Allogeneic hepatocyte transplantation: Contribution of Fas-Fas ligand interaction to allogeneic hepatocyte rejection

Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the rejection of transplanted hepatocytes, induction of donor-specific unresponsiveness to graft without compromising the host immune system would be ideal. We previously reported that the Fas-Fas ligand system plays a critical role in the CD28-independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti-CD80/86 monoclonal antibodies and anti-FasL monoclonal antibody may prolong the survival of transplanted allogeneic hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute.     

Extensive and fatal basal cell carcinoma: a report of three cases

Three cases of basal cell carcinoma (BCC) with extensive invasion are described. The first two patients had meningeal and cerebral involvement with exposure of their dural meninges following full thickness skull erosion. The third patient had bilateral orbital and optic nerve involvement resulting in complete blindness. All three patients subsequently died from their disease.     

PYODERMA GANGRENOSUM: ASSOCIATIONS REVISITED

Fourteen cases of pyoderma gangrenosum were seen over a period of 24 years at the Hull Royal Infirmary Dermatology Department. Several associated conditions were found. Seven cases were associated with rheumatoid arthritis of which five were sero-positive, including one with Felty's syndrome. One case was associated with both ulcerative colitis and psoriasis; one with polycythemia rubra vera; two patients had diverticular disease including one who also had rheumatoid arthritis; one had positive syphilis serology. In three cases there was no significant associated disease identified. Ten out of the fourteen cases were women, indicating a female preponderance by a ratio of about 2F:1M; a figure similar to that stated by Seitzinger. The age of presentation ranged from 30 to 80 years.     

Role of the VEGF 936 C/T polymorphism in diabetic microvascular complications in type 2 diabetic patients

Aim:   Vascular endothelial growth factor (VEGF) is important in the pathogenesis of diabetic microvascular complications and the genetic polymorphism of this gene may contribute to the development and progression of diabetic microvascular complications. In this study, we investigated whether a genetic polymorphism of VEGF is associated with diabetic complications.
Methods:   A total of 398 type 2 diabetic patients and 526 healthy controls were enrolled. The study subjects were divided based on the state of nephropathy, retinopathy and neuropathy. The VEGF 936 C/T polymorphism was evaluated using standard PCR techniques, and plasma and urinary levels of VEGF were determined by enzyme-linked immunosorbent assay.
Results:   There was no difference in VEGF genotype distribution between the control and diabetic patients based on the state of diabetic nephropathy and neuropathy. However, a higher frequency of the TT genotype was observed in patients with proliferative diabetic retinopathy. Additionally, plasma levels of VEGF were significantly higher in the TT genotype. However, urinary levels of VEGF did not show a significant relationship with the VEGF genotype. Urinary VEGF levels showed a significant relationship with urinary albumin excretion, proteinuria, serum creatinine level and creatinine clearance, as well as fasting blood glucose levels, postprandial 2 h glucose levels and C-reactive protein.
Conclusion:   Our study suggests that the 936 C/T polymorphism of the VEGF gene may be an important factor determining plasma VEGF levels and that its polymorphism is related with diabetic retinopathy. Urinary levels of VEGF are not associated with plasma VEGF levels and associated with the stage of diabetic nephropathy.     

Haemolysis in adult and neonatal erythrocytes caused by autoxidation of lipid emulsion (Intralipid)

Lipid emulsion (Intralipid) causes free radical-mediated damage to human cells in vitro. Incubation with 0.44% Intralipid for 17 h caused 40.3 ± 3.8% haemolysis in adult human erythrocytes and 26.5 ± 8.1 % in erythrocytes from term newborns ( p = 0.0001). In adult erythrocytes mean corpuscular volume increased 68.7 ± 8.20%, and in newborn erythrocytes 54.8 ± 10.4% ( p = 0.0012). Initial concentrations of reduced glutathione in adult and newborn erythrocytes were 65.1 ± 2.5 and 62.1 ± 4.0 mg/dl, respectively (ns); after incubation, glutathione concentrations were 21.0 ± 4.0 and in 25.7 ± 5.2 mg/dl in adult and newborn erythrocytes, respectively ( p = 0.0004). After incubation the concentrations of thiobarbituric acid reactive material and conjugated dienes in newborn erythrocytes (2.8 ± 0.2 μM and 0.223 ± 0.019 OD 233, respectively) were higher than those of adult erythrocytes (2.1 ± 0.4 μM and 0.138 ± 0.012 OD 233) ( p = 0.0001). In both adult and newborn erythrocytes, the effects of Intralipid were significantly inhibited by 0.6 mM desferoxamine or 8 mM sodium etidronate. Despite higher susceptibility to lipid peroxidation of the cell membrane, newborn erythrocytes are more resistant than adult erythrocytes to free radical-mediated effects such as depletion of intracellular glutathione, cell swelling and haemolysis.