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Biomedical subjects

J Bill

Publications and source records attributed to J Bill.

At least 19 recordsLinked to original sources

[Typical features of craniofacial growth of the FGFR3-associated coronal synostosis syndrome (so-called Muenke craniosynostosis)].

BACKGROUND: The FGFR3-associated coronal synostosis syndrome (Muenke craniosynostosis) is caused by a point mutation (C749G) on the FGFR3 gene resulting in a Pro250Arg substitution. METHODS: To characterize this malformation, the neuro- and viscerocranium were analyzed by axial CT scans of the skull and cephalometric radiographs of up to 13 affected children before and in part after fronto-orbital advancement. RESULTS: Preoperative analysis of the intracranial volume of four patients showed a mean decrease of 3.6%, indicating a compensatory growth pattern of the skull in cases of coronal synostosis. The typical brachycephaly could be verified by the significant shortening of the skull length of 13.2% on average and by the significant reduction of the anterior cranial base length of maximal 5.9% on average. The anterior part of the skull was characterized by a significant mean increase of the intercoronal distance of 8.6%, which indicates a compensatory transversal growth in this malformation. The widened bilateral interorbital and anterior interorbital distances were increased by 7.3 or 9.0%, respectively, confirming a hypertelorism typical for this syndrome. The "frontal bossing" frequently found in brachycephaly was characterized by the preoperatively increased sagittal extension of the forehead (about 112.9% above the norm) and by the increased height of the frontal prominence (about 47.8% above the norm). Following surgery, both variables defining the morphology of the forehead were reduced and appeared to be constant throughout the follow-up. Hypoplasia of the midface described by Muenke et al. (1997) was confirmed in the present study only by the significant reduction of the sagittal length of the maxillary base, which was decreased by 6.8%. CONCLUSION: In accordance with the current literature, the skull configuration described for Muenke craniosynostosis shows similarities with the Saethre-Chotzen syndrome.

Amino Acid Substitution↗

Identification of T cell ligands in a library of peptides covalently attached to HLA-DR4.

While T cells have been clearly implicated in a number of disease processes including autoimmunity, graft rejection, and atypical immune responses, the precise Ags recognized by the pathogenic T cells have often been difficult to identify. This has particularly been true for MHC class II-restricted CD4+ T cells. Although such cells can be demonstrated to have undergone clonal expansion at sites of pathology, they are frequently difficult to establish as stable T cell clones. Furthermore, in general, larger peptides in higher concentrations are required to stimulate CD4+ T cells than CD8+ T cells, which makes some of the techniques developed to identify CD8+ T cell Ags impractical. To circumvent some of these problems, we developed a model system consisting of two parts. The first part involves the construction of an indicator T cell hybridoma expressing a chimeric TCR comprised of murine constant regions and human variable regions specific for influenza hemagglutinin 307-319 presented by DR4. The second part consists of a library of fibroblasts each expressing multiple peptides as amino terminal covalent extensions of the beta-chain of HLA-DR4 (DRA1*0101, DRB1*0401). Using this model system, we screened approximately 100, 000 peptides and identified three novel peptides stimulatory for the HA1.7 TCR. While there is some convergence at residues known to be important for T cell recognition, all three peptides differ markedly from each other and bear little resemblance to wild-type hemagglutinin 307-319.

Amino Acid Sequence↗

Use of soluble peptide-DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis.

Considerable evidence indicates that CD4(+) T cells are important in the pathogenesis of rheumatoid arthritis (RA), but the antigens recognized by these T cells in the joints of patients remain unclear. Previous studies have suggested that type II collagen (CII) and human cartilage gp39 (HCgp39) are among the most likely synovial antigens to be involved in T cell stimulation in RA. Furthermore, experiments have defined dominant peptide determinants of these antigens when presented by HLA-DR4, the most important RA-associated HLA type. We used fluorescent, soluble peptide-DR4 complexes (tetramers) to detect synovial CD4(+) T cells reactive with CII and HCgp39 in DR4(+) patients. The CII-DR4 complex bound in a specific manner to CII peptide-reactive T cell hybridomas, but did not stain a detectable fraction of synovial CD4(+) cells. A background percentage of positive cells (<0.2%) was not greater in DR4 (DRB1*0401) patients compared with those without this disease-associated allele. Similar results were obtained with the gp39-DR4 complex for nearly all RA patients. In a small subset of DR4(+) patients, however, the percentage of synovial CD4(+) cells binding this complex was above background and could not be attributed to nonspecific binding. These studies demonstrate the potential for peptide-MHC class II tetramers to be used to track antigen-specific T cells in human autoimmune diseases. Together, the results also suggest that the major oligoclonal CD4(+) T cell expansions present in RA joints are not specific for the dominant CII and HCgp39 determinants.

