman mammalian cells with the SeVs, naturally folded human MHC class I/peptide complexes were secreted in the culture supernatants.
View Article and Find Full Text PDFIn order to examine the relationship between corneodesmosin (CDSN) and psoriasis we have determined the presence of CDSN polymorphisms by DNA sequencing in (a) nine B-LCL cell lines of major histocompatibility complex ancestral haplotypes known to be associated with psoriasis vulgaris including 13.1AH, 46.1AH, 46.
View Article and Find Full Text PDFNeonicotinoids, the most important new class of synthetic insecticides of the past three decades, are used to control sucking insects both on plants and on companion animals. Imidacloprid (the principal example), nitenpyram, acetamiprid, thiacloprid, thiamethoxam, and others act as agonists at the insect nicotinic acetylcholine receptor (nAChR). The botanical insecticide nicotine acts at the same target without the neonicotinoid level of effectiveness or safety.
View Article and Find Full Text PDFDiffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease affecting exclusively East Asians. Strong associations of DPB with the class I human leukocyte antigens HLA-B54 in Japan and China and HLA-A11 in Korea suggest that the susceptible locus for DPB is located between the HLA-B and HLA-A genes. We have previously reported that the susceptibility gene for DPB could be localized within a 200-kb segment between the S and TFIIH loci in the HLA class I region, using refined microsatellite-based association mapping.
View Article and Find Full Text PDFWe present a rare case of an infant's palatal polyp associated with an impacted supernumerary tooth. We have previously reported three cases of palatal polyps in infants [1]. In one case, after surgical removal of the palatal polyp at the age of 1 year and 8 months, the lesion subsequently began swelling.
View Article and Find Full Text PDFThe higher toxicity of neonicotinoid insecticides such as N-(6-chloropyridin-3-ylmethyl)-2-nitroiminoimidazolidine (imidacloprid) to insects than mammals is due in large part to target site specificity at the corresponding nicotinic acetylcholine receptors (nAChRs). We propose that neonicotinoids with a protonated N-unsubstituted imine or equivalent substituent recognize the anionic subsite of the mammalian alpha4beta2 nAChR whereas the negatively charged (delta(-)) tip of the neonicotinoid insecticides interacts with a putative cationic subsite of the insect nAChR. This hypothesis can be tested by using two photoaffinity probes that differ only in the N-unsubstituted imine vs negatively charged (delta(-)) tip.
View Article and Find Full Text PDFA rare case of fusion between maxillary primary central incisors and supplemental teeth occurring bilaterally, accompanied by succedaneous supernumerary teeth, is presented. The patient was an 8.5-year-old Japanese boy.
View Article and Find Full Text PDFCCAAT/enhancer binding protein alpha (C/EBPalpha), expressed at a high level in liver, plays an important role in proliferation and differentiation of hepatocytes. Previous studies showed that an expression level of the C/EBPalpha gene in hepatocytes was downregulated in response to proliferation signals and that forced expression of the C/EBPalpha gene in a number of cells caused cell cycle arrest. We compared the expression level of the C/EBPalpha gene in surgical specimens between hepatocellular carcinoma and non-tumorous regions of the same patients.
View Article and Find Full Text PDFToxicol Appl Pharmacol
November 2001
Several nicotinic agonists with the 6-chloro-3-pyridinyl moiety are potent insecticides (e.g., the neonicotinoids imidacloprid and thiacloprid) while others are candidate nonopioid and nonantiinflammatory analgesics (i.
View Article and Find Full Text PDFThe nicotinic acetylcholine receptor (nAChR) is an agonist-regulated ion-channel complex responsible for rapid neurotransmission. The vertebrate nAChR, assembled from five homologous subunits, penetrates the synaptic membrane. Different subunit combinations lead to receptor subtypes with distinctive pharmacological profiles.
View Article and Find Full Text PDFBioorg Med Chem Lett
November 2001
Modification of the major insecticide fipronil (1) by replacing three pyrazole substituents (hydrogen for both cyano and amino and trifluoromethyldiazirinyl for trifluoromethylsulfinyl) gives a candidate photoaffinity probe (3) of high potency (IC(50) 2-28 nM) in blocking the chloride channel of Drosophila and human beta 3 GABA receptors.
View Article and Find Full Text PDFThe nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel in the insect CNS and a target for major insecticides. Here we use photoaffinity labeling to approach the functional architecture of insect nAChRs. Two candidate 5-azido-6-chloropyridin-3-yl photoaffinity probes are evaluated for their receptor potencies: azidoneonicotinoid (AzNN) with an acyclic nitroguanidine moiety; azidodehydrothiacloprid.
View Article and Find Full Text PDFUltrasound is a possible mechanical method to deliver small molecules into target cells. In order to evaluate the therapeutic potentials provided by ultrasound irradiation, we compared anti-tumor effects of electroporation- and ultrasound-mediated chemotherapy and efficacy of gene transfer by the two methods. Electric pulses (5 Hz, 100 V/cm, 8 square-wave/100 microsec) or ultrasound (1 MHz, 2 W/cm(2), 5 min) was delivered to subcutaneous solid tumors of murine lymphoma after the tumor-bearing mice received an intraperitoneal injection of bleomycin (BLM) (2.
View Article and Find Full Text PDFThe human major histocompatibility complex (MHC) class III region spanning approximately 760 kb is characterized by a remarkably high gene density with 59 expressed genes (one gene every 12.9 kb). Recently, susceptibility loci to numerous diseases, such as Graves disease, Crohn disease, and SLE have been suggested to be localized to this region, as assessed by associations mainly with genetic polymorphisms of TNF and TNF-linked microsatellite loci.
View Article and Find Full Text PDFObjective: To assess the characteristics of CD4 and CD8 T cells specific for HIV-1 and cytomegalovirus (CMV) antigens in untreated and treated HIV-1-infected patients.
Methods: Antigen-specific T cell frequencies were determined by flow cytometric detection of antigen-induced intracellular cytokines.
Results: In untreated patients, HIV-1-specific CD4 T cell counts in peripheral blood were less than one tenth of CMV-specific CD4 T cell counts, while the number of specific CD8 T cells was approximately the same for both HIV-1 and CMV.
A 22-year-old man was unable to belch. He could sense intraesophageal gas, but had no chest pain. An upper gastrointestinal X-ray series and endoscopic examination showed no abnormalities.
View Article and Find Full Text PDFWe investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.
View Article and Find Full Text PDFThe favorable selective toxicity of neonicotinoid insecticides (represented here by imidacloprid, thiacloprid, and a nitromethylene analogue) for insects versus mammals is not shared by three of their N-unsubstituted imine derivatives or by nicotine or epibatidine. The same selectivity pattern is evident at the receptor level, i.e.
View Article and Find Full Text PDFInt J Paediatr Dent
January 2001
Aim: The aim of this study was to review clinical findings in 14 impacted primary teeth in 13 cases treated at a Paediatric Dental Clinic over a period of 18 years.
Method: The retrospective study used clinical records, radiographs and oral photographs. Data included age, gender, presenting complaints, location, radiographic findings, aetiological factors, treatment and prognosis of impacted primary teeth and their permanent successors.