Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506. Mean survival time was increased significantly in these animals (p < 0.007) to 40.6 ± 25.6 days as compared with either untreated rats (10.0 ± 2.7 days) or rats treated with 0.04 mg/kg FK-506 alone (13.7 ± 4.2 days). Histologic examination demonstrated a significant reduction in the cellular infiltrate in rats treated with PEG-SOD plus FK-506, as compared with recipients treated with either agent alone or left untreated. Our results therefore suggest a potential approach to reducing immunosuppression in transplantation. (J ALLERGY CLIN IMMUNOL 1995;95:1276-81.)     

Establishment and characterization of αs1-casein–specific T-cell lines from patients allergic to cow’s milk: Unexpected higher frequency of CD8 T-cell lines

To study cow’s milk allergy at the cellular level, we assessed the reactivity of peripheral blood mononuclear cells from patients allergic to cow’s milk to α_s1-casein, which is one of the major allergens in cow’s milk. Proliferation of the cells to α_s1-casein activation showed a rather weak response. Therefore to understand T-cell reactivity to α_s1-casein in more detail, we prepared α_s1-casein–specific T-cell lines from patients allergic to cow’s milk and established 26 T-cell lines. These T-cell lines could be classified into three groups by analyzing their surface marker expression: those containing predominantly CD4⁺CD8^- T cells, those containing both CD4⁺CD8^- and CD4^-CD8⁺ T cells, and those containing predominantly CD4^-CD8⁺ T cells. The CD8⁺ T cells were obtained at an unexpectedly higher frequency from the patients. These T-cell lines produced interferon-γ and IL-4. These results suggest that CD8⁺ T cells specific for α_s1-casein and CD4⁺ T cells were primed by the stimulation with α_s1-casein in patients allergic to milk and that both T cells may play a key role in the onset, progression of, or recovery from cow’s milk allergy. (J ALLERGY CLIN IMMUNOL 1996;97:1342-9.)     

Modification of T-cell receptor Vβ repertoire in response to allergen stimulation in peanut allergy

Background: Peanut is one of the most common foods causing allergic reactions and is the most common cause of fatal and near-fatal food-related anaphylaxis. Little is known of the immunologic mechanisms that underlie peanut allergy. Objectives: In this study we examined clonality of the T-cell response (TCR) to peanut in MHC class II identical, peanut allergy–discordant sibling pairs. Methods: Four sibling pairs were investigated. The TCR repertoire was analyzed before and after in vitro stimulation of PBMCs with crude peanut or PHA, as control for general/nonspecific reactivity. Eighteen TCR-Vβ families were examined by flow cytometry. Where significant differences in incidence of particular TCR-Vβ families were observed, PCR familyspecific cDNA amplification and gene scanning were performed. Results: After stimulation with peanut, no selective expansion of any TCR-Vβ subpopulation was observed with flow cytometry, in either the peanut-allergic or nonallergic siblings, with the exception of 1 peanut-allergic subject who demonstrated a significant increase of TCR-Vβ11⁺ cells (0.3%-5.9% of the total CD3⁺ cells). However, gene scanning revealed predominant single-size PCR products for TCRBV11 in all peanut-allergic subjects after peanut stimulation. TCRBV11 polyclo-nality was observed in allergic and nonallergic subjects before peanut stimulation and in nonallergic subjects after peanut stimulation. In comparison, all subjects, before and after stimulation with peanut, showed polyclonality for TCRBV2.Conclusions: Our results argue for clonal or oligoclonal TCRs to crude peanut and indicate that changes in the TCRBV11 subpopulation are restricted to peanut-allergic subjects after stimulation with crude peanut allergen. (J Allergy Clin Immunol 2001;107:1089-94.)     

Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.     

