An abnormal pulmonary vasculature may be an important component of bronchopulmonary dysplasia (BPD). We examined human infant lung for the endothelial cell marker PECAM-1 and for angiogenic factors and their receptors. Lung specimens were collected prospectively at approximately 6 h after death. The right middle lobe was inflation fixed and part of the right lower lobe was flash frozen. We compared lungs from infants dying with BPD (n = 5) with lungs from infants dying from nonpulmonary causes (n = 5). The BPD group was significantly more premature and had more days of ventilator and supplemental oxygen support, but died at a postconceptional age similar to control infants. PECAM-1 protein and mRNA were decreased in the BPD group. PECAM-1 immunohistochemistry showed the BPD group had decreased staining intensity and abnormal distribution of alveolar capillaries. The dysmorphic capillaries were frequently in the interior of thickened alveolar septa. The BPD group had decreased vascular endothelial growth factor (VEGF) mRNA and decreased VEGF immunostaining, compared with infants without BPD. Messages for the angiogenic receptors Flt-1 and TIE-2 were decreased in the BPD group. We conclude that infants dying with BPD have abnormal alveolar microvessels and that disordered expression of angiogenic growth factors and their receptors may contribute to these abnormalities.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e. delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of Placenta Accreta Spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth. Risk factors for BPD are complex and include prenatal infection and O 2 toxicity. BPD pathology is equally complex and characterized by inflammation and dysmorphic airspaces and vasculature. Due to the limited availability of clinical samples, an understanding of the molecular pathogenesis of this disease and its causal mechanisms and associated biomarkers is limited. Objectives: Apply genome-wide expression profiling to define pathways affected in BPD lungs. Methods: Lung tissue was obtained at autopsy from 11 BPD cases and 17 age-matched control subjects without BPD. RNA isolated from these tissue samples was interrogated using microarrays. Standard gene selection and pathway analysis methods were applied to the data set. Abnormal expression patterns were validated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. Measurements and Main Results: We identified 159 genes differentially expressed in BPD tissues. Pathway analysis indicated previously appreciated (e.g., DNA damage regulation of cell cycle) as well as novel (e.g., B-cell development) biological functions were affected. Three of the five most highly induced genes were mast cell (MC)-specific markers. We confirmed an increased accumulation of connective tissue MC TC (chymase expressing) mast cells in BPD tissues. Increased expression of MC TC markers was also demonstrated in an animal model of BPD-like pathology.Conclusions: We present a unique genome-wide expression data set from human BPD lung tissue. Our data provide information on gene expression patterns associated with BPD and facilitated the discovery that MC TC accumulation is a prominent feature of this disease. These observations have significant clinical and mechanistic implications.

A major clinical challenge in Gaucher disease is the early and presymptomatic discrimination of type 2 (acute neuronopathic) from milder type 1 and type 3 Gaucher patients to enable appropriate management and counseling. Although most patients with Gaucher disease do not have skin abnormalities, a subset of patients with severe type 2 Gaucher disease display ichthyosiform skin. Analogous findings occur in the skin of type 2 (null allele) Gaucher mice. Ultrastructural and functional studies of epidermis from these mice reveal that glucocerebrosidase is required to generate functionally competent membranes for normal epidermal barrier function. We have extended our studies by examining the epidermal lipid content and ultrastructure in all three types of Gaucher patients. Only the type 2 Gaucher patients, some of whom had clinical ichthyosis, demonstrated an increased ratio of epidermal glucosylceramide to ceramide as well as extensive ultrastructural abnormalities, including the persistence of incompletely processed lamellar body-derived contents throughout the stratum corneum interstices. These epidermal alterations may provide a means for early differentiation of type 2 Gaucher disease.

No abstract

The relative importance of the fat and muscle layers of the human abdominal wall in producing ultrasonic wavefront distortion was assessed by means of direct measurements. Specimens employed included six whole abdominal wall specimens and twelve partial specimens obtained by dividing each whole specimen into a fat and a muscle layer. In the measurement technique employed, a hemispheric transducer transmitted a 3.75-MHz ultrasonic pulse through a tissue section. The received wavefront was measured by a linear array translated in the elevation direction to synthesize a two-dimensional aperture. Insertion loss was also measured at various locations on each specimen. Differences in arrival time and energy level between the measured waveforms and computed references that account for geometric delay and spreading were calculated. After correction for the effects of geometry, the received waveforms were synthetically focused. The characteristics of the distortion produced by each specimen and the quality of the resulting focus were analyzed and compared. The measurements show that muscle produces greater arrival time distortion than fat while fat produces greater energy level distortion than muscle, but that the distortion produced by the entire abdominal wall is not equivalent to a simple combination of distortion effects produced by the layers. The results also indicate that both fat and muscle layers contribute significantly to the distortion of ultrasonic beams by the abdominal wall. However, the spatial characteristics of the distortion produced by fat and muscle layers differ substantially. Distortion produced by muscle layers, as well as focal images aberrated by muscle layers, show considerable anisotropy associated with muscle fiber orientation. Distortion produced by fat layers shows smaller-scale, granular structure associated with scattering from the septa surrounding individual fat lobules. Thick layers of fat may be expected to cause poor image quality due to both scattering and bulk absorption effects, while thick muscle layers may be expected to cause focus aberration due to large arrival time fluctuations. Correction of aberrated focuses using time-shift compensation shows more complete correction for muscle sections than for fat sections, so that correction methods based on phase screen models may be more appropriate for muscle layers than for fat layers.

No abstract

Ultrasonic pulse arrival time and energy level variations introduced by propagation through human abdominal wall specimens have been measured. A hemispheric transducer transmitted an ultrasonic pulse that was detected by a linear array transducer after propagation through an abdominal wall section. The array was translated in the elevation direction to collect data over a two-dimensional aperture. Differences in arrival time and energy level between the measured waveforms and calculated references that account for geometric delay and spreading were found. Plots of waveforms compensated for geometric path, maps of time delay differences and energy level fluctuations, and statistics derived from these for water paths and tissue paths characterize the measurement system and describe the time delay differences and energy level fluctuations caused by 14 different human abdominal wall specimens. Repeated measurements using the same specimens show that individual tissue path measurements are reproducible, the results depend on specimen position, and frozen storage of a specimen for three months does not appear to alter the time delay differences and energy level fluctuations produced by the specimen. Comparison of measurements at room and body temperature indicates that appreciably higher time delay differences occur at body temperature while energy level fluctuations and time delay difference patterns are less affected. For the 14 different abdominal wall specimens, the rms time delay differences and energy level fluctuations have average values of 43.0 ns and 3.30 dB, respectively, and the associated correlation lengths of the time delay differences and energy level fluctuations are 7.90 and 2.28 mm, respectively. The spatial patterns of time delay difference and energy level fluctuation in the reception plane appear largely uncorrelated, although some background variations in energy level fluctuation are similar to features in time delay difference maps. The results provide important new information about the variety and range of ultrasonic wave front arrival and energy variations caused by transmission through abdominal wall.