Antineoplastic agents. 41. The beetle Allomyrina dichotomus

The belief that the smooth muscle contracting activity of angiotensin II (angiotensin) in the guinea pig ileum is partly mediated by release of acetylcholine was reexamined, with the following results. 1. Atropine did not reduce the maximum contraction produced by angiotensin, although it caused a shift to the right of the log dose-response curve (dose ratio = 2.2). A similar shift was observed with histamine, bradykinin and BaCl2. 2. A moderate potentiation of angiotensin by eserine was also observed, which was similarly found for the other agonists. 3. A previous report that atropine blocks the fast (phasic) component of the isometric response of the ileum to angiotensin was not confirmed. The disappearance of the phasic component was found to be due to a tachyphylactic change in the response. 4. Depolarization by high doses of nicotine, and inhibition of acetylcholine synthesis by hemicholinium, did not affect the response to angiotensin. 5. Ilei in which the intramural ganglia had been destroyed by incubation at 4 degrees 48-56 h responed maximally to angiotensin, without loss of the phasic component of the response. It is concluded that the available evidence does not support the participation of a cholinergic mechanism in the effect of angiotensin upon the guinea pig ileum.     

Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19

Continued investigation of murine leukemia (P-388) active fractions from the African marine worm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) 1H, 13C, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) microg/mL), a mini panel of human cancer cell lines (GI50 <10(-3) microg/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI50 ca. 10(-9) M).     

Antineoplastic agents. 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (the Republic of Maldives)

The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).     

Multimethod probes of individualism and collectivism.

A theoretical framework concerning cultural patterns labeled individualism and collectivism is probed. As predicted, it is shown that the content of the self includes more group-linked elements in collectivist than in individualist cultures; members of collectivist cultures perceive their ingroups as more homogeneous than their outgroups, and the opposite pattern is found among members of individualistic cultures; and people in collectivist cultures perceive more intimate and subordinate social behaviors as likely toward their ingroup members and more dissociative and superordinate behaviors toward members of their outgroups than do members of individualistic cultures. Collectivists emphasize values that promote the welfare of their ingroup, whereas individualists emphasize values that promote individual goals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

2,2'-Dithiobisbenzamides and 2-benzisothiazolones, two new classes of antiretroviral agents: SAR and mechanistic considerations

Substituted 2,2'-dithiobisbenzamides and 2-benzisothiazolones were prepared and shown to possess low microM activity with high therapeutic indices against HIV-1, HIV-2 and SIV in cell culture. The mechanism of antiviral action was determined to be directed toward the nucleocapsid protein (NCp7), which contains two zinc fingers and plays vital roles in the viral life cycle. The "active sulfides" of this study cause the extrusion of zinc from these zinc fingers. Structure-activity relationships of the 2,2'-dithiobisbenzamides reveal that the disulfide bond and the ortho benzamide functional groups are essential for activity, with the best compounds having a carboxylic acid, carboxamide, or sulfonamide substituent. The 2-benzisothiazolones are formed from the disulfides both chemically and in vivo and their SAR mimics that of the 2,2'-dithiobisbenzamides. The antiviral activity of the disulfides may require cyclization to the isothiazolones. Two agents, PD 159206 and PD 161374, which showed good antiviral activity, physical properties, and excellent pharmacokinetics in mice, were selected for advanced studies.     

Impermeant maleimides. Oriented probes of erythrocyte membrane proteins

Maleimides impermeant to human erythrocyte membranes have been synthesized and applied to studies of the sulfhydryl groups of the membrane. Reaction of radioactive dextran-maleimide and glutathione-maleimide with either intact erythrocytes or ghosts yields sulfhydryl titers for the outer (exofacial) and inner (endofacial) surfaces, respectively, of 1.5 to 1.7 and 27 to 28 amol/cell. Corresponding values for sulfhydryl groups within the membrane interior, as estimated with radioactive N-ethylmaleimide, are 16 to 22 amol/cell. After exofacial labeling of intact cells with [35S]glutathione-maleimide, autoradiography of sodium dodecyl sulfate-polyacrylamide gels demonstrates four bands (alpha, beta, gamma, and delta) containing, respectively, 13%, 63%, 11%, and 13% of the radioactivity. The major beta-band corresponds in position to polypeptides of molecular weight 40,000 to 70,000 and to Coomassie brilliant blue-stained Band 5. Selective extraction demonstrates that the major Band 5 protein is not identical with the labeled beta-band polypeptides. Following endofacial labeling of ghosts with [35S]glutathione-maleimide, autoradiography reveals radioactivity in all of the major Coomassie brilliant blue bands. The impermeant maleimides described are also applicable to studies of discrete functional proteins of the erythrocyte membrane, including the hexose transport mechanism and the major Rho antigenic site.     

