Interferon-gamma and interleukin-10 inhibit antigen presentation by Langerhans cells for T helper type 1 cells by suppressing their CD80 (B7-1) expression

CD80(B7-1) and CD86(B7-2) co-stimulatory molecules have been reported to activate Th1/Th2 development pathways differentially. It is well known that Langerhans cells (LC), potent antigen-presenting dendritic cells in the epidermis, express several co-stimulatory molecules and that this expression is modulated by several cytokines. Based on the recently reported effect of interferon (IFN)-gamma and interleukin (IL-)-10 on the expression of CD80 and CD86 by LC, we examined the effects of these cytokines on the expression of CD54 (intercellular adhesion molecule-1) and CD40 in addition to CD80 and CD86 on LC, and correlated the expression of each co-stimulatory molecule with antigen presentation for a Th1 clone by cultured LC (cLC) treated with these cytokines. LC cultured for 72 h significantly up-regulated MHC class II antigen expression and all the co-stimulatory molecules were examined. As previously reported, IL-10 or IFN-gamma inhibited the up-regulation of CD80 expression. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) partially restored the suppression of CD80 expression induced by IFN-gamma on cultured LC, while it had virtually no effect on the inhibition induced by IL-10. Antigen presentation for the myoglobin-specific syngeneic Th1 clone by cLC, which were pre-incubated with these cytokines, correlated well with their CD80 expression. In addition, among the antibodies for CD80, CD86, CD28 or CD40, the suppression of the Th1 clone stimulation by LC was found to occur only with anti-CD80 and anti-CD28 antibodies. Finally, we studied the effects of IFN-gamma and IL-10 on GM-CSF production by epidermal keratinocytes (KC). We could show that only IFN-gamma, but not IL-10, suppressed GM-CSF production by KC. These findings suggest that both IFN-gamma and IL-10 suppress antigen presentation by LC for Th1 cells by suppressing their CD80 expression. The inhibitory effect of IFN-gamma on CD80 expression on LC appears to be partially mediated through the suppression of GM-CSF production by KC.     

The membrane-proximal region of the E-cadherin cytoplasmic domain prevents dimerization and negatively regulates adhesion activity

Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Deletion of the COOH-terminal residues of the E-cadherin cytoplasmic domain has been shown to abolish its cell adhesive activity, which has been ascribed to the failure of the deletion mutants to associate with catenins. Based on our present results, this concept needs revision. As was reported previously, leukemia cells (K562) expressing E-cadherin with COOH-terminal deletion of 37 or 71 amino acid residues showed almost no aggregation. Cells expressing E-cadherin with further deletion of 144 or 151 amino acid residues, which eliminates the membrane-proximal region of the cytoplasmic domain, showed E-cadherin-dependent aggregation. Thus, deletion of the membrane-proximal region results in activation of the nonfunctional E-cadherin polypeptides. However, these cells did not show compaction. Chemical cross-linking revealed that the activated E-cadherin polypeptides can be cross-linked to a dimer on the surface of cells, whereas the inactive polypeptides, as well as the wild-type E-cadherin polypeptide containing the membrane-proximal region, can not. Therefore, the membrane-proximal region participates in regulation of the adhesive activity by preventing lateral dimerization of the extracellular domain.     

Rapid determination of the membrane potential of mitochondria in small biopsy specimens of the liver

In liver transplantation, graft viability is ideally to be determined before implantation. Integrity of mitochondria may be a prerequisite to a viable graft. A new method is presented, which allows for the determination of the membrane potential of mitochondria (MPM; mV) in state 4 respiration within 50 min in 40-mg specimens, employing rhodamine 123 as a probe. Normal control showed a MPM of 239.2 mV. Storage in saline at 37 degrees C yielded an impaired MPM of 153.5 mV within 3 h. The cold storage at 1 degree C could preserve MPM at quasi-normal after 3 h but reduced it significantly after 24 h to 222.2 mV in saline (p < 0.005 vs. control) and 231.0 mV in UW solution (p < 0.05 vs. control): the difference between the 24-hour values was significant (p < 0.05).     

