Rapid repression of quiescence-specific gene expression by epidermal growth factor, insulin, and pp60v-src.

We isolated a cDNA for p20K, a secreted protein preferentially synthesized in nonproliferating cells. p20K mRNA and protein levels declined rapidly following treatment with various mitogens. DNA sequence analysis of the p20K cDNA predicted a novel protein distantly related to alpha 2 mu-globulin and plasma retinol-binding protein.     

Degradation of bradykinin and its metabolites by rat brain synaptic membranes

Bradykinin (BK) (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) was degraded by rat brain synaptic membranes at a rate comparable to that found for Met-enkephalin, but approximately 40 times the rate for vasopressin and oxytocin. The catabolic pathway for BK and its metabolites was elucidated through the use of high performance liquid chromatography for metabolite identification and peptidase inhibitors for blocking specific cleavage sites. BK was hydrolyzed at three sites: at the -Phe5-Ser6- bond by metalloendopeptidase 24.15, at the -Pro7-Phe8- bond by an apparently novel peptidyl dipeptidase, and at the -Phe8-Arg9 bond by a carboxypeptidase B-like enzyme. Each enzyme contributed about equally to BK degradation under the assay conditions used. Some of the resulting metabolites were further hydrolyzed: BK(1-8) to BK(1-7) + Phe by a DFP inhibitable prolyl carboxypeptidase-like enzyme, BK(1-8) to BK(1-5) + BK(6-8) by metalloendopeptidase 24.15, BK(1-7) slowly to BK(1-5) by a second peptidyl dipeptidase which was captopril inhibited, and Phe-Arg to Phe + Arg by a bestatin-inhibited dipeptidase. A number of properties of the individual enzymes were determined including sensitivity to a variety of peptidase inhibitors. These results provide a starting point for investigating the potential physiological role of each enzyme in BK function in the brain.     

An endogenous 'hypertensive factor' enhances the voltage-dependent calcium current

The effects of an immunoaffinity-purified putative endogenous hypertensive factor (HF) on voltage-dependent calcium current in frog cardiac myocytes were assessed. In 9 out of 10 cells, HF reversibly increased the peak amplitude of the calcium current. HF increased peak calcium current density at -5 mV from a control level of 1.8 +/- 1.3 pA/pF (mean +/- SD) to 4.4 +/- 2.0 pA/pF. HF shifted the peak of the calcium current-voltage relationship in the hyperpolarizing direction. HF shifted the voltage dependence of the inactivation of the calcium current to more negative potentials with prepulses from -80 to 0 mV, but the inactivation was not affected with prepulses more positive than 0 mV. Modulation of the voltage-dependent calcium current by HF may be the mechanism underlying its pressor effects.     

Discrimination of jittered sonar echoes by the echolocating bat,Eptesicus fuscus: The shape of target images in echolocation

1. Behavioral experiments with jittering echoes examined acoustic images of sonar targets in the echolocating bat, Eptesicus fuscus, along the echo delay or target range axis. Echo phase, amplitude, bandwidth, and signal-to-noise ratio were manipulated to assess the underlying auditory processes for image formation. 2. Fine delay acuity is about 10 ns. Calibration and control procedures indicate that this represents temporal acuity rather than spectral discrimination. Jitter discrimination curves change in phase when the phase of one jittering echo is shifted by 180 degrees relative to the other, showing that echo phase is involved in delay estimation. At an echo detectability index of about 36 dB, fine acuity is 40 ns, which is approximately as predicted for the delay accuracy of an ideal receiver. 3. Compound performance curves for 0 degrees and 180 degrees phase conditions match the crosscorrelation function of the echoes. The locations of both 0 degrees and 180 degrees phase peaks in the performance curves shift along the time axis by an amount that matches neural amplitude-latency trading in Eptesicus, confirming a temporal basis for jitter discrimination.     

Complications of Gastroesophageal Reflux

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine.Several specialists have recently recognized that gastrointestinal reflux causes complications resulting in significant disease. It causes discomfort, indigestion, esophagitis, Barrett''s esophagus, and carcinoma of the esophagus. Pediatricians attribute many early pulmonary problems, and even some sudden deaths in infants, to the reflux of gastric contents. Otolaryngologists now recognize that many cases of nonbacterial, nonspecific pharyngitis and laryngitis are due to the reflux of gastrc acid secretions. Contact granuloma and cancer of the larynx may, in some instances, be secondary to nocturnal reflux. Thoracic surgeons and pulmonologists believe chronic tracheobronchitis and some cases of pulmonary disease are attributable to recurrent bathing of the respiratory epithelium by aspirated gastric contents. An awareness of the many complications of gastrointestinal reflux should lead to a multidisciplined attack on the factors responsible for these diseases.     

Colonization by Cladosporium spp. of painted metal surfaces associated with heating and air conditioning systems

Cladosporium cladosporioides and C. hebarum colonized painted metal surfaces of covering panels and register vents of heating, air conditioning and ventilation systems. Hyphae penetrated the paint film and developed characteristic conidiophores and conidia. The colonies were tightly appressed to the metal surface and conidia were not readily detectable via standard air sampling procedures.     

Carbanicotinamide adenine dinucleotide: synthesis and enzymological properties of a carbocyclic analogue of oxidized nicotinamide adenine dinucleotide

The dinucleotide carbanicotinamide adenine dinucleotide (carba-NAD), in which a 2,3-dihydroxycyclopentane ring replaces the beta-D-ribonucleotide ring of the nicotinamide ribonucleoside moiety of NAD, has been synthesized and characterized enzymologically. The synthesis begins with the known 1-aminoribose analogue (+/-)-4 beta-amino-2 alpha,3 alpha-dihydroxy-1 beta-cyclopentanemethanol. The pyridinium ring is first introduced and the resultant nucleoside analogue specifically 5'-phosphorylated. Coupling the racemic carbanicotinamide 5'-mononucleotide with adenosine 5'-monophosphate produces two diastereomeric carba-NAD analogues which are chromatographically separable. Only one diastereomer is a substrate for alcohol dehydrogenase and on this basis is assigned a configuration analogous to D-ribose. The reduced dinucleotide carba-NADH was characterized by fluorescence spectroscopy and found to adopt a "stacked" conformation similar to that of NADH. The analogue is reduced by both yeast and horse liver alcohol dehydrogenase with Km and Vmax values for the analogue close to those observed for NAD. Carba-NAD is resistant to cleavage by NAD glycohydrolase, and the analogue has been demonstrated to noncovalently inhibit the soluble NAD glycohydrolase from Bungarus fasciatus venom at low concentrations (less than or equal to 100 microM).