Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation.

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.     

Hamartoma of the parotid gland: A case report with immunohistochemical and electron microscopic study

Summary A case of a solid parotid tumour in a 16-year-old boy is presented. Histologically, the tumour demonstrated some peculiar findings. An acinar pattern was predominant although every component seen in the normal salivary gland was present, namely, serous and mucous gland acini, ducts, myoepithelial cells, adipose and lymphoid tissue. Large eosinophilic granules were abundant in the large acinar cell cytoplasm. Immunohistochemically, the tumour demonstrated the proteins which are present in the normal parotid gland, for example, amylase, lactoferrin and lysozyme. Electron microscopic features were quite similar to those of normal parotid tissue except for accumulation of a large number of cytoplasmic granules in the acinar cells. There has been no previous report of a tumour with the same features as seen in this case. Our pathological diagnosis is hamartoma, although the possibility of hyperplasia or neoplasia can not be excluded.     

Lymphokine activated killer cells in murine coxsackievirus B3 myocarditis

The purpose of the present study was to determine whether lymphokine activated killer (LAK) cells were involved in the development of coxsackievirus B3 (CB3) myocarditis in both the acute viremic (Experiment I) and the subacute aviremic (Experiment II) stages. To induce LAK cells, recombinant human interleukin-2 (IL-2) was administered to CB3-infected mice subcutaneously daily, starting on day 0 in Experiment I and on day 7 in Experiment II for 7 days, respectively. The treated groups were compared to infected controls. Splenic lymphocytes of IL-2 treated mice were further cultured in vitro in IL-2 containing medium for 7 days, and LAK cell activity, i.e., cytotoxic activity of the lymphocytes against EL-4 tumor cells and against cultured fetal myocytes, was assayed by⁵¹Cr-release method. In Experiment I, histologic scores, myocardial virus titers, and LAK cell activity did not differ significantly between IL-2 treated and untreated groups. In contrast, in Experiment II, there were more cellular infiltration associated with severe necrosis and higher LAK cell activity against EL-4 cells and cultured myocytes in IL-2 treated than in untreated groups. The presence of LAK cells was demonstrated in the subacute stage of murine CB3 myocarditis. Thus, the behavior of LAK cell activity may vary with the course of myocarditis, and enhanced LAK cell activity may be involved in the development of the disease.This work was supported by research grants from the Conference on Coronary Artery Disease, Japanese Education of Science and Walfare (Nos. 08877110 and 09470164), Kanae Shinyaku Foundation, and Japan Cardiovascular Research Foundation.     

Advantages of using the midline incision right retroperitoneal approach for abdominal aortic aneurysm repair

This study was conducted to compare the midline incision right retroperitoneal approach for repairing abdominal aortic aneurysms (AAA) with the transperitoneal approach. The intra- and postoperative course of 15 patients who underwent AAA repair using the transperitoneal approach between 1987 and 1991 and another 15 patients who underwent AAA repair using the retroperitoneal approach between 1991 and 1994 were evaluated. The incidence of postoperative wound complications was also assessed. There was no operative or hospital death in either group. Although a significantly longer interval was required from the incision to the aortic clamp using the extraperitoneal method, there were no statistical differences in the aortic clamping time, total operation time, or blood loss between the two groups. On the other hand, there was a statistically significant improvement in bowel function and a significant reduction in the length of postoperative hospitalization following the extraperitoneal procedure. Furthermore, no wound complications such as those associated with the left flank incision developed after the extraperitoneal procedure. Thus, we recommend the midline incision right retroperitoneal approach for AAA as it does not involve muscle division and is associated with fewer complications.     

Possibility of gene-specific treatment for hereditary arrhythmic diseases]

Recent genetic and molecular technology have shown that genetic abnormalities related to the cardiac ion channels can be a cause of some hereditary arrhythmic diseases. Until now, advanced analysis has proceeded especially in congenital long QT syndrome, and six different subtypes have been identified in Romano-Ward syndrome and 2 subtypes in Jervell & Lange-Nielsen syndrome. Since the mechanism of QT interval prolongation in each subtype is based on the malfunction of different cardiac ion channels, the same pharmacological treatment may show different antiarrhythmic effects for each subtype. In this paper, we review some of the hereditary arrhythmic diseases and discuss the possibility of gene-specific treatment in such diseases.     

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor.

BACKGROUND: In patients on long-term continuous ambulatory peritoneal dialysis (CAPD), peritoneal dysfunction may occur due to loss of peritoneal mesothelial cells, peritoneal fibrosis and neovascularization. Lactate, long used as a buffer in peritoneal dialysates, has been substituted by bicarbonate in recent years. However, their effects on the peritoneum of CAPD patients are unknown. This study investigated the influence of lactate and bicarbonate on peritoneal dysfunction in CAPD patients. METHODS: The mitochondrial activity of human peritoneal mesothelial cells (HPMCs) and their expression of basic fibroblast growth factor (bFGF) were studied after culture under various conditions. We also assessed the mitochondrial-activating effect of the supernatant of those cultures on human peritoneal fibroblasts (HPFBs) and human umbilical vein endothelial cells (HUVECs) and the effect of recombinant human bFGF on the mitochondrial activity of HPFBs and HUVECs. We used the WST-1 assay to determine mitochondrial activity in HPMC. RESULTS: At pH 7.4, the mitochondrial activity of HPMCs was lowest in a medium containing 40 mM (Lac), intermediate in a lactate (15 mM) plus bicarbonate (25 mM) medium (Lac/Bic), and highest in a 40 mM bicarbonate medium (Bic). In culture supernatant, the increase of bFGF was: Lac > Lac/Bic > Bic. Mitochondrial activation of HPFBs and HUVECs was stimulated by HPMC culture supernatants in the following decreasing order: Lac > Lac/Bic > Bic. The effects of these supernatants were suppressed by a bFGF-neutralizing antibody, while recombinant bFGF caused concentration-dependent mitochondrial activation in HPFBs and HUVECs. CONCLUSIONS: The role of bFGF in peritoneal fibrosis and neovascularization may be important. A bicarbonate-containing medium is better than a lactate-containing medium for preserving cell viability in HPMCs and preventing bFGF expression by these cells.     

A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints]

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.     

Promoter methylation and protein expression of the E-cadherin gene in the clinicopathologic assessment of adenoid cystic carcinoma.

Adenoid cystic carcinoma, a relatively uncommon tumor of salivary glands, is characterized by a prolonged clinical course and a fatal outcome. The molecular events underlying their progression are unknown. In this study, we examined the methylation status of E-cadherin gene and its protein expression in 23 cases of adenoid cystic carcinoma and correlated the results with the clinicopathologic factors to determine its role in these tumors. We also analyzed the effect of 5-azacytidine on the re-expression in a methylated cell line of adenoid cystic carcinoma for this gene. In our study, E-cadherin immunoreactivity, although heterogeneous, showed a progressive reduction with high histological grade and in metastatic and recurrent lesions. Promoter methylation was detected in 16 of 23 cases (70%), but there was no correlation with the histological grade or patient prognosis. Microdissection of immuno-negative cells in heterogeneous tumors showed positive methlyation. In the cell line from salivary adenoid cystic carcinoma with methylated E-cadherin, 5-azacytidine restored the E-cadherin expression. Our results indicate that: (1) E-cadherin gene promoter is frequently methylated in adenoid cystic carcinoma, leading to reduced E-cadherin expression, (2) variable E-cadherin expression might result from the intratumoral heterogeneity, and (3) increased extent of methylated areas may be associated with progression and advancement of the disease.