Substance P-inducing massive postmortem bronchoconstriction in guinea pig lungs

To further examine the role that substance P plays in initiating the observed massive postmortem bronchoconstriction in guinea pig lungs and to explore the role of neural reflex in this airway spasm, six groups of animals were employed: control (n = 6), morphine (n = 6), substance P (n = 5), chronic capsaicin pretreatment + substance P (n = 5), tetrodotoxin (TTX) + acute capsaicin (n = 4), and chlorisondamine + acute capsaicin (n = 5). Pressure-volume curves were performed prior to and following the initiation of artificial pulmonary perfusion with 1% bovine serum albumin and 5% dextran in Tyrode's solution. A decrease in inflation volume (the lung volume between transpulmonary pressure of 0 and 30 cmH2O during inflation) was used as an index of bronchoconstriction. In control animals, inflation volume decreased to 20-30% of the base-line value at 15-30 min of perfusion, indicating massive bronchial constriction during this time period. Morphine (an agent inhibiting substance P release) significantly attenuated the spasm, whereas the presence of substance P in the perfusate markedly enhanced the constriction. Depletion of endogenous substance P by chronic capsaicin pretreatment did not affect exogenous substance P-induced spasm. Acute capsaicin-induced bronchoconstriction was significantly attenuated by TTX but was not affected by the ganglionic blocking agent, chlorisondamine. These data suggest that substance P initiates the massive postmortem bronchoconstriction in guinea pig lungs and that substance P is released by local stimulation of sensory nerve endings via axonal reflex.     

Increased incidence of developmental anomalies among descendants of carriers of methylenebisacrylamide-induced balanced reciprocal translocations

N,N'-Methylenebisacrylamide (MBA), a dimer of the monomeric acrylamide, was studied for induction of clastogenic effects in germ cells of male mice. It was found to be effective in inducing dominant-lethal mutations and heritable translocations in maturing sperm. The semisterile translocation carriers and their normal counterparts were used to determine the health impact of transmitted chromosomal rearrangements through anatomical analysis of their immediate descendants in utero. As expected, semisterility resulted primarily from embryonic death during the periimplantation stages presumably caused by sperm segregants with unbalanced chromosome complement fertilizing some of the eggs. Among conceptuses that survived to mid- and late-gestation stages, there was an increased incidence of developmental anomalies including fetal death and phenotypic defects. These anomalies are assumed to be caused by certain types of unbalanced segregants that are compatible with survival beyond the periimplantation period. This class of unbalanced segregants represent in humans a major health problem to the mother and her conceptus.     

Specific binding sites for prohormone atrial natriuretic peptides 1-30, 31-67 and 99-126

Two peptides with vasodilatory properties consisting of amino acids 1-30 and 31-67 of the 98 a.a. N-terminal end of the prohormone of atrial natriuretic factor (proANF) which circulates in man were investigated to determine if they have specific binding sites on membranes isolated from DDT1 MF-2 smooth muscle cells. Smooth muscle is a known biologic target of these peptides. Competitive binding experiments revealed that proANFs (1-30), (31-67), and (99-126) (i.e., C-terminus; ANF) each had specific and separate binding sites. The dissociation constants for proANFs (1-30), (31-67), and (99-126) binding were 0.11 nM, 4 nM, and 7.3 nM, respectively. The binding site concentrations for proANFs (1-30), (31-67), and ANF were 2.57, 59.91 and 40 fmols/10(6) cells, respectively. The number of binding sites per cell were 1548, 36,087, and 24,090, respectively, for proANFs (1-30), (31-67), and (99-126) (ANF). Each peptide bound to DDT1 MF-2 membranes between 10(-8) to 10(-11) M but could only bind to the other peptides' receptors at concentrations of 10(-6) and 10(-7)M. These results suggest that proANF(1-30) and proANF(31-67) do not work through the ANF receptor but rather have their own separate and distinct receptors that mediate their biologic effects.     