Adult↗

A therapeutic concept for the combined orthodontic surgical correction of angle Class II deformities with short-face syndrome: Surgical lengthening of the lower face.

In today's society not only facial esthetics have become important, but also the information on ways to correct adult orthodontic problems is readily available. Subsequently, increasing number of adults seek orthodontic treatment merely to change their facial appearance. In general, these adult patients exhibit such a severe skeletal deformity that it is noticeable even by non-experts. The nature of these adult deformities is such that the only promising treatment is the combined orthodontic-surgical approach. A stable and functional occlusion with a physiologic position for the condyle is the common goal of orthodontic treatment. In patients with skeletal deformities, however, improvement of facial esthetics takes paramount importance. They judge the success of treatment by extraoral appearance. Accordingly, the clinician must assess both the dental and facial appearance, and then inform the patient of different treatment possibilities. In this scenario, patient's input into the decision making process is critical for a mutually satisfactory result. This clinical report describes a concept of systematic approach to treatment of Class II deformities with skeletal deep bite and short lower face (short-face syndrome). This approach emphasizes the soft tissue analysis.

Journal Article↗

[Oral rehabilitation of tumor patients with endosseous implants. Implant success with special reference to peri-implant tissue].

In a prospective study, the influence of the status of the peri-implant hard and soft tissues on the success of enosseous dental implants in tumor patients was assessed. Out of 59 tumor patients with 261 implants, treated between July 1988 and August 1996, a pool of 23 patients with 99 implants provided with dentures for at least 1 year was obtained. Eighteen of these patients suffered from a squamous cell carcinoma of the oral cavity. Seventeen patients underwent preoperative radiation (40 Gy). A total of 68 out of 99 implants were inserted into autologous bone transplanted to reconstruct the mandible. In order to assess the peri-implant hard and soft tissues, the Hygiene Index, the Sulcus Bleeding Index, the Gingiva Index, the pocket-probing depth. the peri-implant bone resorption, and the periotest were used. The results in the tumor patients were compared with the results in a pool of nontumor patients. Tumor patients had significantly worse periimplant parameters than nontumor patients. The peri-implant pocket-probing depth proved to have significant influence on the success rate. The overall success rate was 77.8%.

Adult↗

Selective accumulation of related CD4+ T cell clones in the synovial fluid of patients with rheumatoid arthritis.

The role of T cells in the pathogenesis of rheumatoid arthritis (RA), especially in the perpetuation of advanced disease, remains unclear. Previous studies have focused on the TCR repertoire of synovial T cells in an attempt to determine whether the pattern of expression is characteristic of Ag-stimulated populations. However, the results of past studies have been conflicting. In the present work, we have undertaken an extensive analysis of the TCRs expressed by CD4+ T cells freshly isolated from synovial fluid of different joints and blood in three patients with established RA. Despite marked heterogeneity of synovial TCR expression, the results showed that 20 to 30% of the TCR beta-chain gene (TCRB) sequences found in one joint were also expressed in a second joint, but not in peripheral blood T cells of the same individual. Analysis of expressed TCRB complementarity-determining region 3 sequences showed the presence of multiple expanded clonal populations that were not predicted by quantitation of beta-chain variable region (Vbeta) expression by immunofluorescence staining. These studies also demonstrated sets of related, but different, complementarity-determining region 3 nucleotide sequences that encoded identical or highly homologous beta-chain amino acid sequences. Analysis of matching T cell clones derived from the joint by limiting dilution culture confirmed coexpression of highly homologous TCR alpha-chain gene (TCRA) and TCRB sequences. Together, these studies suggest that a significant proportion of synovial CD4+ T cells has been selected and expanded by conventional Ag(s) in this disease.

Amino Acid Sequence↗

[Long-term outcome after corrective surgery of the neuro- and viscerocranium of patients with simple and syndrome-related premature craniosynostosis].