Theoretical implications of extralist probes for directed forgetting.

In 5 experiments, the authors examined the influence of associative information in list-method directed forgetting, using the extralist cuing procedure (Nelson & McEvoy, 2005). Targets were studied in the absence of cues, but during retrieval, related cues were used to test their memory. Experiment 1 manipulated the degree of resonant connections from associates of the target back to the target. Experiment 2 varied the degree of connectivity of associates of the target. Experiment 3 varied the size of the associative neighborhood of the target. Experiment 4 varied the direct target-to-cue strength, and Experiment 5 varied the indirect strength between the cue and the target. Reliable directed forgetting impairment emerged in all experiments. Furthermore, directed forgetting reduced the effects of the associates contributing to the target activation strength (Experiments 1–2), and it also reduced the effects of the associates contributing to the cue–target intersection strength (Experiments 3–5). Together, these results support the context account and challenge the inhibitory interpretation of directed forgetting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antifungal agents. Part II. The azoles

Before 1978, amphotericin B and flucytosine were the only drugs available for the treatment of systemic fungal infections. The imidazoles, miconazole and ketoconazole, were introduced during the next 3 years. Intravenously administered miconazole served a limited therapeutic role and is no longer available. Orally administered ketoconazole, an inexpensive, effective, and convenient option for treating mucosal candidiasis, was widely used for a decade because it was the only available oral therapy for systemic fungal infections. During the 1990s, use of ketoconazole diminished because of the release of the triazoles--fluconazole and itraconazole. Fluconazole is less toxic and has several pharmacologic advantages over ketoconazole, including penetration into the cerebrospinal fluid. In addition, it has superior efficacy against systemic candidiasis, cryptococcosis, and coccidioidomycosis. Despite a myriad of drug interactions and less favorable pharmacologic and toxicity profiles in comparison with fluconazole, itraconazole has become a valuable addition to the antifungal armamentarium. It has excellent activity against sporotrichosis and seems promising in the treatment of aspergillosis. Itraconazole has replaced ketoconazole as the therapy of choice for nonmeningeal, non-life-threatening cases of histoplasmosis, blastomycosis, and paracoccidioidomycosis and is effective in patients with cryptococcosis and coccidioidomycosis, including those with meningitis. Further investigation into the development of new antifungal agents is ongoing.     

Mothers as family change agents.

Studied the impact of a counseling program for mothers on the perceptions and behavior of family members. The mother, father, and 1 8-12 yr old problem child of 13 experimental and 11 control families were evaluated before and after 7 weekly counseling sessions. Pre- and postexperimental measures included the Family Concept Q Sort, a family decision-making task, and a behavioral data chart maintained by the mother. The experimental spouses experienced a significant increase in perceived family integration. The experimental families reflected a significant increase in the number of positive responses and a significant decrease in the number of negative responses used by the 3 family members. The undesirable behaviors of problem children within the experimental families decreased significantly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Novel euglycemic and hypolipidemic agents. 1

A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.     

Parents as agents of career development.

This study tested the effectiveness of a program for parents to help their adolescent children in career planning. In a pretest–posttest control group design involving 20 families in the experimental group and 20 families as a wait-listed control group, a multivariate analysis of variance (MANOVA) was used to test improvement on five variables concerned with parent–child relations and career development. The MANOVA yielded a significant effect for groups over time. Using an analysis of variance (ANOVA) with repeated measures, four of five univariate tests were also significant. In addition, all parents and six adolescents were interviewed after the program to gain a qualitative assessment of program effectiveness. Interview data tended to support the varied degrees of improvement that the adolescents showed on the quantitative measures. It was concluded that parents can function effectively in fostering the career development of their children, when provided with a structured program that they can follow. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Orienting attention in visual working memory reduces interference from memory probes.

