Report of the Third Banff Conference on Allograft Pathology (July 20-24, 1995) on classification and lesion scoring in renal allograft pathology.
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Atrophy↗
Biomedical subjects
S Yilmaz
Publications and source records attributed to S Yilmaz.
Protocol core biopsy as intermediate efficacy end-point in chronic kidney allograft rejection.
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Biopsy↗
A regenerative approach to the treatment of severe osseous defects: report of an early onset periodontitis case.
The biological principles of guided tissue regeneration (GTR) and graft materials have become widely used as methods for the treatment of severe osseous defects. An early-onset periodontitis case which includes a 3-year follow-up is presented in this case report, which demonstrates the successful use of an expanded polytetrafluoroethylene barrier membrane (ePTFE; Goretex Periodontal Material) in conjunction with natural coral bone graft (Biocoral 450). The results after 3 years illustrate the potential for regenerative periodontal therapy in combination with appropriate prosthetic procedures where limited success might have been expected.
Adolescent↗
A new method for standardization of intraoral radiographs.
Standardization of intraoral radiographs is necessary for longitudinal studies of alveolar bone changes. Several methods of standardizing have been developed. These all involve fixing the geometric relations between the object, the x-ray tube, and the film. This usually involves a film holder, mounted on an occlusal stent and connected to the x-ray tube via an adapter ring. There is, however, a problem of compatibility between various commercial adapter rings and film holder assemblies. In an attempt to overcome this problem, we developed a method of producing cast acrylic adapters by making a plaster cast from a silicon rubber impression of the x-ray tube. The adapter was devised so that radiographs could be taken of all four segments using the same standard commercially available film holder. A total of 128 radiographs were taken from 42 patients who underwent various types of periodontal surgery; 64 were taken preoperatively and 64 at 6 months postoperatively. These pairs were superposed and approximately 58% were found by qualitative inspection to show total matching of geometric outlines as well as maintenance of position on the film, and approximately 73% to show geometric matching. Changes in alveolar bone height were evaluated for 11 of these totally matching pairs by counting millimetric grids and by a computer-based indirect digital imaging system. These were found to correlate satisfactorily (r = .63).
Alveolar Bone Loss↗
The relation of microbiologic data to aspartate aminotransferase enzyme activity in gingival crevicular fluid.
Gingival crevicular fluid (GCF), reflects the immune and inflammatory reactions and is itself a location for specific host-microbe interactions that lead to periodontal diseases. Aspartate aminotransferase (AST) is one of the components of GCF that is released as a result of cell death. In this study, 40 periodontal sites in 10 early onset periodontitis patients before and after nonsurgical periodontal therapy, with and without local metronidazole administration, were first examined for the AST enzyme levels in GCF and then evaluated for microbiological and clinical variables. In each patient, 4 sites (one site/quadrant) with a probing depth of > or = 5 mm were selected and treated with separate treatment protocols. Certain microbial species including Prevotella intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans(A. a.) were found more often and/or in higher levels in AST active sites (36/40 first measurement--9/36 second measurement), while other species (Streptococcus and Actinomyces) were found more often and/or in higher levels in AST inactive sites (4/40 first measurement--8/36 second measurement). Eight post-treatment AST active sites revealed 1.5 mm of attachment loss, whereas 8 post-treatment AST inactive sites showed 1.37 mm of attachment gain. AST activity and microbiological-clinical data presenting such an agreement suggests that, AST level assessment would be beneficial as an adjunctive method alongside other clinical criteria, in guiding the clinician in periodontal treatment.
Adult↗
A clinical and microbiological evaluation of systemic and local metronidazole delivery in early onset periodontitis patients.
The present study describes selected clinical and microbiological results obtained by treatment with local (Elyzol) and systemic (Flagyl) use of metronidazole alone and/or mechanical subgingival debridement in early onset periodontitis (EOP). Twelve patients, with lesions not distributed as in classical localized juvenile periodontitis, were included. They were randomly divided into local and systemic treatment groups each comprising 6 individuals, in each of whom 4 sites (one site/quadrant) with a probing depth of > or = 5 mm were selected and treated with separate treatment modalities. The overall treatment design provided 6 different test groups. Groups of quadrants received 1) scaling and root planing 2) local metronidazole treatment 3) systemic metronidazole treatment 4) local metronidazole combined with scaling and root planing 5) systemic metronidazole combined with scaling and root planing 6) No treatment. The microbiological and clinical effects of treatment modalities were monitored over 42 days. The results demonstrated reductions in mean counts of obligate anaerobic and capnophilic microorganisms coupled with significant improvements in mean clinical measurements (gingivitis, probing depth, attachment level) in all groups, except the untreated. Scaling and root planing provided an initial clinical improvement with a selective reduction of periodontopathogens (92.6% obligate anaerobes, 42.9% capnophilic microorganisms), whereas the combination of local or systemic metronidazole with scaling and root planing were found superior in reducing capnophilic bacteria (93.7% and 93.4%, respectively). It is of critical importance to have a treatment rationale for EOP, since bacterial differences exist in the etiological subforms of periodontitis. Microbial testing may be justified before prescribing the adjunctive antibiotic and selecting the mode of delivery for the successful clinical management of EOP.