A retrospective and partly prospective study was conducted to analyse both clinically and cephalometrically the craniofacial growth pattern of patients with isolated and syndrome-related premature craniosynostosis after standardized fronto-orbital and midface advancement. The file data of 293 children with fronto-orbital advancement were evaluated over an average period of 4.4 years. In addition, lateral teleradiographies of 117 patients from this group were cephalometrically analysed. Moreover, late results of 36 children and 8 adults with midface-advancement with an average follow-up period of 4.5 years were assessed. In contrast to linear craniectomy and so-called lateral canthal advancement, in only 8.2% of cases (24 out of 293 patients) were relapses requiring reoperation found in this study after fronto-orbital advancement. The evaluations indicate that with simple forms of craniosynostosis such as trigonocephaly and plagiocephaly predominantly very good or good growth can be observed. Cephalometric evaluation confirmed the limited potential of growth in the area of the anterior skull base and in the midface in the presence of syndrome-related faciocraniosynostoses. In such cases the cephalometrically confirmed maxillary hypoplasia, which increases in severity in the following order of syndromes 'Saethre-Chotzen-Crouzon-Apert-Pfeiffer', could be influenced only to a limited degree by fronto-orbital advancement. For this reason midface advancement is of secondary importance in children with very severe anomalies. In the present evaluation, a high rate of relapse of midfacial hypoplasia was to be found in children and adolescents after this operation in accordance with other references. Therefore, the indication for Le Fort III osteotomy in the growth period should be limited.

Adult↗

[Osteosynthesis after sagittal division of the mandible. Biomechanical stability of various methods in a pig mandibular model].

Forty years after the introduction of sagittal split osteotomy for transposition of the mandible according to Obwegeser, very different procedures for osteosynthesis are still discussed and practised. In a simple biomechanical model in the porcine mandible, five different methods for osteosynthesis using metallic screws (titanium, cobalt-chromium-molybdenum alloy) and one using a polymer screw (polylactic acid-copolymer blend), as well as the use of miniplates, were studied with regard to the stability of the compound. The Kruskal-Wallis H-test (variance analysis by ranks) showed statistically highly significant differences (P = 0.00017) regarding maximum stability. Osteosynthesis by miniplates was very stable with regard to the maximum load (Fmax = 234 N +/- 47), but not so in terms of three-dimensional stability of the osteosynthesis itself. The highest stability of osteosynthesis with screws only (Fmax = 183 N +/- 65) was found for a 2.7-mm titanium screw in triangular geometry. The use of 2.7-mm cobalt-chromium-molybdenum screws (Fmax = 173 N +/- 42) and 3.5-mm titanium screws (Fmax = 160 N +/- 76) did not make an statistical difference (P = 0.37). The mechanical values of 2.0-mm titanium screws in linear (Fmax = 113 N +/- 37) or triangular (Fmax = 136 N +/- 62) geometry and of 3.5-mm polylactic acid-copolymer blend screws (Fmax = 121 N +/- 33) did not differ statistically from each other (P = 0.75) but they did from the previous group (P = 0.019). In consideration of the low biting forces following sagittal split osteotomy, all tested procedures of osteosynthesis meet the mechanical requirements for clinical practice.

Animals↗

[Interventions for improving the facial profile with osteoinductive bone implants].

Osteoinductive bone allografts (autolyzed, antigen-extracted, allogeneic bone; AAA bone) were implanted in 207 cases. The patients had plastic surgery procedures to improve their profiles and were followed up for a maximum of 72 months. Twenty-two patients had an asymmetric mandible corrected with AAA bone chips. In 14 cases AAA bone implants were used for genioplasties. Forehead defects were reconstructed in 20 patients using AAA bone. Hypoplasia of the midface was corrected in 88 cases by augmentations with AAA bone chips or powder. A total of 63 patients underwent rhinoplasties in which AAA bone chips were used to shape or erect the dorsum nasi. Patient follow-up and reoperations to remove the osteosynthesis material revealed that the AAA bone implants were remodeled in the patients' own bone within several months. Less than 3% of the AAA bone implants were lost due to local infections. Except for rhinoplasties, secondary resorption of the bone allografts was extremely low. However, in cases in which strong tension resulted from scar formation or from lack of soft tissue, considerable resorption was observed, especially when AAA bone was implanted in the nose (25% of the rhinoplasties). On the other hand, this biodynamic behavior protected the implants from soft tissue perforation. In summary, AAA bone implants represent a convenient alternative to bone autografts in recipient beds with strong regenerative capacity. Since they are remodeled into the patient's bone none of the late complications found with alloplastic implants need to be expected.

Adolescent↗

[Rhinoplasty using the coronal approach after extensive facial skull fractures].

