No abstract

We developed an assay to quantify LDL transcytosis across endothelial cells and discovered an unexpected role for SR-BI. Elucidating the mechanisms of LDL transcytosis may identify novel targets for the prevention or therapy of atherosclerosis.

We have used an extremely accurate, dedicated, real time computerized image analysis system to facilitate the manual quantification of changes in the prevalence of mitotic figures and apoptotic bodies in male rat pituitary following surgical adrenalectomy and, 14 days later, dexamethasone treatment. Under basal conditions, the prevalence of mitotic figures and apoptotic bodies was 0.066+/-0.016% and 0.030+/-0.012% (mean+/-SE) respectively. Dexamethasone treatment reduced the prevalence of mitotic figures and, in adrenalectomized animals, produced a highly significant and reproducible burst of apoptotic activity that peaked 48 h after the beginning of treatment (0.261+/-0.022%) before falling sharply to control levels within a further 8 h. Two weeks after the start of dexamethasone treatment, total pituitary cell numbers continued to decline. The rate of accumulation of mitotic figures in vivo after colchicine treatment indicates that mitosis is histologically overt in 2 microm thick hematoxylin and eosin stained sections under the light microscope for around 80 min; that apoptosis--identified as classical apoptotic bodies--is overt for 44 min and that, on average, a young, adult, male rat anterior pituitary cell either dies or divides as frequently as once every 60-70 days. These data show that transient and apparently trivial fluctuations in the prevalence of apoptotic and mitotic events have a profound effect on pituitary cell population dynamics, and demonstrate that dexamethasone treatment of adrenalectomized rats produces a decline in total anterior pituitary cell numbers that continues for at least 2 weeks after the start of glucocorticoid treatment.

Hypertension is characterized by elevated blood pressure (BP) and autonomic dysfunction, both thought to be improved with exercise training. Isometric handgrip (IHG) training may represent a beneficial, time-effective exercise therapy. We investigated the effects of IHG training on BP and traditional and nonlinear measures of heart rate variability (HRV). Pre- and post-measurements of BP and HRV were determined in 23 medicated hypertensive participants (mean ± SEM, 66 ± 2 years) following either 8 weeks of IHG training (n = 13) or control (n = 10). IHG exercise consisted of four unilateral 2-min isometric contractions at 30% of maximal voluntary contraction, each separated by 4 min of rest. IHG training was performed 3 days/week for 8 weeks. IHG training decreased systolic BP (125 ± 3 mmHg to 120 ± 2 mmHg, P < 0.05) and mean BP (90 ± 2 mmHg to 87 ± 2 mmHg, P < 0.05), while sample entropy was increased (1.07 ± 0.1 to 1.35 ± 0.1, P < 0.05) and the fractal scaling distance score was decreased (0.34 ± 0.1 to 0.19 ± 0.1, P < 0.05). No significant changes were observed in traditional spectral or time-domain measures of HRV or control participants. IHG training improves nonlinear HRV, but not traditional HRV, while reducing systolic and mean BP. These results may highlight the benefits of IHG training for patients with primary hypertension.

This study reports on the diagnosis and treatment of chondral delamination in the knees of soccer players. The authors attempted to provide a clinical standard for comparison with emerging cartilage repair techniques. Twenty-three consecutive chondral fractures in a homogeneous population of athletes were evaluated using physical examination, magnetic resonance imaging, and arthroscopic examination. All knees were treated with debridement to a stable border and removal of the calcified cartilage base. Results were graded using the scoring system advocated by proponents of chondral transplant. All patients reported pain that limited soccer activities. Effusions occurred in 48%, joint line tenderness in 33%, and crepitus in 19% of the knees. Results from magnetic resonance imaging correlated with arthroscopic examination in 21% of the knees. Arthroscopic examinations revealed lesions on the medial femoral condyle in eight patients, the patella in six, the lateral femoral condyle in six, and the trochlea in three. Athletes returned to play at an average of 10.8 weeks. Repeat arthroscopic procedures in eight cases revealed fibrocartilage at the initial site. There were 6 excellent, 9 good, 0 fair, and 0 poor results at their 1-year followup examinations (15 knees). The definitive diagnosis of chondral delamination relies on a thorough arthroscopic probing of the articular surface. The early functional results of this treatment compare favorably with the autologous transplantation technique. Caution, however, is recommended when treating articular cartilage injuries because no long-term data exists on whether any treatment modality can prevent the development of degenerative joint disease.