Administration, Oral↗
Evolution of glomerular basement membrane changes in chronic rejection.
We have investigated the evolution of chronic glomerular changes in the absence of the recurrence of original disease in an experimental rat model of chronic renal allograft rejection. Using serial graft needle biopsies and serum creatinine levels, we were able to focus on early glomerular changes that are associated with good graft function. The recipient rats were divided into 5 groups, 2 with allogeneic (DA to WF) transplants and 3 with syngeneic (DA to DA) transplants. In the first 2 allogeneic groups, one group received cyclosporine (CsA) for 2 weeks (n = 7) and the other received CsA for 12 weeks (n = 5). In the 2-week treatment group, all allografts developed chronic rejection, compared with none in the 12-week group. Syngeneic controls received CsA for 2 (n = 3) and 12 weeks (n = 3), or no immunosuppression (n = 2) in order to exclude the effects of CsA. The first detectable ultrastructural event was slight deposition of electron lucent material in the glomerular basement membrane. Contrary to previous morphological studies, the initial deposition was not subendothelial, but was within the lamina densa itself. Examination of allogeneic grafts with good graft function and syngeneic grafts showed glomerular alterations that were similar to the early changes preceding chronic rejection. The intensity of changes in optimally immunosuppressed allografts was mild, and they were arrested early in the evolving stage of glomerular basement membrane changes. In the suboptimally immunosuppressed allografts with chronic rejection, the glomerular basement membrane changes became more pronounced and extensive in subsequent biopsies. Thus, all recipients in different groups showed similar glomerular alterations, but to different intensities. These results suggest a common pathogenetic mechanism which might be endothelial damage. In chronic rejection, the endothelial damage might be immunologically mediated by rejection episodes and progressive, whereas in syngeneic grafts and in allografts without chronic rejection, perioperative trauma, ischemia, and graft reperfusion may be responsible for the self-limiting glomerular changes.
Animals↗
Congenital ocular motor apraxia in two siblings.
Two siblings whose features met Cogan's classic description of congenital ocular motor apraxia were examined. There was first-degree consanguinity in the family. Each had an absence of voluntary and optically-induced horizontal eye movements and demonstrated classic head thrusting.
Apraxias↗
Mycophenolate mofetil (MMF, RS-61443) inhibits inflammation and smooth muscle cell proliferation in rat aortic allografts.
To investigate the impact of mycophenolate mofetil (MMF) on allograft arteriosclerosis (chronic rejection) in rat aortic allograft model, we administrated MMF 20 mg/kg/day from the day of transplantation and sacrificed the rats at 1-12 months afterwards. MMF significantly suppressed all major histological manifestations of allograft arteriosclerosis, i.e. adventitial inflammation, media necrosis and intimal thickening and cellularity. There was a significant decrease in the replication rate (3H-thymidine incorporation) of inflammatory cells in the adventitia and of smooth muscle cells (SMC) in the media. MMF did not have any major effect on mRNA expression of several growth factors, (determined by polymerase chain reaction with inbuilt glyceraldehyde-3-phosphate dehydrogenase control), which have previously been demonstrated to be elevated in nonimmunosuppressed allografts. Immunoperoxidase staining showed a 40% reduction in the number of adventitial interleukin-2 receptors expressing lymphoid cells in MMF-treated allografts. The intensity of SMC alpha-actin staining was also significantly reduced. As the results suggested that MMF may have a direct antiproliferative effect on SMC, this possibility was investigated in primary SMC cultures in vitro and using the carotid denudation model in vivo. Both approaches showed inhibition of SMC proliferation by MMF. Our results indicate that MMF inhibits histopathological changes of chronic rejection by reducing the immune response and possible replication of SMC.
