The mechanisms of hepatic sinusoidal endothelial cell regeneration: A possible communication system associated with vascular endothelial growth factor in liver cells

Vascular endothelial growth factor (VEGF) has been shown to induce proliferation of sinusoidal endothelial cells in primary culture. To elucidate the mechanisms of sinusoidal endothelial cell regeneration in vivo, mRNA expression of VEGF and its receptors, flt-1 and KDR/flk-1, were studied in rat livers. Northern blot analysis revealed that VEGF-mRNA was expressed in hepatocytes immediately after isolation from normal rats. In contrast, non-parenchymal cells, including sinusoidal endothelial cells, expressed VEGF receptor-mRNA. Vascular endothelial growth factor-mRNA expression in hepatocytes was decreased during primary culture, but increased following a peak of DNA synthesis, induced by addition of epidermal growth factor or hepatocyte growth factor to the culture medium at 24 h of plating. In a 70% resected rat liver, VEGF-mRNA expression increased with a peak at 72 h after the operation, and mRNA expression of VEGF receptors between 72 and 168 h. In such a liver, mitosis was maximal in hepatocytes at 36 h and in sinusoidal endothelial cells at 96 h. Also, mRNA expression of both VEGF and its receptors was significantly increased in carbon tetrachloride-intoxicated rat liver compared with normal rat liver. Vascular endothelial growth factor expression was minimal in Kupffer cells isolated from normal rats, but marked in activated Kupffer cells and hepatic macrophages from the intoxicated rats. Vascular endothelial growth factor-mRNA expression was also increased in activated stellate cells from these rats and in the cells activated during primary culture compared with quiescent cells. We conclude that increased levels of VEGF expression in regenerating hepatocytes may contribute to the proliferation of sinusoidal endothelial cells in partially resected rat liver, probably through VEGF receptors up-regulated on the cells. Also, VEGF derived from activated Kupffer cells, hepatic macrophages and stellate cells may be involved in this proliferation in injured rat liver.     

Immunological features of patients with primary biliary cirrhosis (PBC) overlapping systemic sclerosis: A comparison with patients with PBC alone

To characterize the immunological features of patients with primary biliary cirrhosis (PBC) overlapping systemic sclerosis (SSc), 26 patients with PBC were classified according to the presence of scleroderma-related features (Raynaud's phenomenon, sclerodactyly etc.). The patients were classified into 10 patients with PBC overlapping SSc (PBC-SSc), four patients with some scleroderma-related features although not meeting the criteria of SSc (PBC-SSc spectrum) and 12 patients with PBC alone. Sera from PBC-SSc showed a significantly higher positivity to anti-centromere antibody (P < 0.01) and to E1β of pyruvate dehydrogenase complex (P < 0.005) than those from patients with PBC alone. The same tendency was observed in PBC-SSc spectrum patients. Patients with PBC exhibiting scleroderma-related features, in both the PBC-SSc and PBC-SSc spectrum, may comprise a subset in PBC, not only clinically, but also immunologically.     

Intracavitary administration of OK-432 with subcutaneous priming for malignant ascites in a case of advanced renal cell carcinoma

The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma.     

Tachycardia Associated with Twin Atrioventricular Nodes in an Infant with Heterotaxy and Interruption of Inferior Vena Cava

We report a 12‐month‐old boy with heterotaxy and interruption of inferior vena cava who showed sustained tachycardia associated with twin atrioventricular nodes (AVNs). Atrioventricular reciprocating tachycardia with antegrade conduction through the posterior AVN and retrograde conduction through the anterior AVN were successfully ablated using an upper approach from the left internal jugular vein. (PACE 2012; 35:e302–e305)     

Alteration of bile acid metabolism in two-thirds hepatectomized rat

Bile acid metabolism after two-thirds partial hepatectomy (PH) in rat was studied. Bile acid kinetics (i.e. synthesis rate and pool size) were determined by wash out method combined with gas liquid chromatography, and serum bile acids by gas liquid chromatography-mass spectrometry. Serum bile acid concentration was highest on the third day after PH, as the liver regeneration progressed but it gradually decreased with increasing cholic acid (CA)/chenodeoxycholic acid (CDCA), reflecting impaired hepatic uptake of bile acids and/or cholestasis during the early post-hepatectomy period. Predominance of CA in bile acid synthesis, pool, and biliary secretion was also found. On the third day after PH, liver weight recovered to 66% of the control value, but enhancement of bile acid synthesis was not observed. Consequently, pool size remained at 50% of control. On the seventh day, synthesis of bile acid, especially of CA, was enhanced and pool size and liver weight returned to 68 and 72% of the respective control values. Bile acid synthesis was returned to the control value on the fourteenth day with concomitant restoration of liver weight and bile acid pool size. These changes in bile acid kinetics parallel the events during hepatic regeneration after PH.     

A flow cytometric method for measurement of hydrogen peroxide generation by pediatric polymorphonuclear leukocytes stimulated by Staphylococcus aureus and Escherichia coli

The generation of hydrogen peroxide (H₂O₂), one of the reactive oxygen species, by polymorphonuclear leukocytes (PMN) stimulated by Staphylococcus aureus and Escherichia coli was studied in infants by cytofluorography. After heparhized whole blood was incubated with bacteria for 60 min, generated H₂O₂ was measured. The positive rate of H₂O₂ generation of PMN and mean fluorescent intensity of positive PMN stimulated by S. aureus and E. coli were significantly reduced in infants aged < 1 year and H₂O₂ generation increased with advancing age. In 10–15 year old children, the level of generated H₂O₂ reached adult levels. When sera from 1 year old children were added to separated PMN from healthy adults, H₂O₂ generation was reduced. In contrast, H₂O₂ generation by PMN from 1 year old children was increased by the addition of adult sera. These results suggest that the ability to generate H₂O₂ in response to S. aureus and E. coli is lower in infants and that such reduced activity may be related to the susceptibility of such infants to S. aureus and E. coli infections.     

CHRONOLOGICAL STUDY OF OLIGODENDROGLIAL ALTERATIONS AND MYELINATION IN QUAKING MICE

Chronological morphological investigation was carried out in the spinal cord of quaking mice from day 3 to day 130. Numbers of myelinated fibres were far fewer in quaking mice at day 3 compared to controls. However, when the animals became older, myelination progressed and numbers of myelinated fibres increased although myelin sheaths remained far thinner than the size of axons. Many oligodendroglia during day 5 to 15 in quaking mice revealed prominent dilation and proliferation of smooth walled vesicles and cisterns but after 20 days, such changes were no longer observed. Tortuous bizarre oligodendroglial processes, aberrant myelination and myelin figures were very prominent around day 5–15, but such changes also gradually subsided. Density of glial cells during pre-myelination gliosis was similar in both quaking and control mice. However, glial cell population decreased far slower pace than controls when myelination progressed. Thus, glial cell density remained proportionally higher in quaking than controls although the density declined with age in both.