Historically Black Schools of Medicine Radiology Residency Programs: Contributions and Lessons Learned.

Introduction: Black radiologists remain significantly underrepresented in the radiology workforce, despite a 1973 plea by Black radiologists of the National Medical Association to increase training programs for minority radiologists.

Objective: The authors provide a qualitative narrative that highlights the radiology residency programs of three historically Black schools of medicine (HBSOM) in the U.S.

Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease.

Niemann-Pick C (NPC) disease is due to loss of NPC1 or NPC2 protein function that is required for unesterified cholesterol transport from the endosomal/lysosomal compartment. Though lung involvement is a recognized characteristic of Niemann-Pick type C disease, the pathological features are not well understood. We investigated components of the surfactant system in both NPC1 mutant mice and felines and in NPC2 mutant mice near the end of their expected life span.

Keratinocyte growth factor and glucocorticoid induction of human peroxiredoxin 6 gene expression occur by independent mechanisms that are synergistic.

Aims: Peroxiredoxin 6 (Prdx6), a 1-cys Prdx has both peroxidase and phospholipase A2 activities, protecting against oxidative stress and regulating pulmonary surfactant phospholipid metabolism. This study determined the mechanism by which keratinocyte growth factor (KGF) and the glucocorticoid analogue, dexamethasone (Dex), induce increased Prdx6 expression.

Results: Transcriptional activation by KGF in both A549 lung adenocarcinoma cells and rat lung alveolar epithelial type II (ATII) cells utilizes an antioxidant response element (ARE), located between 357 and 349 nucleotides before the PRDX6 translational start, that is also necessary for upregulation of the human PRDX6 promoter in response to oxidative stress.

Stereoscopic digital mammography: improved specificity and reduced rate of recall in a prospective clinical trial.

Purpose: To compare stereoscopic digital mammography (DM) with standard DM for the rate of patient recall and the detection of cancer in a screening population at elevated risk for breast cancer.

Materials And Methods: Starting in September 2004 and ending in December 2007, this prospective HIPAA-compliant, institutional review board-approved screening trial, with written informed consent, recruited female patients at elevated risk for breast cancer (eg, personal history of breast cancer or breast cancer in a close relative). A total of 1298 examinations from 779 patients (mean age, 58.

Characterization of the Niemann-Pick C pathway in alveolar type II cells and lamellar bodies of the lung.

The Niemann-Pick C (NPC) pathway plays an essential role in the intracellular trafficking of cholesterol by facilitating the release of lipoprotein-derived sterol from the lumen of lysosomes. Regulation of cellular cholesterol homeostasis is of particular importance to lung alveolar type II cells because of the need for production of surfactant with an appropriate lipid composition. We performed microscopic and biochemical analysis of NPC proteins in isolated rat type II pneumocytes.

Cytoskeleton disruption in J774 macrophages: consequences for lipid droplet formation and cholesterol flux.

Macrophages store excess unesterified cholesterol (free, FC) in the form of cholesteryl ester (CE) in cytoplasmic lipid droplets. The hydrolysis of droplet-CE in peripheral foam cells is critical to HDL-promoted reverse cholesterol transport because it represents the first step in cellular cholesterol clearance, as only FC is effluxed from cells to HDL. Cytoplasmic lipid droplets move within the cell utilizing the cytoskeletal network, but, little is known about the influence of the cytoskeleton on lipid droplet formation.

Early alveolar epithelial dysfunction promotes lung inflammation in a mouse model of Hermansky-Pudlak syndrome.

Rationale: The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early disease mediators.

Objectives: To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1.

Methods: Mice with mutations in both HPS1/pale ear and HPS2/AP3B1/pearl (EPPE mice) were studied longitudinally.

Role of the PI3-kinase signaling pathway in trafficking of the surfactant protein A receptor P63 (CKAP4) on type II pneumocytes.

Surfactant protein A (SP-A) plays an important role in the maintenance of lung lipid homeostasis. Previously, an SP-A receptor, P63 (CKAP4), on type II pneumocyte plasma membranes (PM) was identified by chemical cross-linking techniques. An antibody to P63 blocked the specific binding of SP-A to pneumocytes and the ability of SP-A to regulate surfactant secretion.

