Retinoic acid is an embryonic morphogen and dietary factor that demonstrates chemotherapeutic efficacy in inducing maturation in leukemia cells. Using HL60 model human myeloid leukemia cells, where ...all-trans retinoic acid (RA) induces granulocytic differentiation, we developed two emergent RA-resistant HL60 cell lines which are characterized by loss of RA-inducible G1/G0 arrest, CD11b expression, inducible oxidative metabolism and p47(phox) expression. However, RA-treated RA-resistant HL60 continue to exhibit sustained MEK/ERK activation, and one of the two sequentially emergent resistant lines retains RA-inducible CD38 expression. Other signaling events that define the wild-type (WT) response are compromised, including c-Raf phosphorylation and increased expression of c-Cbl, Vav1, and the Src-family kinases (SFKs) Lyn and Fgr. As shown previously in WT HL60 cells, we found that the SFK inhibitor PP2 significantly increases G1/G0 cell cycle arrest, CD38 and CD11b expression, c-Raf phosphorylation and expression of the aforementioned regulators in RA-resistant HL60. The resistant cells were potentially incapable of developing inducible oxidative metabolism. These results motivate the concept that RA resistance can occur in steps, wherein growth arrest and other differentiation events may be recovered in both emergent lines. Investigating the mechanistic anomalies in resistant cell lines is of therapeutic significance and helps to mechanistically understand the response to retinoic acid's biological effects in WT HL60 cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tracheobronchial fibromas are very rare, locally-invasive tumors of the airways. Fewer than 30 cases have been reported within the English-speaking literature. Historically, these neoplasms have been ...diagnosed as isolated endobronchial masses, with affected patients presenting with wheezing, cough, stridor, hemoptysis, dyspnea, or pneumonia. We report the case of 39-year-old man with multiple, synchronous endobronchial fibromas causing unilobar emphysema. A computed tomographic scan and bronchoscopy with biopsy were performed preoperatively to diagnose these lesions in the orifices of the anterior segment and the lingula within the left upper lobe. The patient underwent successful video-assisted left upper lobectomy, without recurrence at 3 years. This is the first report of a synchronous presentation of multiple pulmonary endobronchial fibromas within the same patient and the first report of endobronchial fibroma presenting as unilobar air trapping. Recognition of the unusual presentation of this uncommon pathology can lead to timely intervention.
Inflammatory pseudotumor (IPT), also known as plasma cell granuloma, is a rare lesion of unknown etiology that occurs in many organs, especially in the lung. Here we report five cases of IPT arising ...in pulmonary artery mimicking chronic thromboembolic disease, not previously documented in the literature. Those cases were identified at our institute among over 2500 pulmonary endarterectomy (PEA) specimens acquired from 2000 to 2017. The cohort included three men and two women with a median age of 41 years (range: 23–54). All patients presented with dyspnea and radiologic findings of pulmonary artery thromboembolism, some concerning for intimal sarcoma. The duration between disease onset and PEA ranged from 6 months to approximately 3 years. Histologically, all cases showed proliferation of spindle cells with marked inflammatory infiltrates composed predominantly of plasma cells, histiocytes, and small lymphocytes. Ancillary studies were performed in each case and ruled out other possibilities, such as sarcoma, lymphoma, plasmacytoma, IgG4‐related disease, and infection. IPT arising in pulmonary artery presenting clinically as acute or chronic thromboembolic disease is very unusual, in which clinical data, radiographic findings, and histopathologic features have to be integrated for reaching the proper diagnosis.
There are few studies looking at the pulmonary circulation in subjects with bronchiectasis. We aimed to evaluate the intraparenchymal pulmonary vascular structure, using noncontrast chest computed ...tomography (CT), and its clinical implications in smokers with radiographic bronchiectasis. Visual bronchiectasis scoring and quantitative assessment of the intraparenchymal pulmonary vasculature were performed on CT scans from 486 smokers. Clinical, lung function and 6-min walk test (6MWT) data were also collected. The ratio of blood vessel volume in vessels <5 mm
in cross-section (BV5) to total blood vessel volume (TBV) was used as measure of vascular pruning, with lower values indicating more pruning. Whole-lung and lobar BV5/TBV values were determined, and regression analyses were used to assess the differences in BV5/TBV between subjects with and without bronchiectasis. 155 (31.9%) smokers had bronchiectasis, which was, on average, mild in severity. Compared to subjects without bronchiectasis, those with lower-lobe bronchiectasis had greater vascular pruning in adjusted models. Among subjects with bronchiectasis, those with vascular pruning had lower forced expiratory volume in 1 s and 6MWT distance compared to those without vascular pruning. Smokers with mild radiographic bronchiectasis appear to have pruning of the distal pulmonary vasculature and this pruning is associated with measures of disease severity.
