The involvement of TGFβ1 in early avian development: gastrulation and chondrogenesis

We examined the effects of transforming growth factor-β1 (TGFβ1) and a neutralizing monoclonal antibody on two phases of early chick embryo development: gastrulation and chondrogenesis. We carried out experiments in vivo and in vitro on mesoderm cells from the gastrulating embryo at day 1, and on sclerotome cells from day 3 embryos, having previously shown that this factor is present among these cells at these stages of development. Addition of the antibody to cultures of these cells produced a dose-dependent decrease in cell outgrowth and spreading and concomitantly reduced fibronectin deposition. In vivo studies of the effects of TGFβ1 on mesoderm during gastrulation were carried out by grafting beads carrying this agent into gastrulating embryos. We used beads of ion-exchange resin as well as hydrolysed polyacrylamide, and found that the grafts produced an accumulation of mesoderm cells around the implant and, at later stages, the formation of enlarged somites. There was no effect on embryonic axis formation. Studies of bromodeoxyuridine (BrdU) incorporation indicated that the mesoderm accumulation was due, at least in part, to an increase in cell proliferation. However, examination of the effect of TGFβ1 on BrdU incorporation by mesoderm during gastrulation and sclerotome cells in vitro indicated in inhibition of cell proliferation, an inconsistency explained in terms of the variation between the in vivo and in vitro conditions. We conclude that TGFβ1 is both appropriately located, and is able, to influence cell proliferation among the mesodermal cell populations during early development, and that this effect contributes to the overall control of mesodermal morphogenesis. Chondrogenesis was studied in vitro using micromass cocultures of sclerotome cells with notochordon a permeable substratum. Under these conditions, the addition of TGFβ1 caused an increase in the deposition of Alcian blue-stainable material, indicating a stimulation of chondrogenesis. We suggest that this result, coupled with the previous demonstration that TGFβ1 is present among the sclerotome cells in the embryo at this time, supports the contention that this factor exerts a regulatory effect on sclerotome cell differentiation.     

Behavioral and hormonal effects of attachment object separation in surrogate-peer-reared and mother-reared infant rhesus monkeys

Mother-reared and surrogate-peer-reared rhesus monkeys were separated from their respective attachment objects at 6 months of age and tested for the following 9 weeks to determine their home cage behavior and their pituitary-adrenocortical responses to stress. Both groups displayed a strong immediate behavioral response to separation which was characterized by increases vocalization, increased locomotion, and decreased self-play. However, the surrogate-peer-reared infants showed a subsequent recovery in their levels of self-play whereas the mother-reared infants instead developed stereotypic behavior patterns such as repetitive pacing. The 2 groups displayed similar plasma cortisol responses to weekly sessions in an apparatus equipped with animated toy “monsters.” Mother-reared but not surrogate-peer-reared subjects, however, also manifested elevated cortisol levels when an animal in an adjacent cage was captured and removed for stress testing. Mother-reared infant monkeys thus responded in a stronger and more prolonged manner to the loss of their attachment object than surrogate-peer-reared infants. These results suggest that infant rhesus monkeys form stronger attachments to monkey mothers than to inanimate surrogate mothers, a phenomenon which has not been as clearly demonstrated using other indices of attachment strength.     

Methods for obtaining and analyzing unattended polysomnography data for a multicenter study. Sleep Heart Health Research Group

This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.     

Effects of a yearlong moderate-intensity exercise and a stretching intervention on sleep quality in postmenopausal women

STUDY OBJECTIVES: To examine the effects of a moderate-intensity exercise or stretching intervention and changes in fitness, body mass index, or time spent outdoors on self-reported sleep quality and to examine the relationship between the amount and timing of exercise and sleep quality. DESIGN: A randomized intervention trial. SETTING: A cancer research center in Seattle, Washington. PARTICIPANTS: Postmenopausal, overweight or obese, sedentary women not taking hormone replacement therapy, aged 50 to 75 years, and recruited from the Seattle metropolitan area. INTERVENTIONS: A yearlong moderate-intensity exercise (n=87) and a low-intensity stretching (n=86) program. MEASUREMENTS AND RESULTS: Among morning exercisers, those who exercised at least 225 minutes per week had less trouble falling asleep (odds ratio [OR]: 0.3, P < or = .05) compared with those who exercised less than 180 minutes per week. However, among evening exercisers, those who exercised at least 225 minutes per week had more trouble falling asleep (OR: 3.3, P < or = .05) compared to those who exercised less than 180 minutes per week. Stretchers were less likely to use sleep medication (OR = 0.4, P < or = .05) and have trouble falling asleep (OR: 0.7, P < or = .10) during the intervention period compared with baseline. A greater than 10% versus a 1% or less increase in maximum O2 consumption over the year was associated with longer sleep duration (P < or = .05), less frequently falling asleep during quiet activities (P < or = .05), and less use of sleep medication (P < or = .05). Reductions in body mass index and increases in time spent outdoors had inconsistent effects on sleep quality. CONCLUSIONS: Both stretching and exercise interventions may improve sleep quality in sedentary, overweight, postmenopausal women. Increased fitness was associated with improvements in sleep. However, the effect of moderate-intensity exercise may depend on the amount of exercise and time of day it is performed.     