Pathway to lamellar bodies for surfactant protein A.

Alveolar surfactant protein A (SP-A) is endocytosed by type II epithelial cells through clathrin-dependent uptake and targeted to lamellar bodies for resecretion. However, the mechanism for secretion of newly synthesized SP-A, whether regulated exocytosis of lamellar bodies or constitutive secretion, is unresolved. If it is the latter, lamellar body SP-A would represent endocytosed protein.

P63 (CKAP4) as an SP-A receptor: implications for surfactant turnover.

Surfactant protein-A (SP-A) plays an important role in the clearance of surfactant from the lung alveolar space and in the regulation of surfactant secretion and uptake by type II pneumocytes in culture. Two pathways are important for the endocytosis of surfactant by type II cells and the intact lung, a receptor-mediated clathrin-dependent pathway and a non-clathrin, actin-mediated pathway. The critical role of the clathrin/receptor-mediated pathway in normal mice is supported by the finding that SP-A gene-targeted mice use the actin-dependent pathway to maintain normal clearance of surfactant.

Reed-Sternberg cells in breast FNA of a patient with left breast mass.

Hodgkin's lymphoma is a potentially curable malignancy of the lymphatic system characterized by a variable number of scattered and large mononucleated and multinucleated tumor cells, the Hodgkin and Reed-Sternberg cells residing in an abundant heterogeneous admixture of non-neoplastic inflammatory cells. It represents approximately 30% of all lymphomas according to the World Health Organization (WHO). Patients with Hodgkin's lymphoma typically present with painless peripheral adenopathy, fever, night sweats, and weight loss.

15(S)-Lipoxygenase-1 associates with neutral lipid droplets in macrophage foam cells: evidence of lipid droplet metabolism.

15(S)-lipoxygenase-1 (15-LO-1) was present in the whole-cell homogenate of an acute human monocytic leukemia cell line (THP-1). Additionally, 15-LO-1 was detected on neutral lipid droplets isolated from THP-1 foam cells. To investigate if 15-LO-1 is active on lipid droplets, we used the mouse leukemic monocytic macrophage cell line (RAW 264.

Role of P63 (CKAP4) in binding of surfactant protein-A to type II pneumocytes.

We have recently described a putative receptor for lung surfactant protein-A (SP-A) on rat type II pneumocytes. The receptor, P63, is a 63-kDa type II transmembrane protein. Coincubation of type II cells with P63 antibody (Ab) reversed the inhibitory effect of SP-A on secretagogue-stimulated surfactant secretion from type II cells.

Surfactant protein-A plays an important role in lung surfactant clearance: evidence using the surfactant protein-A gene-targeted mouse.

Previous studies with the isolated perfused rat lung showed that both clathrin- and actin-mediated pathways are responsible for endocytosis of dipalmitoylphosphatidylcholine (DPPC)-labeled liposomes by granular pneumocytes in the intact lung. Using surfactant protein-A (SP-A) gene-targeted mice, we examined the uptake of [(3)H]DPPC liposomes by isolated mouse lungs under basal and secretagogue-stimulated conditions. Unilamellar liposomes composed of [(3)H]DPPC: phosphatidylcholine:cholesterol:egg phosphatidylglycerol (10:5:3:2 mol fraction) were instilled into the trachea of anesthetized mice, and the lungs were perfused (2 h).

Expression and biological activity of ABCA1 in alveolar epithelial cells.

The mechanisms used by alveolar type I pneumocytes for maintenance of the lipid homeostasis necessary to sustain these large squamous cells are unknown. The processes may involve the ATP-binding cassette transporter A1 (ABCA1), a transport protein shown to be crucial in apolipoprotein A-I (apoA-I)-mediated mobilization of cellular cholesterol and phospholipid. Immunohistochemical data demonstrated the presence of ABCA1 in lung type I and type II cells and in cultured pneumocytes.

Identification and characterization of p63 (CKAP4/ERGIC-63/CLIMP-63), a surfactant protein A binding protein, on type II pneumocytes.

