No abstract

The pseudohypoparathyroid disorders appear to represent a heterogeneous group with GNAS1 mutations forming the molecular aetiology in approximately 50% of pseudohypoparathyroidism type Ia families. Such mutations can be reliably identified by single-stranded conformational polymorphism and this will help to supplement the clinical evaluation of some patients and their families, particularly as the disease may not be fully penetrant.

Adipsic diabetes insipidus (ADI) occurs in association with a heterogeneous group of conditions. We report vasopressin (AVP) responses to hypotension in nine patients with ADI and nine controls. Hypertonic saline infusion produced absent thirst (1.7 +/- 1.7 to 1.5 +/- 1.7 cm, P = 0.99) and AVP responses (0.3 +/- 0.1 to 0.4 +/- 0.1 pmol/liter, P = 0.99) in the ADI group, who also drank less than the control group (258 +/- 200 ml vs. 1544 +/- 306 ml, P < 0.001). Intravenous infusion of trimetaphan camsylate produced a fall in mean arterial pressure of 31.6% +/- 8.9% in patients and 29.4% +/- 6.1% in controls. Plasma AVP concentrations rose from 1.4 +/- 0.8 to 340.3 +/- 497.4 pmol/liter (P < 0.001) in the control group. In three patients with craniopharyngioma, there was no rise in plasma AVP concentrations (0.3 +/- 0.1 to 0.3 +/- 0.1 pmol/liter, P = 0.96), but plasma AVP rose significantly in response to hypotension in the other six patients (0.4 +/- 0.2 to 204.5 +/- 223.2 pmol/liter, P < 0.001). We concluded that the AVP responses to hypotension in ADI are heterogeneous and reflect the site of the lesion causing the diabetes insipidus.

Large‐scale patterns of correlated growth in development are partially driven by competition for metabolic and informational resources. It is argued that competition between organs for limited resources is an important mesoscale morphogenetic mechanism that produces fitness‐enhancing correlated growth. At the genetic level, the growth of individual characters appears independent, or “modular,” because patterns of expression and transcription are often highly localized, mutations have trait‐specific effects, and gene complexes can be co‐opted as a unit to produce novel traits. However, body parts are known to interact over the course of ontogeny, and these reciprocal exchanges can be an important determinant of developmental outcomes. Genetic mechanisms underlie cell and tissue behaviors that allow organs to communicate with one another, but they also create evolutionarily adaptive competitive dynamics that are driven by physiological and biophysical processes. Advances in the understanding of competitive and closely related coordinative interactions across scales will complement existing research programs that emphasize the role of cellular mechanisms in morphogenesis. Study of the large‐scale order produced by competitive dynamics promises to facilitate advances in basic evolutionary and developmental biology, as well as applied research in fields such as bioengineering and regenerative medicine that aim to regulate patterning outcomes.

Plasma concentrations of ANP, but not BNP, rise in response to acute hyperglycaemia in Type 1 diabetes.