bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scanning whole cells with phage‐display libraries: Identification of peptide ligands that modulate cell function
Authors: Fong Susan , Doyle Laura V. , Devlin James J. , Doyle Michael V. 
Published: January 2005

AbstractA general strategy has been developed for rapidly identifying peptides that alter cellular function, which has revealed a series of peptides that inhibit platelet aggregation. First whole cells—platelets in this case—were used as an affinity matrix to isolate cell‐binding phage from a phage‐display, random‐peptide library. In this step 3 × 107 different filamentous phage, each encoding and displaying a different random peptide, were screened as a single pool. Since it is the peptide displayed on the surface of the phage that presumably causes a particular phage to bind specifically to a cell, synthetic peptides were then made based on the predicted sequences of the displayed peptides. Because the initial affinity selection step had focused attention on a handful of peptides, each of the 17 synthetic peptides could be individually tested in an appropriate functional assay, such as platelet aggregation. The majority of the 17 different peptides that we analyzed inhibited platelet aggregation; these peptides could be grouped into at least five different motifs including the expected RGD motif. It is believed that this strategy, which requires neither purification nor prior knowledge of a particular target receptor, will prove to be generally useful for identifying peptide ligands that influence cellular function. © 1994 Wiley‐Less, Inc.
Synthesis of support‐bound peptides carrying color labels
Authors: Câmpian Eugen , Sebestyén Ferenc , Major Ferenc , Furka Árpád 
Published: January 2005

AbstractIn order to check the possibility of labeling sub‐libraries, we synthesized a colored support by acylation of aminomethyl resin with a special Boc‐amino acid (a red azo dye). Syntheses of model peptides proved that the colored resin is suitable for solid phase peptide synthesis. Color labeling was also made by coupling resin‐bound peptides at their N‐termini with a blue dye. Colored resins as well as labeling at the N‐terminus offer a possibility to simplify the preparation of support‐bound peptide sub‐library kits and their use in sequence determination of bioactive peptides. © 1994 Wiley‐Less, Inc.
Identification of small peptides that interact specifically with a small organic dye
Authors: Lam Kit S. , Zhao Zhan‐Gong , Wade Shelly , Krchňák Viktor , Lebl Michal 
Published: January 2005

AbstractUsing a “one‐bead one‐peptide” combinatorial peptide library method, we have been able to identify peptide ligands that interact specifically with various macromolecular targets such as monoclonal antibodies, streptavidin, avidin, MHC‐Class I molecules, proteases, growth factor receptors, and gpIIb/IIIa integrin. In this paper, we test the hypothesis that small peptides that interact specifically with a small organic molecule can also be identified using this combinatorial peptide method. Using a small organic dye molecule, indigo carmine, as a color probe to screen a random L‐heptapeptide and two D‐hexa and octapeptide libraries, we were able to identify a specific peptide binding motif. Potential applications of this technology are described. © 1994 Wiley‐Less, Inc.
Function and structure of voltage‐dependent potassium channels
Authors: Wible Barbara A. , Brown Arthur M. 
Published: January 2005

AbstractVoltage‐dependent potassium (K+) channels are the largest group of voltage‐dependent ion channels and more cDNAs have been cloned for voltage‐dependent K+ channels than for voltage‐dependent Na+, Ca2+, and Cl− channels, the other main categories of voltage‐dependent ion channels. The cloning result was anticipated from electrophysiological measurements because K+ currents are by far the most diverse of voltage‐dependent ion currents. In this review K+ currents will be classified functionally first and structurally second, an arrangement that follows the historical development of the field. Then, we will examine present attempts to assign the major functions of voltage‐sensing, gating and ion conduction to specific domains of K+ channel proteins. Finally, we will describe present understanding of drug interactions with the ion conduction pathway or pore of K+ channel proteins. © 1994 Wiley‐Liss, Inc.
Advances in the structure‐activity relationships, mechanisms of action, and therapeutic utilities of ATP‐sensitive potassium channel openers
Authors: Atwal Karnail S. 
Published: January 2005

AbstractThe presence of ATP‐sensitive potassium channel (KATP) in a variety of tissues makes it an important therapeutic target for drug research. The existence of small molecules that modulate its activity has attracted a great deal of attention over the past several years. Progress achieved at understanding the structure‐activity relationships of KATP openers, and their therapeutic utilities and mechanism of action are summarized in this review. The compounds combining the features of potent KATP openers cromakalim, pinacidil, and aprikalim retain the biological profiles of their predecessors, indicating the classical KATP openers may be expressing their biological effects through similar structural requirements. Based on these studies, a pharmacophore model which incorporates a lipophilic residue, an electron deficient aromatic ring, and a hydrogen bonding site has been proposed. Although the first generation compounds have served as extremely useful tools., their therapeutic utility is limited due to indiscriminate actions in a variety of tissues. Tissue selective KATP openers are required to advance these compounds into clinical practice. Progress made at the discovery of selective KATP openers that might be useful for the treatment of ischemic heart disease, urinary incontinence, and asthma is described in this article. The molecular mechanism of action of KATP openers is far from being understood. A binding site for these agents has been identified in the rat aortic smooth muscle cells and intact rat aortic tissue. However, the relationship of this binding site to KATP is not understood at the present time. Further work is needed to explore the clinical utility of tissue selective agents and understand their molecular mechanism of action. © 1994 Wiley‐Liss, Inc.
Activators of voltage‐dependent L‐type calcium channels
Authors: Rampe David , Michael Kane J. 
Published: January 2005

AbstractThe L class of voltage‐dependent Ca2+ channels provides an important pathway for Ca2+ entry into a variety of excitable cells. Many drugs have been shown to be blockers of this channel including the clinically available nifedipine, verapamil, and diltiazem. An increasing number of compounds are now being recognized as activators of L‐type Ca2+ channels. The best characterized of these are certain 1,4‐dihydropyridines, typified by Bay K 8644, which act as partial agonists of the channel. The benzoylpyrrole group of molecules, which includes FPL 64176, have proven to be highly efficacious L channel agonists. Certain naturally occurring substances, ranging from toxins to endogenous ligands, have also been proposed as activators of this channel. Activators of L‐type Ca2+ channels have proven to be valuable tools with which to study the structure and function of these channels and could lead to the development of new therapeutic entities. © 1994 Wiley‐Liss, Inc.
Synergistic effect on reduction in blood pressure with coadministration of a renin inhibitor or an angiotensin‐converting enzyme inhibitor with an angiotensin II receptor antagonist
Authors: Fossa Anthony A. , Depasquale Michael J. , Ringer Laura J. , Winslow Roxanne L. 
Published: January 2005

AbstractThe effects of coadministration of a renin inhibitor, terlakiren, and an angiotensinconverting enzyme inhibitor, captopril, with the angiotensin II receptor antagonist, losartan, on blood pressure of sodium‐depleted guinea pigs were studied. Dose‐response relationships for terlakiren (0.1 to 3.0 mg/kg, iv), captopril (0.03 to 1.0 mg/kg, iv), and losartan (0.1 to 6.0 mg/kg, iv) were obtained either alone or in the presence of a submaximal dose of the other inhibitor. The hypotensive response calculated for each compound individually was subtracted from the response to each dose of the combination of inhibitors, and the results showed that statistically significant synergy with terlakiren and captopril occurred in the presence of losartan. The degree of the synergy indicated that to achieve the same response on blood pressure, the dose of each drug could be decreased approximately 2‐ to 7‐fold when administered in combination. These results indicate that by inhibiting multiple sites in the renin‐angiotensin system, synergistic effects can be produced. The relative safety of each inhibitor could be improved by large reductions in dose when used concurrently. © 1994 Wiley‐Liss, Inc.
New 1,4‐benzothiazepine derivative, K201, demonstrates cardioprotective effects against sudden cardiac cell death and intracellular calcium blocking action
Authors: Kaneko Noboru 
Published: January 2005