Spontaneous alpha peak frequency predicts working memory performance across the age span.

Working memory capacity has been consistently shown to decline with increasing age. Mechanisms underlying this decline are poorly understood. One index that has been found to predict performance on memory tests is alpha peak frequency, the peak of spectral alpha power of the EEG. Activity in the alpha band has been also associated with higher cognitive functions including attention and anticipation and has been shown to slow with age. Few studies, however, have examined whether there might be a relationship between WM decline and alpha peak frequency. The present study specifically investigated this relationship. Digit span was used as the index of WM function. The study made use of 550 normal subjects aged between 11 and 70 years in the Brain Resource International Database. The data were acquired from six laboratories located in the USA (2), Europe (2) and Australia (2). Forward and reverse digit span were found to be lower in older relative to younger age groups. Spontaneous alpha peak frequency slowed with age and more so at anterior than posterior sites. Frontal alpha peak frequency was found to be a significant predictor of reverse digit span, with each 1 Hz increase in frequency associated with a 0.21 increase in reverse digit span score and this was independent of age, indicating a positive relationship between alpha peak frequency and working memory performance.     

Growth hormone as an early embryonic growth and differentiation factor

In this review we consider the evidence that growth hormone (GH) acts in the embryo as a local growth, differentiation, and cell survival factor. Because both GH and its receptors are present in the early embryo before the functional differentiation of pituitary somatotrophs and before the establishment of a functioning circulatory system, the conditions are such that GH may be a member of the large battery of autocrine/paracrine growth factors that control embryonic development. It has been clearly established that GH is able to exert direct effects, independent of insulin-like growth factor-I (IGF-I), on the differentiation, proliferation, and survival of cells in a wide variety of tissues in the embryo, fetus, and adult. The signaling pathways behind these effects of GH are now beginning to be determined, establishing early extrapituitary GH as a bona fide developmental growth factor.     

Argyrophil carcinoma of the breast: a cytologic, histochemical, and ultrastructural study of a case

Aspirate from an argyrophil carcinoma ("carcinoid") of the breast showed malignant dispersed epithelial cells. With Diff-Quik, the cytoplasm was seen to be abundant, with prominent eosinophilic granularity. The nuclei were fairly uniform, round or oval, and eccentric and had a finely stippled chromatin pattern. On histology, the tumor appeared typical for argyrophil carcinoma, and staining with Grimelius for argyrophilic granules was positive. Membrane-bound neurosecretory granules were seen on electron microscopy.     

Efficiency of cross presentation of vaccinia virus-derived antigens by human dendritic cells.

Dendritic cells (DC) utilize at least two pathways to process viral antigens onto MHC class I molecules. The conventional endogenous route is used to acquire antigens from both infectious and non-replicating virions. Exogenous pathways are used by DC to acquire and "cross-present" antigens derived from virus-infected donor cells that by themselves lack the ability to activate T cells directly. We analyzed the role of this pathway for antigens derived from vaccinia, a virus which inhibits DC maturation and causes extensive apoptosis of infected cells, yet is highly immunogenic. Using recombinant vaccinia virus encoding the influenza matrix protein as model vector, DC were shown to cross-present vaccinia-derived antigens from both apoptotic and necrotic infected cells to antigen-specific CD8(+) T cells. Efficient cross presentation required uptake of dead cells by immature DC and exposure to maturation stimuli, especially CD40 ligand. The responding CD8(+) T cells secreted IL-2 and IFN-gamma, proliferated and developed into cytotoxic effectors. Quantification of the cross presentation of vaccinia-derived antigens showed this pathway to be highly efficient, corresponding to a peptide pulse of 10-100 nM. While monocytes also phagocytosed apoptotic and necrotic cells, they were far less efficient at cross-presenting vaccinia-derived antigens to CD8(+) T cells. The ability of DC to cross-present vaccinia-derived antigens from infected apoptotic cells or necrotic cell lysates, bypasses the deleterious effects of direct infection of DC and provides one explanation for this pathogen's immunogenicity.     

Differences Between Treatment Seekers in an Obese Population: Medical Intervention vs. Dietary Restriction

This study examined two groups of people who were pursuing treatment for obesity: either medical intervention (a hospital group; N = 20) or support for dietary restriction (a community group; N = 18). This study addressed four questions: (1) Were there differences between the two groups in terms of their psychological distress (as measured by the Symptom Checklist)? (2) Does binge eating moderate psychological distress? (3) Do feelings of ineffectiveness moderate psychological distress? and (4) Which variables best accounted for group membership (i.e., type of treatment sought)? Results suggested that the hospital group was significantly more distressed than the community group. However, there were no differences between the two groups with respect to binge eating or feelings of ineffectiveness. These findings suggest that it is the effects of morbid obesity that are most likely to moderate psychological distress.