Immediate versus delayed midface distraction in a primate model using a new intraoral internal device

The theoretic advantage of distraction osteogenesis of the craniofacial skeleton, especially in cases of severe midface retrusion and in the presence of maxillary scarring, is prevention of relapse following significant advancements. The purpose of this study is to demonstrate the utility of a new low-profile, intraoral, internal device for midface distraction at the conventional or high Le Fort I level. In addition, the present study compares the efficacy of immediate versus delayed distraction on subsequent maxillary relapse. Four adult rhesus Macaca mulatta monkeys were divided into two groups. Group 1 underwent immediate midface distraction; group 2 underwent delayed distraction. All four monkeys underwent a modified Le Fort I osteotomy through an upper buccal sulcus incision and bilateral application of the intraoral midface distraction devices. No other osteotomies or incisions were necessary. Immediate distraction, performed in group 1, entailed intraoperative activation of the devices and distraction of 10 mm followed by a 5-day lag period before postoperative activation and distraction of an additional 10 mm at the rate of 1 mm/day. Delayed distraction, performed in group 2, entailed a 5-day postoperative lag period before device activation and distraction of 20 mm at the rate of 1 mm/day. Both groups thus underwent 20 mm of midface distraction. All devices were removed 6 weeks after completion of distraction. All monkeys tolerated the devices and daily distraction uneventfully. On the basis of serial cephalograms and dental models obtained throughout the experimental period, there was no evidence of relapse in either the immediate or delayed groups 6 months after distraction. In addition, on the basis of histologic, ultrastructural, and dry skull analysis, no significant differences were observed in the quality of regenerate bone obtained when comparing the immediate and delayed distraction groups. Significant midface advancement is thus feasible using this new internal, intraoral distraction device, which presents several advantages over other internal devices that require coronal incisions and additional osteotomies to achieve midface advancement. In addition, immediate distraction may abbreviate the distraction period without adverse sequelae.     

Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis

Cytoplasmic fatty acid-binding proteins (FABPs) are a family of proteins, expressed in a tissue-specific manner, that bind fatty acid ligands and are involved in shuttling fatty acids to cellular compartments, modulating intracellular lipid metabolism, and regulating gene expression. Several members of the FABP family have been shown to have important roles in regulating metabolism and have links to the development of insulin resistance and the metabolic syndrome. Recent studies demonstrate a role for intestinal FABP in the control of dietary fatty acid absorption and chylomicron secretion. Heart FABP is essential for normal myocardial fatty acid oxidation and modulates fatty acid uptake in skeletal muscle. Liver FABP is directly involved in fatty acid ligand signaling to the nucleus and interacts with peroxisome proliferator-activated receptors in hepatocytes. The adipocyte FABP (aP2) has been shown to affect insulin sensitivity, lipid metabolism and lipolysis, and has recently been shown to play an important role in atherosclerosis. Interestingly, expression of aP2 by the macrophage promotes atherogenesis, thus providing a link between insulin resistance, intracellular fatty acid disposition, and foam cell formation. The FABPs are promising targets for the treatment of dyslipidemia, insulin resistance, and atherosclerosis in humans.     

P-glycoprotein misfolds in Escherichia coli: evidence against alternating-topology models of the transport cycle

P-glycoprotein (P-gp) is a drug transporter which pumps toxic hydrophobic compounds out of cells, conferring mutidrug resistance. P-gp is predicted to consist of 12 transmembrane alpha-helices and there is a strong body of experimental support for this model. However, a number of studies, including those on P-gp expressed in E. coli, have reported topologies with fewer than 12 transmembrane alpha-helices, leading to the hypothesis that the transmembrane topology of the protein changes during function. It is well established that P-gp undergoes conformational changes during its transport cycle and it has been recently shown that these changes are large in magnitude and could, potentially, reflect a changing transmembrane topology. One therefore, reassessed the transmembrane topology of P-gp expressed in E. coli and compared it directly with the topology of the protein expressed in mammalian cells. It was clear that the transmembrane topology of the protein was different in the different cell types and that the misfolding of P-gp in E. coli was due to the misrecognition of multiple P-gp sequences as topogenic signals. Thus, the alternative transmembrane topologies reported for P-gp in E. coli are artefacts of the heterologous expression system used, and models based on such data in which the transmembrane topology changes during drug transport are unlikely to be correct. Instead, the large conformational changes observed during the transport cycle are more likely due to changes in alpha-helix packing.     

Apolipoprotein AI as therapy for atherosclerosis: does the future of preventive cardiology include weekly injections of the HDL protein?

