Thermal inhibition of repair of methylmethane sulfonate-damaged DNA in chick embryo fibroblasts

Chick embryo fibroblasts were treated with the monofunctional alkylating agent methylmethane sulfonate at various concentrations for 1 h at 42°C, rinsed and then incubated post-treatment at various temperatures at which the kinetics of alkali-labile bond disappearance was followed. Growth experiments showed that these cells grew similarly at temperatures of either 37°C or 42°C. Repair as assessed by removal of alkali-labile bond was also similar for postincubation in the temperature range 37–42°C for damage due to methylmethane sulfonate treatment at concentrations less than 1.5 mM. When the postincubation temperature was raised higher than 42.5–43°C, this type of repair was stopped. The normal internal body temperature of adult chickens is about 41.6°C. Hence the present finding indicates that chick cells are much more severely restricted in DNA repair at temperatures above normal than are mammalian cells, which can function in this respect for several deg. C above 37°C.     

Parelaphostrongylus tenuis in New Brunswick: the parasite in white-tailed deer (Odocoileus virginianus) and moose (Alces alces)

Research was initiated in 1983 to investigate the ecology of Parelaphostrongylus tenuis in New Brunswick. The objectives were to determine the prevalence and intensity of infection in white-tailed deer, and to determine whether or not moose feces contained first stage larvae, signifying the completion of the life cycle of P. tenuis in this host. Forty-nine percent of deer pellet samples were positive and 60% of deer heads contained adults of P. tenuis. None of the moose pellet samples contained first stage larvae.     

Three theories of stroboscopic motion detection

The three theories derive from three different paradigms. Suprathreshold judgements of perceived quality of motion in multi-flash displays are modelled by space-time Fourier analysis of the motion stimulus. Stroboscopic motion is perceived as being different from real motion to the extent that the additional Fourier components in stroboscopic motion are detectable. Stroboscopic motion of dots along conflicting paths leads to perceptual competition. The theory to describe perceptual I solution derives and proves the uniqueness of strength functions computed only from the time and from the distance between successive points on each path. Time-strength and motion-strength add to determine path-strength; only the strongest path is perceived. Motion-direction detection in continuously drifting two-flash combinations of sinusoidal gratings is described by elaborated Reichardt detectors (ERDs) that compute the covariance of temporal events in two adjacent locations. Other apparently different, detectors that account for direction-detection data are shown to be equivalent to ERDs.     

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular F×1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 ± 198 mg/day compared to a level of 1180 ± 306 seen in the untreated animals (p < 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower doses of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.     

Sulfhydryl Groups in Receptor Binding of Thyrotropin-Releasing Hormone to Rat Amygdala

Abstract: Binding of [³H]-[3-Me-His²]thyrotropin-releasing hormone ([³H]MeTRH) to TRH receptors in rat amygdala was decreased by sulfhydryl reagents in a time-, temperature-, and concentration-dependent manner. A pronounced reduction in receptor density, with little or no change in binding affinity, was apparent following disulfide bond reduction by dithiothreitol (DTT), alkylation of thiol groups by N -ethylmaleimide (NEM), and their oxidation by 5,5'-dithiobis (2-nitrobenzoic acid). Heavy metals (Cd²⁺, Hg²⁺), which complex with reactive -SH residues, also potently inhibited binding. The pharmacological specificity of residual [³H]MeTRH binding in chemically modified amygdala membranes was the same as that in control preparations. Sequential exposure to thiol reagents, in the presence or absence of cations, revealed possible additive effects. Pretreatment of membranes with TRH (10^--⁸-^-10^--⁶ M ), and its continued presence during modification, afforded protection against DTT and NEM. These results indicate the possible importance of thiol groups in the maintenance of TRH receptor conformation.     

Modulation of Receptors for Thyrotropin-Releasing Hormone by Benzodiazepines: Brain Regional Differences

The benzodiazepines (BZDs) chlordiazepoxide (CDE), diazepam (DZM), and flurazepam (FLM) inhibited receptor binding for thyrotropin-releasing hormone (TRH) with low micromolar potency. In contrast, numerous other categories of drugs were previously shown to be inactive. Scatchard analysis of competition data suggested that the BZDs reduced TRH receptor affinity, consistent with competitive inhibition. Receptors from amygdala, retina, and pituitary appeared more sensitive to inhibition by BZDs than those from hypothalamus, hippocampus, spinal cord, or cerebellum. The latter four regions also gave shallower inhibition curves. CDE revealed an apparently biphasic dissociation of [3-Me-His2]TRH([3H]MeTRH) from amygdala membranes at 4 degrees C, with kinetics similar to those with TRH. These results suggest that TRH receptors in the brain are heterogeneous and that certain BZDs in high therapeutic concentrations may exert central effects through actions at TRH receptors or coupled proteins.     

