bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational analysis of the human complement 5a receptor: Identification of a potential role of asp 37 and asp 82 in ligand binding
Authors: Whitman Mary Maureen , Munro Robin , Assal Amy A. , Jarvis Michael F. , Saltzman Alan 
Published: January 2005

AbstractThe receptor for the inflammatory and chemotactic agent complement 5a (C5a) is a member of the G‐protein coupled receptor (GPCR) superfamily. Site‐directed mutagenesis of the human C5a receptor was performed to determine which amino acids were important for ligand binding. Specific regions of the C5a receptor were mutated based on their similarities to the ligand binding domain of other GPCRs. These mutated receptors were then transiently expressed in COS‐7 cells in order to test their ability to bind [125|]C5a. Because of the basic nature of the ligand, we concentrated on mutating acidic amino acid residues located at the N‐terminal and transmembrane regions of the receptor. Mutation of Asp 37, located near the first transmembrane domain, or Asp 82, located within the second transmembrane domain, to valine resulted in a total loss of specific [125l]C5a binding to membrane preparations of transfected cells. Furthermore, mutation of Asp 82 to alanine, leucine, or glutamate also resulted in an absence of specific binding. However, mutation of Asp 82 to asparagine did not eliminate the ability of the receptor to bind [125l]C5a. Mutation of each of the N‐terminal extracellular domain aspartate residues, Asp 282 (located within the seventh transmembrane domain), or Glu 179 or Glu 180 (located within the second extracellular loop) to valine also did not significantly affect [125l]C5a binding. These studies thus identified two acidic amino acid residues of the C5a receptor which are important for binding [125l]C5a. © 1995 Wiley‐Liss, Inc.
Good laboratory practices and other regulatory issues: A regulatory affairs view
Authors: Christian Mildred S. 
Published: January 2005

AbstractCurrent international approaches differ regarding the definition of safety pharmacology studies, the numbers of these studies required for product support and whether it is necessary to conduct these studies in conformance with Good Laboratory Practices (GLPs). The European Union currently requires conformance with GLPs, Japan has a policy allowing full raw data audits of these studies, and the FDA does not require that these studies conform with GLPs unless they are performed in support of studies in the toxicology package (i.e. drug safety). Although the traditional position has been that it is impractical to conduct these studies in conformance with GLPs, reasons for maintaining this position are often incorrect and based on perception, rather than on understanding of the intent and extent of GLPs. Because it is highly possible that safety pharmacology studies may soon be required to conform with GLPs, this manuscript includes a review of GIP requirements, real, rather than perceived, impediments to GLP conformance, and practical suggestions for defining these types of specialized studies and performing them in such a way that they meet GLP requirments. © 1995 Wiley‐Liss, Inc.
Renal effects of FK453: A potent non‐xanthine adenosine A1 receptor antagonist
Authors: Terai Takao , Kita Yasuhiro , Kusunoki Takahiro , Andoh Takeshi , Nagatomi Itzuo , Horiai Haruo , Akahane Atsushi , Shiokawa Youichi , Yoshida Keizo 
Published: January 2005

AbstractThe renal effects of FK453, a potent and selective non‐xanthine adenosine A1 receptor antagonist, were examined and compared with FR113452 (less active enantiomer of FK453), typical adenosine receptor antagonists, and diuretics. In rats FK453 possessed diuretic activity similar to 1, 3‐dipropyl‐8‐cyclopentylxanthine (DPCPX, adenosine A1 receptor antagonist), hydrochlorothiazide, and furosemide, but neither FR113452 nor CP66713 (an adenosine A2 receptor antagonist) possessed diuretic activity. Urinary uric acid excretion in rats increased with FK453, but other drugs had no effect. These diuretic and uricosuric activities of FK453 were also observed in dogs. In anesthetized dogs, FK453 increased the renal blood flow (RBF), inulin clearance (Cin), and p‐aminohippuric acid clearance (CPAH). However, hydrochlorothiazide had no effect on RBF, Cin, and CPAH. Furthermore, osmolar clearance experiments suggested that the renal site of action of FK453 was different from hydrochlorothiazide and furosemide.These results demonstrate that FK453 has diuretic activity and increases urinary uric acid excretion and suggest that the diuretic activity of FK453 is related to adenosine A1 receptor antagonism; also, the diuretic mechanism of action and the renal site of action of FK453 are different from those of hydrochlorothiazide and furosemide. FK453 is a useful compound to clarify the physiological role of the adenosine A1 receptor in the kidney. © 1995 Wiley‐Liss, Inc.
Effect of the selective estrogen receptor modulator raloxifene on explanted uterine growth in rats
Authors: Swisher D. Kim , Tague Robert M. , Seyler David E. 
Published: January 2005