A complete inventory of pituitary trophic responses depends on precise estimates of mitotic activity and apoptotic events, and accurate characterization and quantification of pituitary cell subtypes irrespective of previous and current physiological demand. For a discrete structure that has been so extensively studied, it is disappointing but perhaps not surprising that none of these measures is available and therefore that the relative contributions to changes in the proportions of pituitary cellular subpopulations of trophic activity, differentiation of pluripotent cells and variations in the secretory profiles of apparently committed cells remain almost impossible to determine. To fully appreciate the extent of this dilemma, it should be remembered that conservative estimates of the proportion of corticotrophs in the rat anterior pituitary under basal conditions vary over twofold and that it is still not clear whether the apparent threefold increase in mammotrophs during pregnancy is the result of maturation of uncommitted cells, transdifferentiation of other cells such as somatotrophs, cell division, or a mixture of all three. Equally, while it has been known for some time that adrenalectomy results in a transient increase in anterior pituitary mitotic activity and appropriately timed supraphysiological glucocorticoid replacement with a wave of apoptosis, the precise identity of the cells involved in both of these responses is open to question. Thus, although many of the physiological stimuli associated with apparent changes in the proportions of pituitary cellular subpopulations are known, the precise mechanism of the changes and the consequences of the same remain obscure. This review summarizes the limited literature on pituitary trophic activity and asks what, if anything, analysis of pituitary trophic activity using current technology can tell us.

The rapid detection of gene activation is important for our understanding of gene regulation. We have therefore studied heteronuclear (i.e. nascent) RNA (hnRNA) by using 35S-labelled corticotrophin-releasing hormone (CRH) riboprobes and arginine vasopressin (AVP) oligo-nucleotide probes directed against intronic and exonic sequences of both CRH and AVP transcripts for in situ hybridization studies of transcriptional changes during acute stress. CRH and AVP intronic signals (found in newly synthesized transcripts) were confined to the nuclei of the parvocellular cells in the paraventricular nucleus (PVN) whilst CRH and AVP exonic signals (found in both newly formed and mature transcripts) were primarily located in the cytoplasm of these cells. AVP hnRNA and mRNA were also present at high level, in the magnocellular PVN. The levels of CRH hnRNA and parvocellular AVP hnRNA in the PVN were significantly increased 1 and 2 h after the onset of restraint. The levels of CRH mRNA on the other hand were not significantly increased until 4 h after the onset of restraint. The number of AVP mRNA-expressing neurons in the medial parvo-cellular cells of the PVN significantly increased at 2 h and peaked at 4 h after the onset of stress. In contrast, densitometric analysis indicated that the increase in AVP mRNA levels in these cells did nor reach significant difference from control until 4 h after the onset of restraint. There were no significant changes on AVP hnRNA or AVP mRNA levels in the magnocellular subdivision of PVN at any time point after the onset of restraint.

To determine the degree of shoulder translation in uninjured athletes, we examined 76 Division I collegiate athletes (44 women and 32 men) for passive range of motion in both shoulders and for knee and elbow hyperextension. Translation was based on a scale of 0 to 3+. Shoulders with symptoms of pain or a history of instability or dislocation were excluded from this study. Forty-six shoulders had 0 anterior translation, 75 had 1+, and 31 had 2+. Thirteen shoulders had 0 posterior translation, 56 had 1+, and 83 had 2+. Thirty-eight shoulders had 0 inferior translation, 105 had 1+, and 9 had 2+. No shoulder had translation of 3+ in any direction. Twenty-four athletes, 12 men and 12 women, had translational asymmetry of a minimum of one grade in at least one direction. No shoulder was asymmetric in all three directions. There was a significant correlation between dominant hand and increased translation; 19 of 24 athletes with asymmetric shoulders had greater translation in the nondominant extremity. There was no relationship between translation and range of motion, knee or elbow hyperextension, thumb-to-forearm distance, or years spent in sports participation. Asymmetry of shoulder translation may exist in the normal shoulder. This review shows that up to 2+ translation in any direction cannot be considered abnormal.