Animals↗
Chronic renal allograft rejection can be predicted by area under the serum creatinine versus time curve (AUCCr).
Acute rejection is the most important single risk factor for chronic renal allograft rejection. Numerical quantitation of rejection episodes does not take into account the intensity and length of these episodes, both of which may contribute to the severity of chronic rejection. We propose a single numerical parameter for the frequency, intensity and length of acute rejections, the "Area Under the Serum Creatinine versus Time Curve" (AUCCr) using renal allografts between inbred rat strains. Twenty-seven renal transplantations were performed from the DA to WF rat strain. The rats were immunosuppressed with 5 mg/kg body weight of CyA injected s.c. for 1, 2, 3 and 12 weeks, resulting in differing numbers (0-4) of biopsy-confirmed acute rejections of varying intensity (s-cre: 100-448 mumol/L) and length (3-24 days), all of which were reversed with additional CyA treatment. The intensity of chronic changes in graft histology was quantitated using the "Chronic Allograft Damage Index" (CADI). End-point transplant function was quantitated as level of serum creatinine at sacrifice. The AUCCr from 0 to 3 weeks (AUCCr0-3), encompassing the recovery period after operation, free of rejections, did not correlate with the CADI (r = 0.230, P = 0.249). All AUCCr from 3 weeks onwards correlated with the CADI. The best correlation with the CADI was obtained with AUCCr from 3 to 12 weeks (AUCCr3-12) (r = 0.922, P = 0.0001). This interval coincides with the timing of all acute rejection episodes. AUCCr3-12 correlated equally well to end-point transplant function (r = 0.890, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Involvement of sulfhydryl groups in the stable fluorescent derivatization of proteins by o-phthalaldehyde.
Treatment of human alpha-1-proteinase inhibitor (alpha-1-PI) with o-phthalaldehyde (OPA) at pH 8.0 and 25 degrees C, in the absence of added thiol resulted in the formation of a mixed population of fluorescent and non-fluorescent isoindoles. The stoichiometry of isoindole formation was tentatively calculated to be 6:1 for unreduced alpha-1-PI and 10:1 for inhibitor treated with dithioerythritol, implicating not only cysteine but also non-sulfur nucleophilic centres as reaction partners. Despite the apparent involvement of the single cysteine residue in alpha-1-PI in the over-all derivatization process, the extent of fluorescent derivatization was independent of the redox state of the inhibitor. Hence the fluorescing moiety was not a 1-alkylthio-2-alkyl-substituted isoindole, as generally observed. The finding that isoindole formation in proteins is not limited by sulfhydryl content and that fluorescent products may originate from amino acid(s) other than cysteine cautions against interpreting fluorescent derivatization by OPA as evidence for cross-linking of lysine to cysteine residues.
Animals↗
Generation of a Ni(II) binding site by introduction of a histidine cluster in the structure of human glutathione transferase A1-1.
Two mutant forms of human glutathione transferase (GST) A1-1 with affinity for metal ions were constructed by introduction of His residues by site-directed mutagenesis. A mutant, 2-His, contained the mutations Lys84Gln, Asp85His and Glu88His, and another, 5-His, contained the mutations Tyr79His, Asn80His, Lys84His, Asp85His and Glu88His. The mutant proteins were obtained in good yields (40-150 mg per 3 l culture) by heterologous expression in Escherichia coli. The mutant enzymes possessed novel binding affinities for Ni(II) and Zn(II) ions, as demonstrated by immobilized metal ion affinity chromatography. The mutant with two novel His residues (2-His mutant) did not bind as tightly to immobilized Ni(II) as did the mutant with five novel His residues (5-His mutant). When tested for affinity to immobilized Zn(II), only the 5-His mutant remained bound to the column. The affinity of the 5-His mutant for Ni(II) ions in solution was determined by binding experiments in an aqueous polymeric two-phase system. Analysis of the binding curve showed two binding sites per enzyme subunit and a dissociation constant of 6.7 +/- 1.6 mu M. The kinetic constants kcat, Km and kcat/Km for the reaction with glutathione and 1-chloro-2,4-dinitrobenzene were determined by steady-state kinetic analysis and the parameter values for the mutant forms were found to be indistinguishable from those obtained for the wild-type GST A1-1. The differences in surface charge in the mutant proteins as compared with the wild-type enzyme did not alter the pH dependence of kcat. The results provide an alternative method for purification of fully active recombinant GST A1-1 by the introduction of novel metal binding sites. The data also showed that two His residues are sufficient for Ni(II) binding.
