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1.
Am Psychol ; 56(2): 128-65, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11279806

RESUMO

This article summarizes evidence and issues associated with psychological assessment. Data from more than 125 meta-analyses on test validity and 800 samples examining multimethod assessment suggest 4 general conclusions: (a) Psychological test validity is strong and compelling, (b) psychological test validity is comparable to medical test validity, (c) distinct assessment methods provide unique sources of information, and (d) clinicians who rely exclusively on interviews are prone to incomplete understandings. Following principles for optimal nomothetic research, the authors suggest that a multimethod assessment battery provides a structured means for skilled clinicians to maximize the validity of individualized assessments. Future investigations should move beyond an examination of test scales to focus more on the role of psychologists who use tests as helpful tools to furnish patients and referral sources with professional consultation.


Assuntos
Diagnóstico Diferencial , Determinação da Personalidade , Testes Psicológicos , Humanos , Metanálise como Assunto , Reprodutibilidade dos Testes
2.
J Pers Assess ; 75(2): 212-24, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11020140

RESUMO

This study compared Rorschach records of nondissociative outpatients with histories of (a) definite sexual abuse (n = 22), (b) suspected but unconfirmed sexual abuse (n = 13), or (c) no sexual abuse (n = 43) on selected variables hypothesized to be associated with sexual abuse. As predicted, clients with definite sexual abuse scored significantly higher than clients known not to be sexually abused on Armstrong and Loewenstein's (1990) Trauma Content index (TC/R), with an effect size greater than 1 SD. Contrary to prediction, there was no significant difference in the frequency of their Aggressive Past (AgPast; Gacono & Meloy, 1994) scores. AgPast scores, however, did positively correlate with sexual abuse that was violent or sadistic. As a test of discriminant validity, we hypothesized that 2 Rorschach variables (PER and Sc) would be unrelated to sexual abuse. This was supported by our data. Although TC/R was strongly associated with the presence and severity of sexual abuse, it could not discriminate sexually abused from nonsexually abused clients with great accuracy. The TC/R score is 1 factor among many that can be used to assess the validity of clients' claims of past sexual abuse.


Assuntos
Agressão/psicologia , Teste de Rorschach , Delitos Sexuais/psicologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/etiologia
3.
Mol Pharmacol ; 56(5): 1087-93, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10531417

RESUMO

Gamma-aminobutyric acid type A (GABA(A) )receptors are targets for allosteric modulation by general anesthetics. Mutation of Ser270 within the second transmembrane domain of the GABA(A) receptor alpha subunit can ablate the modulation of the receptor by the anesthetic ether isoflurane. To investigate further the function of this critical amino acid residue, we made multiple amino acid substitutions at Ser270 and analyzed the concentration-dependent gating by GABA and regulation by isoflurane in each mutant receptor. There is a strong negative correlation between the EC(50) for GABA and the molecular volume of the amino acid residue at position 270. Replacement of Ser by large residues such as His and Trp produced a shift of the GABA concentration-response curve to the left, whereas replacement of Ser with Gly had the opposite effect. There also was a strong negative association between the molecular volume of the amino acid residue at 270 and the degree of enhancement of submaximal GABA responses by isoflurane. These results indicate the significance of the amino acid at position alpha270 in gating of the GABA(A) receptor. In addition, the data on isoflurane are consistent with the existence of a cavity of finite size in the region of alpha270 that may be filled by the anesthetic molecule or by the side chain of a larger residue at alpha270. The introduction of isoflurane, or of a large residue, into this cavity may stabilize the open state of the GABA(A) receptor relative to the closed state.