AbstractIn order to find drugs with suppressive effects against sudden cardiac cell death due to myofibrillar overcontraction, the cardioprotective effects of a new 1,4‐benzothiazepine derivative, 4‐[3‐{1‐(4‐benzyl)piperidinyl}propionyl]‐7‐methoxy‐2,3,4,5‐tetrahydro‐1,4‐benzothiazepine, K201, in comparison with five other compounds, including a representative α‐antagonist, β‐antagonist, and Ca2+ channel antagonists, were investigated in an experimental myofibrillar overcontraction model of isolated rat heart. In addition, the effects of K201 on the contraction of isolated vascular smooth muscle of rat aorta and on the binding of cardiac annexin V with actin were compared with those of diltiazem and KT362. The degree of myofibrillar overcontraction was histologically scored on a four‐grade scale (0, 1, 2, and 3) as myocardial injury score (MIS). Suppressive effects of myofibrillar overcontraction could not be observed with nicorandil and prazosin at 10−5 M. Propranolol at 10−5 M, verapamil at 10−6 M, and diltiazem at 10−6 M demonstrated a significant suppressive effect with MIS of 1.0 ± 0.4 (P < 0.01), 1.5 ± 0.3 (P < 0.01), and 1.5 ± 0.3 (P < 0.01), respectively. K201, even at 10−7 M, displayed significant suppression with MIS of 1.8 ± 0.2 (P < 0.01). K201 inhibited contraction of isolated vascular muscle induced by K+ (40 mM) and NE (1 μM) at almost the same concentration. The lC50 ratio (NE/K+) of K201 was 2.3. The inhibition by K201 of the response to K+ was less marked than that by diltiazem. Its inhibition of the response to NE was greater than that by diltiazem or KT362. K201 demonstrated an inhibitory effect on binding of cardiac annexin V with actin dependent on calcium concentration, but diltiazem and KT362 did not demonstrate any action to inhibit this reaction. These results indicate that K201 was a more effective cardioprotectant than propranolol, verapamil, and diltiazem in the experimental myofibrillar overcontraction model. K201 has intracellular Ca2+ blocking action in addition to weak α‐1 adrenergic blocking activity and Ca2+ blocking activity. © 1994 Wiley‐Liss, Inc.
Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen
Authors: Boyd Michael R. , Paull Kenneth D. 
Published: January 2005

AbstractDuring 1985–1990 the U.S. National Cancer Institute (NCI) phased out its murine leukemia P388 anticancer drug screening program and developed as the replacement a new in vitro primary screen based upon a diverse panel of human tumor cell lines. For each substance tested, the screen generates a remarkably reproducible and characteristic profile of differential in vitro cellular sensitivity, or lack thereof, across the 60 different cell lines comprising the panel. Several investigational approaches to display, analysis, and interpretation of such profiles and databases, derived from the testing of tens of thousands of substances during the past 4–5 years since the NCI screen became fully operational, have been explored. A variety of useful, practical applications of the in vitro screen have become apparent. As these applications continue to evolve, they are proving to be complementary to diverse other anticancer screening and drug discovery strategies being developed or pursued elsewhere. Reviewed herein are some practical considerations and selected specific examples, particularly illustrating research applications of the NCI screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Human thrombin receptor‐activating peptide‐induced proliferation of cultured vascular smooth muscle cells exhibits species specificity
Authors: McNamara Coleen A. , Sarembock Ian J. , Gimple Lawrence W. , Fenton John W. , Owens Gary K. 
Published: January 2005

AbstractThrombin receptor stimulation in vitro signals many cellular events that are associated with the response to vascular injury in vivo. Indeed, we have previously shown that human α‐thrombin and the 14‐amino acid human thrombin receptor‐activating peptide (huTRAP‐14) stimulate proliferation of cultured rat aortic smooth muscle cells (SMC). In the present studies, the mitogenic response of rabbit vascular SMC to thrombin and huTRAP‐14 was assessed using [3H]thymidine incorporation and cell number. Results demonstrated that thrombin stimulated mitogenesis of rabbit vascular SMC in culture and that the thrombin response was dependent on proteolytic activity. However, huTRAP‐14 was not mitogenic for rabbit vascular SMC. Thus, there are species differences in huTRAP‐14 responsiveness. As rat and rabbit models continue to be used extensively to evaluate mechanisms and potential therapies for human restenosis, it is important to identify any species differences in the mechanism whereby thrombin exerts its biological effects. © 1995 Wiley‐Liss, Inc.
Stimulation of nitric oxide synthesis in macrophage cell line raw 264.7 cells by several traditional chinese herbal medicines
Authors: Izumi Shigeru , Ohno Naohito , Miura Noriko N. , Takada Katsutoshi , Yadomae Toshiro 
Published: January 2005