Immunochemical characterization of edible bird’s nest allergens

Background: We have previously described anaphylaxis induced by edible bird’s nest (BN) and demonstrated that this condition is IgE mediated. Objectives: This study aimed at describing the immunochemical properties of the BN allergens. Comparative studies between 3 commercially available sources (according to the country of origin) of BN were also made. Methods: Crude extracts of commercially available processed BN from Sarawak (Malaysia), Thailand, and Indonesia and fresh unprocessed BN from the caves of Sarawak were obtained by means of aqueous extraction. Specific IgE toward these sources were determined by using fluorescence allergosorbent tests (FASTs). Cross-reactivity studies between the 3 sources of commercially available processed BN were carried out by means of FAST inhibition. Immunochemical characterization by means of IgE immunoblot, periodate treatment, and heat stability studies were carried out on fresh unprocessed BN from Sarawak. Results: Serum from allergic patients showed differences in IgE binding to the 3 sources of commercially available BN, with the highest levels of specific IgE recorded with the Sarawak source (P < .0001). Of these, only the Sarawak and Thailand sources showed considerable cross-reactivity. Further work on the unprocessed fresh Sarawak source identified a putative 66-kd major allergen containing several isoforms. Periodate treatment resulted in loss of IgE binding. Despite a progressive decline in the molecular weights of allergens on SDS-PAGE with increasing periods of boiling, IgE binding, as assessed by means of FAST, was not affected. N-terminal sequence of the major putative allergen (66 kd) showed homology to a domain of an ovoinhibitor precursor in chicken (SWISS-PROT accession No. P10184). Conclusions: We have described the immunochemical properties of BN allergens. Edible BN from different sources are allergenically dissimilar. The putative major allergen is a 66-kd protein. (J Allergy Clin Immunol 2001;107:1082-8.)     

Granulocytic sarcoma occurring in the maxillary gingiva demonstrated by magnetic resonance imaging

We report the case of a 43-year-old woman presenting with a painless swelling that had developed over 8 months in the maxillary labial vestibule. An oral examination revealed an exophytic, firm, black-pigmented lesion measuring 3.5 x 1.5 cm that bled on palpation. Periapical radiographs showed a slightly enlarged periodontal ligament space of the left central incisor and bone resorption in the region of the missing lateral incisor. Panoramic and other conventional radiographs showed no obvious lytic area, and a magnetic resonance imaging examination demonstrated a low signal intensity lesion on both the T1-weighted and the T2-weighted images. Therefore, granulocytic sarcoma was suspected.Granulocytic sarcoma of the oral cavity is a rare condition, and its diagnosis is usually difficult. Increased awareness of this entity may minimize misinterpretation of radiographic and clinical findings and can assist suitable treatment planning that is essential to this pathosis.     

Effects of recycling on the mechanical properties and the surface topography of nickel-titanium alloy wires

The purpose of this study was to investigate the changes in mechanical properties, surface topography, and frictional forces of various nickel-titanium wires after recycling. Three types of nickel-titanium wires were separated into 3 groups: as-received condition (T0, control group), treated in artificial saliva for 4 weeks (T1), and treated in artificial saliva and autoclaved (T2). Strength changes were observed by tensile testing, and surface topography was assessed by scanning electron microscope and 3-D profilogram. Frictional coefficients were tested by friction test, and fatigue by bending fatigue test. Our findings showed that there were no statistically significant differences between the wires in maximum tensile strength, elongation rate, modulus of elasticity, and bending fatigue. Two wires demonstrated increased pitting and corrosion after recycling. The same 2 wires also demonstrated significantly greater surface roughness and maximum frictional coefficients compared with the control wires (P <.05), but the third wire showed no significant difference. However, surface roughness and frictional coefficient of the 2 wires after recycling were not greater than those of the third wire before treatment. Recycling increased the surface roughness and friction coefficients, but these seemed to have limited clinical significance.     