Given a changing visual environment, and the limited capacity of visual working memory (VWM), the contents of VWM must be in constant flux. Using a change detection task, the authors show that VWM is subject to obligatory updating in the face of new information. Change detection performance is enhanced when the item that may change is retrospectively cued 1 s after memory encoding and 0.5 s before testing. The retro-cue benefit cannot be explained by memory decay or by a reduction in interference from other items held in VWM. Rather, orienting attention to a single memory item makes VWM more resistant to interference from the test probe. The authors conclude that the content of VWM is volatile unless it receives focused attention, and that the standard change detection task underestimates VWM capacity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Program evaluation using hierarchical linear modeling with curriculum-based measurement reading probes.

Used hierarchical linear modeling (HLM) to evaluate 99 ethnically diverse 2nd-Graders' growth in oral reading fluency using curriculum-based measurement (CBM) over the course of the school year. Five statistical advantages of the use of HLM are described and four are highlighted in this example: (a) The potential for improved accuracy in slope estimation of the empirical Bayes method used in HLM; (b) HLM provided the flexibility to test the effects of independent variables on the initial status of the slope and the change in slope over time; (c) HLM provided an analysis of the nested effects of the classroom on individual performance; and (d) HLM provided a statistical test for both group effects and individual variation in reading growth. Results showed 1st-Grade reading performance significantly predicted initial 2nd-Grade reading performance. Individual growth curves of 28 students who attended summer school showed that all of them made statistically significant growth in reading ability. 71% of the summer school students scored between the 1st and 2nd quartile of the spring, norming distribution at the end of summer school. This example shows that the use of HLM with normative CBM reading probes provided additional information not available with other statistical techniques. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Baby's first 10 words.

Although there has been much debate over the content of children's first words, few large sample studies address this question for children at the very earliest stages of word learning. The authors report data from comparable samples of 265 English-, 336 Putonghua- (Mandarin), and 369 Cantonese-speaking 8- to 16-month-old infants whose caregivers completed MacArthur-Bates Communicative Development Inventories and reported them to produce between 1 and 10 words. Analyses of individual words indicated striking commonalities in the first words that children learn. However, substantive cross-linguistic differences appeared in the relative prevalence of common nouns, people terms, and verbs as well as in the probability that children produced even one of these word types when they had a total of 1-3, 4-6, or 7-10 words in their vocabularies. These data document cross-linguistic differences in the types of words produced even at the earliest stages of vocabulary learning and underscore the importance of parental input and cross-linguistic/cross-cultural variations in children's early word-learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

10 years of illusions.

A decade ago, S. Aglioti, J. F. X. DeSouza, and M. A. Goodale (1995) published an experiment that has had a big influence on the way that visual information is thought to control human behavior. Their findings have often been simplified as suggesting that action is immune to perceptual illusions. The current authors critically analyze the 4 steps involved in this simplification and argue that research during the last 10 years has shown that the validity of 3 of the 4 steps is doubtful. They conclude that this experiment cannot be regarded as firm support for the 2-visual-systems hypothesis (i.e., that the ventral stream is for perception and the dorsal stream is for visually guided actions). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Kinder therapy: Teachers as therapeutic agents.

The purpose of this article is to describe Kinder Therapy (from the German, kindergarten), a process that is based on the model of Filial Therapy developed by B. Guerney (1964) and the theoretical constructs of Individual Psychology. The authors developed and designed Kinder Therapy to train teachers to become therapeutic agents. This article presents a background on the development of Filial Therapy, an overview of the principles of Individual Psychology, and an explanation of Kinder Therapy. A case study illustrates the successful application of Kinder Therapy with a kindergarten child, the classroom teacher, and the school counselor. Also included are suggestions for variations on the Kinder Therapy approach, along with suggestions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)