Originally regarded as a rare affliction notable for its distinctive evolution to “bronze diabetes,” hereditary hemochromatosis is now recognized as the most common genetic disorder in populations of ...European ancestry. Recent advances in our understanding of iron metabolism, the identification of the gene responsible for hemochromatosis, and large epidemiologic studies have changed the diagnostic approach toward patients with hereditary hemochromatosis and other forms of iron overload. This article reviews the pathophysiology, epidemiology, clinical features, diagnostic testing, and management of hemochromatosis for the primary care provider.
Abstract Purpose To assess the effect of radiation dose reduction on the appearance and visual quantification of specific CT patterns of fungal infection in immuno-compromised patients. Materials and ...methods Raw data of thoracic CT scans (64 × 0.75 mm, 120 kVp, 300 reference mAs) from 41 consecutive patients with clinical suspicion of pulmonary fungal infection were collected. In 32 patients fungal infection could be proven (median age of 55.5 years, range 35–83). A total of 267 cuboids showing CT patterns of fungal infection and 27 cubes having no disease were reconstructed at the original and 6 simulated tube currents of 100, 40, 30, 20, 10, and 5 reference mAs. Eight specific fungal CT patterns were analyzed by three radiologists: 76 ground glass opacities, 42 ground glass nodules, 51 mixed, part solid, part ground glass nodules, 36 solid nodules, 5 lobulated nodules, 6 spiculated nodules, 14 cavitary nodules, and 37 foci of air-space disease. The standard of reference was a consensus subjective interpretation by experts whom were not readers in the study. Results The mean sensitivity and standard deviation for detecting pathological cuboids/disease using standard dose CT was 0.91 ± 0.07. Decreasing dose did not affect sensitivity significantly until the lowest dose level of 5 mAs (0.87 ± 0.10, p = 0.012). Nodular pattern discrimination was impaired below the dose level of 30 reference mAs: specificity for fungal ‘mixed nodules’ decreased significantly at 20, 10 and 5 reference mAs ( p < 0.05). At lower dose levels, classification drifted from ‘solid’ to ‘mixed nodule’, although no lesion was missed. Conclusion Our simulation data suggest that tube current levels can be reduced from 300 to 30 reference mAs without impairing the diagnostic information of specific CT patterns of pulmonary fungal infections.
This article provides a guideline for radiology residency programs to prepare and respond to the impact of coronavirus disease 2019, by offering specific examples from three programs, and provides a ...list of resources for distance learning and maintaining well-being.
•We surveyed common myeloid leukemia cell lines undergoing differentiation therapy.•Lineage progression in induced leukemia cell lines differs from nonmalignant cells.•Aberrant transcription factor ...expression occurs in acute myeloid leukemia cells.•A given differentiation therapy elicits different effects in specific cell lines.•Although potent tools, cell lines must be employed with circumspection.
Transcription factors that drive non-neoplastic myelomonocytic differentiation are well characterized but have not been systematically analyzed in the leukemic context. We investigated widely used, patient-derived myeloid leukemia cell lines with proclivity for differentiation into granulocytes by retinoic acid (RA) and/or monocytes by 1,25-dihyrdroxyvitamin D3 (D3). Using K562 (FAB M1), HL60 (FAB M2), RA-resistant HL60 sublines, NB4 (FAB M3), and U937 (FAB M5), we correlated nuclear transcription factor expression to immunophenotype, G1/G0 cell cycle arrest and functional inducible oxidative metabolism. We found that myelomonocytic transcription factors are aberrantly expressed in these cell lines. Monocytic-lineage factor EGR1 was not induced by D3 (the monocytic inducer) but instead by RA (the granulocytic inducer) in lineage bipotent myeloblastic HL60. In promyelocytic NB4 cells, EGR1 levels were increased by D3, while Gfi-1 expression (which promotes the granulocytic lineage) was upregulated during D3-induced monocytic differentiation in HL60, and by RA treatment in monocytic U937 cells. Furthermore, RARα and VDR expression were not strongly correlated to differentiation. In response to different differentiation inducers, U937 exhibited the most distinct transcription factor expression profile, while similarly mature NB4 and HL60 were better coupled. Overall, the differentiation induction agents RA and D3 elicited cell-specific responses across these common FAB M1-M5 cell lines.
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