Suppressor activity and potency among regulatory T cells is discriminated by functionally active CD44

CD4CD25(+) regulatory T cells are fundamental to the maintenance of peripheral tolerance and have great therapeutic potential. However, efforts in this regard have been hampered by limiting cell numbers in vivo, an anergic phenotype in vitro, and a rudimentary understanding of the molecular basis for the functional state of CD4CD25(+) regulatory T cells (Treg cells). Here we show heterogeneity of suppressor activity among activated CD4CD25(+) Treg cells and that, within this population, the functionally active, hyaluronan-binding form of CD44 (CD44(act)) is strikingly correlated with superior suppressor activity. Within 16 hours after in vitro activation, CD44(act) can discriminate enhanced suppressive function in in vitro proliferation assays and in an in vivo bone marrow engraftment model. The expression of other surface markers and that of Foxp3 are similar irrespective of hyaluronan binding and associated degree of suppressor potency. Furthermore, CD44(act) is induced on resting CD4CD25(+) cells in vivo by allogeneic stimulation, with similar functional consequences. These results reveal a cell-surface marker that delineates functional activity within a population of activated CD4CD25(+) regulatory T cells, thereby providing a potential tool for identifying regulatory activity and enriching for maximal suppressor potency.     

Accuracy and Diagnostic Sensitivity of Radiographic Absorptiometry of the Second Metacarpal

The accuracy of a radiographic absorptiometry (RA) technique called digital image processing (DIP), discriminative ability of RA for osteoporotic fracture, and the relationship between RA and dual X-ray absorptiometry (DXA) of the spine and forearm were evaluated. We measured 16 cadaver hands, 32 healthy non-black premenopausal women, 39 healthy non-black postmenopausal women, and 35 non-black osteoporotic postmenopausal females. The overall correlation between the ash weights of the entire metacarpal and the DIP values was excellent (r = 0.954, P < 0.001, SEE = 0.14, CV = 6.4%). Short-term precision error of DIP was 3.5%. Age-related bone loss determined by DIP is comparable to that of spinal and forearm DXA: annual BMD decreases were 0.46% for DIP, 0.45% for forearm, and 0.32% for the spine. DIP of the 2nd metacarpal shows a gradient of risk for spinal fracture only slightly below that of forearm DXA, but substantially below that of spinal DXA. Age-adjusted odds ratios were 1.81 for RA, 2.45 for spinal DXA, and 1.94 for forearm DXA. Received: 2 July 1996 / Accepted: 2 July 1997     

Intracranial metastatic parathyroid carcinoma: case report

OBJECTIVE AND IMPORTANCE: Parathyroid carcinoma is a rare entity, and fewer than 200 cases have been described. It is a slowly progressive disease characterized by frequent recurrences and local metastases. Most patients with parathyroid carcinoma die from metabolic complications of hyperparathyroidism. Five-year survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who undergo surgery for hypercalcemia. A review of the literature revealed only one other reported case of metastatic intracranial parathyroid carcinoma, in a patient who experienced local recurrence and metastatic disease when she was diagnosed with an intracranial lesion. CLINICAL PRESENTATION: We report the case of a 44-year-old African-American man with recent-onset, right lower-extremity weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated enhancing left mesial frontoparietal mass. A systemic Cardiolite study demonstrated a single focus of radiotracer uptake in this region. No abnormal uptake was demonstrated in the neck or elsewhere. INTERVENTION: The patient underwent a frameless stereotactic interventional magnetic resonance imaging-guided resection via a parasagittal interhemispheric approach. Pathological findings were consistent with parathyroid carcinoma. After resection, his right lower-extremity weakness and secondary hyperparathyroidism resolved. CONCLUSION: The typical natural history of parathyroid carcinoma concludes with death from complications of hyperparathyroidism. This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications. In this patient, intraoperative magnetic resonance imaging was helpful to ensure complete resection.     

Diffuse alveolar hemorrhage and pulmonary capillaritis due to propylthiouracil

Propylthiouracil (PTU) has recently been observed to be associated with antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis, resulting in crescentic glomerulonephritis and, infrequently, diffuse alveolar hemorrhage (DAH). We describe a case of a 23-year-old pregnant woman who developed a perinuclear ANCA and antimyeloperoxidase-positive small vessel vasculitis manifesting as DAH and crescentic glomerulonephritis after she began taking PTU. An open lung biopsy was consistent with pulmonary capillaritis. She responded to corticosteroid therapy and discontinuation of PTU. DAH can be caused by pulmonary capillaritis, bland hemorrhage, or diffuse alveolar damage. To our knowledge, this represents the first documentation of an underlying pulmonary capillaritis in a case of PTU-induced DAH.