Morphological changes of epithelial rests of Malassez in rat molars induced by local administration of N-methylnitrosourea

The objective was to examine the possibility that epithelial rests of Malassez can give origin to odontogenic tumours. A mixture of N-methylnitrosourea (MNU) and alginate impression material for dental use was injected onto the periosteum of the buccal side of the left mandible of 5-week-old, male Wistar rats (300 mg/kg body wt). The mixture was left at the site for several months. The rats were killed 1, 3, 5, and 8 months after the injection. After 5 and 8 months, the epithelial rests of Malassez in the cervical and bifurcational regions of the first, second, and third left mandibular molars were significantly enlarged and the alveolar bone around the lesion was resorbed by multinucleated cells in all rats. The epithelial masses were characterized by enamel organ-like structures, deposition of eosinophilic amorphous material, duct-like structures, and squamous metaplasia. In addition to these masses in the molar regions, odontogenic tumours were induced in the incisal region and carcinomas and sarcomas in the buccal region, knee, bladder, and skin. Local administration of a mixture of MNU and alginate impression material can induce odontogenic tumours from the epithelial rests of Malassez at high incidence.     

Increasing the biosafety of analytical systems in the clinical laboratory

Biosafety is an important part of the know-how of all clinical laboratory professionals. Biosafely must have high priority in the design and use of analytical systems. Attention should be focused on reducing the handling of biological specimens, reducing biohazards to laboratory personnel, and on improving the labelling and containment of biohazardous materials. In this paper, biosafety issues are discussed in relation to the design of analytical systems, their use and maintenance.     

Biocomposites Made from Short Abaca Fiber and Biodegradable Polyesters

Natural fiber‐reinforced biodegradable polyester composites were prepared from biodegradable polyesters and surface‐untreated or ‐treated abaca fibers (length ca. 5 mm) by melt mixing and subsequent injection molding. Poly(butylene succinate)(PBS), polyestercarbonate (PEC)/poly(lactic acid)(PLA) blend, and PLA were used as biodegradable polyesters. Esterifications using acetic anhydride and butyric anhydride, alkali treatment, and cyanoethylation were performed as surface treatments on the fiber. The flexural moduli of all the fiber‐reinforced composites increased with fiber content. The effect of the surface treatment on the flexural modulus of the fiber‐reinforced composites was not so pronounced. The flexural strength of PBS composites increased with fiber content, and esterification of the fiber by butyric anhydride gave the best result. For the PEC/PLA composites, flexural strength increased slightly with increased fiber content (0–20 wt.‐%) in the case of using untreated fiber, while it increased considerably in the case of using the fiber esterified by butyric anhydride. For the PLA composite, flexural strength did not increase with the fiber reinforcement. The result of soil‐burial tests showed that the composites using untreated fiber have a higher weight loss than both the neat resin and the composites made using acetylated fiber.

Flexural modulus of PBS composites as a function of fiber content.     

Preparation of gelatinous aluminium hydroxide by urea from aqueous solutions containing chloride,nitrate and sulphate of aluminium

The preparation of gelatinous aluminium hydroxide from aqueous solutions containing a mixture of the chloride, nitrate or sulphate of aluminium and urea by heating at 95°C has been investigated under different conditions. The pH value of aqueous solutions, on heating for a given period of time, gradually increases, rises steeply at pH 4.0–7.5 and finally approaches a constant value. The precipitate appears at about pH 7 in the presence of chloride or nitrate ions and about pH 4 in the presence of sulphate ions. Although the gelatinous precipitates in the chloride and nitrate systems are apparently different from the granular, filterable one in the sulphate system, their compositions are not influenced by the species of aluminium salt. The fresh precipitates exist in an amorphous state, and go to pseudoboehmite by ageing. It seems that the amount of pseudoboehmite increases as the concentration of aluminium salt in aqueous solution decreases. However, the transformation from amorphous aluminium hydroxide to pseudoboehmite is reduced in the presence of sulphate ions. Furthermore, it is found that the X-ray diffraction peak for the (200) plane, as an orthorhombic structure, in the pseudoboehmite precipitated from chloride or nitrate solution is more intense than that from sulphate solution.