Assuntos
Anestésicos Inalatórios/farmacologia , Agonistas GABAérgicos/farmacologia , Ativação do Canal Iônico , Isoflurano/farmacologia , Receptores de GABA-A/metabolismo , Células Cultivadas , Eletrofisiologia , Humanos , Mutagênese Sítio-Dirigida , Conformação Proteica , Estrutura Terciária de Proteína , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/genética , Transfecção
4.
Mol Pharmacol ; 53(3): 530-8, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9495821

RESUMO

Both volatile and intravenous general anesthetics allosterically enhance gamma-aminobutyric acid (GABA)-evoked chloride currents at the GABA type A (GABAA) receptor. Recent work has revealed that two specific amino acid residues within transmembrane domain (TM)2 and TM3 are necessary for positive modulation of GABAA and glycine receptors by the volatile anesthetic enflurane. We now report that mutation of these residues within either GABAA alpha2 (S270 or A291) or beta1 (S265 or M286) subunits resulted in receptors that retain normal or near-normal gating by GABA but are insensitive to clinically relevant concentrations of another inhaled anesthetic, isoflurane. To determine whether receptor modulation by intravenous general anesthetics also was affected by these point mutations, we examined the effects of propofol, etomidate, the barbiturate methohexital, and the steroid alphaxalone on wild-type and mutant GABAA receptors expressed in human embryonic kidney 293 cells. In most cases, these mutations had little or no effect on the actions of these intravenous anesthetics. However, a point mutation in the beta1 subunit (M286W) abolished potentiation of GABA by propofol but did not alter direct activation of the receptor by high concentrations of propofol. These data indicate that the receptor structural requirements for positive modulation by volatile and intravenous general anesthetics may be quite distinct.


Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Isoflurano/farmacologia , Propofol/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Sítios de Ligação , Células Cultivadas , Sinergismo Farmacológico , Etomidato/farmacologia , Humanos , Metoexital/farmacologia , Mutagênese Sítio-Dirigida , Ácido gama-Aminobutírico/farmacologia
5.
Neuroreport ; 9(3): 379-83, 1998 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-9512375

RESUMO

Two sets of chimeras between alphaxalone-sensitive GABA(A) receptor alpha2 or beta1 subunits and the alphaxalone-insensitive glycine receptor alpha1 subunit were constructed to determine the structural domains important for the modulatory actions of neuroactive steroids. These data suggest that the site of action for neurosteroids on GABA(A) receptors is not the same as that for volatile anesthetics and ethanol, but is on the N-terminal side of the middle of TM2.


Assuntos
Agonistas de Receptores de GABA-A , Pregnanodionas/farmacologia , Receptores de Glicina/efeitos dos fármacos , Esteroides/farmacologia , Anestésicos , Linhagem Celular , Etanol/farmacologia , Etomidato/farmacologia , Humanos , Técnicas de Patch-Clamp
6.
J Pharmacol Exp Ther ; 284(3): 934-42, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9495852

RESUMO

The actions of 2,2,2,-trichloroethanol were studied on agonist-activated Cl- currents in gamma-aminobutyric acid type A (GABAA), glycine and GABA rho 1 receptors by use of the whole-cell patch-clamp technique. Recombinant wild-type and mutant receptor subunits were transiently expressed in human embryonic kidney (HEK) 293 cells. Trichloroethanol enhanced currents elicited by submaximal (EC20) agonist concentrations at GABAA alpha 2 beta 1 receptors and glycine alpha 1 homomeric receptors in a reversible, concentration-dependent manner. Trichloroethanol, at concentrations of < or = 2 mM, did not significantly alter the magnitude of submaximal GABA currents at GABA rho 1 receptors, whereas higher concentrations inhibited submaximal GABA currents. Recent work has identified residues within putative transmembrane domains 2 and 3 as critical for positive modulation of GABAA and glycine receptors by n-alkanols and volatile ether anesthetics. Submaximal glycine currents at receptors containing either of two specific mutations within the glycine receptor alpha 1 subunit (S267I and A288W) were not enhanced by low concentrations of trichloroethanol and were inhibited by higher concentrations of trichloroethanol. In the GABAA alpha 2 beta 1 receptor, a specific mutation within transmembrane domain 3 of the beta 1 subunit (M286W) also abolished positive modulation by trichloroethanol. Mutations within the GABAA alpha 2 receptor subunit did not alter positive modulation by TCEt, whereas such mutations ablate positive modulation by n-alkanols and volatile anesthetics. In summary, trichloroethanol modulation of GABAA, glycine and GABA rho 1 receptors shares some, but not all, features in common with the requirements for modulation by n-alkanols and volatile anesthetics.


