Mapping the site of interaction between murine IgE and its high affinity receptor with chimeric Ig

We have investigated the interaction of mouse (m) IgE with its Fc epsilon RI on rat basophilic leukemia cells using a set of chimeric Ig that were constructed by exchanging homologous H chain C domains between human (hu) IgG1 and mIgE. Binding affinities were examined with equilibrium and kinetic measurements, and we found that epsilon/C gamma 3 (mIgE with C epsilon 4 replaced by C gamma 3) was indistinguishable from mIgE. The huIgG1 and the other chimeric Ig, which did not contain both C epsilon 2 and C epsilon 3, did not bind detectably to rat basophilic leukemia cells (Ka less than 10(6) M-1). The ability of these chimeric Ig to stimulate a cellular response (degranulation) in the presence of multivalent Ag was also tested. The epsilon/C gamma 3 was indistinguishable from mIgE in eliciting a high level of degranulation, whereas the other chimeric Ig stimulated no response even when they were preaggregated to enhance their binding avidity. These results demonstrate that C epsilon 4 may be replaced by C gamma 3 without affecting the binding and cell activating properties of mIgE. The lack of binding by the other chimeric Ig indicates that both C epsilon 2 and C epsilon 3 are necessary for the binding interaction.     

Changes in glycosylated haemoglobin after poor control in insulin-dependent diabetics.

Glycosylated haemoglobin (HbA1) was measured in seven insulin-dependent diabetic patients before, during, and after a seven-day period of monitored poor control. There was considerable individual variation in the pattern and degree of change in HbA1 concentration induced by poor control and the time when it occurred. Greater increases in HbA1 were seen during the period of metabolic derangement than in the subsequent two months. More information is required before HbA1 estimations are widely used clinically to monitor control in individual diabetics.     

Phenotypic plasticity in Daphnia magna Straus: variable maturation instar as an adaptive response to predation pressure

Life history responses of four Daphnia magna clones at two food levels were studied to assess the importance of maturation instar on the plasticity of fitness responses under simulated mortality regimes. Females of the clones studied could vary offspring size with consequent effects on their maturation time. Significant genetic variability in life history and fitness responses, measured as the intrinsic rate of population increase, within and across food levels was observed, but most of this variation could be attributed to maturation instar differences among clones within and across environments. In the laboratory, without extrinsic mortality, females maturing earlier always had higher fitness than those maturing later, indicating a clear fitness cost of delaying maturity. Nevertheless using a model, we showed that the observed maturation instar effects on life history responses can lead to differences in fitness under different size-selective predation regimes, such that females with delayed maturity have higher fitness under invertebrate predation while females maturing earlier have higher fitness under fish predation regimes. These results suggest that intraclonal variation in offspring size and hence in the number of maturation instars can be an adaptation to living in habitats subject to temporal fluctuations in fish and invertebrate predation pressure.     

Synthesis and in vitro bioactivity of C-terminal deleted analogs of human growth hormone-releasing factor

A series of C-terminal deleted analogs of human growth hormone-releasing factor (hGRF) with either an amidated or a free carboxylic acid C-terminus were synthesized by solid phase methodology. Their capacity to release growth hormone was tested on rat anterior pituitary cells in monolayer culture. A gradual decrease of bioactivity down to 23% relative to hGRF was noted when the C-terminal amino acids were deleted to hGRF (1-34)OH. Further deletions, however, did not decrease the bioactivity because the potencies of the fragments, hGRF(1-31)NH2, (1-30)NH2 and (1-29)NH2 remained at about 50% of that of hGRF. Continual deletion of residues to hGRF(1-23)NH2, (1-22)NH2 and (1-21)NH2 still yielded bioactive fragments with full intrinsic activity despite very low potency. Only with the deletion down to hGRF(1-19)NH2 did the bioactivity completely disappear. Thus, together with the data published in a previous paper (1), the minimal biologically active core of hGRF with full intrinsic activity comprises the fragment (3-21).     

Initial Intensive Care in an Accident and Emergency Department

The work in the resuscitation room is initial intensive care. This must be always available independent of inpatient resources. This demands investment in adequate equipment and staffing. Much of the work is medical rather than surgical and appropriate for physicians to treat. Our experience might help others to plan for the future.