0000000000326701
AUTHOR
Reinhold E. Schmidt
A phase-II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma.
Recent preclinical and clinical studies that have demonstrated antitumor activity of high-dose recombinant interleukin-2 (rIL-2), and animal models that demonstrated a synergistic effect of low-dose cyclophosphamide, led us to study rIL-2 (Cetus Corp., Emeryville, Calif) in a phase II clinical trial in combination with low-dose cyclophosphamide in 32 patients, 18 with malignant melanoma and 14 with renal cell carcinoma. rIL-2 was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for 2 x 5 days in cycles II and III respectively; if tolerated, the dose was increased to a maximum of 6 x 10(6) U m-2 day-1; the cycles, separated by 1 week treatment-free interval…
Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations
Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESU…
Azithromycin Differentially Alters TCR-Activated Helper T Cell Subset Phenotype and Effector Function
In addition to their antibiotic activities, azithromycin (AZM) exhibits anti-inflammatory effects in various respiratory diseases. One of the potent anti-inflammatory mechanisms is through inhibition of CD4+ helper T (Th) cell effector function. However, their impact on specific Th subset is obscure. Herein, we demonstrate the cellular basis of phenotypic and functional alterations associated with Th subsets following AZM treatment in vitro. Using well-characterized Th subset specific chemokine receptors, we report significant suppression of T cell receptor (TCR)-stimulated hyperactivated CCR4+CXCR3+ (Th0) expansion compared to CCR4-CXCR3+ (Th1-like) and CCR4+CXCR3- (Th2-like) cells. Intere…
New loci associated with kidney function and chronic kidney disease
Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea 60 ml/min/1.73 m 2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P 5 × 10 8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or…