Expression of polyglutamine-expanded Huntingtin activates the SEK1-JNK pathway and induces apoptosis in a hippocampal neuronal cell line

Huntington's disease is one of a growing number of hereditary neurodegenerative disorders caused by expansion of a polyglutamine stretch at the NH2 terminus of huntingtin. To explore whether polyglutamine-expanded huntingtin induces neuronal toxicity, I examined the expression of the full-length of huntingtin with 16, 48, or 89 polyglutamine repeats in a rat hippocampal neuronal cell (HN33). Expression of mutated huntingtin with 48 or 89 polyglutamine repeats stimulated c-Jun amino-terminal kinases (JNKs) activity and induced apoptotic cell death in HN33 cells while expression of normal huntingtin with 16 polyglutamine repeats had no toxic effect. The JNK activation precedes apoptotic cell death and co-expression of a dominant negative mutant form of stress-signaling kinase (SEK1) nearly completely blocked activation of JNKs and neuronal apoptosis mediated by mutated huntingtin. Taken together, my studies demonstrate that expression of polyglutamine-expanded huntingtin induces neuronal apoptosis via activation of the SEK1-JNK pathway.     

Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy

From April 1990 to December 1993, 140 patients were recruited to a randomized study to evaluate transcatheter hepatic arterial chemoembolization (TACE) as an adjuvant therapy for primary liver carcinoma after hepatectomy. This study investigated the principle, techniques and results of TACE. The results showed that the intrahepatic recurrence rate was 48.9% in the patients who underwent radical resection only, but only 21.3% in the patients who also underwent TACE 3-4 weeks after hepatectomy (P < 0.01). The 1-, 2-, 3-, and 4-year survival rates were 72.3%, 52.7%, 35.1%, and 35.1% respectively for the patients who underwent radical resection only, and were 97.9%, 85.5%, 69.5%, and 56.9% for the patients who also underwent TACE 3-4 weeks after radical resection (P < 0.001). The 1-, 2-, 3-, and 4-year survival rates were 38.9%, 0%, 0%, and 0% for the patients who underwent palliative resection only, and were 68.3%, 32.3%, 21.5%, and 21.5% respectively for the patients undergoing TACE 3-4 weeks after palliative hepatectomy (P < 0.001).     

Effect of lanthanide ions on the phase behavior of dipalmitoylphosphatidylcholine multilamellar liposomes

The effect of lanthanide ions (Ln3+) and their coordination compounds of diethylenetriamine pentaacetic acid (DTPA) on the phase behavior of dipalmitoylphosphatidylcholine (DPPC) multi-lamellar liposomes has been studied by differential scanning calorimetry (DSC), Raman spectroscopy, and freeze-fracture electron microscopic techniques. The displacement of Ca2+ binding on DPPC liposomes by lanthanide ions was also studied. The results show that the binding degree of four kinds of chloride salts with DPPC liposomes is: YbCl3 > GdCl3 > LaCl3 > CaCl2. Lanthanide ions increase the phase transition temperature of DPPC liposomes and decrease the membrane fluidity. Freeze-fracture electron microscopic results show that La3+ enhances the order of DPPC membrane. The effect of coordination compounds of lanthanides with DTPA on the phase behavior of DPPC liposomes is smaller than that of their chlorides. La3+, Gd3+, and Yb3+, can displace Ca2+ binding on DPPC liposomes, but there coordination compounds of DTPA can hardly displace Ca2+. Raman spectroscopic results show that a very slight effect in lateral packing order of DPPC liposomes was observed at various concentrations of lanthanides.     

Effects of halothane anesthesia on the motility of the sphincter of Oddi and transsphincteric flow in Australian brush-tailed possums

We evaluated the effect of halothane anesthesia on the motility of the sphincter of Oddi and simultaneous transsphincteric flow in Australian Brush-tailed possums (Trichosurus vulpecula). Halothane levels in the range of 0.25 to 2% were administered and decreased transsphincteric flow in a dose-dependent manner. Sphincter of Oddi basal pressure was higher than normal, but not in a dose-dependent manner. Additionally, halothane anesthesia influenced the sphincter of Oddi motility by decreasing the motility index (mean amplitude multiplied by frequency of contractions). This decrease was dose dependent. These findings indicate that sphincter of Oddi basal pressure is a major component of sphincter of Oddi motility responsible for regulating transsphincteric flow in this species. For studies of the sphincter of Oddi motility in anesthetized Australian Brush-tailed possums, we recommend anesthetic induction with ketamine (50 mg/kg, i.m.) and the inspired halothane level should not exceed 0.75% during the study period, as the effects we have demonstrated were most evident at levels greater than 0.75%. If higher halothane levels are required to maintain satisfactory anesthesia, an alternative anesthetic agent should be considered.     

Limitations of serodiagnosis in chlamydial genital tract infections

Infection with Chlamydia trachomatis results in the formation of a variety of antibodies with group, species, subspecies and serovarspecificity. Sera from patients with genital tract infections often show broad reactivity in serological tests. This may be due to the presence of cross-reacting antibodies, repeated infections by different serotypes or concurrent genital and respiratory infections by different chlamydial species. Other factors contributing to difficulties in interpretation include how antibody titres in acute mucosal infections, the occurrence of latent infections and reactivations, and the persistence of IgG which does not allow the differentiation of past from current infections. For these reasons, serology alone is inadequate for the diagnosis of uncomplicated lower genital tract infections. In upper genital tract infections, however, because of difficulties with sampling from the infected site, a positive serology may be the only indications of chlamydial involvement. This paper discusses the principles of chlamydial antibody assays, difficulties with their interpretation and their role in the diagnosis of upper and lower genital tract infections.