Distortion of chest wall and work of diaphragm in preterm infants

Chest wall distortion is common in infants and is especially visible in preterm infants. It has been suggested that this distortion increases the volume displacement of the diaphragm during inspiration, which may be associated with muscular fatigue and apnea. We studied 10 preterm infants who had no evidence of lung disease, investigating the effect of chest wall distortion on the volume displacement and work of the diaphragm. The volume changes of the respiratory system were partitioned using an inductance plethysmograph. The minute volume displacement and the work of the diaphragm were calculated using the partitioned abdominal volume change and the gastric and esophageal pressures. The paradoxical movement of the chest wall lasted an average of 36% of inspiration. The minute volume displacement of the diaphragm ranged from 72 to 176% of the minute pulmonary ventilation, and diaphragmatic work ranged from 94 to 793% of that performed on the lungs. The amount of chest wall distortion, as reflected by the duration of the paradoxical chest wall movement, the minute volume excursion, or work of the diaphragm, was not related to the mechanical properties of the lungs. This estimated work load may represent a significant expenditure of calories in these infants and may contribute to the development of diaphragmatic fatigue, apnea, and a prolonged need for mechanical ventilation.     

Immunoglobulin allotypes of Kenyan olive baboons: Troop frequencies,linkage disequilibria,and comparisons with other studies

Sera from a total of 564 olive baboons collected at six different localities in west central Kenya were examined for the presence of cross-reactive immunoglobulin allotypes with reagents used for human sera. Serum samples were tested for Km (1 and 3), Glm (1–3 and 17), andG3m (5, 6, 10, 11, 13–16, 21, 24, and 26). Polymorphism was found for Glm (1 and 17) and G3m (10, 13, and 15). These findings on antigen presence, absence, and polymorphism show broad similarities to, along with some differences from, previous studies of baboons. Our data support the view that there are variations in allotype frequencies between troops at single localities, as well as differences among geographically separated areas. Linkage disequilibria for Gm allotypes differ in strength and direction among the various local Kenya olive baboon populations.     

Guanethidine and Pupillary Reaction

Local application of guanethidine to the eye results in miosis. The sympathicolytic action of guanethidine on the pupil was proved by the consistent appearance of a Horner''s syndrome after instillation of a 10% solution into the conjunctival sac. Lack of cocaine mydriasis and unimpaired adrenaline mydriasis after guanethidine application are further evidence of this mode of action. Guanethidine is the first drug that can be consistently relied upon to produce miosis by inhibiting sympathetic impulses to the intraocular pupillary muscles; it also inhibits sympathetic impulses to Horner''s muscle of the upper lid. It is a reliable sympathicolytic agent for testing the reaction of abnormal pupils.     

ENTRANCE INTO STAGE III FASTING BY STARVELING NORTHERN ELEPHANT SEAL PUPS

Blood metabolites and urea kinetics were determined in starveling elephant seal pups to assess the transition to stage III fasting in this fasting-adapted species. Five postmolt and two premolt starvelings, denned as having a mass <50 kg, were studied until death or departure to sea. Premolt starvelings died on the rookery while postmolt starvelings departed to sea. Increased mass loss and a significant inverse relationship between mass and the ratio of blood urea nitrogen to creatinine suggested that premolt starvelings had enrered stage III starvation prior to death while urea kinetics suggested that postmolt pups engaged stage III starvation prior to departure. The mean rate of protein catabolism was estimated at 19.4 g/d for departing starvelings, twice the absolute rate and about four times the mass-specific rate estimated in healthy weanlings after eight weeks of fasting. Three starvelings stranded after departure, possibly as a result of thermoregulatory challenges and inefficient dive behavior. Entrance into stage III fasting interrupts the development of diving in emaciated pups (<50 kg) suggesting that an increased rate of protein catabolism might be linked to the cue to forage. This biochemical trigger is possibly different than the cue to feed in healthy weanlings, which depart the rookery with substantial fat stores.     

The eukaryotic cofactor for the human immunodeficiency virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12–p13: three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2

The eukaryotic initiation factor 5A (eIF-5A) has been identified as an essential cofactor for the HIV-1 trans-activator protein Rev. Rev plays a key role in the complex regulation of HIV-1 gene expression and thereby in the generation of infectious virus particles. Expression of eIF-5A is vital for Rev function, and inhibition of this interaction leads to a block of the viral replication cycle. In humans, four different eIF-5A genes have been identified. One codes for the eIF-5A protein and the other three are pseudogenes. Using a panel of somatic rodent—human cell hybrids in combination with fluorescence in situ hybridization analysis, we show that the four genes map to threedifferent chromosomes. The coding eIF-5A gene (EIF5A) maps to 17p12–p13, and the three pseudogenes EIF5AP1, EIF5AP2, and EIF5AP3 map to 10q23.3, 17q25, and 19q13.2, respectively. This is the first localization report for a eukaryotic cofactor for a regulatory HIV-1 protein.     

