Neonatal respiratory distress: potential for prevention.

A prospective study was conducted of 100 consecutive admissions to the neonatal intensive care unit of the Hospital for Sick Children, Toronto, of infants with respiratory distress syndrome or transient tachypnea of the newborn. It was found that in 15% of cases the illness was completely preventable, being the result of unintentionally premature termination of pregnancy. Significant intrapartum asphyxia occurred in 44% of the infants in whom respiratory distress syndrome developed. Factors placing the pregnancy at high risk were present antenatally in most cases, and most of the deliveries took place in hospitals without adequate facilities or staff, or both, for the requirements of the infant at and following birth.     

A 31P-NMR study of tissue respiration in working dog muscle during reduced O2 delivery conditions.

To investigate the role of tissue oxygenation as one of the control factors regulating tissue respiration, 31P-nuclear magnetic resonance spectroscopy (31P-NMR) was used to estimate muscle metabolites in isolated working muscle during varied tissue oxygenation conditions. O2 delivery (muscle blood flow x arterial O2 content) was varied to isolated in situ working dog gastrocnemius (n = 6) by decreases in arterial PO2 (hypoxemia; H) and by decreases in muscle blood flow (ischemia; I). O2 uptake (VO2) was measured at rest and during work at two or three stimulation intensities (isometric twitch contractions at 3, 5, and occasionally 7 Hz) during three separate conditions: normal O2 delivery (C) and reduced O2 delivery during H and I, with blood flow controlled by pump perfusion. Biochemical metabolites were measured during the last 2 min of each 3-min work period by use of 31P-NMR, and arterial and venous blood samples were drawn and muscle blood flow measured during the last 30 s of each work period. Muscle [ATP] did not fall below resting values at any work intensity, even during O2-limited highly fatiguing work, and was never different among the three conditions. Muscle O2 delivery and VO2 were significantly less (P < 0.05) at the highest work intensities for both I and H than for C but were not different between H and I. As VO2 increased with stimulation intensity, a larger change in any of the proposed regulators of tissue respiration (ADP, P(i), ATP/ADP.P(i), and phosphocreatine) was required during H and I than during C to elicit a given VO2, but requirements were similar for H and I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the hinge protein on the heme iron site of cytochrome c1

X-ray absorption spectroscopic (XAS) studies on cytochrome C1 from beef heart mitochondria were conducted to identify the effect of the hinge protein [Kim, C.H., & King, T.E. (1983) J. Biol. Chem. 258, 13543-13551] on the structure of the heme site in cytochrome c1. A comparison of XAS data of highly purified "one-band" and "two-band" cytochrome c1 [Kim, C.H., & King, T.E. (1987) Biochemistry 26, 1955-1961] demonstrates that the hinge protein exerts a rather pronounced effect on the heme environment of the cytochrome c1: a conformational change occurs within a radius of approximately 5 A from the heme iron in cytochrome c1 when the hinge protein is bound to cytochrome c1. This result may be correlated with the previous observations that the structure and reactivity of cytochrome c1 are affected by the hinge protein [Kim, C.H., & King, T.E. (1987) Biochemistry 26, 1955-1961; Kim, C.H., Balny, C., & King, T.E. (1987) J. Biol. Chem. 262, 8103-8108].     

Reduction of tumor growth following treatment with a glutamine antimetabolite

Assessment of arterial-venous differences across transplanted methylcholanthrene-induced sarcomas in rats revealed significant decreases in plasma concentrations of glutamine, serine and glucose. Treatment with the glutamine antimetabolite, acivicin, significantly reduced tumor weights by 65% at the conclusion of the experiment 34 days after tumor induction. These results suggest that glutamine is an essential metabolic substrate for tumor growth and that blockade of glutamine utilization can inhibit the growth of these transplantable sarcomas.     

Movement of Fe with respect to the heme plane in the R-T transition of carp hemoglobin. An extended x-ray absorption fine structure study

Carp Hb undergoes a well known change in kinetics over the pH range 6-9. X-ray absorption spectroscopy, in conjunction with refined data analysis procedures, shows no difference in iron-ligand distances when carp HbCO is switched from R (high affinity) to T (low affinity) states. These distances are 2.015 +/- 0.015 A for the average iron-pyrrole nitrogen distance, 2.14 +/- 0.04 A for the iron-nitrogen (of histidine) distance, and 1.89 +/- 0.05 A for the Fe-C (of CO) distance. Examination of the region from 30 to 100 eV above the threshold, called the ligand field indicator region, reveals spectral differences, which when compared to model compounds suggest that the iron and the heme are less coplanar in the T-like forms. These results are consistent with the iron being 0.1 A more out of the mean heme plane in both carp HbCO and carp Hb T states, relative to the R forms, and that the change in iron position on ligation to either T or R state is four times larger than that occurring with the quaternary switch.