Assuntos
Etilenocloroidrina/análogos & derivados , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA/efeitos dos fármacos , Receptores de Glicina/efeitos dos fármacos , Sequência de Aminoácidos , Células Cultivadas , Relação Dose-Resposta a Droga , Etilenocloroidrina/farmacologia , Humanos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade
7.
J Biol Chem ; 273(6): 3314-9, 1998 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-9452448

RESUMO

Glycine and gamma-aminobutyric acid (GABA)A receptors are members of the "superfamily" of ion channels, and are sensitive to allosteric modulation by n-alcohols such as ethanol and butanol. We recently demonstrated that the mutation of Ser-267 to Ile in the alpha1 subunit abolished ethanol regulation of glycine receptors (Gly-R). In the present study, a pair of chimeric receptors was studied, in which a 45-amino acid domain comprising transmembrane domains 2 and 3 was exchanged between the Gly-Ralpha1 and gamma-aminobutyric acid rho1 subunits. Detailed pharmacologic analysis of these chimeras confirmed that this domain of the Gly-R confers enhancement of receptor function by ethanol and butanol. An extensive series of mutations at Ser-267 in the Gly-Ralpha1 subunit was also prepared, and the resulting homomeric receptors were expressed and tested for sensitivity to glycine, and allosteric modulation by alcohols. All of the mutant receptors expressed successfully in Xenopus oocytes. Mutation of Ser-267 to small amino acid residues such as Gly or Ala produced receptors in which glycine responses were potentiated by ethanol. As we have reported previously, the mutant Gly-Ralpha1 (Ser-267 --> Ile) was completely insensitive to ethanol; mutation of Ser-267 to Val had a similar effect. Mutation of Ser-267 to large residues such as His, Cys, or Tyr resulted in inhibition of Gly-R function by ethanol. These results demonstrate that the size of the amino acid residue at position alpha267 plays a crucial role in determining the functional consequences of allosteric modulation of the Gly-R by alcohols.


Assuntos
Etanol/farmacologia , Receptores de Glicina/agonistas , Serina/química , Animais , Linhagem Celular , Humanos , Mutagênese Sítio-Dirigida , Receptores de GABA/genética , Receptores de Glicina/química , Receptores de Glicina/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Xenopus
8.
Nature ; 389(6649): 385-9, 1997 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-9311780

RESUMO

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.


Assuntos
Anestésicos Inalatórios/farmacologia , Enflurano/farmacologia , Etanol/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Receptores de Glicina/efeitos dos fármacos , Alanina/fisiologia , Sequência de Aminoácidos , Anestésicos Intravenosos/farmacologia , Animais , Sítios de Ligação , Linhagem Celular , Eletrofisiologia , Glicina/farmacologia , Humanos , Dados de Sequência Molecular , Mutagênese , Propofol/farmacologia , Receptores de GABA-A/genética , Receptores de Glicina/genética , Proteínas Recombinantes de Fusão/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Homologia de Sequência de Aminoácidos , Serina/fisiologia , Triptofano/fisiologia , Xenopus
9.
J Pers Assess ; 67(3): 543-57, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16367674

RESUMO

Many clinicians are committed to giving feedback to clients about assessment results, but puzzle over how to integrate Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Rorschach findings when talking to clients. When the two tests agree, findings may be combined and assessors may use the language of clients' Rorschach percepts to frame findings from the MMPI-2 or the Structural Summary. When the Rorschach shows more disturbance than the MMPI-2, assessors may discuss "levels of personality," praise clients for their usual coping mechanisms, and raise the possibility of underlying problems. When the Rorschach depicts less psychopathology than the MMPI-2, clinicians may talk with Clients about factors influencing them to present as needing help. Alternatively, assessors may hypothesize that clients constrict emotionally in interpersonal, unstructured situations.

