PMID- 9880689
OWN - NLM
STAT- MEDLINE
DCOM- 19990129
LR  - 20191102
IS  - 0179-0358 (Print)
IS  - 0179-0358 (Linking)
VI  - 14
IP  - 1-2
DP  - 1998 Nov
TI  - Upregulated tumor necrosis factor-alpha gene expression in the hypoplastic lung 
      in patients with congenital diaphragmatic hernia.
PG  - 21-4
AB  - Recent studies using animal models of congenital diaphragmatic hernia (CDH) have 
      reported a reduction in both surfactant (SF) phospholipids and proteins in CDH 
      lungs compared to controls, resulting in biophysical and physiologic impairment 
      of SF function in the hypoplastic CDH lung. Furthermore, SF replacement has been 
      shown to improve physiological function in CDH lungs. Tumor necrosis factor-alpha 
      (TNF-alpha) is a polypeptide whose overproduction has been implicated in the 
      pathogenesis of a number of pathological conditions, such as neonatal and adult 
      respiratory distress syndrome. TNF-alpha has been shown to selectively inhibit 
      the de-novo synthesis of SF phospholipid components in type II pneumocytes. It 
      has been demonstrated that TNF-alpha is synthesized locally in lung and functions 
      in an autocrine/paracrine mode. The aim of this study was to investigate 
      TNF-alpha messenger RNA (mRNA) expression in hypoplastic CDH lung using in-situ 
      hybridization histochemistry, to determine the molecular basis of the SF 
      deficiency in the hypoplastic CDH lung. Lung-tissue samples were obtained at 
      autopsy from 7 full-term newborns (age range: 1-21 days) with CDH and 4 
      stillborns with CDH. Normal lung tissue from eight infants with sudden infant 
      death syndrome (age range: 5-30 days) acted as controls. In-situ hybridization 
      was performed using TNF-alpha specific and digoxigenin-labeled oligonucleotide 
      probe and visualized by nitroblue tetrazolium staining. In control lung tissue, 
      mRNA expression of TNF-alpha was absent or weak in type II pneumocytes and 
      alveolar macrophages. In contrast, mRNA expression of TNF-alpha was markedly 
      increased in both type II pneumocytes and alveolar macrophages in hypoplastic CDH 
      lung. Our findings of up-regulated TNF-alpha gene expression in CDH lung suggest 
      that the SF deficiency observed in hypoplastic CDH lung may be the result of 
      increased local production of TNF-alpha.
FAU - Ohshiro, K
AU  - Ohshiro K
AD  - Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin 12, 
      Ireland.
FAU - Miyazaki, E
AU  - Miyazaki E
FAU - Taira, Y
AU  - Taira Y
FAU - Puri, P
AU  - Puri P
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Pediatr Surg Int
JT  - Pediatric surgery international
JID - 8609169
RN  - 0 (Pulmonary Surfactants)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Case-Control Studies
MH  - Gene Expression
MH  - *Hernias, Diaphragmatic, Congenital
MH  - Humans
MH  - In Situ Hybridization
MH  - Infant, Newborn
MH  - Lung/*abnormalities/metabolism
MH  - Pulmonary Surfactants/*deficiency
MH  - RNA, Messenger/genetics
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
MH  - Up-Regulation
EDAT- 1999/01/09 00:00
MHDA- 1999/01/09 00:01
CRDT- 1999/01/09 00:00
PHST- 1999/01/09 00:00 [pubmed]
PHST- 1999/01/09 00:01 [medline]
PHST- 1999/01/09 00:00 [entrez]
AID - 10.1007/s003830050427 [doi]
PST - ppublish
SO  - Pediatr Surg Int. 1998 Nov;14(1-2):21-4. doi: 10.1007/s003830050427.