Katsuya Akashi

Thermoreversible gelation polymer induces the emergence of hepatic stem cells in the partially injured rat liver.

Focal injury of the adult liver causes formation of granulomatous tissue and fibrosis. When thermoreversible gelation polymer (TGP) was applied to such defects of the rat liver, complete recovery of hepatic tissues was observed without granulation. We analyzed the mechanism of the regeneration. TGP is a chemically synthesized biocompatible polymer material whose sol‐gel transition is reversible by changing the temperature. Cooled TGP was poured into a penetration lesion of the rat liver. Immunohistochemistry and polymerase chain reaction were carried out using tissues and cultured cells isolated from ductular structures. Immunocytochemical and ultrastructural analyses were also conducted. Seven days after TGP treatment, ductular reactions were observed around the wound and ductules elongated to the injured area. Cells in the structures were alpha‐fetoprotein (AFP) positive, albumin+, CK19+, c‐Kit+, and Thy1+. Hepatocyte‐like cells possessing glycogen appeared around the tips of the ductules from day 9. The defect was completely replaced with hepatocytes by day 28. Cells isolated from the ductules expressed Musashi‐1, c‐Kit, Thy1, AFP, albumin, transferrin, connexin 43, and CK19. When the cultured cells were covered by TGP, they rapidly proliferated to form colonies, whereas without TGP cells gradually died. Morphologically and ultrastructurally the cells were similar to hepatocytes. They expressed not only albumin and transferrin but TAT, CYP2E1, and CCAAT/enhancer binding protein α. Some cells formed bile canaliculus‐like structures. In conclusion, TGP may trigger the initiation of hepatic stem cells in biliary ductules, and stem cell activation may occur even in the regeneration of the normal liver. (HEPATOLOGY 2006;43:1053–1062.)

Ductular Cell Proliferation in Islet Cell Neogenesis Induced by Incomplete Ligation of the Pancreatic Duct in Dogs

PurposeIt has been suggested that islet neogenesis can be induced by incomplete ligation of the pancreatic duct in small animals; however, there has been no report of neogenesis and the proliferation of islets occurring in larger animals. When this procedure was performed in the Vervet monkey, it produced a noticeable increase in duct proliferation, but islet neogenesis was not observed, although the number of monkeys examined was very small. We conducted this study to evaluate whether islet neogenesis and ductular proliferation could be induced in larger animals such as the dog, by partial obstruction of the pancreatic duct.MethodsIncomplete ligation of the pancreatic duct was induced by tying the pancreas around the ventral side of the head with 2-0 silk and reducing the circumference by about 80% to cause partial obstruction.ResultsBy 2 weeks after ligation, we saw hyperplasia of the epithelial cells, multilayering of cuboidal cells, and proliferation of ductular cells. The terminal ductules involved in the formation of immunohistochemically insulin-positive islets, and islets, formed adjacent to the alignment of the ductular cells. By 8 weeks after ligation we saw scattered islets, less than 50 µm in diameter and less than 1 000 µm2 in area. These cells were immunolabeled for both insulin and cytokeratin, and there was continuity between these insulin-positive cells and terminal ductular cells. Glucagon-positive cells and somatostatin-positive cells were also found adjacent to the alignment of ductular cells.ConclusionsThese results suggest that islets may be differentiated from precursor cells in the pancreatic duct, and that stem cells exist even in adults.

Plasma leptin levels in patients with burn injury: a preliminary report

The purpose of this study was to investigate the relationship between the plasma leptin level and clinical parameters in patients with burn injury. Six patients with burn injury were admitted to the Emergency and Critical Care Medicine Center of St. Marianna University Hospital within 1h after injury. Plasma levels were monitored for leptin, proinflammatory cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF alpha)), stress-related parameters (adrenocorticotropic hormone (ACTH), cortisol, and C-reactive protein (CRP)). The change in individual plasma leptin levels did not show similar pattern in all these patients. However, leptin levels remained within the normal range, except in a patient (Case 1) complicated with severe hypovolemic shock. Plasma ACTH and cortisol levels were also elevated in most of the patients. Examination of relationships among plasma leptin, proinflammatory cytokines, and stress-related parameters revealed a significant positive correlation between the plasma leptin level and IL-1 beta or IL-6. These results suggest that the plasma leptin level may have some relations to plasma proinflammatory cytokines in pathophysiologic responses to critical conditions of burn injury.

The persistence of an open anterior fontanel in a 4-year-old girl

Case reportA 3-year-old girl was transferred to our hospital with a history of persistent open anterior fontanel. The patient was conscious and had no neurological deficits. Upon arrival, the patient appeared normal for her age and had no defects or anomalies other than the aforementioned lesion. The initial skull X-ray and CT were significant for a 20-mm open anterior fontanel. All other findings were normal.OutcomeAfter a follow-up period of 1.5 years, the anterior fontanel was still open, with a slight decrease in size to 15 mm. Delayed closure of the anterior fontanel without intracranial hypertension is associated with various disorders. The pathogenesis of the current patient’s condition is unclear. Due to the patient’s normal appearance and stable neurological status, we will follow her conservatively for any changes in condition.

Clinical trial of argatroban, a direct thrombin inhibitor, as an anticoagulant in cardiopulmonary support and apheresis in emergency patients: a preliminary report

Abstract To evaluate the safe and effective use of argatroban, a competitive direct thrombin inhibitor, as an alternative anticoagulant for percutaneous cardiopulmonary support (PCPS) and continuous hemofiltration or hemodiafiltration (CHF/CHDF), a preliminary multicenter clinical trial was conducted between October 1999 and September 2000. Nine patients who underwent PCPS and/or CHF/CHDF were enrolled in the study during this period. The dosage of argatroban was controlled so that the activated clotting time (ACT) was maintained at around 180 to 200 s. The mean duration of argatroban administration was 82 ± 92 h, and the mean dose was 0.67 ± 0.40 μg kg+1 min−1. Severe hemorrhagic complications requiring the discontinuation of argatroban administration were not observed in any of the patients. Platelet loss was prevented to some degree, and plasma levels of fibrinogen were well preserved during PCPS/CHDF. Except for two patients undergoing CHDF, clot formation within the extracorporeal circulation circuit was not identified macroscopically after the discontinuation of the procedures. We conclude that argatroban might be useful as an alternative anticoagulant in cases where heparin cannot be safely used because of the increased risk of bleeding complications, thrombocytopenia, and/or hypofibrinogenemia. Although the optimal dose of argatroban has not been established, we propose an initial starting dose of 0.7 to 1.0 μg kg−1 min−1, followed by adjustments to maintain an ACT of between 180 and 250 s.