Base Sequence↗
Stabile D-peptide analog of insulin-like growth factor-1 inhibits smooth muscle cell proliferation after carotid ballooning injury in the rat.
Restenosis after angioplasty is believed to result from stimulation of smooth muscle cells (SMC) by various growth-promoting factors as a consequence of endothelial injury. In this study we have tested the hypothesis that insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) interaction is a rate-limiting step for SMC replication by blocking this interaction with a synthetic D-amino acid peptide structurally resembling the D-domain of IGF-1. After rat carotid artery denudation, semiquantitative PCR analysis demonstrated a significant elevation of IGF-1, platelet-derived growth factor B, transforming growth factor beta 1, and epidermal growth factor mRNAs 10 days after endothelial injury, concomitantly with the induction of intimal SMC proliferation and intimal thickening. Administration of 10-30 micrograms.kg-1.day-1 of D-analog of IGF-1, devoid of proteolytic degradation in body fluids, reduced intimal SMC replication by 60-70%. The peptide also inhibited [3H]TdR incorporation and [3H]glycine incorporation in cultured SMCs by 60-80%, whereas a "scrambled" control peptide consisting of the same amino acids had no effect. The results suggest that IGF-1/IGF-1R interaction is a rate-limiting step for SMC replication. Blocking of this interaction with stabile D-peptide analog of IGF-1 at the level of IGF-1R may offer an entirely new approach for the prophylaxis and treatment of restenosis after cardiac revascularization procedures.
Amino Acid Sequence↗
A small supernumerary marker chromosome X identified by in situ hybridization.
Cytogenetic analysis of a girl with moderate mental retardation and dysmorphic features revealed a 46,XX/47,XX,+mar karyotype. Fluorescence in situ hybridization using chromosome specific alpha satellite probes showed that the supernumerary marker originated from the X chromosome. To our knowledge, this is the first reported case of a female patient mosaic for a supernumerary small marker chromosome derived from X, and hence mosaic for trisomy of the pericentric region of the X chromosome.
Child↗
Pilomatrixoma of the earlobe.
BACKGROUND: Pilomatrixoma most commonly occurs in the head and neck region, appearing primarily in the first two decades of life. The lesion is described as a tumor with differentiation toward hair cells and surgical excision is the treatment of choice. OBJECTIVE: We report an uncommon localization of a perforating type pilomatrixoma of 5 x 4 x 4 cm in size that developed from the earlobe. METHODS: Histopathological examination revealed pilomatrixoma. Total resection of the tumor was performed. The earlobe was reconstructed by forming a posterior-superior pedicled skin flap. RESULTS: No recurrence was observed and a good cosmetic result was obtained. CONCLUSION: Local recurrence does not generally occur if the tumor is completely removed. The case we present is of interest in having a history of trauma to the region and a relatively rapid growth with perforation of the overlying skin.
Child↗
Role of growth factors in graft vessel disease.
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Animals↗
Chronic renal allograft rejection can be predicted by the surface area under the serum creatinine versus time curve.
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Animals↗
Partial inhibition of allograft arteriosclerosis (chronic rejection) by 15-deoxyspergualin.
15-deoxyspergualin (DSG) is an immunosuppressive drug that suppresses monocyte/macrophage function and/or T cell induction and early differentiation of B lymphocytes. It is as effective as cyclosporine in the prevention of acute rejection. We have investigated the effects of DSG on rat aortic allograft arteriosclerosis (chronic rejection). DSG was administered to the recipient rat at a dose of 0.3-10 mg/kg/day i.p. for 1-3 months, after which recipients were sacrificed. Histological changes were quantitated from paraffin sections. DSG is effective in chronic rejection in rat aortic allografts and reduces all three manifestations in the vascular wall--adventitial inflammation, media necrosis, and intimal thickening. At the dose of 1.0 mg/kg/day we demonstrated significant inhibition of adventitial inflammation from 10.6 point score units (psu) to 4.7 psu (P < 0.05), of media necrosis (P = 0.004) and of intimal thickening from 2.9 psu to 0.8 psu (P = 0.008). The therapeutic window was small in the long-term experiment. Doses of 3-10 mg/kg/day were toxic and 0.3 mg/kg/day was ineffective. In vitro smooth muscle cell proliferation was not inhibited by DSG and in the in vivo carotic denudation model DSG had no inhibitory effects either. These results suggest that DSG works via suppression of the immune/inflammatory response rather than via a direct antiproliferative effect on smooth muscle cells.
Animals↗