Unfolding of Plasmodium falciparum triosephosphate isomerase in urea and guanidinium chloride: evidence for a novel disulfide exchange reaction in a covalently cross-linked mutant

The conformational stability of Plasmodium falciparum triosephosphate isomerase (TIMWT) enzyme has been investigated in urea and guanidinium chloride (GdmCl) solutions using circular dichroism, fluorescence, and size-exclusion chromatography. The dimeric enzyme is remarkably stable in urea solutions. It retains considerable secondary, tertiary, and quaternary structure even in 8 M urea. In contrast, the unfolding transition is complete by 2.4 M GdmCl. Although the secondary as well as the tertiary interactions melt before the perturbation of the quaternary structure, these studies imply that the dissociation of the dimer into monomers ultimately leads to the collapse of the structure, suggesting that the interfacial interactions play a major role in determining multimeric protein stability. The Cm(urea)/Cm(GdmCl) ratio (where Cm is the concentration of the denaturant required at the transition midpoint) is unusually high for triosephosphate isomerase as compared to other monomeric and dimeric proteins. A disulfide cross-linked mutant protein (Y74C) engineered to form two disulfide cross-links across the interface (13-74') and (13'-74) is dramatically destablized in urea. The unfolding transition is complete by 6 M urea and involves a novel mechanism of dimer dissociation through intramolecular thiol-disulfide exchange.     

Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer

The influence of the biological medium on high-intensity focused ultrasound (HIFU) therapy for ablating experimental liver cancer was studied. In study 1, the temperature rise in the focal zone in the presence of iodized oil or castor oil was observed in vitro. The results showed that HIFU with iodized oil produced a higher and faster temperature rise than did HIFU with castor oil, whether high-power (500 W/cm2) or relatively low-power (136 W/cm2) conditions were used (P = 0.0008 and P = 0.0004 respectively). With the excised liver samples, the temperature also rose higher and more rapidly after injection of iodized oil into the liver than when castor oil was injected (P = 0.0239), and the target liver tissue revealed more radically and extensive destruction with iodized oil than with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM4 implanted subcutaneously, were randomly divided into four groups. Group I (n = 12) were the controls, group II (n = 12) were injected with iodized oil alone, group III (n = 12) received HIFU treatment, and group IV (n = 12) were exposed to HIFU after iodized oil injection. Significant inhibition of tumor growth was seen in groups III and IV as compared with group I or group II (P < 0.05), the tumor growth inhibition rate on the 28th day after treatment being 87% and 93% respectively. Significantly improved survival was noted in groups III and IV compared with groups I and II (P < 0.05). Histologically, group IV showed more complete tumor necrosis than did group III. These data suggest that HIFU combined with iodized oil might have achieve of synergism, location and targeting in the treatment of liver cancer.     

Multiple symmetric lipomatosis in the Chinese: ultrasound, CT and MR imaging

We report four cases of multiple symmetric lipomatosis in the Chinese population. We believe that multiple symmetric lipomatosis in the Chinese is not uncommon and may be related to the increasing incidence of alcoholism. The ultrasound appearances of these lipomatous masses are presented for the first time. Heterogeneous echogenic masses with fine fibrous strands that insinuate around fascial planes, lymph nodes and vascular tissues are typical findings. Unlike diseases affecting the Western population, multiple symmetric lipomatosis in the Chinese appears to be limited to the head and neck.     

Lifestyle, gender and occupational status as determinants of dental health behavior

A 23-year-old patient suffered from episodic angioedema of the face and neck, accompanied by diarrhea and abdominal pain. Additionally, the patient had bronchial asthma, recurrent nasal polyps and allergic rhinoconjunctivitis. Blood examination revealed leucocytosis with eosinophilia. Histological studies showed eosinophilic infiltrates in the skin and the gastrointestinal mucosa. Allergic food reactions and parasites were ruled out. With systemic corticosteroid treatment, the clinical symptoms and the eosinophilia disappeared. This case shows some parallels to previously described syndromes (eosinophilic gastroenteritis, Samter's syndrome, episodic angioedema with eosinophilia), but to the best of our knowledge this combination of symptoms has not yet been reported.