title: Cellular turnover and expression of hypoxic-inducible factor in acute acalculous and calculous cholecystitis.
abstract: BACKGROUND
  Epithelial corrective and destructive mechanisms have not been studied in inflammatory gallbladder disease.
  
  
  METHODS
  Epithelial apoptosis, cell proliferation and expression of hypoxia-inducible factor (HIF)-1alpha were compared in gallbladders from patients with acute acalculous cholecystitis (AAC; n = 30) and acute calculous cholecystitis (ACC; n = 21), and from patients undergoing surgery for other reasons (normal gallbladders; n = 9), which were removed during open cholecystectomy. The immunohistochemical stains included antibodies to Ki-67 (proliferation), M30 (apoptosis) and HIF-1alpha. Proliferation and apoptosis were expressed as percentages of positive cells. HIF-1alpha expression was expressed as absent, weak, or strong.
  
  
  RESULTS
  Apoptosis (median [25th to 75th percentile]) was significantly increased in AAC (1.31% [0.75% to 1.8%], P < 0.001) and ACC (1.10% [0.63% to 1.64%], P = 0.001), compared with control samples (0.20% [0.07% to 0.45%]. The proliferation rate was significantly increased in AAC (8.0% [4.0% to 17.0%], P < 0.001) and ACC (14% [7.5% to 26.5%], P = 0.001) compared with control samples (1.0% [1.0% to 3.0%]). Strong HIF-1alpha staining was observed in 57% of AAC, in 100% of ACC and in 44% of control specimens (P < 0.001). Intense HIF-1alpha expression was associated with increased cell proliferation (P = 0.002).
  
  
  CONCLUSIONS
  Cell proliferation and apoptosis were increased in AAC and ACC, as compared with normal gallbladders. Expression of HIF-1alpha was lower in AAC than in ACC.
authors.affiliation: Department of Anesthesiology, Division of Intensive Care, Oulu University Hospital, Kajaanintie 52, Oulu, Finland, FIN-90029.
authors.forename: Merja
authors.initials: M
authors.lastname: Vakkala
authors.forename: Jouko J
authors.initials: JJ
authors.lastname: Laurila
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.forename: Vesa
authors.initials: V
authors.lastname: Koivukangas
authors.forename: Hannu
authors.initials: H
authors.lastname: Syrjälä
authors.forename: Tuomo
authors.initials: T
authors.lastname: Karttunen
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Tero I
authors.initials: TI
authors.lastname: Ala-Kokko
mesh_terms: D042101:Acalculous Cholecystitis / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002764:Cholecystitis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005704:Gallbladder / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit