Spatially distinct head and heart inducers within the Xenopus organizer region.

BACKGROUND: The mouse anterior visceral endoderm, an extraembryonic tissue, expresses several genes essential for normal development of structures rostral to the anterior limit of the notochord and has been termed the head organizer. This tissue also has heart-inducing activity and expresses mCer1 which, like its Xenopus homolog cerberus, can induce markers of cardiac specification and anterior neural tissue when ectopically expressed. We investigated the relationship between head and heart induction in Xenopus embryos, which lack extraembryonic tissues. RESULTS: We found three regions of gene expression in the Xenopus organizer: deep endoderm, which expressed cerberus; prechordal mesoderm, which showed overlapping but non-identical expression of genes characteristic of the murine head organizer, such as XHex and XANF-1; and leading-edge dorsoanterior endoderm, which expressed both cerberus and a subset of the genes expressed by the prechordal mesoderm. Microsurgical ablation of the cerberus-expressing endoderm decreased the incidence of heart, but not head, formation. Removal of prechordal mesoderm, in contrast, caused deficits of anterior head structures. Finally, although misexpression of cerberus induced ectopic heads, it was unable to induce genes thought to participate in head induction. CONCLUSIONS: In Xenopus, the cerberus-expressing endoderm is required for heart, but not head, inducing activity. Therefore, this tissue is not the topological equivalent of the murine anterior visceral endoderm. We propose that, in Xenopus, cerberus is redundant to other bone morphogenetic protein (BMP) and Wnt antagonists located in prechordal mesoderm for head induction, but may be necessary for heart induction.

Effects of luteinizing hormone (LH)-releasing hormone pulse amplitude and frequency on LH secretion by perifused rat anterior pituitary cells.

Recent studies have shown that LH secretion in vivo is pulsatile. In the present study, a cell perifusion system was employed to characterize the pituitary response to changes in LHRH pulse amplitude and frequency. Increases in pulse amplitude consistently elevated both mean LH levels and the amount of LH released in response to individual LHRH pulses. The EC50 for LHRH was approximately 3 nM. Increases in pulse frequency also increased mean LH levels, but frequencies of three or more pulses per h were associated with a decrease in the amount of LH released per pulse. Alterations in LHRH pulse characteristics changed qualitative as well as quantitative aspects of LH secretion, with high frequency, high amplitude pulses producing a biphasic response to LHRH. Initially a self-priming response was seen during the second and third hours of stimulation; this was followed by increasing desensitization of the cultures to LHRH. These results, by defining the pituitary response to specific conditions of stimulation, will help to clarify the relationship of LHRH stimulation to LH secretion in vivo.

Gonadal steroids modulate pulsatile luteinizing hormone secretion by perifused rat anterior pituitary cells.

Recent studies have shown that LH secretion is pulsatile and that LH pulse characteristics are affected by the prevailing steroid environment in both male and female rats. In the present study, a cell perifusion system was used to examine the effects of testosterone (T) and 17 beta-estradiol (E) on LHRH-stimulated pulsatile LH secretion. T inhibited LH secretion, increasing the EC50 for LHRH, while E stimulated secretion, lowering the EC50. Steroid effects were independent of both LHRH pulse amplitude and frequency. E also affected the pattern of LH secretion by facilitating both LHRH self-priming and desensitization to LHRH. These results show that steroids can affect pulsatile LH secretion by actions exerted at the pituitary level and that steroids can induce both quantitative and qualitative changes in LH secretion in the presence of an invariant LHRH stimulus. These results help to elucidate the mechanisms underlying steroid feedback in vivo, since reduction in pituitary responsiveness to LHRH may play an important role in T feedback, while facilitation by E of both self-priming and desensitization may serve to increase the magnitude and shorten the duration of the proestrous LH surge.

Effect of age on cisternal cerebrospinal fluid concentrations of monoamine metabolites in nonhuman primates.

There are conflicting reports of the effects of aging on human neurotransmitter systems as estimated by monoamine metabolite concentrations in cerebrospinal fluid (CSF). These discrepancies may be due to sampling site, age or sex of the subjects or other variables that affect CSF metabolite determinations. Cisternal CSF concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenyl-ethylene glycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), major metabolites of dopamine, norepinephrine and serotonin, respectively, were measured in rhesus monkeys (Macaca mulatta) of two age groups. Concentrations of HVA and MHPG were significantly lower in the older group of monkeys, whereas no changes in 5-HIAA were found. This supports the hypothesis that brain catecholamine concentrations decline with age.

Combined effects of compression and hypotension on nerve root function. A clinical case.

Previous animal experiments suggest that mild compression may increase susceptibility of nerve roots to the effects of hypotension. The authors report the case of a patient with an unstable L2 burst fracture whose motor skills and senses were intact. During fracture reduction and spinal distraction, sensory-evoked potentials were recorded from the epidural space after right and left femoral and tibial nerve stimulation. Induced hypotension was used during the surgery. All responses were normal at the outset of the surgery. With hypotension, a marked drop in the amplitude of the right femoral evoked potential amplitude occurred; left femoral and both tibial responses remained unchanged. Evoked potential changes were reversible with reversal of hypotension. Postoperatively, the patient was neurologically intact. Further analysis revealed a significant correlation between the right femoral evoked potential amplitude and systolic blood pressure (r = 0.63, P < 0.005), whereas amplitudes of the other responses were not significantly correlated with systolic blood pressure. This report provides clinical evidence to support the hypothesis that hypotension and local compression exert additive adverse effects on nerve root function.

Evaluating a phone system: one approach.

Following is a guide which outlines both the financial and nonfinancial aspects to consider when evaluating different phone system proposals.

Wnt antagonism initiates cardiogenesis in Xenopus laevis.

Heart induction in Xenopus occurs in paired regions of the dorsoanterior mesoderm in response to signals from the Spemann organizer and underlying dorsoanterior endoderm. These tissues together are sufficient to induce heart formation in noncardiogenic ventral marginal zone mesoderm. Similarly, in avians the underlying definitive endoderm induces cardiogenesis in precardiac mesoderm. Heart-inducing factors in amphibians are not known, and although certain BMPs and FGFs can mimic aspects of cardiogenesis in avians, neither can induce the full range of activities elicited by the inducing tissues. Here we report that the Wnt antagonists Dkk-1 and Crescent can induce heart formation in explants of ventral marginal zone mesoderm. Other Wnt antagonists, including the frizzled domain-containing proteins Frzb and Szl, lacked this activity. Unlike Wnt antagonism, inhibition of BMP signaling did not promote cardiogenesis. Ectopic expression of GSK3beta, which inhibits beta-catenin-mediated Wnt signaling, also induced cardiogenesis in ventral mesoderm. Analysis of Wnt proteins expressed during gastrulation revealed that Wnt3A and Wnt8, but not Wnt5A or Wnt11, inhibited endogenous heart induction. These results indicate that diffusion of Dkk-1 and Crescent from the organizer initiate cardiogenesis in adjacent mesoderm by establishing a zone of low Wnt3A and Wnt8 activity.

Burn-associated peripheral polyneuropathy. A search for causative factors.

This study sought to evaluate the timing of burn-associated polyneuropathy (BAPN) and its relationship to burn severity or size. Seventeen burned subjects were studied 1 wk after thermal burns. Eleven subjects remained in the study to complete 6-wk follow-up studies. Nerve conduction studies were done on at least three nerves in two unburned limbs; results were numerically summarized by calculating Z scores for each parameter. A composite Z score, termed Ztotal, measured global nerve function. One week postburn, motor and sensory distal latencies were prolonged (mean Z, -0.72 and -0.85, respectively), motor conduction velocities slowed (mean Z, -1.31) and sensory nerve action potentials reduced in amplitude (mean Z, -0.66). Associations of Ztotal scores with total burn surface area and depth were not statistically significant. Those with severe neuropathy had higher levels of c-reactive protein (Spearman correlation, -0.624; P = 0.0129). There were no significant changes in Z scores at 6 wk. We conclude that BAPN is common after thermal injury, and the electrophysiologic manifestations of BAPN are present within the first week. Thermal injuries may induce an inflammatory cascade that results in alterations of nerve function.