Heme oxygenase (EC 1.14.99.3) is the rate-limiting enzyme in heme catabolism that cleaves heme at the ␣-methene bridge to form biliverdin IX␣, carbon monoxide, and iron (1, 2). Biliverdin IX␣ is immediately converted by biliverdin reductase to bilirubin IX␣ that is transported to the liver for conjugation and excretion into bile (3). There are two isozymes of heme oxygenase, heme oxygenase-1 (HO-1) 1 and heme oxygenase-2 (HO-2) (4, 5). HO-1 is inducible whereas HO-2 is constitutively expressed in human cells (6). Expression of HO-1 mRNA is highly increased in human cells by the substrate heme (7), heavy metals (8, 9), UV irradiation (10), and nitric oxide donors (11)(12)(13)(14). Because bilirubin IX␣ functions as a natural radical scavenger (15, 16), induction of HO-1 probably represents a protective response against oxidative stress. The physiological importance of HO-1 has been confirmed by the phenotypic consequences of the HO-1-deficient mice (17) and a patient with HO-1 deficiency (18).Induction of HO-1 has been extensively studied for the last few decades by many investigators. In contrast, repression of HO-1 expression has been largely ignored, despite its physiological importance (3). We have shown that HO-1 is not induced or rather reduced by heat shock in human cells (19), whereas rat HO-1 is a heat shock protein (20,21). The expression levels of HO-1 are also decreased in human glioblastoma cells by the treatment with interferon-␥ (22). In addition, hypoxia represses HO-1 mRNA expression in primary cultures of human umbilical vein endothelial cells (HUVECs), human astrocytes, and human coronary arterial endothelial cells (23). On the other hand, hypoxia increased HO-1 expression in rat liver (24) and heart (25) and in various cultured animal cells, including Chinese hamster ovary cells (26), rat ventricular smooth muscle cells (27,28), and rat myocytes (29). These results suggest the inter-species difference in the regulation of HO-1 gene expression by hypoxia between human and animal cells.The inter-species variations in the hypoxic response are of clinical significance because hypoxia is involved in the pathophysiology of various disorders, including ischemic heart disease, cerebrovascular disease, cancer, sleep apnea syndrome, and chronic obstructive pulmonary disease, which account for common causes of death and disability in the developed world. Mammalian cells respond to hypoxia in part by increased expression of several genes coding for erythropoietin (30), vascular endothelial growth factor (31), adrenomedullin (32, 33), and glycolytic enzymes (34,35), all of which cooperate to protect cells and tissues against the hypoxic state. Hypoxia-inducible

Oligodeoxynucleotides containing CpG motifs have been highlighted as potent Th1 activators. We previously reported that Ag and CpG, when conjugated together, synergistically promoted the Ag-specific Th1 development and inhibited the Th2-mediated airway eosinophilia. In this study, we examined the mechanisms underlying the synergism of the covalent conjugation. The CpG-OVA conjugate enhanced the Th1 activation and development. These characteristic features of the conjugate could not be ascribed to the polymerization of OVA, but mirrored the augmented binding of the CpG-tagged Ag to dendritic cells (DCs) in a CpG-guided manner, because phycobiliprotein, R-PE, conjugated to CpG stained a higher proportion of DCs with higher intensity than the mixture. R-PE fluorescence was emitted from cytoplasmic portions of the DCs, which simultaneously expressed costimulatory molecules and IL-12. The CpG-conjugated R-PE trafficking described above actually served as a potent Ag. These results indicate that CpG conjugated to Ag exhibit novel joint properties as promoters of Ag uptake and DC activators, thereby potentiating the ability of DCs to generate Th1 cells. The DNA-mediated promotion of Ag uptake would be advantageous for evoking host immune responses against invading microorganisms.

Studies on pulsatile and nonpulsatile perfusion have long been performed. However, investigators have not reached a conclusion on which is more effective. In the present study, pulsatile cardiopulmonary bypass (CPB) was investigated in terms of the effects on cytokines, endothelin, catecholamine, and pulmonary and renal functions. Twenty-four patients who underwent coronary artery bypass grafting were divided into a pulsatile CPB group and a nonpulsatile CPB group. Parameters examined were hemodynamics, interleukin-8 (IL-8), endothelin-1 (ET-1), epinephrine, norepinephrine, lactate, arterial ketone body ratio, urine volume, blood urea nitrogen, creatinine, renin activity, angiotensin-II, lactate dehydrogenase, plasma-free hemoglobin, tracheal intubation time, and respiratory index. The IL-8 at 0.5, 3, and 6 h after CPB, and ET-1 at 3, 6, 9, and 18 h after CPB were significantly lower in the pulsatile group. Both epinephrine and norepinephrine were significantly lower in the pulsatile group. The respiratory index was significantly higher in the pulsatile group. In the present study, inhibitory effects on cytokine activity, edema in pulmonary alveoli, and endothelial damage were shown in addition to the favorable effects on catecholamine level, renal function, and peripheral circulation that have already been documented.

In situ replacement with excision of infected tissue, lavage using 10 l saline solution, and omentum plasty for PIAAA successfully resolved the condition. High local concentrations of rifampin-soaked grafts or superficial femoral vein may also be an alternative for an in situ replacement conduit.

The purpose of this study was evaluate the operative procedure and outcome of abdominal aortic aneurysm (AAA) patients with aortocaval fistula (ACF) and iliac vein fistula. From 1982 through 2004, we experienced five AAA patients associated with spontaneous aortocaval and aortoiliac venous fistula who underwent repair of AAA. Three patients were in hypovolemic shock, including one patient with cardiopulmonary arrest on admission who required cardiopulmonary resuscitation before surgery. These three ACF patients with hypovolemic shock underwent emergency operation and two patients with stable hemodynamic state underwent urgent operation. One of two ACF patients with stable condition was associated with unstable angina. One AAA patient with ACF-complicated angina underwent AAA repair with coronary artery bypass grafting; the remaining four patients underwent 3 bifurcated graft and 1 tube graft implantation. All surgical treatment of the fistula included direct closure within the aorta under digital compression in four patients and inferior vena cava clamp in one. The mortality rate was 25%. One ACF patient with retroperitoneal hematoma died of bleeding. Survival for ACF depends on early diagnosis and prompt surgical repair. Aortocaval fistula complicated with a rupture of aneurysm into retroperitoneal space had a severe fatal prognosis compared with uncomplicated ACF.