Transforming growth factor-β in breast milk: A potential regulator of atopic disease at an early age

Background: According to data from animal and in vitro studies, transforming growth factor-β (TGF-β) has a crucial effect on 2 essential parts of the mucosal immune system: IgA production and oral tolerance induction. Objective: We sought to ascertain whether TGF-β in breast milk is associated with specific IgA production and atopic disease in human subjects. Methods: Forty-seven infants with several atopic family members were followed during their first year of life. The concentrations of TGF-β1 and TGF-β2 in maternal colostrum, mature milk, and the infants’ sera were determined. The enzyme-linked immunospot assay was used to assess the infants’ specific IgA production in response to β-lactoglobulin, casein, gliadin, and ovalbumin. Results: At 12 months, atopic dermatitis was confirmed in 29 of 47 infants; in 11, atopic disease had begun during exclusive breast-feeding (preweaning onset), whereas in 18 the disease manifested itself after weaning (postweaning onset). The concentrations of both TGF-β1 and TGF-β2 were higher in maternal colostrum, but not in mature milk and infants’ serum, in infants with postweaning-onset atopic disease compared with those with preweaning-onset disease (P = .0008 and P = .015, respectively). The concentration of TGF-β2 was, and that of TGF-β1 tended to be, higher in the colostrum of mothers whose infants had specific IgA-secreting cells at 3 months in response to at least one of the dietary antigens tested compared with those who did not have such cells (P = .048 and P = .076, respectively). Conclusion: TGF-β in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects. (J Allergy Clin Immunol 1999;1251-7.)     

Rigid versus wire fixation for mandibular advancement: Skeletal and dental changes after 5 years

The bilateral sagittal split osteotomy (BSSO) is the most common surgical procedure for the correction of mandibular retrognathism. Commonly, the proximal and distal segments are fixated together with either wire or rigid screws or plates. The purpose of this study was to compare long-term (5 years) skeletal and dental changes between wire and rigid fixation after BSSO. In this multisite, prospective, randomized clinical trial, the rigid fixation group received three 2-mm bicortical position screws, and the wire fixation group received inferior border wires and 6 weeks of skeletal maxillomandibular fixation with 24-gauge wires. Cephalometric films were obtained 2 weeks before surgery and at 1 week, 8 weeks, 6 months, 1 year, 2 years, and 5 years after surgery. Linear cephalometric changes were referenced to a cranial base coordinate system. Before surgery, both groups were comparable with respect to linear and angular measurements of craniofacial morphology. Both groups underwent similar surgical changes. Skeletal and dental movements occurred in both groups throughout the study period. Five years after surgery, the wire group had 2.2 mm (42%) of sagittal skeletal relapse, while the rigid group remained unchanged from immediately postsurgery. Surprisingly, at 5 years, both groups had similar changes in overbite and overjet. This was attributed to dental changes in the maxillary and mandibular incisors. Although rigid fixation is more stable than wire fixation for maintaining the skeletal advancement after a BSSO, the incisor changes made the resultant occlusions of the 2 groups indistinguishable.     

Predicting lower lip and chin response to mandibular advancement and genioplasty

The purposes of this retrospective study were to examine the multidimensional nature of soft tissue changes associated with mandibular advancement and genioplasty and to develop predictive models. Longitudinal lateral cephalograms of 62 nongrowing patients (27 men and 35 women) were taken in centric relation with the lips in repose within 4 weeks before surgery and at least 6 months postoperatively (median postsurgical duration was 11 months). The mandibular incisor and pogonion were advanced surgically approximately 6 mm and 11 mm, respectively. The lower lip lengthened slightly (2.5 +/- 3.8 mm), and its surface contour straightened because of thinning at labrale inferior (-2.8 +/- 2.0 mm); there was a slight thickening at the labiomental fold (1.0 +/- 2.3 mm) and a slight thinning at soft tissue pogonion (-0.8 +/- 2.2 mm). Multiple regression models (explaining from 80% to 94% and 66% to 82% of the variation for horizontal and vertical movements, respectively) showed that soft tissue response to advancement surgery depended on pretreatment tissue thickness, horizontal skeletal movement, vertical skeletal movement, and the position of the maxillary incisors. Similar amounts of variation were explained when the models were applied to an independent validation sample of 15 subjects. It was concluded that lower lip and chin response to mandibular advancement and genioplasty is multifactorial but can be accurately and reliably predicted.