Spherical harmonics analysis reveals cell shape-fate relationships in zebrafish lateral line neuromasts.

Cell shape is a powerful readout of cell state, fate and function. We describe a custom workflow to perform semi-automated, 3D cell and nucleus segmentation, and spherical harmonics and principal components analysis to distill cell and nuclear shape variation into discrete biologically meaningful parameters. We apply these methods to analyze shape in the neuromast cells of the zebrafish lateral line system, finding that shapes vary with cell location and identity. The distinction between hair cells and support cells accounted for much of the variation, which allowed us to train classifiers to predict cell identity from shape features. Using transgenic markers for support cell subpopulations, we found that subtypes had different shapes from each other. To investigate how loss of a neuromast cell type altered cell shape distributions, we examined atoh1a mutants that lack hair cells. We found that mutant neuromasts lacked the cell shape phenotype associated with hair cells, but did not exhibit a mutant-specific cell shape. Our results demonstrate the utility of using 3D cell shape features to characterize, compare and classify cells in a living developing organism.

Robust regeneration of adult zebrafish lateral line hair cells reflects continued precursor pool maintenance.

We have examined lateral line hair cell and support cell maintenance in adult zebrafish when growth is largely complete. We demonstrate that adult zebrafish not only replenish hair cells after a single instance of hair cell damage, but also maintain hair cells and support cells after multiple rounds of damage and regeneration. We find that hair cells undergo continuous turnover in adult zebrafish in the absence of damage. We identify mitotically-distinct support cell populations and show that hair cells regenerate from underlying support cells in a region-specific manner. Our results demonstrate that there are two distinct support cell populations in the lateral line, which may help explain why zebrafish hair cell regeneration is extremely robust, retained throughout life, and potentially unlimited in regenerative capacity.

There and back again: development and regeneration of the zebrafish lateral line system.

The zebrafish lateral line is a sensory system used to detect changes in water flow. It is comprised of clusters of mechanosensory hair cells called neuromasts. The lateral line is initially established by a migratory group of cells, called a primordium, that deposits neuromasts at stereotyped locations along the surface of the fish. Wnt, FGF, and Notch signaling are all important regulators of various aspects of lateral line development, from primordium migration to hair cell specification. As zebrafish age, the organization of the lateral line becomes more complex in order to accommodate the fish's increased size. This expansion is regulated by many of the same factors involved in the initial development. Furthermore, unlike mammalian hair cells, lateral line hair cells have the capacity to regenerate after damage. New hair cells arise from the proliferation and differentiation of surrounding support cells, and the molecular and cellular pathways regulating this are beginning to be elucidated. All in all, the zebrafish lateral line has proven to be an excellent model in which to study a diverse array of processes, including collective cell migration, cell polarity, cell fate, and regeneration.

Hypovitaminosis D and valvular calcification in patients with dilated cardiomyopathy.

BACKGROUND: In patients with dilated (idiopathic) cardiomyopathy (DCM), little is known about the presence of valvular calcification and its association with hypovitaminosis D, which may predispose affected tissues to calcification. Our objectives were 2-fold: to conduct a retrospective assessment of echocardiographic evidence of valvular calcification in patients with DCM who were known to have hypovitaminosis D (25(OH)D <30 ng/mL) and to conduct a prospective assessment of serum 25(OH)D in patients with DCM, who had demonstrated echocardiographic evidence of valvular calcification. METHODS: The retrospective study consisted of 48 African American patients (34 men, 14 women; 52.3 +/- 1.5 years) having DCM and ejection fraction <35% with serum creatinine <2.0 mg/dL and 25(OH)D <30 ng/mL; and 20 white patients in the prospective study (20 men; 71.0 +/- 3.0 years) having DCM and ejection fraction <35% with serum creatinine <2.0 mg/dL and echocardiographic evidence of valvular calcification. In the retrospective study, a transthoracic echocardiogram was obtained to address mitral valvular and annular calcification, aortic valvular calcification, and sinotubular calcification; whereas in the prospective study, serum 25(OH)D level was monitored in patients with known valvular calcification. Serum parathyroid hormone (PTH) was monitored in both studies. RESULTS: In the retrospective study, hypovitaminosis D was found in 19 patients (31%) with valvular calcification and in whom serum PTH was increased (83 +/- 8 pg/mL). In the prospective study, 15 of 20 elderly patients (80%) with known DCM and valvular calcification were found to have hypovitaminosis D (25(OH)D <30 ng/mL), whereas serum PTH was normal (43 +/- 4 pg/mL). CONCLUSIONS: In patients with DCM without marked renal dysfunction, valvular calcification was seen more frequently and associated with hypovitaminosis D, whereas in elderly patients with valvular calcification, hypovitaminosis D is common, suggesting that the duration of vitamin D deficiency may determine the extent of valvular calcification. The role of hypovitaminosis D in the appearance of valvular calcification deserves further study.