AbstractRaloxifene is a selective estrogen receptor modulator known to have antiestrogenic effects on uterine tissue. In this study, the effects of raloxifene on uterine explant growth were evaluated in rats. Rats were ovariectomized, implanted with an estradiol pellet, and an endometriosis‐like state was artificially created by suturing uterine explants near mesenteric blood vessels. Approximately 21 days after explant surgery, rats with confirmed uterine explant growth were given raloxifene orally at doses of 0 or 10 mg/kg/day for 7 or 14 days. After 7 days of raloxifene treatment, explant weight and volume were significantly decreased. Fourteen days of raloxifene treatment, also caused a decrease in explant weight and volume, though not statistically significant. In addition, raloxifene treatment caused weight of the remaining uterine horn to decrease. Histological examination of the explants confirmed the presence of endometrial tissue similar to that seen in the uterus. In this study, raloxifene suppressed explanted uterine growth in a rat model designed to mimic human endometriosis. © 1995 Wiley‐Liss, Inc.
Cholesterol‐lowering effect of an acyl‐coenzyme A: Cholesterol acyltransferase inhibitor, FR145237, in hypercholesterolemic rabbits fed a high‐cholesterol diet and a cholesterol‐free casein diet
Authors: Matsuo Masahiko , Aketa Miho , Ozaki Reiko , Tomoi Masaaki , Shimomura Kyoichi 
Published: January 2005

AbstractCholesterol‐lowering effects of a new acyl‐coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, FR145237, in hypercholesterolemic rabbits fed a high‐cholesterol die or a cholesterol‐free casein diet were evaluated. In the cholesterol‐fed rabbits, FR145237 at the doses of 0.032, 0.1, and 0.32 mg/kg/day (0.060, 0.19, and 0.60 μmol/kg/day) reduced the plasma cholesterol level by 37%, 70%, and 94%, respectively. Cholesterol content in the liver was reduced at 0.1 and 0.32 mg/kg/day (0.19 and 0.60 μmol/kg/day). Cholesterol and phospholipid concentrations in the gallbladder bile was also reduced by FR145237 treatment, but bile acids concentration was not affected. In the hypercholesterolemic rabbits fed a cholesterol‐free casein diet, FR145237 also had a plasma cholesterol‐lowering activity but the effective dose [0.5 mg/kg/day (0.93 μmol/kg/day)] was higher than that in cholesterol‐fed rabbits. Cholesterol content in the liver of the casein‐fed rabbits was reduced in a parallel manner. Cholesterol and phospholipid concentrations in the gallbladder bile were not significantly affected, whereas bile acids concentration was significantly elevated by FR145237 treatment. The results suggest that the cholesterol‐lowering activity of ACAT inhibitors may be partly due to their effect on cholesterol metabolism in the liver, especially at the stages of bile acid synthesis, in addition to inhibition of cholesterol absorption in the intestine. © 1995 Wiley‐Liss, Inc.
Position discrimination in the salamander, Ambystoma tigrinum
Authors: Schwartz Joseph M. , Cogan Dennis C. 
Published: January 2005