10.
Neuropharmacology ; 35(9-10): 1445-56, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9014160

RESUMO

GABAA and glycine receptors are close relatives in the "gene superfamily" of ligand-gated ion channels, but have distinctly different pharmacology. For example, barbiturates have two effects on GABAA receptors (GABAA-R): at low micromolar concentrations (2-5 microM), the anesthetic barbiturate methohexital potentiates submaximal chloride current responses to GABA; at higher concentrations (20-50 microM), the barbiturate causes direct gating of the channel in the absence of agonist. Neither of these barbiturate effects is seen on the glycine receptor (Gly-R). In order to study the structural parts of the GABAA-R involved in this barbiturate pharmacology, two unique restriction sites were introduced into the cDNAs encoding the alpha 2 and beta 1 subunits of the human GABAA-R and the alpha 1 subunit of the human gly-R. The first site ('X') corresponded to the C-terminal end of the third transmembrane domain (M3) in each subunit and enabled exchange of C-terminal fragment of approximately 100 amino acids (which includes the large 'cytoplasmic loop' and M4 segment) between GABAA-R and Gly-R subunits. The second site ('S') was approximately 30 amino acids 3'- from the N-terminal end of each subunit and enabled exchange of a small N-terminal fragment between GABAA-R and Gly-R subunits. Several chimeric receptor subunit cDNAs were constructed and the resulting receptors tested for their ability to respond to GABA and glycine and for sensitivity to the barbiturate methohextial (MTX). The results show that neither the large C-terminal fragment nor the smaller N-terminal fragment is associated with the enhancement or direct activation of the GABAA-R by MTX. These results demonstrate the viability of chimeric GABAA/Gly-R and suggest that the method will be suitable for further investigation of the molecular basis of the barbiturate pharmacology of the GABA-R.


Assuntos
Barbitúricos/farmacologia , Receptores de GABA-A/biossíntese , Receptores de GABA-A/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Anestésicos Gerais/farmacologia , Células Cultivadas , DNA/biossíntese , Eletrofisiologia , Glicina/farmacologia , Humanos , Potenciais da Membrana/efeitos dos fármacos , Metoexital/farmacologia , Mutagênese Sítio-Dirigida , Sondas de Oligonucleotídeos/farmacologia , Técnicas de Patch-Clamp , Receptores de GABA-A/efeitos dos fármacos , Receptores de Glicina/efeitos dos fármacos , Receptores de Glicina/genética , Ácido gama-Aminobutírico/farmacologia
11.
Psychol Med ; 20(4): 843-8, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1980954

RESUMO

This study developed a method for measuring subjective costs and benefits of psychiatric treatments. Forty-one patients rates the relative bothersomeness of symptoms of schizophrenia and side effects of neuroleptics. Thirty-four psychiatrists made parallel ratings from the perspective of the average patient (individual utility) and of the patient's family and society (institutional utility). Psychiatrists predicted patients' ratings moderately well, but misjudged the bothersomeness to patients of 24% of side effects and 20% of symptoms. When considering the patient's perspective, both schizophrenic patients and psychiatrists rated symptoms as no more bothersome than side effects. However, psychiatrists saw side effects as significantly less bothersome than symptoms when considering costs to society. The subjective utility of neuroleptic medications for schizophrenia is most justifiable from an institutional perspective.


Assuntos
Antipsicóticos/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Papel do Doente , Antipsicóticos/uso terapêutico , Atitude do Pessoal de Saúde , Comportamento do Consumidor , Humanos , Escalas de Graduação Psiquiátrica
12.
Am J Physiol ; 255(6 Pt 1): G807-12, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2904770

RESUMO

Isolated circular smooth muscle cells from the rabbit distal colon were used to study the effect of prostaglandin E2 (PGE2) on bethanechol-stimulated smooth muscle cell contraction. Contraction was expressed as the percentage decrease in mean cell length compared with unstimulated cells. Incubation with different concentrations of PGE2 (10(-10)-10(-6) M) did not cause contraction or relaxation of unstimulated smooth muscle cells. Bethanechol stimulated a dose-dependent contraction that was maximal at 30 s. The threshold for bethanechol-stimulated contraction was 10(-11) M; the ED50 was 10(-10) M; and the maximum contraction (23.0 +/- 1.8%) occurred at 10(-8) M. Preincubation with PGE2 reduced both the efficacy and potency of bethanechol-stimulated contraction. Preincubation with 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or dibutyryl-cAMP reduced the efficacy of bethanechol-stimulated contraction without affecting potency. Increasing concentrations of PGE2 stimulated a dose-dependent increase in the production of intracellular cAMP (P less than 0.05). These studies show that PGE2 inhibits bethanechol-stimulated contraction of isolated colonic circular myocytes and is associated with increased production of intracellular cAMP. There is also a cAMP-independent effect of PGE2 on the potency of bethanechol stimulation.