Echocardiographic aspects of hiatal hernia: A review.

It was realized 20 years ago that the sonographic appearance of a diaphragmatic hernia could simulate a left atrial mass. Many papers have appeared on this topic since then, but they mainly consist of single case reports. Clinical symptoms due to cardiac compression by the hernia are uncommon but may occur if the hernia is very large; such patients have presented with episodes of syncope or dyspnea, typically after a large meal. Sonographers, cardiologists, gastroenterologists, and internists are generally not yet aware that sonographic presentations can be varied and are often perplexing. These include the combination of hiatal hernia with gastroesophageal reflux demonstrable in the subcostal view, and hiatal hernia in patients with ascites.

Three-dimensional echocardiographic appearances of pericardial effusion with tamponade.

A patient with pericardial effusion and tamponade was studied by routine two-dimensional as well as three-dimensional echocardiogram. Chamber "collapses" of the right atrium, left atrium, right ventricle, and inferior vena cava were visualized by both modalities, but were better appreciated on three-dimensional echo imaging, perhaps because three-dimensional echo imaging is more suited to depicting three-dimensional changes in chamber shape.

Incompetence of the internal jugular venous valve: spectrum of echo-Doppler appearances.

The echocardiographic literature contains very scant reference to incompetence of the valve in the internal jugular vein. However, we found frequent Doppler evidence of such incompetence, especially in patients with congestive failure. This incompetence manifests as a variety of color Doppler and pulsed Doppler patterns, illustrated here in 3 patients.

Left ventricular endocardial calcification in a patient with myeloproliferative disease.

The case of a 57-year-old male with a history significant for myeloproliferative disease, chronic renal failure, hypertension, and prostate cancer is described. His complete blood count was remarkable for neutrophilia and, notably, eosinophilia. Subsequent to two syncopal episodes, a transthoracic echocardiogram was performed as part of the workup, which showed an unusual calcified mass in the left ventricular apical region but separate from the apical myocardium, with normal left ventricular systolic function. A transesophageal echocardiogram and computed tomography of the chest confirmed the presence of extensive calcification in the left ventricle of unusual location and shape. This patient probably had Loeffler endocarditis related to myeloproliferative disorder, complicated by calcification of the endocardial sclerotic lesions.

Local intense mosaic pattern at site of flail mitral leaflet: report of a new color Doppler sign.

Color flow Doppler has been useful in diagnosing the presence and severity of mitral regurgitation (MR). We noted a hitherto unreported sign of MR due to flail mitral leaflet: intense local mosaic pattern at the site of the flail leaflet. This sign was seen well in 11 of 14 patients (79%) with the two-dimensional echocardiographic features of flail mitral leaflet, all with moderate or severe MR. In 3 other patients, the sign was absent; two of those had flail mitral leaflet with severe MR. No local mosaic pattern was seen on color Doppler in 20 other patients with MR but no flail mitral leaflet. We speculate that the focal intense mosaic color Doppler morphology may have been caused by intrusion of the flail leaflet into the MR stream, or to a Coanda-like effect of the MR jet "adhering" to the flail leaflet.

Echocardiography of the superior vena cava.

The anatomy and applied echocardiographic anatomy of the superior vena cava (SVC) are briefly described. Right supraclavicular interrogation of the SVC has been in use for many years, but supraclavicular two-dimensional (2-D) imaging of the SVC has been virtually ignored. We have recently shown that supraclavicular 2-D imaging can provide excellent views of the SVC and its main tributaries. Transthoracic echocardiography (TEE) is suitable for imaging of the lower (juxtaatrial) SVC. Persistence of a left SVC is an uncommon variant, diagnosed echocardiographically by coronary sinus dilatation and passage of contrast into it from a left arm vein. Extensive SVC compression by mediastinal masses is well known, but recently intravascular SVC obstruction has been increasingly reported as a complication of radiofrequency ablation for ectopic atrial tachycardia, for thrombosis of the SVC or its main tributaries following indwelling catheters, or following insertion of pacemaker leads. Doppler interrogation or TEE imaging of the SVC have been used in recent years to elucidate such pathology.

Sonolucent space posterior to left atrium: unusual echocardiographic appearance in a cardiac transplant patient.

The usual echocardiographic appearances of the atria in heart transplant patients are well known. We report a case of an 81-year-old man with a 16-year-old cardiac transplant who showed a "new" echocardiographic left atrial abnormality. Two-dimensional echocardiography showed a large sonolucent space behind the donor left atrium (DLA), which was at first perplexing. This space, the distorted and partly displaced recipient left atrium (RLA), could be shown to communicate with the donor left atrium, by the use of unconventional imaging and by optison opacification.