Functional, aesthetically perfect restoration of the face of patients suffering from a severely smashed facial skeleton requires exact centrifugal repositioning and miniplate osteosynthesis of all bony fragments. Nevertheless, the original height and form of the nose will not be restored with these means in some cases. Therefore, in 23 cases with shattered noses out of 487 midface-trauma patients in the years 1990-1995 the noses were onlay-grafted as the primary procedure in 9 cases via the coronal approach and as the secondary one when the metal plates were removed in 10 cases. A combination of primary and secondary procedures was done in 4 cases. Five times autogenous bone from outer calvarium was used and 22 times allogenic, conserved bone from organ donors (AAA bone). According to extent of the damage, mini-screws and/or mini-plates served to fixate the graft. In addition to the group of 13 patients in the years 1990-1993 with nasal bone grafts via the coronary approach, another group the same size with the same amount of trauma but without rhinoplasty was defined and compared to the first group. An aesthetic analysis was done by grading the results according to simple criteria from 0 to 6 points by the patient and by the examiner. Noses grafted via the coronary approach were evaluated as being significantly (P = 0.004, t-test for independent samples, SPSS) better (2.1 points on average +/- 1.1 SD) than conventionally treated noses (3.5 points on average +/- 0.8 SD).

Bone Plates↗

[Treatment outcome and complications of surgical and conservative management of mandibular fractures].

Retrospective analysis of 712 patients with 1166 mandibular fractures and follow up-study of 374 patients with 593 fractures was performed for discrimination of differences in wound- and bone-healing as well as late results between operative and conservative fracture treatment. 46.1% (328) of all patients have been treated conservatively, 53.9% (384) have been treated by operation. The follow up was performed on 255 patients with operative fracture treatment and 119 patients with conservative treatment. In 3.0% of the operatively treated patients bacterial infections occurred, in comparison to 8.7% of conservatively treated patients. From the viewpoint of functional aspects, such as occlusion, articulation and mandibular movement as well as radiological signs in the fractured region patients after operative treatment have shown partly significantly better results during the follow up compared to the group of conservatively treated patients. Neurological testings of inferior alveolar nerve and mental nerve have shown significantly better results in the group of conservatively treated patients. Since the functional results are much better after operative treatment, osteosynthesis with miniplates should be performed if there are no contraindications. The more precise reconstruction and stabilization of the fragments shortens time of hospitalization and leads to sooner functionality of the mandible.

Bone Plates↗

Cell surface expression of class II MHC proteins bound by a single peptide.

On normal cells, the peptide-binding grooves of class II MHC proteins contain a wide spectrum of peptides. For some purposes, however, it would be helpful to have cells bearing class II proteins engaged by only one peptide species. In an attempt to make such cells we constructed a gene for a MHC class II beta-chain, IA beta b, covalently linked to a peptide, E alpha 52-68, which is known to bind to the peptide-binding groove of IAb. This gene, together with the gene for IA alpha b, was transfected into B lymphoma cells and fibroblasts. The IAb-E alpha complex was expressed on the surfaces of these cells where it could be recognized by a mAb and T cells specific for IAb plus E alpha 52-68. Most of the peptide on fibroblasts remained covalently attached to the IAb beta-chain, but the covalent linker and/or peptide were degraded to some extent on B lymphoma cells. Nearly all of the IAb expressed by transfected fibroblasts was occupied by the E alpha peptide. Of 16 IAb-reactive T cell hybridomas, only 3 could respond to the IAb-E alpha complex on fibroblasts, confirming the idea that recognition of MHC may often involve recognition of the peptides bound to the MHC as well.

Amino Acid Sequence↗

Repair of human skull defects using osteoinductive bone alloimplants.

To estimate the efficacy of cranioplasty in clinical practice, autolyzed, antigen-extracted, allogenic (AAA) bone was prepared from cortical bones of human organ donors. AAA bone implants consisted of completely demineralized bone powder, completely demineralized pliable bone chips, surface-demineralized bone chips with pliable crevices, surface-demineralized rigid bone chips, or combinations thereof. 21 patients received AAA bone cranioplasties and were followed-up for between 12 and 58 months (average: 29 months). No infection or rejection of any of the AAA bone implants occurred. X-ray assessments as well as bone scintigraphies revealed osseous integration and remodelling of the AAA bone implants with minimal resorption, with the exception of completely demineralized AAA bone chips which showed partial resorption (2 cases). However, the partial resorption of completely demineralized AAA bone chips ceased after the implants had been remodelled. In 4 cases, the osteosynthesis material was removed between 10 and 18 months after the cranioplasty. In another case, a re-entry was necessary because of recurrence of an intracranial tumor. All of these five AAA bone reconstructions showed bleeding surfaces and osseous consolidations at the time of re-entry. A bone biopsy taken from one of these cranioplasties showed osteoinduction on the surface of the AAA bone implants. This first clinical review of cranial reconstructions using osteoinductive AAA bone implants emphasizes the therapeutical application of AAA bone for cranioplasty. Large AAA bone chips from human skull bones facilitate the reproduction of the skull's convexity especially when combined with preoperative stereolithography-based planning.