Assuntos
Colo/fisiologia , Dinoprostona/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Animais , Atropina/farmacologia , Betanecol , Compostos de Betanecol/farmacologia , Colo/citologia , Colo/efeitos dos fármacos , AMP Cíclico/metabolismo , Técnicas In Vitro , Masculino , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Coelhos , Rubídio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
14.
In Vitro Cell Dev Biol ; 24(8): 787-94, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3045072

RESUMO

Although cultured vascular smooth muscle cells have been extensively characterized and investigated, there are very few studies of cultured intestinal smooth muscle cells. The aim of this study was to culture colonic smooth muscle (CSM) cells from the rabbit colon. Freshly isolated CSM cells from the circular muscle layer of the distal colon were prepared by collagenase digestion. In primary culture, CSM cells attached to the culture vessels by 48 to 72 h, proliferated by 3 to 7 d, and reached confluency by 14 to 17 d with a "hill-and-valley" pattern. Spontaneous contractions were not observed at any time at 21 degrees or 37 degrees C. Confluent primary cultures were greater than 95% CSM cells, as identified by intensely positive immunofluorescent staining to smooth muscle actin-specific CGA7 and muscle-specific HHF-35 monoclonal antibodies. Transmission electron microscopy of freshly isolated and proliferating CSM cells revealed ultrastructural features consistent with smooth muscle cells. We successfully cultured CSM cells of the rabbit from freshly isolated cells and validated these CSM cells by electron microscopy and immunocytochemical staining. These highly pure primary cultures may be used to investigate numerous aspects of CSM cell metabolism and physiology.


Assuntos
Colo/citologia , Músculo Liso/citologia , Animais , Divisão Celular , Células Cultivadas , Imunofluorescência , Microscopia Eletrônica , Coelhos
16.
J Pers Soc Psychol ; 50(4): 813-8, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3712223

RESUMO

An investigation was made of the hypothesis of Bloom (1964) and others that the stability of personality is greater among older than younger adults. The subjects were 459 men in two cohorts, followed from 1947 to 1977 as part of a longitudinal medical study. Self-ratings were obtained over the 30-year period on 15 item-factor scales from the Minnesota Multiphasic Personality Inventory and on two higher order factors. There was no selective attrition in the sample with respect to baseline personality scores. Thirty-year uncorrected stability coefficients ranged from .08 to .88 across the two cohorts. There was substantial evidence of greater stability on many traits in the older than in the younger age/cohort group. Furthermore, in late adulthood, traits related to the higher order factor Constraint were more stable than were traits related to Positive vs. Negative Affectivity. The study is not a definitive test of Bloom's hypothesis because cohort and age effects are confounded. However, the results are supportive of the hypothesis and the study improves on existing research in a number of ways.


Assuntos
Doença das Coronárias/psicologia , MMPI , Desenvolvimento da Personalidade , Adolescente , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria
19.
J Homosex ; 8(2): 45-9, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-7166642

RESUMO

Recent research on gay male and lesbian couples suggests that traditional gender-role-playing sometimes occurs in their relationships, though it is less common than in the relationships of heterosexuals. This paper briefly explores three issues raised by these findings. First, we consider reasons why partners of the same gender might engage in gender-role-playing. Second we discuss the processes that might be involved in allocating masculine and feminine roles to partners in a couple. Finally, we consider the finding that traditional gender roles are associated with diminished satisfaction and suggest possible reasons why this might be so.


Assuntos
Identidade de Gênero , Homossexualidade , Identificação Psicológica , Relações Interpessoais , Adulto , Feminino , Humanos , Estilo de Vida , Masculino , Satisfação Pessoal
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