Phenytoin and carbamazepine are rarely associated with serious hematologic side effects but can include impairment of either humoral or cell-mediated immunity. We describe a patient who developed severe granulocytopenia while taking phenytoin. The phenytoin was replaced by carbamazepine and the patient subsequently developed erythroid hypoplasia, neutropenia and persistent thrombocytopenia. In vitro studies demonstrated a phenytoin-dependent antigranulocyte antibody directly implicating phenytoin in the leukopenia. An extremely high titre of platelet-associated IgG was found which was independent of the presence of carbamazepine. Autoantibodies directed against the patient's red cells, granulocytes and lymphocytes were also demonstrated. In vitro marrow culture studies failed to detect cellular or humoral inhibitors and were suggestive of a stem cell defect. These studies indicate that anticonvulsant therapy can result in sustained humoral abnormalities as well as in nonimmune mediated marrow suppression.
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http://dx.doi.org/10.1159/000205599 | DOI Listing |
J Clin Invest
January 2025
Department of Medicine, University of California San Francisco, San Francisco, United States of America.
Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment, which express the protein thrombospondin-1 that functionally activates TGF-beta to cause vascular disease.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Herlev Hospital, Herlev, Denmark
Background: Arginase-1 (Arg1) expressing tumor-associated macrophages (TAMs) may create an immune-suppressive tumor microenvironment (TME), which is a significant challenge for cancer immunotherapy. We previously reported the existence of Arg1-specific memory T cells among peripheral blood mononuclear cells (PBMCs) and described that Arg-1-based immune modulatory vaccines (IMVs) control tumor growth and alter the M1/M2 macrophage ratio in murine models of cancer. In the present study, we investigated how Arg1-specific T cells can directly target TAMs and influence their polarization.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Nonunion is a significant complication in fracture management for surgeons. Salvianolic acid A (SAA), derived from the traditional Chinese plant Salviae miltiorrhizae Bunge (Danshen), exhibits notable anti-inflammatory and antioxidant properties. Although studies have demonstrated its ability to promote osteogenic differentiation, the exact mechanism of action remains unclear.
View Article and Find Full Text PDFJ Orthop Translat
January 2025
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
Background: RANKL and SCLEROSTIN antibodies have provided a strong effective choice for treating osteoporosis in the past years, which suggested novel molecular target identification and therapeutic strategies development are important for the treatment of osteoporosis. The therapeutic effect of verapamil, a drug previously used for cardiovascular diseases, on diabetes was due to the inhibition of TXNIP expression, which has also been reported as a target in mice osteoporosis. Whether verapamil-inhibited TXNIP expression is related to osteoporosis and how it works on the molecular level is worthy to be explored.
View Article and Find Full Text PDFEMBO Rep
January 2025
Department of Oncological Sciences and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
To directly examine the interplay between mutant p53 or Mdm2 and wild type p53 in gene occupancy and expression, an integrated RNA-seq and ChIP-seq analysis was performed in vivo using isogenically matched mouse strains. Response to radiation was used as an endpoint to place findings in a biologically relevant context. Unexpectedly, mutant p53 and Mdm2 only inhibit a subset of wild type p53-mediated gene expression.
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