Significance of molecular biomarkers in idiopathic pulmonary fibrosis: A mini review

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible condition with poor prognosis that is characterized by a variable clinical course in each patient, which renders it a complex disease with unknown causes. Despite the proven efficacy of novel antifibrotic therapies, including pirfenidone and nintedanib, the diagnosis and follow-up of IPF remain challenging. Hence, the identification of molecular biomarkers for early detection of IPF and to predict biologically determined individual clinical courses, has recently piqued the interest of researchers. Previous studies have demonstrated the diagnostic and prognostic efficacy of blood proteins such as KL-6, Surfactant protein (SP)-A, and SP-D, in patients with IPF. Due to their use in clinical practice in Japan, for approximately twenty years, a significant amount of data about these biomarkers has been accumulated. This paper reviews the recent literature on molecular biomarkers for IPF that have been developed in Japan as well as other potential molecular biomarkers.     

Treatment options for patients with large cell neuroendocrine carcinoma of the lung

Large cell neuroendocrine carcinoma (LCNEC) of the lung is categorized as a variant of large cell carcinomas, and LCNEC tumors display biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. Because patients with LCNEC have a poor prognosis, surgery alone is not sufficient. Multimodality therapies, including adjuvant chemotherapy, appear promising for improved prognosis in patients with LCNEC. In this review article, we discuss treatment options for patients with LCNEC of the lung.     

Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells

BACKGROUND/AIMS: Histamine H2 receptor antagonists are considered to exert their effects on gastric acid secretion more rapidly than proton pump antagonists. However, there are no reports concerning the direct interaction of a histamine H2 receptor antagonist with the human H2 receptor in terms of onset of action. This study aims to characterize how rapidly famotidine and ranitidine, the most widely used histamine H2 receptor antagonists, interact with the human histamine H2 receptor. METHODS: HEK293 cell lines, stably expressing human histamine H2 receptors, were obtained. The dose- and time-dependent effects of famotidine and ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production were analyzed. RESULTS: Ranitidine inhibited both [3H]-tiotidine binding and histamine-stimulated cAMP production more promptly than did famotidine. Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively. [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while the ranitidine Cmax had produced saturation by 15 min. CONCLUSION: Ranitidine inhibits the human histamine H2 receptor very rapidly.     

Effects of recombinant human interleukin-3 on CD34-enriched normal hematopoietic progenitors and on myeloblastic leukemia cells

Induction of proliferation and differentiation in response to recombinant human interleukin-3 (hIL-3) was studied in liquid and semisolid cultures of umbilical cord blood and bone marrow cells that were fractionated by "panning" with anti-My10 antibody according to expression of CD34 antigen. Cells from enriched fractions (70% to 90% CD34+) were found to proliferate strongly in response to hIL-3. Phenotypic analysis and morphologic characterization of the proliferating cells demonstrated a rapid decrease in CD34+ cells and an exponential increase in the number of cells belonging to the neutrophilic, eosinophilic, monocyte/macrophage, and thrombocytic lineages. When combined with recombinant human erythropoietin, burst colonies and cells expressing glycophorin-A were detected, thereby demonstrating the effects of hIL-3 on erythroid progenitors. Further, the development of mixed-erythroid colonies indicated that multipotential cells within CD34-enriched fractions responded to hIL-3. In addition, we examined the effect of hIL-3 on the proliferation of primary acute myeloblastic leukemia cells in liquid culture. We found that hIL-3 was able to induce cell proliferation in a proportion of the cases tested. Heterogeneity of the responses to hIL-3 was in part related to French-American-British classification but could not be correlated with CD34 antigen expression by the leukemic cells. These results indicate that, although the effects of hIL-3 on proliferation and differentiation of cells obtained from normal hematopoietic specimens were primarily borne by CD34+ cells, expression of the CD34 molecule per se is an insufficient condition to determine a growth response to this lymphokine.     

Cardiac sarcoidosis underlies idiopathic dilated cardiomyopathy: importance of mediastinal lymphadenopathy in differential diagnosis.

BACKGROUND: Cardiac sarcoidosis is frequently overlooked or misdiagnosed as idiopathic dilated cardiomyopathy (DCM), primarily because of difficulties in its diagnosis. This is a crucial issue because appropriate therapy with immunosuppressive agents can be initiated if early diagnosis is achieved. METHODS AND RESULTS: Thoracic computed tomography (CT) was retrospectively analyzed in detail with special reference to lymph node swelling (LNS) in the mediastinum of 8 patients diagnosed with idiopathic DCM who underwent left ventriculoplasty (LVP), and were later proven to have active cardiac sarcoidosis by histological evaluation of the resected myocardium. Twenty age-matched patients with idiopathic DCM who also underwent LVP served as controls. On conventional chest radiographs, none of the cardiac sarcoidosis patients exhibited lymph node involvement, including bilateral hilar lymphadenopathy. However, CT demonstrated significant mediastinal LNS in 7 (88%) of them and in only 1 (5%) of the 20 controls. There was a significant difference in the incidence of LNS in the 2 groups (p=0.00005). CONCLUSION: Evaluation of mediastinal lymphadenopathy by CT is an easy and valuable initial screening method for distinguishing cardiac sarcoidosis from idiopathic DCM.