The quality of adolescent friendships: long-term effects?

Retinoic acid (RA) has been implicated in cardiac morphogenesis by its teratogenic effects on the heart, although its role in normal cardiogenesis remains unknown. To define the parameters of RA action in cardiac morphogenesis, we analyzed the patterns of ligand synthesis, response, and inactivation in the developing mouse heart. Activation of a lacZ transgene controlled by an RA response element (RARE) was compared to the localization of the retinaldehyde-oxidizing dehydrogenase RALDH2, the earliest RA synthetic enzyme in the mouse embryo, and to the expression of a gene encoding an RA-degrading enzyme (P450RA). We observed that RALDH2 localization and RA response were virtually superimposable throughout heart development. Initially, both RALDH2 and RARE-LacZ activity were restricted to the sinus venosa in unlooped hearts, but were high in the dorsal mesocardium, while P450RA expression was restricted to the endocardium. Later stages were characterized by a sequential, noncontiguous progression of RALDH2 accumulation and RA response, from the sinus venosa to atria, dorsal-medial conotruncus, aortic arches, and the epicardium. This dynamic pattern of RA response was a direct result of localized RALDH2, since hearts of cultured embryos were uniformly competent to respond to an exogenous RA challenge. These observations support a model in which the influence of endogenous RA on heart development depends upon localized presentation of the ligand, with only limited diffusion from the source of its synthesis.     

Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.     

Geometric and mechanical properties of the coracoacromial ligament and their relationship to rotator cuff disease

One of the most common causes of pain and disability in the upper limb is inflammation of the rotator cuff tendons. When no significant bony abnormality exists in the surrounding structures, the coracoacromial ligament has been implicated as a possible cause of impingement on the cuff tendons. Geometric and mechanical properties of 20 coracoacromial ligaments, 10 from shoulders with rotator cuff tears and 10 from normal shoulders, were accurately determined. In comparing rotator cuff tear and normal specimens, statistically significant changes in geometric properties were measured in the lateral band, but not in the medial band, of the ligament. The lateral band, which is the region most likely to impinge on the rotator cuff, was shorter and had a larger cross-sectional area in specimens with rotator cuff tears. Although there were no statistical differences in structural properties of the ligament between normal and rotator cuff tear groups, significant changes were evident in material properties. Previously reported histologic differences in the ligament in shoulders with rotator cuff tears are supported by the decreased material properties measured in the current study. Whether the differences in the coracoacromial ligament cause impingement or are due to impingement is still unknown at this time.     

BCL-2 overexpression attenuates cortical cell loss after traumatic brain injury in transgenic mice

The proto-oncogene, BCL-2, has been suggested to participate in cell survival during development of, and after injury to, the CNS. Transgenic (TG) mice overexpressing human Bcl-2 (n = 21) and their wild-type (WT) littermates (n = 18) were subjected to lateral controlled cortical impact brain injury. Lateral controlled cortical impact brain injury resulted in the formation of a contusion in the injured cortex at 2 days, which developed into a well-defined cavity by 7 days in both WT and TG mice. At 7 days after injury, brain-injured TG mice had a significantly reduced cortical lesion (volume = 1.99 mm3) compared with that of the injured WT mice (volume = 5.1 mm3, P < 0.01). In contrast, overexpression of BCL-2 did not affect the extent of hippocampal cell death after lateral controlled cortical impact brain injury. Analysis of motor function revealed that both brain-injured WT and TG mice exhibited significant right-sided deficits at 2 and 7 days after injury (P < 0.05 compared with the uninjured controls). Although composite neuroscores (sum of scores from forelimb and hind limb flexion, lateral pulsion, and inclined plane tests) were not different between WT and TG brain-injured mice, TG mice had a slightly but significantly reduced deficit in the inclined plane test (P < 0.05 compared to the WT mice). These data suggest that the cell death regulatory gene, BCL-2, may play a protective role in the pathophysiology of traumatic brain injury.     

Effect of intravenous pyridoxine on plasma prolactin in hyperprolactinemic subjects

Intravenous pyridoxine has been reported to lower plasma PRL in normal subjects and in patients with the amenorrhea-galactorrhea syndrome. We tested the effect of pyridoxine (300-mg iv bolus) on plasma PRL in nine patients with hyperprolactinemia due to a variety of causes. There was no effect of pyridoxine on elevated plasma PRL in any of the nine hyperprolactinemic subjects. The potential utility of pyridoxine in the long term treatment of the galactorhea-amenorrhea syndrome will require further study.