Conventional wisdom suggests that halting or reversing long-term atherosclerosis requires increasing the amount of circulating high-density lipoprotein (HDL) coursing through the vasculature. However, recent evidence seems to indicate that reducing the size of cholesterol-containing lipid plaques might be accomplished by methods that either do not raise or, in fact, lower the amount of circulating HDL. Carriers of apoAI(Milano), a variant of apoprotein AI (a component of HDL), have reduced levels of circulating low-density lipoprotein (LDL). Intriguingly, these individuals have reduced amounts of circulating HDL and total apoAI. Infusions of the ApoAI(Milano) variant given to patients with coronary atherosclerosis appear to lead to disease regression and reduced plaque size. However, larger studies are required to provide definitive proof of apoAI(Milano)'s benefits. What is certain is that attention should be focused on the removal of cholesterol from plaques rather than simply desiring to raise HDL concentrations in patients.     

Body image concerns of breast augmentation patients

This study investigated the body image concerns of women who sought cosmetic breast augmentation. Thirty breast augmentation candidates completed several measures of body image before their initial surgical consultation. Thirty physically similar women who were not interested in breast augmentation were recruited from the medical center and university community and also completed the measures. Breast augmentation candidates, as compared with women not seeking augmentation, reported greater dissatisfaction with their breasts. Augmentation candidates rated their ideal breast size, as well as the breast size preferred by women, as significantly larger than did controls. In addition, women interested in breast augmentation reported greater investment in their appearance, greater distress about their appearance in a variety of situations, and more frequent teasing about their appearance. Finally, breast augmentation candidates also reported more frequent use of psychotherapy in the year before the operation as compared with women not seeking augmentation. These results replicate and extend previous studies of body image in cosmetic surgery patients.     

Metopic synostosis: Defining the temporal sequence of normal suture fusion and differentiating it from synostosis on the basis of computed tomography images

Only the metopic suture normally fuses during early childhood; all other cranial sutures normally fuse much later in life. Despite this, metopic synostosis is one of the least common forms of craniosynostosis. The temporal sequence of normal physiologic metopic suture fusion remains undefined and controversial. Therefore, diagnosis of metopic synostosis on the basis of computed tomography images alone can prove misleading. The present study sought to determine the normal sequence of metopic suture fusion and characterize both endocranial and ectocranial suture morphology. An analysis of computed tomography scans of 76 trauma patients, ranging in age from 10 days to 18 months, provided normative craniofacial data that could be compared to similar data obtained from the preoperative computed tomography scans of 30 patients who had undergone surgical treatment for metopic synostosis. Metopic suture fusion was complete by 6 to 8 months in all nonsynostotic patients, with initiation of suture fusion evident as early as 3 months of age. Fusion was found to commence at the nasion, proceed superiorly in progressive fashion, and conclude at the anterior fontanelle. Although an endocranial ridge was not commonly seen in synostotic patients, an endocranial metopic notch was virtually diagnostic of premature suture fusion and was seen in 93 percent of synostotic patients. A metopic notch was not seen in any nonsynostotic patient. The morphologic and normative craniofacial data presented permit diagnosis of metopic synostosis based on computed tomography images obtained beyond the normal fusion period.     

Phase variation of a beta-1,3 galactosyltransferase involved in generation of the ganglioside GM1-like lipo-oligosaccharide of Campylobacter jejuni

Ganglioside mimicry by Campylobacter jejuni lipo-oligosaccharide (LOS) is thought to be a critical factor in the triggering of the Guillain-Barré and Miller-Fisher syndrome neuropathies after C. jejuni infection. The combination of a completed genome sequence and a ganglioside GM1-like LOS structure makes C. jejuni NCTC 11168 a useful model strain for the identification and characterization of the genes involved in the biosynthesis of ganglioside-mimicking LOS. Genome analysis identified a putative LOS biosynthetic cluster and, from this, we describe a putative gene (ORF Cj1139c), which we have termed wlaN, with a significant level of similarity to a number of bacterial glycosyltransferases. Mutation of this gene in C. jejuni NCTC 11168 resulted in a LOS molecule of increased electrophoretic mobility, which also failed to bind cholera toxin. Comparison of LOS structural data from wild type and the mutant strain indicated lack of a terminal beta-1,3-linked galactose residue in the latter. The wlaN gene product was demonstrated unambiguously as a beta-1,3 galactosyltransferase responsible for converting GM2-like LOS structures to GM1-like by in vitro expression. We also show that the presence of an intragenic homopolymeric tract renders the expression of a functional wlaN gene product phase variable, resulting in distinct C. jejuni NCTC 11168 cell populations with alternate GM1 or GM2 ganglioside-mimicking LOS structures. The distribution of wlaN among a number of C. jejuni strains with known LOS structure was determined and, for C. jejuni NCTC 12500, similar wlaN gene phase variation was shown to occur, so that this strain has the potential to synthesize a GM1-like LOS structure as well as the ganglioside GM2-like LOS structure proposed in the literature.     

