In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos

Mice deficient in the Flk-1 receptor tyrosine kinase are known to die in utero because of defective vascular and hematopoietic development. Here, we show that flk-1(-/-) embryonic stem cells are nevertheless able to differentiate into hematopoietic and endothelial cells in vitro, although they give rise to a greatly reduced number of blast colonies, a measure of hemangioblast potential. Furthermore, normal numbers of hematopoietic progenitors are found in 7.5-day postcoitum flk-1(-/-) embryos, even though 8. 5-day postcoitum flk-1(-/-) embryos are known to be deficient in such cells. Our results suggest that hematopoietic/endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal.     

Hepatic and mesenteric nitric oxide synthase expression in a rat model of CCl(4)-induced cirrhosis

BACKGROUND: Cirrhosis and portal hypertension are frequently linked with changes in expression of nitric oxide synthase (NOS) and/or endotoxaemia. AIMS: This study tested the following hypothesis: that inducible (i)NOS activity is increased within the visceral circulation concurrently with decreased constitutive (c)NOS activity in the hepatic sinusoids and that the concentration of NO metabolites in portal blood is consequent on endotoxin concentration. MATERIALS AND METHODS: Plasma concentrations of (nitrite + nitrate) and endotoxin, together with hepatic and mesenteric NOS activity (arginine/citrulline method) and protein expression (histochemistry) plus portal and arterial blood pressure, were determined in rats made severely cirrhotic by intragastric CCl(4) over 14 weeks (n = 6) compared with age-matched controls (n = 5). The concentrations of [nitrite + nitrate] and endotoxin in portal plasma were also directly compared in rats made cirrhotic for a period of 8-14 weeks (n = 10). RESULTS: In rats with advanced cirrhosis, arterial [nitrite + nitrate] was 93.1 (22.4) micromol/L (mean, SEM) compared with 29.1 (6.1) micromol/L in controls (P < 0.05); portal plasma [NO(2)(-) + NO3(-)] was 127.1 (27.2) compared with 24.7 (4.7) micromol/L in controls (P < 0.05). Cirrhotic rats had higher endotoxin concentration in plasma compared with controls (systemic: 85.0 (24.5) versus 1.7 (0.2) EU/ml, P < 0.05; portal: 180.3 (47.9) versus 1.7 (0.2) EU/ml, P < 0.05). The same severely cirrhotic rats possessed decreased cNOS activity in liver (2.95 [0.40] versus 5.29 [0.85] pmol/min/g; P < 0.05) and increased iNOS activity in mesentery (4.83 [1.23] versus 1.47 [0.15] pmol/min/g; P < 0.05) compared with controls. Histochemical observations confirmed these findings. Rats given CCl(4) for a period of 8-14 weeks possessed high endotoxin concentration in portal plasma, with correspondingly high [nitrite + nitrate] (r(2) = 0.954; P < 0.001). CONCLUSIONS: An endotoxin-induced increase in mesenteric iNOS activity and a decrease in hepatic cNOS activity may account for, respectively, the hyperdynamic visceral circulation and the increased intrahepatic resistance of cirrhosis.     

Cerebral infarct in patients with hemorrhagic shock and encephalopathy syndrome

The syndrome of hemorrhagic shock and encephalopathy (HSE) was first described by Levin et al. in 1983 [1] but not until recently has it been considered to be a newly identified devastating disorder [2, 3]. The main features of this syndrome consist of sudden onset of shock, coma, convulsions, coagulopathy, renal and hepatic dysfunction. The mortality rate is very high with surviving patients suffering from severe neurologic sequelae [4]. In review of the literature [1], we did not find any reports of cerebral infarcts. Recently we managed two patients with this syndrome, both of whom had CT scand findings consistent with cerebral infarctions.     

Computed tomography of temporal bone pneumatization: 2. Petrosquamosal suture and septum

The degree of visualization of the petrosquamosal (K?rner's) septum on high-resolution axial computed tomography (CT) in 141 temporal bones (100 subjects) was analyzed. The superior and inferior parts of the septum were assessed separately and were seen in 75% and 41% of cases, respectively. There was no relation between the size of K?rner's septum and pneumatization. The clinical relevance of this finding is discussed. The CT features of the ventral petrosquamosal suture also were investigated. The crista tegmentalis, a contribution of the petrosal tegmen to the mandibular fossa, was seen on CT as a polypoid excrescence projecting from the ventrolateral petrous pyramid. This knowledge is useful in the radiographic analysis of the course of longitudinal fractures of the petrous bone.