Plasmodium berghei: a mouse model for the "sudden death" and "malarial lung" syndromes

A mouse model for the "sudden death" and "malarial lung" syndromes is described. Mice of the C3H/z strain succumb suddenly approximately 7 days after an infection with Plasmodium berghei becomes patent, at a time when parasitemia is still moderate (6 to 8%). Death could be shown to be due to anaphylactoid shock, probably induced by soluble immune complexes. Increased vascular permeability caused transudation and leakage of serum proteins into the interstitium and the alveoli. The lungs were found to be edematous, with a fine granular precipitate in the alveoli and adherent to the vascular walls. The precipitates reacted with antiglobulins G and M, and could be shown to also contain malaria antigens and C3/4. A dramatic drop in hematocrit was recorded several hours before death, indicating the sudden release of malaria antigens. The myocardium of animals that had died very suddenly showed a patchy loss of phosphorylase activity. This loss of activity was much more extensive, and sometimes almost total, when there had been an agonal period of several (1 to 3) hours before death. In these cases the irreversibility of the myocardial damage was also indicated by the loss of activity of the dehydrogenases, as well as by typical inflammatory reactions of granulocytic and histiocytic infiltrations. The hearts thus presented a typical picture of the acute and peracute shock syndromes. In acute shock cardiac insufficiency develops so suddenly that death ensues before irreversible damage has occurred, and cardiac insufficiency can only be demonstrated by the most sensitive of enzyme histochemical means. In the present case shock was induced by the anaphylactoid activity of immune complexes with the lung as target organ. The described syndrome appears analogous to human "malarial lung."     

Proton magnetic resonance studies of 7 Fe ferredoxins: Lower potential of the [4 Fe–4 S] redox center than the [3 Fe–3 S] cluster

Two types of iron-sulfur clusters, [3 Fe–3 S] and [4 Fe–4 S], were identified by ¹H-NMR in ferredoxins from Thermus thermophilus, Mycobacterium smegmatis and Pseudomonas ovalis. The [4 Fe–4 S] clusters always showed the redox couples which had potentials lower than that of the [3 Fe–3 S] clusters.     

Calcium-dependent activation and deactivation of rod outer segment phosphodiesterase is calmodulin-independent

ATP-dependent activation and deactivation of retinal rod outer segment phosphodiesterase is affected by calcium [Kawamura, S. and Bownds, M. D., J. Gen. Physiol. 77:571-591(1981)]. Our data demonstrate that although calmodulin has been found in rod outer segments [Liu, Y. P. and Schwartz, H., Biochim. Biophys. Acta 526:186-193(1978); Kohnken, R. E. et al, J. Biol. Chem. 256:12517-12522(1981)], this protein is not involved in calcium-dependent phosphodiesterase activation at light levels at which calcium clearly affects this enzyme's activity. Furthermore, calmodulin does not mediate the calcium-dependent deactivation of phosphodiesterase.     

Effects of terbium on the hemocyanin pore formation rate in phosphatidylcholine planar bilayers

Megathura crenulata hemocyanin forms ionic channels in planar lipid bilayer membranes. It was found that hemocyanin is more potent as a channel former if TbCl₃ is added to the bathing solution. Furthermore membranes separating symmetrical TbCl₃ solutions show a pore formation rate which depends exponentially on the applied voltage, positive potentials favouring the insertion of new channels. The slope of this voltage dependence, which gives a measure of the effective charge displaced during the incorporation of one channel, increases and saturates with TbCl₃ concentration. The dose response curve indicates that binding of Tb³⁺ to the phosphatidylcholine bilayer is involved in creating the effective charge.     

Monoclonal antibody-directed immunopurification and identification of cytochromes P-450

A 28 amino acid peptide with diuretic and natriuretic activity has been purified from rat atrial muscle. The primary structure of this atrial peptide is H-Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly- (sequence in text) Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-(Arg)-Tyr-OH. The biological activity of this peptide is identical to that of atrial natriuretic factor and cardionatrin I isolated from rat atria.     

alpha-N-acetyl-beta-endorphin1-26 from the neurointermediary lobe of the rat pituitary: isolation, purification, and characterization by high-performance liquid chromatography