QUANTIFICATION OF ENTRY INTO AND EXIT FROM THE CELL CYCLE IN HUMAN LYMPHOCYTE CULTURES

A mathematical model is presented for the analysis of transition between cycling and non-cycling compartments by cells responding to a growth stimulus. the cellular age distribution as a function of time is derived from sequential [³H]thymidine pulse labeling indices. Rates of entry into and exit from the cycling compartment are determined on the basis of labeling indices obtained after instantaneous and long duration [³H]thymidine pulses. Analysis of an experiment involving sequential measurements over the whole lifespan of a human lymphocyte culture stimulated by phytohemagglutinin is presented as an example of the application of this method.     

Analysis of biological thiols: derivatization with monobromotrimethylammoniobimane and characterization by electrophoresis and chromatography

A new method for analysis of biological thiols based upon their conversion to fluorescent derivatives by reaction with monobromotrimethylammoniobimane (qBBr) is described. The derivatives are separated by chromatography and by electrophoresis on cellulose thinlayer chromatography plates. The use of two-dimensional mapping makes it possible to differentiate between a wide variety of biological thiols including N-acetylcysteine, CoA, cysteine, cysteinylglycine, cysteamine, ergothioneine, glutathione, γ-glutamylcysteine, homocysteine, mercaptopyrimidine, pantetheine, 4′-phosphopanetheine, thiosulfate, and thiouracil. For applications to biological samples thiols were isolated from crude extracts by binding to a mercuriagarose gel. Following removal from the gel with dithiothreitol, the thiols were derivatized with qBBr. The methods were tested by showing that glutathione is the major thiol in human red blood cells, that glutathione and ergothioneine are the major thiols in Neurospora crassa conidia, and that Bacillus cereus vegetative cells lack glutathione but contain cysteine, pantetheine, and an unidentified thiol in significant amounts.     

Phosphorylation-dependent binding of a synthetic MARCKS peptide to calmodulin

A 25-amino acid peptide, containing the four protein kinase C (PKC) phosphorylation sites and the calmodulin (CaM) binding domain of the myristoylated alanine-rich C kinase substrate (MARCKS) protein, has been synthesized and used to determine the effects of phosphorylation on its binding and regulation of CaM. PKC phosphorylation of this peptide (3.0 mol of Pi/mol of peptide) produced a 200-fold decrease in its affinity for CaM. PKC phosphorylation of the peptide resulted in its dissociation from CaM over a time course that paralleled the phosphorylation of 1 mol of serine/mol of peptide. The peptide inhibited CaM's binding to myosin light chain kinase and CaM's stimulation of phosphodiesterase and calcineurin. PKC phosphorylation of the peptide resulted in a rapid release of bound CaM, allowing its subsequent binding to myosin light chain kinase (t1/2 = 1.6 min), stimulation of phosphodiesterase (t1/2 = 1.2 min) and calcineurin (t1/2 = 1.7 min). Partially purified MARCKS protein produced a similar inhibition of CaM-phosphodiesterase which was reversed by PKC phosphorylation. PKC phosphorylation of the peptide occurred primarily at serine 8 and serine 12, and phosphorylation of serine 12 regulated peptide affinity for CaM. Thus, PKC phosphorylation of the peptide and the MARCKS protein results in the rapid release of CaM and the subsequent activation of CaM-dependent enzymes. This process might allow for interplay between PKC and CaM-dependent signal transduction pathways.     

Analysis of potassium conductance in squid giant axons

Assuming a model of facilitated ionic transport across axonal membranes proposed by McIlroy (1975) and extended by McIlroy and Hahn (1978), it is shown that if the selectivity coefficient, π_K, of the potassium conducting system ?59 the permeabilityP _Ks, of the periaxonal barrier of the squid giant axon for K⁺ ions?(1.2±0.44)×10^?4 cm sec^?1 and the thickness of the periaxonal space ?477±168 Å. Using a value (10^?4 cm sec^?1) ofP _Ks in the foregoing range the experimental curves for the steady state membrane ionic conductance versus measured membrane potential difference (p.d.), ?, of Gilbert and Ehrenstein (1969) are corrected for the effect of accumulation of K⁺ in the periaxonal space. This correction is most marked for the axon immersed in a natural ionic environment, whose conductance curve is shifted ?70mV along the voltage axis in the hyperpolarization direction. By assuming that the physico-chemical connection between a depolarization of the axonal membrane and the consequent membrane conductance changes is a Wien dissociative effect of the membrane's electric field on a weak electrolyte situated in the axolemma, the position of the peaks of the corrected conductance versus ? curves can be identified with zero membrane electric field and hence with zero p.d.across the axolemma. A set of values for the double-layer p.d.s at the axonal membrane interfaces with the external electrolytes in the vicinity of the K⁺ conducting pores can therefore be deduced for the various external electrolytes employed by Gilbert and Ehrenstein. A model of these double-layer p.d.s in which the membrane interfaces are assumed to possess fixed monovalent negatively charged sites, at least in the neighbourhood of the K⁺ conducting pores, is constructed. It is shown that, using the previously deduced values for the doublelayer p.d.s, such a model has a consistent, physically realistic solution for the distance between the fixed charged sites and for the dissociation constants of these sites in their interaction with the ions of the extramembrane electrolytes.