Surfactant protein A (SP-A) binds to alveolar type II cells through a specific high-affinity cell membrane receptor, although the molecular nature of this receptor is unclear. In the present study, we have identified and characterized an SP-A cell surface binding protein by utilizing two chemical cross-linkers: profound sulfo-SBED protein-protein interaction reagent and dithiobis(succinimidylpropionate) (DSP). Sulfo-SBED-biotinylated SP-A was cross-linked to the plasma membranes isolated from rat type II cells, and the biotin label was transferred from SP-A to its receptor by reduction.

Pulmonary abnormalities due to ABCA1 deficiency in mice.

Mice gene targeted for ATP-binding cassette transporter A1 (ABCA1; Abca1(-/-)) have been shown to have low-serum high-density lipoprotein and abnormal lung morphology. We examined alterations in the structure and function of lungs from -/- mice (DBA1/J). Electron microscopy of the diseased mouse lung revealed areas of focal disease confirming previous results (47).

Pathways for clearance of surfactant protein A from the lung.

Uptake and degradation of (125)I-surfactant protein A (SP-A) over a 1-h period was studied in alveolar cells in culture and in isolated perfused lungs to elucidate the mechanism for clearance of the protein from the alveolar space. Specific inhibitors of clathrin- and actin-dependent endocytosis were utilized. In type II cells, uptake of SP-A, compared with controls, was decreased by 60% on incubation with clathrin inhibitors (amantadine and phenylarsine oxide) or with the actin inhibitor cytochalasin D.

Paracrine stimulation of surfactant secretion by extracellular ATP in response to mechanical deformation.

We developed a heterologous system to study the effect of mechanical deformation on alveolar epithelial cells. First, isolated primary rat alveolar type II (ATII) cells were plated onto silastic substrata coated with fibronectin and maintained in culture under conditions where they become alveolar type I-like (ATI) cells. This was followed by a second set of ATII cells labeled with the nontransferable, vital fluorescent stain 5-chloromethylfluorescein diacetate to distinguish them from ATI cells.

Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) in humans represents a family of disorders of lysosome-related organelle biogenesis associated with severe, progressive pulmonary disease. Human case reports and a mouse model of HPS, the pale ear/pearl mouse (ep/pe), exhibit giant lamellar bodies (GLB) in type II alveolar epithelial cells. We examined surfactant proteins and phospholipid from ep/pe mice to elucidate the process of GLB formation.

IL-4 induces production of the lung collectin surfactant protein-D.

Background: Surfactant protein (SP)-D is an epithelial cell product of the distal air spaces that aids uptake and clearance of inhaled pathogens and allergens. Allergic airway inflammation significantly increases SP-D levels in the bronchoalveolar lavage fluid in asthmatic patients and mouse models, but the mechanisms involved remain unknown.

Objective: To investigate the effects of the TH2-type cytokine IL-4 on SP-D production by isolated pulmonary epithelial cells.

Identification and characterization of rodent ABCA1 in isolated type II pneumocytes.

ATP-binding cassette transporter A1 (ABCA1) promotes transfer of cholesterol and phospholipid from cells to lipid-free serum apolipoproteins. ABCA1 mRNA and protein expression in primary cultures of rodent type II cells was sensitive to upregulation with 5 microM 9-cis-retinoic acid (9cRA) and 6.2 microM 22-hydroxycholesterol (22-OH).

Effect of surfactant protein A on granular pneumocyte surfactant secretion in vitro.

Surfactant secretion by lung type II cells occurs when lamellar bodies (LBs) fuse with the plasma membrane and surfactant is released into the alveolar lumen. Surfactant protein A (SP-A) blocks secretagogue-stimulated phospholipid (PL) release, even in the presence of surfactant-like lipid. The mechanism of action is not clear.

SP-A is necessary for increased clearance of alveolar DPPC with hyperventilation or secretagogues.

The role of surfactant protein-A (SP-A) in pulmonary uptake and metabolism of [(3)H]dipalmitoylphosphatidylcholine ([(3)H]DPPC) was studied in SP-A gene-targeted mice (SP-A -/-). Unilamellar liposomes were instilled into the trachea of anesthetized mice. Uptake was measured as dpm in lungs plus liver and kidney for in vivo experiments and in lungs and perfusate for isolated lung experiments.