Excessive portal flow causes graft failure in extremely small-for-size liver transplantation in pigs

AIM: To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely small-for-size liver transplantation in pigs. METHODS: The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups: graft without portocaval shunt (n = 11) and graft with portocaval shunt (n = 11). Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated. RESULTS: In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h after transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2±26.9 mL/min/100 g liver tissue and 270.5±72.9 mL/min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2±27.8 mL/ min/100 g liver tissue and 42.7±32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed after reperfusion, but these findings were not recognized in the group with portocaval shunt. CONCLUSION: These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.     

A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins

We cloned from the rat brain a novel gene, tanc (GenBank Accession No. AB098072), which encoded a protein containing three tetratricopeptide repeats (TPRs), ten ankyrin repeats and a coiled-coil region, and is possibly a rat homolog of Drosophila rolling pebbles (rols). The tanc gene was expressed widely in the adult rat brain. Subcellular distribution, immunohistochemical study of the brain and immunocytochemical studies of cultured neuronal cells indicated the postsynaptic localization of TANC protein of 200 kDa. Pull-down experiments showed that TANC protein bound PSD-95, SAP97, and Homer via its C-terminal PDZ-binding motif, -ESNV, and fodrin via both its ankyrin repeats and the TPRs together with the coiled-coil domain. TANC also bound the alpha subunit of Ca2+/calmodulin-dependent protein kinase II. An immunoprecipitation study showed TANC association with various postsynaptic proteins, including guanylate kinase-associated protein (GKAP), alpha-internexin, and N-methyl-D-aspartate (NMDA)-type glutamate receptor 2B and AMPA-type glutamate receptor (GluR1) subunits. These results suggest that TANC protein may work as a postsynaptic scaffold component by forming a multiprotein complex with various postsynaptic density proteins.     

Anti-DFS70 antibodies in 597 healthy hospital workers

OBJECTIVE: Autoantibodies against DFS70 (dense fine speckles 70) antigen (also known as lens epithelium-derived growth factor) have been recently identified among the antinuclear antibodies (ANAs) in patients with atopic disorders. We undertook this study to examine the frequency of anti-DFS70 antibodies in a large number of healthy people. METHODS: Sera of 597 healthy individuals working in a hospital (142 men, 455 women) were analyzed for ANAs and for anti-DFS70 antibodies by indirect immunofluorescence (IIF) with HEp-2 cells as a substrate and by immunoblotting using DFS70 recombinant protein and whole HeLa cell extract. RESULTS: ANAs were present in 20% of all individuals by IIF. Nine percent of subjects were ANA positive at a serum dilution of 1:40, 4.0% at 1:80, 5.5% at 1:160, 1.0% at 1:320, and 0.3% at 1:640. There were 64 anti-DFS70 antibody-positive individuals. Surprisingly, this was 11% of the whole population and 54% of the ANA-positive population. The percentage of female anti-DFS70 antibody-positive subjects (86%; 55 of 64 subjects) was higher than the percentage of female anti-DFS70 antibody-negative subjects (75%; 398 of 533 subjects) (P < 0.05). The prevalence of anti-DFS70 antibody-positive sera decreased with increasing age (P = 0.0017). CONCLUSION: Considering that anti-DFS70 antibody positivity is rare in patients with systemic autoimmune diseases, introducing the anti-DFS70 antibody examination as a screening test for ANA-positive persons could be used to rule out systemic autoimmune diseases, resulting in considerable cost-saving potential. In addition, this test defines a subpopulation of healthy people in whom long-term followup might reveal health-related implications of this finding, since anti-DFS70 antibodies have been shown to be associated with some illnesses.     

Differentiation of hepatitis B virus genotypes D and E by ELISA using monoclonal antibodies to epitopes on the preS2-region product

An enzyme-linked immunosorbent assay (ELISA) has been described for serological determination of hepatitis B virus genotypes, using monoclonal antibodies (mAb) against seven distinct epitopes (b, m, k, s, u, f and g) on the preS2-region products of hepatitis B surface antigen (HBsAg). The usefulness of this method for serological detection of genotype E, however, was theoretical, because no HBsAg samples of this genotype were included in the original test panel. Moreover, the predicted serotype of genotype E (bksufg) closely resembled that of genotype D (bksu, bksuf or bksug). Four HBsAg samples of genotype E were tested by the original described ELISA. The epitope g, predicted to be present in these samples by amino acid sequences, was not detected when HBsAg of genotype E was captured on a solid phase by mAb to the common determinant 'a' of HBsAg and then reacted with mAb to g (5156) labeled with horseradish peroxidase. However, the four examples of HBsAg of genotype E were captured by mAb 5156 to g on a solid phase; they were then detected by labeled mAb to the common determinant 'a'. Since epitopes f and g co-occurred on HBsAg of genotype E, HBsAg samples of this genotype were also detected, by 'sandwiching' them between immobilized mAb to g and labeled mAb to f. By contrast, HBsAg of genotype D in 90 sera was not reactive when sandwiched between mAb to f and g. Thus, this modified ELISA enables the serological determination of all six genotypes of HBsAg and, by inference, of hepatitis B virus.     

Cardiovascular risk factors are really linked in the metabolic syndrome: this phenomenon suggests clustering rather than coincidence

BACKGROUND: The accumulation of cardiovascular risk factors can be seen in a single person but it needs to be determined if this occurs more frequently than might be explained by mere coincidence. METHODS: This study involved 119,412 adults: 41,819 males and 77,593 females, who were 40 years of age or older and who underwent an annual health examination. From the clinical and biochemical data, the actual prevalence of a combination of 3 or more factors: abnormal body mass index (> or =25.0), hypertension, high triglyceride (> or =150 mg/dl), low HDL cholesterol (<40 mg/dl) and abnormal fasting glucose metabolism (fasting blood sugar > or =110 mg/dl or HbA1c. > or =5.5%) was determined. Then, the prevalence of a corresponding combination of 3-5 factors was predicted from the prevalence of each factor on the assumption that their combination occurs as a result of coincidence. RESULTS: The criteria of metabolic syndrome (> or =3 risk factors) was met in 17,842 (14.9%) of the examinees. The actual prevalence of any combination of 3-5 factors of metabolic syndrome was more frequent than those expected to occur by coincidence (P < 0.001). When compared with the prevalence of the total examinees, the prevalence of obesity and insulin resistance was 2.5 and 2.9 times higher in metabolic syndrome compared to that in the total examinees but it was 1.7 to 2.1 times higher in hypertension and high triglyceride. The former two were clustering more than hypertension or high triglyceride in metabolic syndrome. Abnormal levels of serum creatinine and total cholesterol were found more often in metabolic syndrome. CONCLUSION: Combinations of risk factors of metabolic syndrome were found more frequently than coincidental phenomenon in the subjects from the general population. These finding suggest that these risk factors do cluster and obesity and insulin resistance were suggested to be linked with metabolic syndrome more than hypertension or high triglyceride.