Major depressives' and dysthmics' performance on the Wisconsin Card Sorting Test

Despite awareness that depression may affect performance on commonly used neuropsychological tests, little research has been conducted on the relative impact of severity and type of depression on higher problem-solving ability. Major depressives (n = 13), dysthymics (n = 17), and non-psychiatric comparison subjects (n = 18) were administered the Wisconsin Card Sorting Test (WCST). Although diagnostic category was related only marginally to some WCST measures after controlling for intellectual function, depressive symptom severity emerged as an independent predictor of Total Errors, Perseverative Responses, and Failure to Maintain Set. These findings lend support to the suggestion that neuropsychological test batteries should include assessment for depression and suggest that even relatively mild depression may affect WCST scores.     

Matrix regulation of skeletal cell apoptosis II: role of Arg-Gly-Asp-containing peptides.

This investigation was based on the assumption that arg-gly-asp (RGD)-containing peptides are released from the extracellular matrix of bone and cartilage during the remodeling cycle. We asked the question: Can RGD peptides influence skeletal cell viability? Primary human osteoblasts, mouse MC-3T3-E1 cells, and chick chondrocytes were incubated with purified RGD-containing peptides and cell viability was determined. The RGD peptide did not kill osteoblasts, chondrocytes, or MC-3T3-E1 cells. In contrast, RGDS and GRGDSP peptides killed all three cell types. Osteoblast death was quite rapid, occurring within 6 h of treatment. transferase uridyl mediated nick end labeling (TUNEL) and transmission electron microscopy (TEM) analysis indicated that death was mediated by apoptosis. To learn if mitochondria transduced the death signal, cells were treated with RGDS and organelle function was evaluated using a voltage-sensitive fluorescent probe. It was observed that there was no net loss of fluorescence and, hence, it was concluded that mitochondria were not the primary effectors of the apoptotic response. Experiments were performed with enzyme inhibitors to determine the import of the caspase pathway on RGDS-mediated osteoblast apoptosis. Results of these studies, as well as a study conducted using a fluorescent substrate, pointed to caspase 3 mediating the effector stage of the apoptotic process. Finally, using a purified labeled-RGDS peptide, we showed that the molecule was not restricted by the plasma membrane because it was accumulated in the cytosolic compartment. Results of the investigation support the view that resorption of the extracellular matrix generates peptide products that can induce apoptosis of vicinal cells.     

Distribution and origin of serotoninergic afferents to guinea pig cochlear nucleus

The distribution of serotoninergic fibers in the guinea pig cochlear nucleus was studied with serotonin immunohistochemistry. In addition, the origin of the serotoninergic fibers was determined by combining the retrograde transport of wheat germ agglutinin-apohorseradish peroxidase (gold conjugated) with serotonin immunohistochemistry. Immunoreactivity was present in varicose and nonvaricose fibers that were unevenly distributed throughout the cochlear nucleus. The fibers were most prominent in the superficial layers of the dorsal cochlear nucleus and the anterior spherical cell area of the anteroventral cochlear nucleus. Although less prominent, serotonin-positive fibers were also present in the remaining part of the anteroventral cochlear nucleus and the posteroventral cochlear nucleus. A few positive fibers were present in the auditory nerve root and the dorsal and intermediate acoustic stiae. Double-labeled cells were found throughout the rostral- caudal extent of the serotoninergic system from the caudal linear nucleus to the nucleus raphe pallidus. However, most were confined to the dorsal (52%) and median (18%) raphe nuclei. Some serotoninergic cell groups contained retrogradely labeled cells that were not serotonin immunoreactive, indicating nonauditory afferents to cochlear nucleus containing other neurotransmitter substances. Serotonin may tonically modulate auditory processing within the cochlear nucleus as well as influence certain ascending auditory pathways. Most of the serotonin in the cochlear nucleus comes from superior raphe nuclei that also project to basal ganglia motor systems and limbic strctures. Therefore, the effect of serotonin on the cochlear nucleus may be related to level of arousal or behavioral state. © 1995 Willy-Liss, Inc.     

Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training

To study the effects of physical conditioning on the hypothalamic-pituitary-adrenal axis, we examined the plasma ACTH, cortisol, and lactate responses in sedentary subjects, moderately trained runners, and highly trained runners to graded levels of treadmill exercise (50, 70, and 90 percent of maximal oxygen uptake) and to intravenous ovine corticotropin-releasing hormone (1 microgram per kilogram of body weight). Basal evening concentrations of ACTH and cortisol, but not of lactate, were elevated in highly trained runners as compared with sedentary subjects and moderately trained runners. Exercise-stimulated ACTH, cortisol, and lactate responses were similar in all groups and were proportional to the exercise intensity employed. These responses, however, were attenuated in the trained subjects when plotted against applied absolute workload. Only the highly trained group had diminished responses of ACTH and cortisol to ovine corticotropin-releasing hormone, consistent with sustained hypercortisolism. We conclude that physical conditioning is associated with a reduction in pituitary-adrenal activation in response to a given workload. Alterations of the hypothalamic-pituitary-adrenal axis consistent with mild hypercortisolism and similar to findings in depression and anorexia nervosa were found only in highly trained runners. Whether these alterations represent an adaptive change to the daily stress of strenuous exercise or a marker of a specific personality profile in highly trained athletes is unknown.     

