Osborn, Thomas G.

A lung ultrasound surface wave elastography (LUSWE) technique is developed for assessing interstitial lung disease (ILD). In LUSWE, a 0.1 second harmonic vibration is generated on the chest wall of a subject using a handheld vibrator. An ultrasound probe is aligned with the vibration indenter in the same intercostal region to measure the generated surface wave speed of the lung. A human subject is examined in a sitting position. The lung is tested at the total lung volume. The upper anterior lungs are tested through the second intercostal space in the mid-clavicular line. The lower lateral lungs are tested in the mid-axillary line and the lower posterior lungs are tested in the mid-scapular line. In a prospective clinical study, we measure both lungs through the six intercostal regions for patients and healthy controls. The surface wave speed is measured at 100 Hz, 150 Hz, and 200 Hz. Significant differences of wave speed between patients and controls were found in all lung regions at all frequencies. We also found positive correlation between LUSWE and CT analyses. LUSWE is a safe and noninvasive technique for generating and measuring surface wave propagation on the lung. LUSWE may be useful for assessing ILD.

ObjectiveSystemic lupus erythematosus (SLE) is frequently characterized by activation of the type I interferon (IFN) pathway. We previously observed that a missense single‐nucleotide polymorphism (rs1049564) in the purine nucleoside phosphorylase (PNP) gene was associated with high levels of IFN in SLE. PNP is a key enzyme involved in purine metabolism. In this study, we performed functional follow‐up of this polymorphism in human cells.MethodsType I IFN was measured in patient sera, using a reporter cell assay. Structural modeling of the PNP variant was performed using PyMOL software. PNP messenger RNA (mRNA) and protein levels and type I IFN–induced gene expression were measured in lymphoblastoid cell lines with known PNP rs1049564 genotypes. The cell cycle was assayed using flow cytometry.ResultsStructural modeling indicated no major disruption in folding related to rs1049564. We observed that homozygous rs1049564 TT lymphoblastoid cells had decreased PNP mRNA expression and protein levels, and that cells with the TT genotype had reduced PNP enzymatic activity even when the amount of PNP was controlled. Cells with the TT genotype had a 2‐fold increase in S‐phase block as compared with cells with the homozygous CC phenotype. The S‐phase block could be pharmacologically reversed with hypoxanthine and adenosine, supporting the notion that relative PNP deficiency is the cause of the S‐phase block. Type I IFN–induced transcripts were increased in a dose‐response manner related to the rs1049564 T allele, at both baseline and after type I IFN stimulation.ConclusionThe PNP rs1049564 T allele is a loss‐of‐function variant that induces S‐phase block and IFN pathway activation in lymphocytes. The S‐phase block could be rescued in our in vitro experiments, suggesting the potential for personalized treatment.

Objectives Important findings can be masked in gene expression studies of mixed cell populations. We examined single-cell gene expression in SLE patient monocytes in the context of clinical and immunological features. Methods Monocytes were purified from patients with SLE and controls, and individually isolated for single-cell gene expression measurement. A panel of monocyte-related transcripts were measured in individual classical (CL) and non-classical (NCL) monocytes. Results Analyses of both CL and NCL monocytes demonstrated that many genes had a lower expression rate in SLE monocytes than in controls. Unsupervised hierarchical clustering of the CL and NCL data sets demonstrated independent clusters of cells from the patients with SLE that were related to disease activity, type I interferon (IFN) and medication use. Thus, each of these factors exerted a different impact on monocyte gene expression that could be identified separately, and a number of genes correlated uniquely with disease activity. We found within-cell correlations between genes directly induced by type I IFN-induced and other non–IFN-induced genes, suggesting the downstream biological effects of type I IFN in individual human SLE monocytes which differed between CLs and NCLs. Conclusions In summary, single-cell gene expression in monocytes was associated with a wide range of clinical and biological features in SLE, providing much greater detail and insight into the cellular biology underlying the disease than previous mixed-cell population studies.

Ultrasonography is not widely used in clinic for lung assessment because ultrasound cannot image deep lung tissue. In this abstract, we present a novel technique, lung ultrasound surface wave elastography (LUSWE), for measuring the elastic properties of superficial lung tissue. In LUSWE, a small, local, and 0.1 second harmonic vibration is generated on the chest of a subject. The speed of surface wave on the lung is measured by using an ultrasound probe. We are evaluating LUSWE for assessing patients with interstitial lung disease (ILD). LUSWE may be useful for assessing ILD because most ILD patients have typical fibrotic scars in the peripheral and subpleural regions of the lung. In a large clinical study of ILD patients, we measure both lungs through six intercostal spaces for patients and controls. The surface wave speed is measured at 100 Hz, 150 Hz, and 200 Hz. In an example, the surface wave speed is 1.88 ± 0.11 m/s and 3.3 ± 0.37 m/s, respectively, for a healthy subject and an ILD patient at 100 Hz and in the same intercostal space. LUSWE may compliment the clinical standard high-resolution computed tomography for assessing ILD. LUSWE may be useful for assessing other lung disorders.

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria.

Relapsing polychondritis (RP) is an inflammatory disease of the cartilaginous tissue primarily affecting the cartilaginous structures of the ear, nose, joints, and the respiratory system. Cardiovascular complications of RP are associated with high morbidity and mortality and occur most commonly as valvular disease. Pericarditis is a less common complication, occurring in 4% of patients with RP and has not previously been described at presentation. We describe a case of relapsing polychondritis with acute pericarditis at presentation.

Characterization of the viscoelastic mechanical properties of skin is important for improving accurate medical examination and diagnosis of disorders involving cutaneous and subcutaneous tissues; more thoroughly understanding skin biophysical and physiological properties; identifying normal and abnormal skin aging and disease processes; developing and applying improved pharmacologic and other therapeutic interventions; as well as cosmetic applications. Several noninvasive methods have been developed for measurement of mechanical properties of skin [1]. However, most methods measure a stiffness parameter but not the material properties of skin. For example, the suction method measures the displacement of skin in response to suction. The measurement is dependent on the aperture and fixation of probes and also difficult to interpret.