AbstractThe effect of 18 traditional Chinese herbal medicines [Kampo medicines (KMs)] on nitric oxide (NO) synthesis in vitro was assessed by using macrophage cell line RAW 264.7 cells. All of the prescriptions enhanced NO synthesis, and eight prescriptions showed strong activity relative to the other remaining prescriptions. After dialysis of the water‐soluble part of the prescriptions, the retaintate showed significant activity, suggesting that macromolecular fractions enhanced NO synthesis. Egg white lysozyme, which can bind to lipopolysaccharide (LPS) and neutralize its biological activities, abrogated NO synthesis of a part of the macromolecular fractions. These results suggest that KM‐stimulated NO synthesis was independent of the contaminated LPS. The NO synthesis was inhibited by NG‐monomethyl‐L‐arginine acetate, an inhibitor of nitric oxide synthase (NOS), showing that induced NO resulted from the activation of inducible NOS but not from nitrite in crude drugs. © 1995 Wiley‐Liss, Inc.
Maternal food restriction: Effects on offspring behavior and development
Authors: Ottinger Donald R. , Tanabe Gilfred 
Published: January 2005

AbstractPregnant rats were placed on reduced food intake or remained on adequate diet during gestation and lactation. Offspring were cross‐fostered to provide for independent experiences of prenatal and/or postnatal mother malnutrition. All offspring were placed on an ad lib diet at time of weaning. When evaluated in adulthood, offspring whose mother was food‐deprived during the lactation period showed body weight deficits and increased errors on the Hebb‐Williams maze as compared to controls. There were no observed effects of the prenatal deprivation.
Mice reared with rats: Elimination of odors, vision, and audition as significant stimulus sources
Authors: Denenberg Victor H. , Paschke Richard , Zarrow M. X. , Rosenberg Kenneth M. 
Published: January 2005

AbstractPrior research has found that mice reared and nursed by a lactating rat mother, or reared in the presence of a nonlactating adult female rat, give a significantly smaller adrenocortical response to a novel stimulus than do control mice. The purpose of this paper was to determine whether this phenomenon could be mediated through stimuli that do not require physical contact between the adult rat and the young mouse. Experimental mice were born and reared in a cage that separated them from an adult nonlactating female rat by means of a double mesh wall. Thus, they could see, hear, and smell the rat, but no physical contact was possible. Control mice were reared similarly in the presence of an adult nonlactating female mouse. At the time of weaning the corticosterone response of both groups to a novel stimulus was virtually identical. The data support the hypothesis that direct physical contact between the mouse and rat is necessary to cause physiological and behavioral changes in the mouse.
Postnatal behavioral alterations resulting from prenatal administration of d1‐alphamethylparatyrosine
Authors: Lydiard R. B. , Sparber S. B. 
Published: January 2005

AbstractWe have previously reported that injection of d1‐alphamethylparatyrosine methylester (AMPT) into the yolk sac of fertilized chicken eggs prior to incubation results in dose‐related increases in the specific activity of tyrosine hydroxylase (TH) at 29 days postnatally. We now report that injection of 10.0 and 33.3 mg/kg of AMPT prior to incubation results in dose‐related increases in acquisition rates of 2 operant responses. Between 1 and 3 weeks of postnatal age, we observed a dose‐related decrease in latency to perform a detour response and, at 55–60 days of postnatal age, an increased rate of acquisition of a key peck response in an autoshaping paradigm. We could not discern any significant alteration in several measures of unconditioned behaviors in an open field situation at 3 weeks of postnatal age. Our data support the contention that early catecholamine (CA) depletion can produce long‐term alterations in postnatal behavior.
Development of locomotion toward home nesting material in neonatal rats
Authors: Szerzenie Victoria , Hsiao Sigmund 
Published: January 2005