AbstractTwenty larval tiger salamanders (Ambystoma tigrinum) were collected from a playa lake in West Texas and maintained in the laboratory for 7 days prior to the beginning of position training. Ten subjects in the larval state were trained on a position problem in a T‐maze for 5 trials per day to a criterion of 80% correct responses, using a self‐correction procedure. Following metamorphosis to the adult stage, these subjects were tested for retention. The remaining 10 subjects were allowed to metamorphose prior to training on the position problem. The results indicate reliably faster learning in the adult (terrestrial) subjects, and reliable retention of the response following metamorphosis. These results, taken in conjunction with informal observation of the behavior of the subjects in the experimental environment, suggest that the performance of the adult subjects was a result of their better perceptual apparatus.
Relative maturity of cebus and squirrel monkeys at birth and during infancy
Authors: Elias Marjorie F. 
Published: January 2005

AbstractCebus monkey were less mature at birth than squirrel monkeys in terms of body wieght and brain weight in proportion to adult weight. Postnatally, cebus were slower to develop locomotion, perceptual‐motor capacities, and object permanence. The differences in rate of development between the species increased with age. The findings indicate that the cebus have a longer period of infancy before becoming skilled at locomotion and manipulation. In view of the cebus monkey's recognized skill as a manipulator and problem solver, the long period of infancy suggests that cebus have evolved further in the direction of higher primates.
Brief periods of socialization and later behavior in the rat
Authors: Einon Dorothy F. , Morgan Michael J. , Kibbler Christopher C. 
Published: January 2005

AbstractJuvenile rats were allowed short daily periods of social contact to see if this would reduce the known effects of isolation rearing upon habituation of locomotor activity and object contact in the open field. Animals totally deprived of social experience (ISOL) were slower to habituate than animals living in small social groups (SOC). Rats allowed 1 hr of social contact (partial isolates, PI), but living otherwise in isolation, were intermediate between ISOL and SOC animals. In further experiments the quality of social interactions in the daily period was altered by drugging one of the partners, either with amphetamine or with chlorpormazine. In later tests in the open field, the rats that had interacted with amphetamine‐injected or chlorpromazine‐injected partners differed from PI animals in the direction of resembling complete isolates (ISOL); this was particularly true of those paired with amphetamine animals. Observation revealed that injection of 1 of the partners considerably altered social interactions in the pair. A further test showed that 1 hr of contact a day considerably alleviated the deleterious effects of isolation rearing upon response reversal. We conclude that normal development in the rat may depend upon the flexibility of behavior encouraged by the early social situation.
Competitive social strategies in groups of deprived and experienced rhesus monkeys
Authors: Anderson Clark O. , Mason William A. 
Published: January 2005

AbstractBehavior during competition for water was observed in 2 social groups of young rhesus monkeys (3 females, 3 males in each). Monkeys in one group were socially deprived and those in the other were socially experienced (raised with mother and agemates). Social status, based on dyadic recording of displacements at the water bottle, was predictive of a number of measures related to water consumption and social orientation in both groups, but this measure was less reliable and predictive for the experienced group than for the deprived group. A major reason for the comparatively low predictive value and reliability of status among experienced monkeys was their ability to influence the behavior of higher status members through responses directed to a 3rd party and other elaborate social strategies, many of which depended on responding to status relations between 2nd and 3rd parties. The fact that such strategies were only observed in the experienced group is a clear indication that the development of higher orders of social cognition is dependent on early social experience.
Polygraphic studies of kitten development: Respiratory rate and variability during sleep‐waking states
Authors: Stevenson Michael , McGinty Dennis J. 
Published: January 2005

AbstractThe developmental course of respiration rate and variability during sleep states and waking was measured in chronically prepared kittens. Kittens had higher respiration rates during active sleep (AS) as compared to quiet sleep (QS) at all ages, with rates declining developmentally in both sleep states. Compared to waking, respiration rate and variability were decreased during sleep. The decrease was greatest in the youngest animals and during QS. Minute‐to‐minute respiratory variability declined from 10 to 40 days of age for each state, whereas breath‐to‐breath variability declined during the same period only during QS. Respiratory variability was higher in AS than QS in older kittens. Heart rate and variability were found to be correlated with respiratory parameters only during QS. These observations support the hypothesis that the control and development of respiration during sleep is achieved by different processes in QS and AS.
Olfactory and visual differentiation of synthetically scented surrogates by infant squirrel monkeys
Authors: Kaplan Joel N. , Cubicciotti Daniel D. , Redican William K. 
Published: January 2005