The nitrogen requirements and dietary nitrogen utilization for the gecarcinid land crab Gecarcoidea natalis

The nitrogen requirements for tissue maintenance, moulting, and oogenesis were determined experimentally for the herbivorous land crab Gecarcoidea natalis. The maintenance nitrogen requirements for intermoult animals was very low (4.83+/-1.68 mmol N kg-1 dry body wt d-1), but during oogenesis the total requirement was much higher (8. 6 mmol N kg-1 dry body wt d-1). Gecarcoidea natalis could potentially assimilate enough nitrogen from rain forest leaf litter or leaves of Ficus or Erythrina to satisfy not only the maintenance nitrogen requirements but the observed rate of incorporation of nitrogen into the ovaries during oogenesis. The ovaries developed slowly over a period of 2 mo (mid-July to late September) and had a final nitrogen content of 359+/-15.9 (n=18) mmol kg-1 dry body wt. This was equivalent to 9.3%+/-0.4% of the total body nitrogen. A substantial nitrogen debt was incurred during ecdysis (658+/-126 mmol kg-1 dry body wt). This nitrogen debt could be satisfied slowly, from leaf litter, over a period of 1-3 mo. After ecdysis, the majority of the nitrogen and urate within the animal prior to moulting was retained within the soft crab (85.0%+/-1.2% total nitrogen, 82.0%+/-1.2% nonurate nitrogen and 99.56% urate), while only a minority was lost with the exuviae (18.0%+/-1.2% total nitrogen, 14.7%+/-1.2% nonurate nitrogen, and 0.4%+/-0.4% urate). The urate deposits in G. natalis were not mobilized as a source of nitrogen in animals maintained on a nitrogen-free diet.     

Feeding, growth, and fecundity of Abarenicola pacifica in relation to sediment organic concentration

For marine deposit-feeding invertebrates, the distribution of species with different life history strategies has long been known to be correlated with sediment organic concentration. Large populations of opportunistic species are found in sediments with enriched organic concentration, while equilibrium species populate low organic concentration sediments. Differences in both behavioral (e.g. feeding rate) and physiological (e.g. growth rate, reproductive output) adaptations determine the ability of species to establish populations in different environments. By systematically documenting differences in the way these factors vary as sediment organic concentration varies for both opportunistic and equilibrium species, we can better understand the mechanisms underlying this correlation between sediment organic concentration and species distributions. Here, we present the results of experiments examining the interactions among food concentration, feeding rate, growth rate, and reproductive output (measured as egg number and size) for the equilibrium species Abarenicola pacifica. A. pacifica is a large, long-lived, iteroparous, sub-surface deposit-feeding polychaete. Individual worms were reared throughout most of one generation in sediments differing only in the concentration of organic matter. Juveniles (<20 mg AFDW) had higher feeding rates and growth rates in sediments of higher organic concentration throughout the range tested. These results are consistent with the predictions from optimal foraging theory. As worms grew, however, these patterns changed. Once worms reached a mean body size of approximately 50 mg AFDW, feeding rate was greater on sediments of lower organic concentration (although it took worms in the sediments with lower organic concentration longer to reach this size). Differences in growth rates among treatments decreased as worms grew. For worms >100 mg AFDW, growth rates were uniformly low ( approximately 1%/day) on all sediments, but the early advantage obtained by worms in the high organic treatments resulted in much greater body sizes after 200 days. Worms had higher tissue triacylglyceride concentrations and produced more eggs (independent of worm size) as sediment organic concentration increased. We conclude that A. pacifica alters its feeding rate in response to variations in food resources in such a way as to maximize its energy intake and thereby maximize fitness. Future studies should investigate whether opportunistic species (as well as other equilibrium species) also have this ability.     

The Escherichia coli ATP-binding cassette (ABC) proteins

The recent completion of the Escherichia coli genome sequence ( Blattner et al ., 1997 ) has permitted an analysis of the complement of genomically encoded ATP-binding cassette (ABC) proteins. A total of 79 ABC proteins makes this the largest paralogous family of proteins in E . coli . These 79 proteins include 97 ABC domains (as some proteins include more than one ABC domain) and are components of 69 independent functional systems (as many systems involve more than one ABC domain). The ABC domains are often, but not exclusively, the energy-generating domains of multicomponent membrane-bound transporters. Thus, 57 of the 69 systems are ABC transporters, of which 44 are periplasmic-binding protein-dependent uptake systems and 13 are presumed exporters. The genes encoding these ABC transporters occupy almost 5% of the genome. Of the 12 systems that are not obviously transport related, the function of only one, the excision repair protein UvrA, is known. A phylogenetic analysis suggests that the majority of ABC proteins can be assigned to 10 subfamilies. Together with statistical and, importantly, biological evidence, this analysis provides insight into the evolution and function of the ABC proteins.