Adolescent↗

Activation of autoreactive T-cell clones from NZB.H-2bm12 mice.

We have previously established H-2bm12-restricted autoreactive T-cell clones from NZB.H-2bm12 mice which induce in-vitro production of IgG anti-dsDNA antibodies by syngeneic B cells. However, the mechanism underlying the activation of autoreactive T cells is not clear. We have taken advantage of the existence of L cells which were co-transfected with the A alpha b gene and independent A beta genes comprising all the permutations of amino acid residues distinguishing A beta b from A beta bm12. Using this panel of L cells expressing recombinant I-A molecules, 6/6 autoreactive T-cell lines responded significantly to the FT7.2 L cell transfectant expressing wild-type I-Abm12 as well as control APC from NZB.H-2bm12 or B6.C-H-2bm12 mice, but not to the other recombinant L-cell transfectants or to allogeneic APC. The fixation of APC with paraformaldehyde prior to co-culture led to dramatically diminished reactivity of all the autoreactive cloned T-cell lines tested. Interestingly, the inability of FT7.2 L cells to induce T-cell activation after paraformaldehyde fixation could be reconstituted by the addition of B/monocyte cells, but not T cells, from NZB.H-2bm12, NZB.H-2b or NZB(H-2d) mice and to a significantly lesser extent, from C57BL/6 (H-2b) and BALB/c (H-2d) mice. Conversely, when treated with either mitomycin C or cycloheximide, before incubation with autoreactive T cells and fixed FT7.2 cells, the ability of spleen cells from NZB.H-2b mice to reconstitute reactivity was reduced. Controls for these observations included KLH-specific T-cell clones from NZB.H-2bm12 mice, the T-cell hybridoma H66.3.6.54 specific for beef insulin and restricted to I-Ab, the IBM026 hybridoma specific for OVA and restricted to I-Abm12, and the TH2.2 hybridoma, and I-Ab antigen-presenting cell line.

Animals↗

[Microsurgical scapula transplants for reconstruction of the facial skull--experiences with 44 patients].

Great versatility gives composed scapular flaps a particular significance for the reconstruction of defects in face and skull: According to individual requirements one up to five separate elements may be transferred with one vascular pedicle. Anatomical studies of 120 scapulas measured a mean length of 13.4 cm and a mean diameter of 1.2 cm of the lateral margin offering sufficient bone for most indications in the visceral skull. Up to three cutaneous flaps may cover nearly every defect in the head. 44 patients were treated in the years 1989 to 1993 using scapular flaps, most of them combinations consisting of bone and skin elements. In two patients a so called 4-in-1-flap was transferred including the latissimus-dorsi-flap. All donor sites could be closed primarily. Venous thrombosis caused one loss of a flap. Infections healed without sequelae. Medical gymnastics brought full rehabilitation of the donor site within 6 months.

Bone Transplantation↗

Conformational difference of T cell antigen receptors revealed by monoclonal antibodies to mouse V beta 5 T cell receptor for antigen determinants.

The mAb MR9-4 and MR9-8 react with T cells expressing the V beta 5.1 and -5.2 chains of the TCR. T cells expressing V beta 5.1 TCR were stained by both antibodies with similar surface fluorescence intensity. For the T cell clones and hybridomas expressing V beta 5.2 TCR, staining intensity with MR9-8 varied from negative to comparable to that stained with the anti-pan V beta 5 mAb MR9-4, whereas every V beta 5-positive T cell can be activated with either MR9-4 or -9-8 mAb, suggesting a differential binding affinity of MR9-8 mAb to V beta 5 TCR molecules. Analysis of J beta segment and V alpha chain usage in the V beta 5-positive T cell hybridomas revealed that a differential binding of MR9-8 mAb to the V beta 5.2 chain is not dependent on either the J beta segment usage or the associating V alpha chain alone. These results suggest that the differential binding of MR9-8 mAb to V beta 5.2 TCR is due to the conformational change of the V beta chain created by a combination of the V alpha (possibly J alpha) and D beta-J beta segment associating with the V beta 5.2 chain.

Animals↗