AbstractTwelve infant squirrel monkeys were reared with distinctively colored and scented inanimate surrogates (Green/Floral or Black/Clove) and tested monthly from 1 to 6 months of age in 3 paired‐comparison conditions that assessed the efficacy of synthetic olfactory cues and color cues as attractive properties of the surrogates. The infants developed specific attractions to both the rearing odor and color of the surrogates by approximately the end of Month 4, although substantial differences existed between the 2 rearing groups, particularly with respect to color responsiveness. When compared with previous findings on infant squirrel monkeys reared with naturally scented surrogates, odor preferences developed relatively late, suggesting that natural, species‐typical odors may have inherently stronger attractive properties for Saimiri than arbitrary synthetic odors.
The effects of preparturient avoidance conditioning on postnatal caretaker behavior and offspring catecholamine levels and behavior in C57BL/6J mice
Authors: Rohner Evelyn C. , Werboff Jack 
Published: January 2005

AbstractAvoidance conditioning during pregnancy, changes in caretaker behavior during lactation, and changes in offspring catecholamine levels and behavior were investigated in C57BL/6J mice. Three equal groups of mice were employed. One group was avoidance conditioned prior to pregnancy and continued to avoid shock during pregnancy; a 2nd group was avoidance conditioned during pregnancy; and the 3rd group served as untreated controls. Offspring were crossfostered after birth. During lactation the proportion of time the caretaker spent on the nest was observed. At weaning pups were individually housed. Offspring dopamine concentrations were measured in the corpus striatum at birth and at days 22 and 42 of age. Their performance was evaluated in the open field at Day 42 of age. The results showed that mice receiving avoidance conditioning prior to parturition were more likely to cannibalize their offspring at parturition than were control animals. Furthermore, preparturiently avoidance conditioned mice spent less time on the nest if they reared offspring from biological mothers who had been avoidance conditioned when compared to similarly treated caretakers who reared offspring from untreated control biological mothers. Regardless of postnatal experiences, adult offspring from avoidance conditioned biological mothers had significantly reduced levels of dopamine in tissue from the corpus striatum and were significantly less active in the open field when compared with offspring from control biological mothers. Behavioral results support the findings of others that the prenatal environment plays an important role in shaping the later behavior of offspring. The decrease in dopamine levels suggests that avoidance training as one form of psychosocial stimulation during pregnancy can be disruptive to the development of the dopamine regulatory mechanisms.
Effect of neonatal stunting on development of rats: Large litter rearing
Authors: Fleischer Susan F. , Turkewitz Gerald 
Published: January 2005

AbstractAt nurslings, rat pups reared in large litters showed reduced frequencies of returns to their nest from other parts of the home cage and reached maximum levels of nest returns at older ages than control animals from small litters. These differences were not due to differences in activity level or attraction to the nest but appeared to be perceptual in nature. As adults, animals from large litters showed deficits in learning the 1st 2 problems in a series of visual discriminations in a modified version of the Lashley jumping stand technique in which food reinforcement was not used. The deficits were confined to male animals only and were the result of stronger position habits in the early part of training, rather than an inability to make the discriminations. A comparison of these results with those obtained when other methods of stunting animals are employed revealed that different methods of stunting may result in both common and divergent effects on behavior. One long‐term consequence of large litter rearing appears to be increased emotional response to novel situations.
Development of the acoustic startle response in the rat: Ontogenetic changes in the magnitude of inhibition by prepulse stimulation
Authors: Parisi T. , Ison James R. 
Published: January 2005

AbstractThree experiments examined the development of the acoustic startle reflex and its modification by a preliminary stimulus in the infant rat during the 2nd and 3rd postnatal weeks. The 1st experiment employed a white noise S1 (20 msec, 70 dB), the 2nd a cutaneous S1 (.5 msec, .5 mA and 1.0 mA shock), and the 3rd identical S1‐S2 pairs (20 msec, 10 kHz, 110 dB tones). The results demonstrate a similar maturation of the prepulse modification pattern over days in the 3 experiments, evidenced mainly in the growth of inhibition. The findings indicate peripheral and central mechanisms that are maturing during the period of life under observation and that contribute to the developmental patterns of modification.
Influence of neonatal injections of testosterone propionate on sexual behavior and plasma testosterone levels in the male house mouse
Authors: Batty Jennifer 
Published: January 2005