AbstractNeonatal rats were individually placed in a narrow choice zone between home and fresh nesting materials. At Day 2 postpartum the pups made significantly more home‐choosing responses (vs responses for fresh nesting material). At a mean of 5.6 days (range, 4 to 9 days) the pups reached a criterion of 2 consecutive days of responses all for home nesting material. The number of head contacts increased abruptly upon reaching the criterion. In a 2nd experiment we observed that the pups which were repeatedly tested performed no better than those which were tested for the 1st or the 2nd time. Thus, (a) home‐seeking responses appear to emerge substantially earlier than previously reported by other investigators, (b) head‐contact responses appear to be related to successful home‐choosing, and (c) some maturational rather than experiential factors are important for the development of both head‐contact and home‐choosing responses.
Effect of handling on maternal behavior following return of pups to the nest
Authors: Villescas Ramiro , Bell Robert W. , Wright Linda , Kufner Michael 
Published: January 2005

AbstractHandling rat pups during the 1st week after birth altered adult behavior in the open‐field, whereas simply separating the pups from their mothers during the same period produced differences in body weight at weaning. Observations of mother‐infant interaction following pup treatment yielded different patterns of maternal behavior. Moreover, pups receiving early treatment were more active as adults in a novel environment and had a greater body weight at weaning. The quality of maternal care and the immediate effects of infantile stimulation on the mother‐infant relation should be considered in specifying a mediating mechanism for the effects of early experience.
Effects of parental environment on the prevalence of convulsive seizures in Onychomys torridus
Authors: McCarty Richard , Southwick Charles H. 
Published: January 2005

AbstractMale and female southern grasshopper mice (Onychomys torridus) were reared in 1 of 3 different parental environments: (a) with the natural male and female parents; (b) with the female parent only; or (c) with foster parents of a closely related species, Peromyscus leucopus. All mice were weaned at 25 days of age, then observed individually in an open field arena at 10‐day intervals from 30 to 100 days of age. Twenty‐seven of 59 subjects (45.8%) that were reared by the natural parents exhibited convulsive seizures during at least 1 of the 8 tests in the open field arena. The prevalence of convulsive seizures increased significantly in subjects that received altered parental care: 27 of 41 subjects (65.9%) reared by the female parent only or by Peromyscus foster parents seized during at least 1 of the 8 tests in the open field. Subjects from the 3 treatment groups did not differ in the mean number of seizures observed during the 8 open field tests. These results demonstrate a significant influence of the preweaning parental environment on the prevalence of convulsive seizures in Onychomys torridus.
Construction of low‐variability litters of preweaning mice
Authors: Epstein Herman T. , Goldstein Larry B. 
Published: January 2005

AbstractMouse litter variation at weaning stems from a combination of genetic makeup, intrauterine experience, and postnatal maternal care. The 1st 2 factors may be matched at birth by making up separate litters out of littermate pairs whose birth weights are equal (± .02 g). Maternal competence may be matched by exchanging the mothers between the 2 cages each day. These tactices yield litters at weaning whose variability has been very much reduced. The range of litter‐average body weights has been reduced from about 40% to about 5% and the range of litter‐average brain weights has been reduced from about 15% to about 1‐2%.
Species‐specific auditory discrimination in bobtail quail neonates
Authors: Barrow Heaton Marieta , Miller David B. , Goodwin Donna G. 
Published: January 2005

AbstractIncubator‐hatched bobwhite quail neonates were tested individually in a variety of single call and simultaneous auditory choice tests involving 6 adult quail vocalizations and a chicken exodus call. The quail showed a high degree of responsiveness (100%) to 3 adult quail vocalizations and significantly less responsiveness (40–50%) to 3 other quail calls and to the chicken exodus call in single call tests. In simultaneous choice tests, the quail were selectively responsive to a call of their own species over the chicken call, and they also showed certain intraspecific preferences. Because of their high degree of responsiveness, coupled with the selectivity of their approach responses, bobwhite quail neonates are ideal for the laboratory investigation of the development of auditory perception.
Effects of undernutrition in neonatal rats on physical development and food and water regulation
Authors: Look Jared Jay 
Published: January 2005

AbstractThe effects of neonatal undernutrition in rats on food and water regulation, external indices of development, and long‐term regulatory behavior were investigated. Undernutrition produced retardation in some external indices of development. The ability to eat, drink, and maintain body weight at weaning were not seriously affected by the undernutrition. Longer term deficiencies in feeding efficiency, osmotic regulation, prandial drinking, and activity were found for experimental subjects. The involvement of peripheral‐systemic factors as well as neurological retardation in producing feeding and drinking deficits following undernutrition are discussed.