Recommendations on performance characteristics of diagnostic exposure meters: report of AAPM Diagnostic X-Ray Imaging Task Group No. 6.

Task Group 6 of the Diagnostic X-Ray Imaging Committee of the American Association of Physicists in Medicine (AAPM) was appointed to develop performance standards for diagnostic x-ray exposure meters. The recommendations as approved by the Diagnostic X-Ray Imaging Committee and the Science Council of the AAPM are delineated in this report and provide specifications on meter precision, calibration accuracy, calibration reference points, linearity, energy dependence, exposure rate dependence, leakage, amplification gain settings, directional dependence, the stem effect, constancy checks, and calibration intervals. The report summarizes recommendations for meters used in mammography, general purpose radiography including special procedures, computed tomography, and radiation safety surveys for x-ray radiography.     

Modulation of level response areas and stimulus selectivity of neurons in cat primary auditory cortex

Sounds commonly occur in sequences, such as in speech. It is therefore important to understand how the occurrence of one sound affects the response to a subsequent sound. We approached this question by determining how a conditioning stimulus alters the response areas of single neurons in the primary auditory cortex (AI) of barbiturate-anesthetized cats. The response areas consisted of responses to stimuli that varied in level at the two ears and delivered at the characteristic frequency of each cell. A binaural conditioning stimulus was then presented > or =50 ms before each of the stimuli comprising the level response area. An effective preceding stimulus alters the shape and severely reduces the size and response magnitude of the level response area. This ability of the preceding stimulus depends on its proximity in the level domain to the level response area, not on its absolute level or on the size of the response it evokes. Preceding stimuli evoke a nonlinear inhibition across the level response area that results in an increased selectivity of a cortical neuron for its preferred binaural stimuli. The selectivity of AI neurons during the processing of a stream of acoustic stimuli is likely to be restricted to a portion of their level response areas apparent in the tone-alone condition. Thus rather than being static, level response areas are fluid; they can vary greatly in extent, shape and response magnitude. The dynamic modulation of the level response area and level selectivity of AI neurons might be related to several tasks confronting the central auditory system.     

Theology and bioethics: a marriage not made in heaven

Boone reviews the 20th volume in the Philosophy and medicine series, Theology and Bioethics: Exploring the Foundations and Frontiers, edited by Earl E. Shelp (D. Reidel; 1985). The volume's theme, if and how "theology can make a unique contribution to bioethics in our time," is addressed by L. Walters, B. Mitchell, R. McCormick, M. Farley, P. Lehmann, C. Hartshorne, H.T. Engelhardt, S. Hauerwas, J. Childress, and W. Frankena, with a prologue by J. Nelson and an epilogue by J. Cobb. Boone briefly summarizes and critiques each essay. While he responds favorably to the volume, he also believes the work would have been stronger if more attention had been focused directly on the metaethical issues arising from the "gap between theological belief and moral action."     

A functional three-dimensional microphysiological human model of myeloma bone disease

Human myeloma bone disease (MBD) occurs when malignant plasma cells migrate to the bone marrow and commence inimical interactions with stromal cells, disrupting the skeletal remodeling process. The myeloma cells simultaneously suppress osteoblastic bone formation while promoting excessive osteoclastic resorption. This bone metabolism imbalance produces osteolytic lesions that cause chronic bone pain and reduce trabecular and cortical bone structural integrity, and often culminate in pathological fractures. Few bone models exist that enable scientists to study MBD and the effect therapies have on restoring the bone metabolism imbalance. The purpose of this research was to develop a well characterized three-dimensional (3D) bone organoid that could be used to study MBD and current or potential treatment options. First, bone marrow stromal cell–derived osteoblasts (OBs) mineralized an endosteal-like extracellular matrix (ECM) over 21 days. Multiple analyses confirmed the generation of hydroxyapatite (HA)-rich bone-like tissue fragments that were abundant in alkaline phosphatase, calcium, and markers of osteoblastic gene expression. On day 22, bone marrow macrophage (BMM)–derived osteoclasts (OCs) were introduced to enhance the resorptive capability of the model and recapitulate the balanced homeostatic nature of skeletal remodeling. Tartrate-resistant acid phosphatase 5b (TRAcP-5b), type I collagen C-telopeptide (CTX-1), and gene expression analysis confirmed OC activity in the normal 3D organoid (3D in vitro model of normal bonelike fragments [3D-NBF]). On day 30, a human multiple myeloma (MM)–derived plasmacytoma cell line was introduced to the 3D-NBF to generate the 3D-myeloma bone disease organoid (3D-MBD). After 12 days, the 3D-MBD had significantly reduced total HA, increased TRAcP-5b levels, increases levels of CTX-1, and decreased expression of osteoblastic genes. Therapeutic intervention with pharmaceutical agents including an immunomodulatory drug, a bisphosphonate, and monoclonal restored HA content and reduced free CTX-1 in a dose-dependent manner. This osteogenically functional model of MBD provides a novel tool to study biological mechanisms guiding the disease and to screen potential therapeutics. © 2021 American Society for Bone and Mineral Research (ASBMR).