A theoretical and experimental study of ionic shifts induced by K depletion and replacement.

The mutual synchronization or entrainment of inter-connected self-oscillatory systems is relevant in a number of biological models. It forms the basis of a currently-accepted model for the electrical “slow-wave” activity in the mammalian gastro-intestinal tract, and is of interest in oscillator population studies for circadian rhythm research. In this paper, conditions of almost-entrainment when periodic fluctuations in amplitude and/or frequency occur are analysed using the method of harmonic balance. The effects of oscillator non-linearity and different types of coupling component are demonstrated, and results are compared with spectral analysis of simulated oscillators.     

Immunity to Heligmosomoides polygyrus induced by subcutaneous vaccination with post-infection larvae

The objective of this study was to investigate, using the Heligmosomoides polygyrus (= Nematospiroides dubius)-mouse model, whether live post-infection trichostrongylid larvae recovered from the intestinal wall of donor animals and placed subcutaneously would serve as vaccine protecting against oral challenge by third-stage (infective) larvae (L3). Experiments were conducted to determine the effect of number and age of post-infective larvae as well as age and sex of host on vaccination. Vaccinated BALB/cByJ mice were challenged with 30 L3 and total adult worm burdens compared between vaccinated groups and sham-treated controls (greater than 90% infection rates). All mice subcutaneously vaccinated with either five or 10 larvae harbored significantly fewer challenge parasites in their intestines than did sham-treated controls (P less than 0.001). Both young and mature mice were significantly protected against challenge by the subcutaneous larval vaccine. Adult female mice had significantly (P less than 0.05) fewer parasites than adult male mice. The age of the larvae (indicated as the days between infection and harvesting of the larvae) was important in that day-4 or day-6 larvae (L4) were significantly more protective (P less than 0.001) than day-2 (L3) or day-8 larvae (L5-preadult). Reduction in worm burden for young vaccinated animals ranged from 31 to 39% (P less than 0.001) and for mature animals from 88 to 100% (P less than 0.001). Passive transfer to serum resulted in the reduction of worm burdens by 26-40% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of the substrate dissociation constant of a solubilized membrane carrier. Substrate stabilization of OxlT, the anion exchange protein of Oxalobacter formigenes.

OxlT, a secondary carrier found in Oxalobacter formigenes, mediates the exchange of divalent oxalate and monovalent formate. Because OxlT has an unusually high turnover number (greater than or equal to 1000/s), and because formate, one its substrates, shows high passive membrane permeability as formic acid, it has been difficult to obtain information on protein-substrate interactions using traditional methods in membrane biology. For this reason, we devised a new way to measure substrate dissociation constants. Detergent-solubilized material was exposed to inactivating temperatures in the absence or presence of OxlT substrates, and periodic reconstitution was used to monitor the kinetics of thermal decay. The data were consistent with a simple scheme in which only unliganded OxlT was temperature-sensitive; this premise, along with the assumption of equilibrium between liganded and unliganded species, allowed calculation of substrate dissociation constants for oxalate (18 +/- 3 microM), malonate (1.2 +/- 0.2 mM), and formate (3.1 +/- 0.6 mM). Further analysis revealed that substrate binding energy contributed at least 3.5 kcal/mol to stabilization of solubilized OxlT. Accordingly, we suggest that substrate binding energy is directly involved in driving protein structure reorganization during membrane transport. This new approach to analyzing protein-substrate interactions may have wider application in the study of membrane carriers.     

Myocardial Revascularization in High-Risk Coronary Patients

It is recognized that postoperative mortality, infarction and the need for inotropic support are increased following myocardial revascularization in highrisk patients. Operations were carried out in 57 such patients in whom one or more of the following factors were present: ventricular dysfunction—ejection fraction less than 0.4 (17), unstable (8) or preinfarction angina (29), evolving infarction (8), recent infarction (less than two weeks before) (5) and refractory ventricular tachyarrhythmia (4). Combined risk factors were present in nine patients. The following principles were utilized to minimize ischemic injury: (1) avoidance of prebypass hypertension and hypotension, (2) avoidance of extreme hemodilution, (3) avoidance of ventricular fibrillation, (4) maintenance of beating empty heart, when possible, (5) the limiting of ischemic periods to less than 12 minutes (hypothermia 32°C) and (6) repaying myocardial oxygen debt with total (vented) bypass, when necessary. The following results were obtained: inotropic support was required in five patients (9 percent), “new” postoperative infarction occurred in five patients (9 percent) and one patient died (2 percent). These results are comparable to those reported in good-risk patients, and indicate that optimal myocardial protection will allow safe revascularization in a high-risk patient.     

GRANULOCYTE DYNAMICS AND THE QUESTION OF INEFFECTIVE GRANULOPOIESIS

A simple analysis was developed to compare granulocyte production in marrow with granulocyte turnover in peripheral blood of the dog. the analysis is anchored to the relative number of granulopoietic and erythropoietic cells that are flashlabeled with tritiated thymidine. This provides a convenient measure of relative production rates, since there is little, if any, difference in the duration of the respective DNA synthesis periods. the latter was confirmed in the present work by comparison of myeloid and erythroid cells in respect to (1) labeled mitosis curves and (2) changes in labeling intensity with constant infusion of tritiated thymidine. the ratio of flash-labeled granulocyte to erythrocyte progenitors was unity (1.02 ± 0.05) in the eight dogs studied, which means that gross production rates were essentially the same. Since net production as revealed by peripheral blood turnover is greater for erythrocytes than for granulocytes, it follows that there must be some ineffective granulopoiesis. This may correspond to over half of the total production. It is suggested that this phenomenon, which apparently occurs in man as well as in dog, could represent an important feature of granulocyte regulation.