Detecting non-neutral heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence

Natural selection, in the form of balancing selection or selective sweeps, can result in a decoupling of the amounts of molecular polymorphism and divergence. Thus natural selection can cause some areas of DNA sequence to have greater silent polymorphism, relative to divergence between species, than other areas. It would be useful to have a statistical test for heterogeneity in the polymorphism to divergence ratio across a region of DNA sequence, one that could identify heterogeneity greater than that expected from the neutral processes of mutation, drift, and recombination. The only currently available test requires that a region be arbitrarily divided into sections that are compared with each other, and the subjectivity of this division could be problematic. Here a test is proposed in which runs of polymorphic and fixed sites are counted, where a "run" is a set of one or more sites of one type preceded and followed by the other type. The number of runs is smaller than otherwise expected if polymorphisms are clumped together. By simulating neutral evolution and comparing the observed number of runs to the simulations, a statistical test is possible which does not require any a priori decisions about subdivision.      

Identifying resuspended particles using isotope ratios

Three simple methods were developed to estimate the proportion of particles in lake water derived from resuspended material. These techniques use the different distributions of long and short-lived radioisotopes sorbed onto particles and were tested in the three basins of Lake Erie using ⁷Be, ¹³⁷Cs and ²¹⁰Po/²¹⁰Pb.While the concentration of ²¹⁰Po on particles did not vary significantly in the lake, resuspended particles were characterized by high concentrations of ¹³⁷Cs and low concentrations of ⁷Be. The distribution of these radioisotopes is consistent with a simple mixing model in which the fraction of particles in the lake water derived from resuspension ranged from 8% to about 100%. Higher concentrations of resuspended particles were found in deeper samples from the nepheloid layer and in the shallow western basin where thermal stratification was very weak.     

Blockade of alpha-adrenergic receptors by analogues of phosphatidylcholine

The experimental evidence reviewed in this article suggests that the kidneys may have an additional function in regulating blood pressure besides their role in controlling both blood volume by urine formation and the relative state of vasoconstriction by the renin-angiotensin system. That is, the kidneys may have an additional influence upon the vasculature of a hormonal vasodilating system. The interstitial cells of the renal medulla appear to be mediating this activity and lipid compounds have been extracted from the renal medulla which display depressor activity. One such compound, the antihypertensive polar renomedullary lipid (APRL), has been demonstrated to consist of specific alkyl ether analogues of phosphatidylcholine. The vascular responses to these compounds include vasodilation of both arterioles and venules, rapid lowering of arterial blood pressure with little or no tachycardia, increased depressor activity in hypertensive animals, and blockade of vascular smooth muscle alpha 1-adrenergic receptors. Most recently, APRL and a synthetic analogue, 1-0-octadecyl-2-acetyl-sn-glycero-3-phosphorylcholine, have been used to demonstrate alpha-adrenergic receptor blockade on a smooth muscle cell line (DDT1) by radioligand assays. This action may be due to the insertion of these compounds into cell membranes causing subsequent steric interactions and blockade of the alpha-adrenergic receptor.     

Cellular lysis of Streptococcus faecalis induced with triton X-100.

Lysis of exponential-phase cultures of Streptococcus faecalis ATCC 9790 was induced by exposure to both anionic (sodium dodecyl sulfate) and nonionic (Triton X-100) surfactants. Lysis in response to sodium dodecyl sulfate was effective only over a limited range of concentrations, whereas Triton X-100-induced lysis occurred over a broad range of surfactant concentrations. The data presented indicate that the bacteriolytic response of growing cells to Triton X-100: (i) was related to the ratio of surfactant to cells and not the surfactant concentration per se; (ii) required the expression of the cellular autolytic enzyme system; and (iii) was most likely due to an effect of the surfactant on components of the autolytic system that are associated with the cytoplasmic membrane. The possibility that Triton X-100 may induce cellular lysis by releasing a lipid inhibitor of the cellular autolytic enzyme is discussed.