Biochemical and autoradiographic studies of TRH receptors in sections of rabbit spinal cord

Receptors for thyrotropin-releasing hormone (pGlu-His-Pro-NH2, TRH) on thaw-mounted sections of rabbit spinal cord have been identified biochemically and visualized by light microscopic autoradiography. Binding of [3H] [3-Me-His2]TRH to 20 microns sections exhibited high apparent affinity and a pharmacological specificity almost identical to that previously demonstrated for spinal TRH receptors in membranes. In autoradiograms, the highest density of TRH receptors appeared in the substantia gelatinosa of the dorsal gray and around the central canal, with intermediate levels in the ventral gray.     

Ca2+ displacement by Polymyxin B from sarcolemma isolated by 'gas dissection' from cultured neonatal rat myocardial cells

Amphiphilic, cationic Polymyxin B is shown to displace Ca2+ from 'gas dissected' cardiac sarcolemma in a dose-dependent, saturable fashion. The Ca2+ displacement is only partially reversible, 57% and 63%, in the presence of 1 mM or 10 mM Ca2+, respectively. Total Ca2+ displaced by a non-specific cationic probe, lanthanum (La3+), at maximal displacing concentration (1 mM) was 0.172 +/- 0.02 nmol/microgram membrane protein. At 0.1 mM, Polymyxin B displaced 42% of the total La3+-displaceable Ca2+ or 0.072 +/- 0.01 nmol/microgram protein. 5 mM Polymyxin displaced Ca2+ in amounts equal to those displaced by 1 mM La3+. Pretreatment of the membranes with neuraminidase (removal of sialic acid) and protease leads to a decrease in La3+-displaceable Ca2+ but to an increase in the fraction displaced by 0.1 mM Polymyxin from 42% to 54%. Phospholipase D (cabbage) treatment significantly increased the La3+-displaceable Ca2+ to 0.227 +/- 0.02 nmol/microgram protein (P less than 0.05), a gain of 0.055 nmol. All of this phospholipid specific increment in bound Ca2+ was displaced by 0.1 mM Polymyxin B. The results suggest that Polymyxin B will be useful as a probe for phospholipid Ca2+-binding sites in natural membranes.     

The influence of auxin, cacodylic Acid, and amitrole on the abscission of petiole explants

The influence of indoleacetic acid, cacodylic acid (hydroxy-dimethylarsine oxide), and amitrole (3-amino-1,2,4-triazole) on the petiole explant abscission rate was studied in three species. Indoleacetic acid increased the abscission rate in both bean (Phaseolus vulgaris L. var. Red Kidney) and Coleus (Coleus blumei Benth) at 10⁻³ and 10⁻⁴m but had no effect on abscission in privet (Ligustrum ovalifolium). Cacodylic acid was found to stimulate abscission in explants of beans and privet, but not in Coleus. Amitrole did not stimulate abscission under any circumstance tested. In no case was the abscission rate dependent on the time at which any of the chemicals was applied. These data do not support the two-phase response of explants to applied auxin.     

Microbiological and Pharmacological Behavior of 7-Chlorolincomycin

Replacement of the 7-(R) hydroxyl group of lincomycin by a 7-chloro-substituent produced a compound with greater in vitro activity than the parent. Laboratory studies of this compound showed it to be highly active against all of the following strains of gram-positive organisms examined, including penicillinase- and nonpenicillinase-producing staphylococci, Diplococcus pneumoniae, Streptococcus viridans and Streptococcus pyogenes. The enterococci, as well as all the gram-negative organisms tested, with the exception of some strains of Haemophilus, were uniformly insensitive to this agent. The activity of 7-chlorolincomycin was not affected by serum or inoculum size. Resistance developed in a slow stepwise pattern. Peak levels of approximately 2 mug/ml were achieved in the serum of volunteers after ingestion of 150 mg either in the fasting state or after a meal. No untoward effects were noted. The antibiotic appears to be of potential value in the treatment of infections due to gram-positive organisms, with the exception of enterococcus.