堀田 訓久

癒着胎盤のため,帝王切開術中に大量出血をきたした症例を報告する。術中の大量出血が予測され,止血コントロールを目的として,術前に両側内腸骨動脈バルーンカテーテルを挿入し手術を行うことになった。一症例は夜間の予期せぬ出血により,やむを得ず緊急帝王切開術を行った。両側内腸骨動脈バルーンカテーテルは緊急手術であったため使用することができなかった。急速な出血により循環動態が不安定となることがあったが,迅速な対応により,母子ともに救命することができた。もう一症例は,両側内腸骨動脈バルーンカテーテルの使用により出血速度のコントロールが可能であったため,術中の循環動態が安定し無事に手術を終えることができた。癒着胎盤は生命にかかわる疾患であり,緊急時の対応を含めた術前の綿密な手術計画が重要である。

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has an important role in the regulation of airway smooth muscle tone and reactivity. We have shown previously that TNF-alpha upregulates the expression of Gai-2 protein without significantly increasing G(s)alpha protein and enhances adenylyl cyclase inhibition by carbachol in cultured human airway smooth muscle cells (Hotta K, Emala CW, and Hirshman CA. Am J Physiol Lung Cell Mol Physiol 276: L405-L411, 1999). The present study was designed to investigate the molecular mechanisms by which TNF-alpha upregulates G alpha(i-2) protein in these cells. TNF-alpha pretreatment for 48 h increased the expression of G alpha(i-2) protein without significantly altering the G alpha(i-2) protein half-life (41.0 +/- 8.2 h for control and 46.8 +/- 5.2 h for TNF-alpha-treated cells). Inhibition of new protein synthesis by cycloheximide blocked the increase in G alpha(i-2) protein induced by TNF-alpha. Furthermore, TNF-alpha treatment for 12-24 h increased the steady-state level of G alpha(i-2) mRNA without significantly altering G alpha(i-2) mRNA half-life (9.0 +/- 0.75 h for control and 8.9 +/- 1.1 h for TNF-alpha-treated cells). The transcription inhibitor actinomycin D blocked the increase in G alpha(i-2) mRNA induced by TNF-alpha. These observations indicate that the increase in G alpha(i-2) protein induced by TNF-alpha is due to an increased rate of G alpha(i-2) protein synthesis, most likely as a consequence of the transcriptional increase in the steady-state levels of its mRNA.

Chronic inflammation is a characteristic feature of asthma. Multiple inflammatory mediators are released within the asthmatic lung, some of which may have detrimental effects on signal transduction pathways in airway smooth muscle. The effects of tumor necrosis factor (TNF)-alpha on the expression and function of muscarinic receptors and guanine nucleotide-binding protein (G protein) alpha-subunits were examined in human airway smooth muscle cells. Cultured human airway smooth muscle cells were incubated in serum-free culture medium for 72 h in the presence and absence of 10 ng/ml of TNF-alpha, after which the cells were lysed and subjected to electrophoresis and G alpha(i-2), G(q)alpha, and G(s)alpha protein subunits were detected by immunoblot analysis with specific antisera. TNF-alpha treatment for 72 h significantly increased the expression of G alpha(i-2) and G(q)alpha proteins and enhanced carbachol (10(-7) M)-mediated inhibition of adenylyl cyclase activity and inositol phosphate synthesis. These data provide new evidence demonstrating that TNF-alpha not only increases expression of G alpha(i-2) and G(q)alpha proteins but also augments the associated signal transduction pathways that would facilitate increased tone of airway smooth muscle.