The development of process and outcome measures in orthodontics lends itself to retrospective clinical studies. Once valid and reliable measures have been tested, prospective studies may utilize these measures to assess the quality of orthodontic treatment outcome and the duration and process of treatment. The findings from two retrospective studies comparing the quality of outcome using the peer assessment rating (PAR) occlusal index and duration of treatment are reported. Class I and Class II treatment comparisons indicate the duration of treatment time is increased on average 5 months in Class II, division 1 patients. In the second study, the effect of extraction/non‐extraction treatment in a sample that included all types of malocclusion indicates that, on average, treatment time is increased by approximately 5 months when extractions are included as part of the orthodontic treatment plan.

Many pathogens have co-evolved with their human hosts to develop strategies for immune evasion that involve disruption of the intracellular pathways by which antigens are bound by class I and class II molecules of the major histocompatibility complex (MHC) for presentation to T cells. Here the molecular events in these pathways are reviewed and pathogen interference is documented for viruses, extracellular and intracellular bacteria and intracellular parasites. In addition to a general review, data from our studies of adenovirus, Chlamydia trachomatis and Coxiella burnetii are summarized. Adenovirus E19 is the first viral gene product described that affects class I MHC molecule expression by two separate mechanisms, intracellular retention of the class I heavy chain by direct binding and by binding to the TAP transporter involved in class I peptide loading. Coxiella and Chlamydia both affect peptide presentation by class II MHC molecules as a result of their residence in endocytic compartments, although the properties of the parasitophorous vacuoles they form are quite different. These examples of active interference with antigen presentation by viral gene products and passive interference by rickettsiae and bacteria are typical of the strategies used by these different classes of pathogens, which need to evade different types of immune responses. Pathogen-host co-evolution is evident in these subversion tactics for which the pathogen crime seems tailored to fit the immune system punishment.

The actin cytoskeleton has been implicated in the maintenance of discrete sites for clathrin-coated pit formation during receptor-mediated endocytosis in mammalian cells, and its function is intimately linked to the endocytic pathway in yeast. Here we demonstrate that staining for mammalian endocytic clathrincoated pits using a monoclonal antibody against the AP2 adaptor complex revealed a linear pattern that correlates with the organization of the actin cytoskeleton. This vesicle organization was disrupted by treatment of cells with cytochalasin D, which disassembles actin, or with 2,3-butanedione monoxime, which prevents myosin association with actin. The linear AP2 staining pattern was also disrupted in HeLa cells that were induced to express the Hub fragment of the clathrin heavy chain, which acts as a dominant-negative inhibitor of receptor-mediated endocytosis by direct interference with clathrin function. Additionally, Hub expression caused the actin-binding protein Hip1R to dissociate from coated pits. These findings indicate that proper function of clathrin is required for coated pit alignment with the actin cytoskeleton and suggest that the clathrin-Hip1R interaction is involved in the cytoskeletal organization of coated pits.

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Clathrin-coated vesicles execute receptor-mediated endocytosis at the plasma membrane. However, a role for clathrin in later endocytic trafficking processes, such as receptor sorting and recycling or maintaining the organization of the endocytic pathway, has not been thoroughly characterized. The existence of clathrin-coated buds on endosomes suggests that clathrin might mediate later endocytic trafficking events. To investigate the function of clathrin-coated buds on endosomal membranes, endosome function and distribution were analyzed in a HeLa cell line that expresses the dominant-negative clathrin inhibitor Hub in an inducible manner. As expected, Hub expression reduced receptor-mediated endocytosis at the plasma membrane. Hub expression also induced a perinuclear aggregation of early endosome antigen 1-positive early endosomes, such that sorting and recycling endosomes were found tightly concentrated in the perinuclear region. Despite the dramatic redistribution of endosomes, Hub expression did not affect the overall kinetics of receptor sorting or recycling. These data show that clathrin function is necessary to maintain proper cellular distribution of early endosomes but does not play a prominent role in sorting and recycling events. Thus, clathrin's role on endosomal membranes is to influence organelle localization and is distinct from its role in trafficking pathways at the plasma membrane and trans-Golgi network. INTRODUCTIONClathrin-coated vesicles (CCV) mediate the selective transport of integral membrane proteins between some cellular membranes (Kirchhausen, 2000). At the plasma membrane, CCV facilitate receptor-mediated endocytosis (RME), whereby cell surface receptors and their ligands are internalized and delivered to the endocytic pathway (Schwartz, 1995). After RME, the fates of internalized receptors and ligands vary (reviewed by Mukherjee et al., 1997). Some progress to the late endocytic pathway where they are degraded in lysosomes (Carpenter and Cohen, 1976;Fox and Das, 1979). Others, such as transferrin (Tf) and low density lipoprotein (LDL) receptors, are sorted to a recycling compartment (Dunn et al., 1989;Mayor et al., 1993), from which they return to the plasma membrane (Anderson et al., 1982;Hopkins and Trowbridge, 1983). Although it is known that these receptors are endocytosed via CCV (Anderson et al., 1977;Willingham et al., 1979;Bleil and Bretscher, 1982), the degree to which clathrin mediates subsequent sorting and recycling of the proteins has been a subject of debate.The early endocytic pathway is composed of both sorting and recycling endosomes (Ghosh et al., 1994). Sorting endosomes separate endocytosed material that is to be recycled from material destined for the lysosome. Recycling components proceed to recycling endosomes from which they return to the plasma membrane. Clathrin-coated buds have been observed on early endosomes (Stoorvogel et al., 1996), making it a logical hypothesis that clathrin might mediate receptor sorting in the recycling pathway. A compelling findin...

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