Faculty Bibliography

Scurvy is a nondiscriminatory disease process resulting from a nutritional deficiency of ascorbic acid (vitamin C). The severe vitamin deficiency produces a breakdown in the cellular structure of the body. This case report describes a middle-age woman with a history of edema, bruising of the lower extremities, anemia, and severe periodontal disease. Her presentation and medical history are classic for the signs of scurvy. Scurvy is now only uncommonly seen in developed countries, but there are still vulnerable populations whose nutritional status can lead to scurvy. The aim of this report is to help the clinician identify and treat scurvy, a disease that was once feared for its high mortality but is now easily treatable, even in cases that have progressed to multiple organ dysfunction and failure.

OBJECTIVES: We determined the prevalence of asthma and estimated baseline asthma symptoms and asthma management strategies among children aged 0-12 years in Central Harlem. METHODS: The Harlem Children's Zone Asthma Initiative is a longitudinal, community-based intervention designed for poor children with asthma. Children aged 0-12 years who live or go to school in the Harlem Children's Zone Project or who participate in any Harlem Children's Zone, Inc, program were screened for asthma. Children with asthma or asthma-like symptoms were invited to participate in an intensive intervention. RESULTS: Of the 1982 children currently screened, 28.5% have been told by a doctor or nurse that they have asthma, and 30.3% have asthma or asthma-like symptoms. To date, 229 children are enrolled in the Harlem Children's Zone Asthma Initiative; at baseline, 24.0% had missed school in the last 14 days because of asthma. CONCLUSION: The high prevalence of asthma among children in the Harlem Children's Zone Project is consistent with reports from other poor urban communities. Intensive efforts are under way to reduce children's asthma symptoms and improve their asthma management strategies.

Thin-film bioceramic coatings are potential alternatives to overcome the limitations provided by other commercially available coating techniques like PSHA, where variable bioceramic dissolution added to a metalloceramic weak link are process- inherent. The purpose of this investigation was to determine the overall and site specific (to 0.5 mm from implant surface) levels of osseoactivity around a thin-film (IBAD processed) coated titanium alloy implant versus a non surface modified (sand-blasted/acid etched) titanium alloy implant in a canine model. The surgical model comprised the proximal tibiae epiphyses with four implants placed in each limb remaining for 2 and 4 weeks in-vivo. 10 mg/Kg oxytetracycline was administered 48 hours prior to euthanization. The limbs were retrieved by sharp dissection, reduced to blocks, and subsequently nondecalcified processed for fluorescent microscopy. Micrographs (20x mag) were acquired around the implant perimeter and merged for overall biological response evaluations, and four micrographs (40x mag. subdivided in rectangles) were acquired along one of the implant sides for tetracycline labeled area fraction quantification. The results showed biocompatible and osseoconductive properties for the thin-film coated and uncoated titanium alloy implants. Tetracycline labeled area fraction analyses showed that the thin-film coated implants presented significantly higher overall and site specific osseoactivity levels at 2 and 4 weeks. The site specific osseoactivity values were significantly higher compared to overall values for control and thin-film coated implants at both times in-vivo. According to the results obtained in this study, thin-film coated implants enhanced biological response at the early implantation times evaluated.

Molecular profiling of human biopsies and surgical specimens is frequently complicated by their inherent biological heterogeneity and by the need to conserve tissue for clinical diagnosis. We have developed a set of novel 'tissue print' and 'print-phoresis' technologies to facilitate tissue and tumor-marker profiling under these circumstances. Tissue printing transfers cells and extracellular matrix components from a tissue surface onto nitrocellulose membranes, generating a two-dimensional anatomical image on which molecular markers can be visualized by specific protein and RNA- and DNA-detection techniques. Print-phoresis is a complementary new electrophoresis method in which thin strips from the print are subjected to polyacrylamide gel electrophoresis, providing a straightforward interface between the tissue-print image and gel-based proteomic techniques. Here we have utilized these technologies to identify and characterize markers of tumor invasion of the prostate capsule, an event generally not apparent to the naked eye that may result in tumor at the surgical margins ('positive margins'). We have also shown that tissue-print technologies can provide a general platform for the generation of marker maps that can be superimposed directly onto histopathological and radiological images, permitting molecular identification and classification of individual malignant lesions.