The neurointermediary lobes from 190 rat pituitaries were homogenized in an acidic medium which inhibits peptidase activity and maximizes the solubilization of undamaged peptides. Octadecylsilyl-silica (ODS-silica) was used to extract the supernatant of the tissue homogenate. The ODS-silica eluate, now largely protein and salt free, was subjected to reversed-phase high-performance liquid chromatography (HPLC) employing 0.1% trifluoroacetic as counter ion. The column eluates were monitored for beta-endorphin immunoreactivity. Five immunoreactive components were observed. The most hydrophobic of these was repurified on the same HPLC column using 0.13% heptafluorobutyric acid as counter ion. Characterization of the purified peptide by gel permeation HPLC, amino acid analysis, and tryptic fragmentation indicated that it corresponded in structure to alpha-N-acetyl-beta-endorphin1-26. Amino acid analysis of the native peptide and its trypsin and carboxypeptidase fragments indicated that an alanyl residue occupies position 26. This finding is in contrast to the sequence predicted for the beta-lipotropin/corticotropin precursor by recombinant DNA techniques which suggests that the 26th residue of the beta-endorphin molecule should be valine.     

Changes in composition and function of thylakoid membranes as a result of photosynthetic adaptation of chloroplasts from pea plants grown under different light conditions

The hypothesis that chloroplasts having different light-saturated rates of photosynthesis will have different proportions of the intrinsic thylakoid complexes engaged in light-harvesting and electron transport (Anderson, J.M. (1982) Mol. Cell. Biochem. 46, 161–172) has been tested. Peas were grown in light regimes which varied in light intensity, quality and time of irradiance, and ranged from sunlight through red to blue-enriched light of very low radiation. The electron-transport capacity at saturating light of Photosystem I and Photosystem II of chloroplasts isolated from light-adapted peas was 2-fold and 5–6-fold lower, respectively, in the lowest radiation compared to sunlight. There was a marked increase in the amount of total chlorophyll associated with the main chlorophyll $\text{a}\text{b-}\text{proteins}$ (LHCP¹, LHCP² and LHCP³) and a 2-fold decrease in the core reaction centre complex of Photosystem II (CP a) as the radiation decreased; the $\text{LHCP}{}^{\mathrm{1–3}}\text{CP}$ a ratio changed from 3.5 to 9.0. The amount of chlorophyll associated with Photosystem I varied from 34% in sunlight to 27% in the lowest radiation, but the antenna size of Photosystem I was not markedly different; there was a 2-fold decrease in the amount of cytochrome f on a chlorophyll basis, which partly accounted for the decreased electron-transport capacity of Photosystem I. Since the increases or decreases in the levels of each of the components correlated with decreasing radiation, it is clear that the light-adaptation of both light-harvesting and electron-transport components is indeed closely co-ordinated.     

Testosterone 5 alpha-reductase in rat brain

We describe a simple procedure for the microassay of testosterone 5 alpha-reductase in homogenates of rat brain. This enzyme converts testosterone to dihydrotestosterone. We have used this assay to characterize the enzymatic activity and to map its distribution. The apparent Km is 4.1 x 10(-6) M and the Vmax is 85.6 pmol/mg protein/h. The pH optimum is broad and extends from pH 6.0 to 8.0. For the brain regions surveyed, testosterone 5 alpha-reductase activity varied over a 10-fold range. The highest activities were observed in homogenates of the midbrain and pons (37-39 pmol/mg protein/h). The lowest were seen in homogenates of the thalamus, caudate nucleus, frontal cortex, hippocampus, hypothalamus, olfactory tubercle, and preoptic area (3-7 pmol/mg protein/h).     

Norepinephrine Metabolism in Humans Studied by Deuterium Labelling: Turnover of 4–Hydroxy-3–methoxyphenylglycol

Abstract: D, L(±)-4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with three deuterium atoms was used to study turnover of plasma free HMPG following an intravenous injection. Ten healthy men were given a pulse dose of either 4.3 μmol or 2.2 μmol of labelled HMPG ([²H₃]HMPG piperazine salt). Plasma and urine levels of both endogenous and labelled HMPG were subsequently followed by gas chromatography-mass spectrometry with selected ion detection. Kinetic calculations based upon a single-compartment model were consistent with a monoexponential elimination of plasma free HMPG. The half-life of HMPG was 0.46 and 0.78 h (mean values in the two dose groups). The HMPG production rate was 2.01 and 2.35 μmol/hour, and the urinary excretion rate of HMPG (free and conjugated) was 0.48 and 0.47 μmol/h. The endogenous plasma level of free HMPG was 25 and 33 nmol/L. The results show that HMPG turns over rapidly and that HMPG is further metabolized extensively. About one-fourth of the HMPG produced is excreted in urine as free and conjugated HMPG.