Citations

SummaryBackgroundKisspeptin is a novel hypothalamic peptide which stimulates endogenous gonadotrophin releasing hormone (GnRH) secretion. A single subcutaneous bolus injection of kisspeptin‐54 increases circulating luteinizing hormone (LH) levels in women, but its acute effects on LH pulsatility are not known.AimsTo investigate the effects of a single subcutaneous (sc) injection of kisspeptin‐54 administration on LH pulsatility in healthy female volunteers.MethodsSix healthy female adult volunteers underwent 10‐minute blood sampling for serum LH measurement for 8 h during the follicular phase of menstrual cycle. Sc bolus injection of saline or kisspeptin‐54 (0·15, 0·30 or 0·60 nmol/kg) was administered 4 h after commencing the study. A previously described, blinded deconvolution method was used to detect LH pulses.ResultsMean number of LH pulses was increased significantly following 0·30 and 0·60 nmol/kg kisspeptin‐54 when compared with saline (mean increase in number of LH pulses per 4 h, following injection: −0·17 ± 0·54, saline; +2·33 ± 0·56, 0·30 nmol/kg kisspeptin‐54, P < 0·05 vs saline; +2·33 ± 0·80, 0·60 nmol/kg kisspeptin‐54, P < 0·05 vs saline). LH pulse secretory mass increased following injection of 0·60 nmol/kg in five of six subjects, but the mean change in all subjects was non‐significant when compared with saline (mean increase in pulse secretory mass in IU/l following injection: +0·35 ± 0·40, saline; +2·61 ± 1·17, 0·60 nmol/kg kisspeptin‐54, P = 0·10 vs saline).ConclusionsA single injection of kisspeptin‐54 temporarily stimulates the number of LH pulses in healthy women. Further studies are required to investigate the therapeutic potential of kisspeptin‐54 injection to restore LH pulsatility in patients with reproductive disorders caused by impaired GnRH secretion.

Abstract Recently, patients with mutations in DOCK8 have been reported to have a combined immunodeficiency characterized by cutaneous viral infections and allergies. NK cells represent a first-line defense against viral infections, suggesting that DOCK8 might participate in NK cell function. In this study, we demonstrate that DOCK8-suppressed human NK cells showed defects in natural cytotoxicity as well as specific activating receptor-mediated NK cytotoxicity. Additionally, compared with control NK cells, NK cells depleted of DOCK8 showed defective conjugate formation, along with decreased polarization of LFA-1, F-actin, and cytolytic granules toward the cytotoxic synapse. Using a proteomic approach, we found that DOCK8 exists in a macromolecular complex with the Wiskott-Aldrich syndrome protein, an actin nucleation-promoting factor activated by CDC42, as well as talin, which is required for integrin-mediated adhesion. Taken together, our results demonstrate an important role for DOCK8 in NK cell effector function and provide important new mechanistic insight into how DOCK8 regulates F-actin and integrin-mediated adhesion in immune cells.

The amyloidoses are a group of protein misfolding diseases in which the precursor protein undergoes a conformational change that triggers the formation of amyloid fibrils in different tissues and organs, causing cell death and organ failure. Amyloidoses can be either localized or systemic. In localized amyloidosis, amyloid deposits form at the site of precursor protein synthesis, whereas in systemic amyloidosis, amyloid deposition occurs distant from the site of precursor protein secretion. We review the type of proteins and cells involved and what is known about the complex pathophysiology of these diseases. We focus on light chain amyloidosis to illustrate how biochemical and biophysical studies have led to a deeper understanding of the pathogenesis of this devastating disease. We also review current cellular, tissue, and animal models and discuss the challenges and opportunities for future studies of the systemic amyloidoses.

Ultrasound-stimulated vibro-acoustic spectrography is a recently-developed method that employs the radiation force of two intersecting continuous ultrasound beams to remotely vibrate an object at an arbitrary low frequency. Object vibration produces a sound field (acoustic emission) in the medium, which is a function of object mechanical properties. By measuring the acoustic emission field, one can obtain information about the mechanical parameters of the object. In this paper, we use this method for remote (noncontact) measurement of the dynamic Young's modulus of a rod based on its fundamental resonance frequency. Experimental results on an aluminum rod agree with the published data.

Order statistics filters are nonlinear filters that suppress impulsive and Gaussian noise while preserving edges. These features are particularly useful for cardiac boundary detection in ultrasound images. Based on these facts, we have analyzed performance of a combined ranked order statistics filter. The filter subtracts ranks of ordered highest and lowest intensity values of pixels encompassed in a filter window. The rank extent and window size selection allow adjustment of filter properties for a particular application. Increasing the rank fosters the low-pass characteristics of the filter. Increasing the window size supports noise removal but reduces anatomic selectivity. The filter highlights cardiac boundaries in clinical echocardiograms with intensity proportional to the local probability of a presence of the boundary.

Limited diffraction beams, such as Durnin's J 0 Bessel beam, are a class of nonspreading solutions to the isotropic/homogeneous scalar wave equation. These beams can be approximately produced with finite aperture and energy over a deep depth of field. In this paper, we report the application of a broadband J 0 Bessel beam to nondestructive evaluation (NDE) of materials. Pulse-echo images of a stainless steel block phantom were obtained with both the Jo Bessel beam and a conventional focused Gaussian beam. Results show that uniformly high resolutions were obtained with the J 0 Bessel beam over a large distance. In addition, the lateral resolution of the J 0 Bessel beam is almost independent of the speed of sound of the materials inspected. In contrast, the lateral resolution of images obtained with the conventional focused Gaussian beam changes dramatically with the distance and the focal length of the beam in water is greatly reduced by the steel block. Therefore, limited diffraction beams could be useful for nondestructive evaluation of materials of different speeds of sound. Restoration of pulse-echo images obtained with these beams could be simplified.

A method to obtain a good compromise between the depth of field and the lateral resolution of “X waves” is proposed. The original X waves are theoretically nondiffracting beams generated by a specially phased infinite transmit aperture. When generated by a finite aperture, X waves are diffracting beams but have a large depth of field, maintaining uniform lateral field profiles. The proposed modification of the wave equation solution for X waves replaces a constant parameter representing the propagation angle of ultrasound with a function of radial distance at the aperture surface, and results in modified X waves that have a larger depth of field than the original X waves. Computer simulations show that a proper choice of the modification function can produce a new beam with improved field properties compared with the original X waves, promising images with higher lateral resolution and increased contrast over a large depth of field in high frame rate medical imaging. Experimental results are presented to verify the simulation results of the proposed method.