A major step in purifying membrane bound proteins involves the solubilization of the protein of interest from the cell membranes. Glycosylphosphatidyl inositol (GPI)-anchored proteins pose a singular problem in this solubilization step since they are found in detergent-resistant membrane complexes and accordingly are insoluble in cold Triton X-100. In this study we have developed a modified cell ELISA that determines the solubility of these cell surface proteins under various solubilization conditions. Using this non-radioactive method we show that the combination of saponin/Triton X-100 at 4 degrees C solubilized GPI-anchored proteins more efficiently than Triton X-100 at 4 degrees C. The combination of saponin/Triton X-100 at 4 degrees C avoids the potential of activating proteases that occurs when using Triton X-100 at 37 degrees C. Furthermore, our method also shows the saponin/Triton X-100 solubilized GPI-anchored proteins equivalent to the more expensive octyl beta-glucoside. This is a particularly important consideration in large-scale protein purification. This method obviates the need to use radioactivity, gel electrophoresis and immunoblotting procedures. The solubilization conditions determined by this modified ELISA are readily translated to the practical application of large-scale protein purification as demonstrated in the purification of two different recombinant GPI-anchored proteins, GPI-hB7-1 (CD80) and GPI-mICAM-1 (CD54).

The purpose of this retrospective study was to evaluate the extent to which an early Le Fort III osteotomy affects the position and eruption of the permanent maxillary first and second molars. To test the null hypothesis that there are no changes in eruption patterns, 31 patients diagnosed with craniosynostoses (13 with Crouzon's syndrome, nine with Apert's syndrome, eight with Pfeiffer's syndrome, and one with Carpenter's syndrome) with a mean age at the time of surgery of 5.3 +/- 1.3 years were studied. All patients underwent a Le Fort III osteotomy performed by a single surgeon to correct the anatomical deformity for functional and psychosocial reasons. Eighteen patients with craniosynostoses who had not been operated on (11 with Crouzon's syndrome, four with Apert's syndrome, and three with Pfeiffer's syndrome) served as controls; they had a mean age of 21.2 +/- 9.5 years. First and second molar positions and eruption patterns were assessed separately on panoramic radiographs by three observers. For the patients who underwent surgery, long-term evaluation showed that although 79 percent of all first molars erupted compared with 100 percent for the control group (p < 0.001), only 18 percent of all second permanent molars erupted compared with 89 percent for the control group (p < 0.0001). The authors conclude that in a significant minority of cases, early Le Fort III osteotomy affects first molar eruption, whereas the probability of second molar eruption is significantly decreased in the majority of cases. Therefore, Le Fort III osteotomy sites should be positioned distal to the second molar tooth buds. If this is not possible, patients, parents, and dental professionals should be made aware of these early postosteotomy sequelae so that later treatment planning can be enhanced.

Assembly of the HIV-1 virus involves, in part, strong interactions between the capsid (CA) domains of the Gag polyprotein. During maturation, the core of HIV-1 virions undergoes profound morphological changes due primarily to proteolysis of the CA domain from other Gag domains which may allow for more efficient disassembly of the viral core in the early stages of infection. The host protein cyclophilin A (CypA), a cis-trans prolyl isomerase, in some way seems to assist in this assembly/disassembly process. Using an unproteolyzed construct of CA, we show that binding of CypA induces a large-scale conformational change in CA that is independent of its cis-trans prolyl isomerase activity. This change appears to be mediated by Cys-198 of CA since mutation to Ala renders CypA unable to induce this change and alters the kinetics and stability of protein cores that may ultimately result in inefficient disassembly of viral cores. Alternately, mutation of the second CA Cys (C218A) allows for CypA-induced conformational changes but alters the kinetics and morphology of the protein cores that may ultimately result in inefficient assembly of viral cores. These studies show the importance of the CA Cys residues in mediating the contacts needed for viral assembly and disassembly.

In fetal tissues, both soft and hard tissue healing (in long bones) have been found to be scarless. However, healing of membranous bone in the fetal craniofacial skeleton has not been well documented. Pregnant ewes (gestational age range, 80-95 days) underwent a hysterotomy, and fetal lambs had a full-thickness excision of the entire mandibular symphysis region (10 mm). Nonoperated controls were used for comparison (n = 8). After 10 days and 2 weeks, fetuses showed incomplete regeneration of the anterior mandible by examination, computed tomographic scan, and histology. By 4 weeks postoperatively, the mandibular defect had completely closed, but regenerated bony volume was less than control specimens. At 6 weeks postoperatively, the specimen demonstrated complete bony healing without scar or inflammation. Computed tomographic scan measurements for mandibular shape (length over width) was similar in experimental and control specimens. The data indicate that fetal lamb membranous bone defects heal in a scarless fashion and suggest preprogrammed migration of osteogenic tissue