Posttransplant lymphoproliferative disorder presenting in the head and neck.

OBJECTIVE: To determine the incidence of focal head and neck posttransplant lymphoproliferative disorder (PTLD) in children, its clinical presentation, associated risk factors, and outcome following treatment. STUDY DESIGN: Retrospective. METHODS: The authors conducted a 5-year retrospective study of 61 children with liver transplants at the University of California, San Francisco. Suspected head and neck lesions were evaluated and biopsies were performed by an otolaryngologist. Diagnosis was made via histologic and immunohistochemical features and in situ Epstein-Barr virus (EBV) localization. RESULTS: Eight patients (13.1%) developed PTLD, five (8.2%) in the head and neck. Four patients had large tonsils, and one presented with airway obstruction from a supraglottic mass. Negative pretransplant EBV serology was a risk factor for PTLD. Treatment consisted of antiviral therapy and decreased immunosuppression. All patients with head and neck PTLD are disease free with excellent liver function. CONCLUSIONS: A high incidence of PTLD was found, with 63% presenting in the head and neck. While Waldeyer's ring is most commonly involved, PTLD may also present in the supraglottis. Adjunctive antiviral therapy and decreased immunosuppression are effective forms of treatment. Given the increasing number of pediatric liver transplants being performed, otolaryngologists should be familiar with PTLD and have a high index of suspicion in this at-risk population.

Thapsigargin stimulates intracellular calcium mobilization and inhibits parathyroid hormone release.

Ca2+ and other divalent cations like Sr2+, Ba2+, and Mg2+ stimulate rapid and sustained increases in intracellular Ca2+ ([Ca2+]i) and 1,4,5-inositol trisphosphate (1,4,5-InsP3) presumably by interacting with recently identified parathyroid cell membrane Ca2+ receptors. We used thapsigargin (THAPS), an inhibitor of the microsomal Ca(2+)-ATPase, to deplete InsP3-sensitive intracellular Ca2+ stores to determine whether sustained increases in [Ca2+]i due to divalent cations require intact cytosolic Ca2+ pools. In Fura 2-loaded parathyroid cells, THAPS produced a gradual increase in [Ca2+]i which reached a steady-state level by 2-3 minutes. The effect of THAPS (3 x 10(-6) M) was substantial with [Ca2+]i, rising from 281 +/- 27 nM at 0.5 mM Ca2+ to a peak value of 684 +/- 30 nM (p < 0.0001). The addition of Sr2+ to cells at 0.5 mM extracellular Ca2+ induced an immediate 2- to 3-fold increase in [Ca2+]i which stabilized at a [Ca2+]i above baseline for > or = 10 minutes. THAPS (3 x 10(-6) M) pretreatment for > or = 5 minutes blocked this sustained-phase increment in [Ca2+]i due to Sr2+. In the absence of extracellular Ca2+, there was a slight but nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not change the levels of 3H-inositol phosphates (InsP3, InsP2, and InsP1) or alter Sr(2+)-induced accumulation of InsP3, InsP2, and InsP1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of high extracellular calcium and strontium on inositol polyphosphates in bovine parathyroid cells.

The addition of Ca2+ or a variety of divalent cations increases intracellular Ca2+ in parathyroid cells and suppresses secretion. Since 1,4,5-inositol trisphosphate (IP3) and 1,3,4,5-inositol tetrakisphosphate (IP4) mediate Ca2+ mobilization in other systems, we examined high Ca(2+)- and Sr(2+)-induced accumulation of IP3 and IP4 isomers by anion-exchange HPLC and measured 1,4,5-IP3 mass in parathyroid cells. Raising extracellular [Ca2+] from 0.5 to 3.0 mM increased 3H-1,4,5-IP3 within 5 s, which was confirmed by mass measurements. 3H-1,3,4-IP3 rose gradually by 10 s and increased for 60 s after the addition of Ca2+. Although we detected no change in 3H-1,3,4,5-IP4, the increase in 3H-1,3,4-IP3 suggests that 3H-1,3,4,5-IP4 was being formed. The addition of 4 mM SrCl2 produced similar changes in 1,4,5-IP3, which were confirmed by mass assay. 3H-1,3,4,5-IP4 did not change. However, Sr2+ induced a gradual increase in 3H-1,3,4-IP3, which remained above control levels for 5 minutes. Isotopic labeling studies in this system may underestimate changes in 1,4,5-IP3 mass, but both mass and radioisotopic analyses indicate that high extracellular Ca2+ and Sr2+ stimulate substantial increases in 1,4,5-IP3 without significant accumulation of 1,3,4,5-IP4. These studies suggest a role for 1,4,5-IP3 in intracellular Ca2+ mobilization by divalent cations in parathyroid cells.