Effects of the augmenter of liver regeneration on the biological behavior of hepatocellular carcinoma

To take advantage of the small interfering ribonucleic acid [siRNA] targeting the human augmenter of liver regeneration [hALR] and anti-hALR monoclonal antibody [McAb] to inhibit the function of hALR, and to demonstrate whether the growth of hepatoma is influenced by siRNA targeting hALR and anti-hALR McAb through inhibiting expression of hALR. This study was conducted in the Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Chongqing Medical University, China, between January 2005 and May 2007. We transfected siRNA plasmid pSIALR-A, which targeted the complementary deoxyribonucleic acid [cDNA] of hALR and the unrelated control plasmid pSIALR-B into human hepatocellular liver carcinoma cell line [HepG2] cells. Then, the proliferation of HepG2 cells, after being treated with pSIALR-A and anti-hALR McAb was detected. The growth of the xenograft tumor was observed after being treated with pSIALR-A and anti-hALR McAb in nude mice. We successfully constructed expressing plasmid pSIALR-A and pSIALR-B. The pSIALR-A inhibited the expression of hALR in HepG2 cells significantly. The siRNA targeting hALR and anti-hALR McAb inhibited obviously the growth of HepG2 cells in vitro. siRNA targeting hALR and anti-hALR McAb significantly inhibited the growth of xenograft tumor in 5 nude mice. Anti-hALR McAb inhibited apparently the autonomous growth of HepG2 cells. Our results demonstrated that anti-hALR McAb inhibited the autonomous growth of hepatoma cells obviously, moreover, hALR maintained the autonomous growth of hepatoma cells in vitro through an autocrine mechanism

A Thai boy with hereditary enzymopenic methemoglobinemia type II.

Individuals with methemoglobin exceeding 1.5 g/dl have clinically obvious central cyanosis. Hereditary methemoglobinemia is due either to autosomal dominant M hemoglobins or to autosomal recessive enzymopenic methemoglobinemia. Four types of enzymopenic methemoglobinemia have been described. In addition to methemoglobinemia, individuals with type II, which is the generalized cytochrome b5 reductase deficiency, have severe and progressive neurological disabilities. Here we report a 3-year-old Thai boy with type II hereditary enzymopenic methemoglobinemia. He was born to a second-cousin couple. His central cyanosis was first observed around 10 months of age. His neurological abnormalities were seizures beginning at 1 year of age, microcephaly, and inability to hold his head up. His cardiovascular and pulmonary evaluations were unremarkable. Methemoglobin level by spectral absorption pattern was 18 per cent. A qualitative enzymatic assay confirmed the deficiency of the cytochrome b5 reductase enzyme. With this definite diagnosis, a prenatal diagnosis for the next child of this couple will be possible.

Methaemoglobinaemia in areas with high nitrate concentration in drinking water.

BACKGROUND: An epidemiological investigation was undertaken in all age groups to assess the prevalence of methaemoglobinaemia in areas with high nitrate concentration in drinking water. METHODS: Five areas were selected with an average nitrate concentration (as nitrate) of 26, 45, 95, 222 and 459 mg nitrate ions/litre in drinking water. These areas were visited and the house schedule (containing name, age, sex and weight of the family members) prepared in accordance with the statistically designed protocol. In all, 178 persons, matched for age and weight, were selected and arranged in five age groups. They constituted 10% of the total population of each of these areas. A detailed history of the selected population was taken, medical examination conducted and blood samples taken to ascertain the level of methaemoglobin. The collected data were subjected to statistical analysis to ascertain a relationship between nitrate concentration and methaemoglobinaemia. RESULTS: High nitrate concentrations cause severe methaemoglobinaemia (7%-27% of Hb) in all age groups, especially in the age group of less than 1 year and above 18 years. The lower levels of methaemoglobin in the age group of 1-18 years is probably due to better reserve of cytochrome b5 reductase activity and its adaptation to increasing nitrate concentration in water to compensate for methaemoglobinaemia in this age group. CONCLUSION: We conclude that high nitrate ingestion causes methaemoglobinaemia in all age groups. Cytochrome b5 reductase activity and its adaptation with increasing water nitrate ingestion plays a role in compensating for the methaemoglobinaemia.