Stimulation of non-specific host resistance against Sendai virus and Escherichia coli infections by chitin derivatives in mice

The efficacy of chitin derivatives on non-specific host resistance to Sendai virus and Escherichia coli infections was studied in mice. Seventy percent deacetylated chitin (DAC-70) and N-trimethylated DAC-70 [DAC-70(Me)₃] showed protective activity against Sendai virus infection; however, carboxymethyl-chitin (CM-chitin) did not. DAC-70 also showed protective activity against E. coli infection.     

Acute membrane responses to viral action

The effects of Sendai, a paramyxovirus, on the functional activity of 3 cell types, have been studied in vitro to establish whether a virus alone can cause pathophysiological changes. Neuronal cells are depolarized and suffer a loss of excitability which was attributed to an increase in membrane conductance. Spontaneously beating cardiac cells initially stop beating and then beat more rapidly and asynchronously. Anterior pituitary cells release hormones. In all 3 cases the effects are transient and the cells recover completely.     

仙台病毒HN基因真核表达质粒对幼鼠免疫效果的评价

目的：评价仙台病毒HN基因真核表达质粒pcDNA3.HN对幼鼠的免疫效果.方法：使用去内毒素的构建质粒肌内注射免疫幼鼠,设立阳性对照和阴性对照组,观察靶器官的变化和免疫应答效果.结果：仙台病毒HN基因可以很好地诱导实验小鼠的细胞免疫和体液免疫,能够很大程度地保护肺组织免受随后仙台病毒的攻击.结论：仙台病毒HN基因真核表达质粒良好的免疫效果为今后开发基因疫苗提供了理论和实践依据.     

A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease

Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979 g, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G > C; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.     

Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.