AbstractThe effects of neonatal testosterone injections on adult male sexual behavior and plasma testosterone levels were investigated in several strains of male house mice. Both sexual behavior and plasma testosterone levels were increased in the testosterone‐treated groups from some strains, but the 2 variables did not change concomitantly.
The compensatory role of food‐motivation in the maze learning performance of lactationally undernourished rats
Authors: Katz Hillary B. , Rosett Robert E. , Ostwald Rosemarie 
Published: January 2005

AbstractTo test the hypothesis that the motivational effects of neonatal undernutrition might conceal the detrimental effects on learning, we tested previously undernourished and normally nourished Sprague‐Dawley rats on learning of a novel maze pattern under either latent learning (nonappetitive) or food‐motivated conditions. Under the nonappetitive conditions, the previously under‐nourished rats learned significantly less than the normal controls, but when motivated for food, the undernourished rats performed as well as the controls. When learning performance measures are sensitive to motivation, differential motivation between undernourished and normal subjects must be controlled or eliminated.
Ontogenesis of spontaneous activity and habituation of activity in the rat pup
Authors: Shaywitz Bennett A. , Gordon Judith W. , Klopper Jeffrey H. , Zelterman Daniel A. , Irvine John 
Published: January 2005

AbstractIndividual components of activity and habituation of activity were determined throughout the 1st month of life in the rat pup. Total activity increased from 25% at 8 days of age to 68% at 22 days before declining to 49% at 26 days. Total slight activity (predominantly sniffing) increased to a maximum of 33% at 15 days whereas total very active behavior (predominantly ambulation) reached its maximum of 38% at 22 days. Habituation of activity expressed as the mean slope of decrement of activity over the 1st 30 min of the observation period was observed in rats as young as 8 days of age. By 12 days, habituation of total activity had increased significantly reflecting a 3‐fold increase in habituation of slight activity, an effect observed at 15 days as well. However, by 19 days the slope of activity decrement had declined to half of its 15‐day value, indicating an impairment of habituation and reflecting the attenuation of very active behavior, predominantly ambulation. This decline in habituation continued through 22 days but by 26 days habituation of activity had increased again reaching a maximum for the 1st month of postnatal life. Our results suggest that the phenomenon of behavioral arousal observed in the developing rat pup 19 days of age reflects an inability of the organism to modulate his activity as effectively as the 15‐day‐ or 26‐day‐old animal.
Ontogeny of ultradian and nocturnal activity rhythms in the isolated albino rat
Authors: Teicher Martin H. , Flaum Lawrence E. 
Published: January 2005

AbstractThe activity of isolated rats from 6 to 25 days of age was analyzed at 10‐min intervals. Ultradian peak activity rhythms, with a rough 1‐2‐hr periodicity, developed between 9 and 12 days of age, and reached an extreme at 15 days. Ultradian periods of attenuated activity were however detectable even in 6‐day‐olds. Isolated rats at 15 days of age displayed greatly accentuated profiles characterized not only by heightened activity levels, but by an extreme cyclicity. These subjects spent most of their time oscillating between periods of marked activity and marked inactivity. Both the average and total duration of these extreme periods were greater in 15‐day‐olds than any of the other ages. Free‐running nocturnal activity rhythms were also observed to develop in isolated rats tested in continuous darkness by the 15th day.
Ontogenetic study of the Miwh gene in mice
Authors: Marzetta Carol A. , Nash Donald J. 
Published: January 2005

AbstractOntogenetic and adult behavioral tests were conducted on an extreme non‐agouti strain of mice carrying the Miwh mutation. Except for startle response, no significant differences were seen in any aspect of the preweaning reflex and neuromuscular tests. The lack of startle response seen in Miwh/Miwh and Miwh/+ mice can be attributed to abnormalities found in the inner ear of these genotypes. Among adult mice, significant differences were found in the open field and visual cliff tests.