GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting GDF-8 receptor binding.

GDF-8 is a new member of the TGF-beta superfamily which appears to be a negative regulator of skeletal muscle mass. Factors which regulate the biological activity of GDF-8 have not yet been identified. However, the biological activities of TGF-beta superfamily members, TGF-beta1, -beta2 and -beta3, can be inhibited by noncovalent association with TGF-beta1, -beta2 and beta3 propeptides cleaved from the amino-termini of the TGF-beta precursor proteins. In contrast, the propeptides of other TGF-beta superfamily members do not appear to be inhibitory. In this investigation, we demonstrate that purified recombinant GDF-8 propeptide associates with purified recombinant GDF-8 to form a noncovalent complex, as evidenced by size exclusion chromatography and chemical crosslinking analysis. Furthermore, we show that GDF-8 propeptide inhibits the biological activity of GDF-8 assayed on A204 rhabdomyosarcoma cells transfected with a (CAGA)12 reporter construct. Finally, we demonstrate that GDF-8 propeptide inhibits specific GDF-8 binding to L6 myoblast cells. Collectively, these data identify the GDF-8 propeptide as an inhibitor of GDF-8 biological activity.

Group caregiver language checklist.

Because young children with language disabilities frequently are placed in group-care settings, there is a need to make judgments concerning the language environment of those settings. The GCLC is offered as one procedure for assessment of the language environment provided by the caregiver(s) in a group setting. The assessment provides information that may assist in matching the environment to a particular child's needs and may provide a basis for assisting caregivers in improving the language environment and addressing a child's needs. The authors welcome comments from the readers.

A stereoselective central hypotensive action of atenolol.

Previous studies have demonstrated that propranolol can lower arterial pressure through an action within the central nervous system. The purpose of this study was to determine 1) whether the hydrophilic beta blocking drug atenolol which is devoid of membrane stabilizing activity can reduce arterial pressure through a central action and 2) whether this action is stereoselective for the (-)-, or beta receptor blocking enantiomer. Studies were conducted in the anesthetized spontaneously hypertensive (SH) rats in which the cardiovascular effects of (-)- and (+)- atenolol were compared after i.v. or intracisternal administration. Intravenous injection of 100 micrograms/kg of (-)-atenolol reduced mean arterial pressure 25 +/- 5 mm Hg (P less than .02) and lowered heart rate 58 +/- 7 bpm (P less than .02). The same dose of (+)-atenolol i.v. produced no significant changes in either mean arterial pressure or heart rate. Similarly, intracisternal (-)-atenolol, 66 micrograms/kg, significantly (P less than .05) reduced mean arterial pressure and heart rate whereas the same dose of the (+)-isomer was without effect. When the i.v. dose of (-)-atenolol was lowered to 33 micrograms/kg, heart rate was decreased markedly but mean arterial pressure was not reduced. In contrast, 33 micrograms/kg of intracisternal (-)- atenolol significantly reduced mean arterial pressure 17 +/- 6 mm Hg and reduced heart rate. These results suggest that atenolol possesses a central hypotensive action that is selective for the (-)-, beta receptor blocking enantiomer.

The development of the eyelids. Part I. External features.

The sequence of developmental events leading to the formation of the eyelids is described in staged human embryos. By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode (Stage 13). A few days later (about 32 days, Stage 14) the lens placode is indented by the lens pit. A day or two later (about 33 days, Stage 15) the lens pit is closed: however, the lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it (stage 16, 37 days). As these grooves deepen, in Stages 17--19, eyelid folds develop, first below, and then above, the eye. In Stages 19--22 the eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19. The inner canthus is established a few days later in Stage 20. Closure of the eyelids is complete in Stage 23.

Differences in attitudes toward terminal patients among selected medical specialities of physicians.

Medical specialty of physicians was related to attitudes toward dying patients to determine if differences occur as suggested by the literature. Data from a questionnaire completed by 1,012 physicians from the classes of 1972--1975 in five selected medical schools were analyzed using the chi-square distribution to test the relationship between the response to each of the 11 Likert-type statements and the medical specialty of the physicians. Mean responses by medical specialty to the statements were ranked and correlated to Rea's ranking with respect to the probability of dealing with terminal patients by specialty using a Spearman Rank Correlation Coefficient. Support was found for Rea's conclusion that physicians such as oncologists with a high probability of relating to dying patients tended to be more open with the patient whereas a specialty like obstetrics-gynecology with a low probability tended to operate in more of a closed awareness context.

The early innervation of the developing deciduous teeth.

Ingrowth of dental nerve fibres into the mesenchyme of the tooth-bearing areas of the mouth takes place at an relatively early stage, when the dental laminae are forming but the tooth buds are undeveloped. By the time a developing tooth has reached the cap and bell stages small nerve bundles have begun to enter the mesenchyme from which the dental papilla and sac arise.

Death education in selected medical schools as related to physicians' attitudes and reactions toward dying patients.

These data obtained from 1093 recent graduates of five selected medical schools suggest that the physician who chose to take a medical school course on relating to dying patients tends to actually relate better to the dying patient than does the physician who did not take such a course.