Back to basics.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M West.
Explore the source record for details and available documents.
This experiment was conducted to determine whether the amount of preoperative training influences the effects, on retention, of amygdala lesions induced 30 days after escape training. Rats received 1 or 10 footshock-motivated escape training trials; 30 days later, sham or neurotoxic amygdala lesions were induced. Results of an inhibitory avoidance test performed 4 days after surgery indicated that amygdala lesions impaired retention performance; however, increased preoperative training partially attenuated the retention deficit. Increased preoperative training also attenuated the impairing effects of the lesions on retention assessed in a continuous multiple-trial inhibitory avoidance task given 36 days after the original escape training. The finding that amygdala-lesioned rats remembered the escape training suggests that the amygdala is not a critical locus of the changes underlying the long-term retention of footshock-motivated escape training.
Explore the source record for details and available documents.
The excitatory amino acid subtype receptor agonists, N-methyl-D-aspartate (NMDA) and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, a non-NMDA agonist), produce specific dose-related heart rate and vasoconstrictor responses when given by injection into the upper thoracic or lumbar intrathecal space of the conscious rabbit. The responses are inhibited by prior intrathecal injection of the specific excitatory amino acid subtype receptor antagonist, 2-amino-5-phosphonovaleric acid (AP-5) or 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. Baroreceptor heart rate reflex function is inhibited by AP-5 and by DNQX applied to the upper thoracic spinal cord. In contrast baroreflex vasoconstrictor function is blocked by AP-5 but not by DNQX given in the lumbar intrathecal space. The experiments support previous evidence that spinal excitatory amino acids are important as neurotransmitters at the level of the sympathetic preganglionic neuron and as such exert tonic and reflex control of autonomic cardiovascular function. It is concluded that 1) intrathecal activation of NMDA and non-NMDA subtype receptors has similar but independent effects on heart rate and on blood pressure and 2) NMDA receptors alone participate in mediation of baroreflex vasoconstrictor function, whereas both sets of receptors determine reflex sympathetic heart rate effects.
One hundred and eighty-seven adolescents referred to outpatient and residential services in three Canadian cities were assessed for lifetime suicidal ideation and attempt, and administered the Parental Bonding Instrument (PBI). Suicidal adolescents of both genders reported lower care and higher over-protection in relation to their mothers than non-suicidal subjects, and female subjects reported this pattern for their fathers as well. Male subjects did not show clear differentiation between groups on PBI ratings for their fathers. Mean PBI scores for female subjects indicated subjects with no suicidal ideation, those with suicidal ideation only, and those having made suicide attempts to be on a continuum, but findings for males did not. The findings extend previous reports of higher "affectionless control" in suicidal adults, but suggest that this pattern may be stronger in females than males, and that maternal influences may be stronger than paternal influences.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Rearrangement of T-cell antigen receptor and immunoglobulin genes occurs in immature lymphoid cells by an unknown mechanism. To identify components of the rearrangement machinery, we isolated a population of murine thymocytes enriched for rearranging pre-T cells. In the nuclear fraction of these cells, we detected a protein that specifically bound the recombination sequences that flank T-cell receptor and immunoglobulin genes and are required for their rearrangement. This protein recognized both heptamer and nonamer motifs of the recombination sequence, separated by either 12 or 23 bp. The protein complexed with the recombination sequence oligonucleotide had an apparent molecular mass of 30 kDa. The binding characteristics of the protein and its presence in rearranging thymocytes and cell lines suggest that it could serve as the recognition unit of a recombinase complex.
OBJECTIVE: To establish a program for the prevention of rheumatic fever and rheumatic heart disease in a semi-isolated Aboriginal community in far north Queensland and to test its efficacy. DESIGN: A prevalence study of acute rheumatic fever and chronic rheumatic heart disease was conducted in the community in 1985 and subjects with possible acute rheumatic fever were assessed. A prophylactic antibiotic program was instituted. Records were kept of the prevalence of acute rheumatic fever for six years after the 1985 survey. A second survey of the community was held in 1991 to detect chronic rheumatic carditis resulting from undetected acute rheumatic fever. SETTING: The Yarrabah Aboriginal community in north Queensland (latitude 17 degrees S). The program was conducted by the Yarrabah Health Team, a part of the North Queensland Aboriginal Health Division. PARTICIPANTS: The whole Yarrabah community (population 1250) was invited to participate. In 1985, after the completion of an educational program, 89% of the community cooperated in the survey. There was no educational program before the 1991 survey and the compliance rate was much lower. Importantly, however, 87% of the vulnerable group (4-16 year olds) were examined. INTERVENTIONS: After the 1985 survey, all community members aged 4-16 years had throat swabs taken three times each year. Those with swabs showing Group A streptococci were treated; their contacts were also swabbed and treated if Group A streptococci were found. RESULTS: Before the institution of the swabbing program there were four new cases of acute rheumatic fever each year in the Yarrabah community. In the six years after the program was introduced only one case of acute rheumatic fever occurred. This was at a time when swabbing had temporarily lapsed for a three-month period. CONCLUSIONS: These results support the use of a prophylactic antibiotic program in Aboriginal communities as a cost effective and efficient method for the prevention of rheumatic fever. The cooperation of the community is an integral part of its success and this can be obtained by community education.
Bayesian inference techniques have been applied to the analysis of fluctuation of post-synaptic potentials in the hippocampus. The underlying statistical model assumes that the varying synaptic signals are characterized by mixtures of (unknown) numbers of individual gaussian, or normal, component distributions. Each solution consists of a group of individual components with unique mean values and relative probabilities of occurrence and a predictive probability density. The advantages of bayesian inference techniques over the alternative method of maximum likelihood estimation (MLE) of the parameters of an unknown mixture distribution include the following: (1) prior information may be incorporated in the estimation of model parameters; (2) conditional probability estimates of the number of individual components in the mixture are calculated; (3) flexibility exists in the extent to which the estimated noise standard deviation indicates the width of each component; (4) posterior distributions for component means are calculated, including measures of uncertainty about the means; and (5) probability density functions of the component distributions and the overall mixture distribution are estimated in relation to the raw grouped data, together with measures of uncertainty about these estimates. This expository report describes this novel approach to the unconstrained identification of components within a mixture, and provides demonstration of the usefulness of the technique in the context of both simulations and the analysis of distributions of synaptic potential signals.
Traditionally, an excess of interpersonal dependency has been used to characterize disturbed interpersonal relationships in adults. This approach stands in sharp contrast to that of attachment theorists who conceptualize attachment as functionally distinct from dependency. Attachment theory focuses on anxious attachment in the definition and dynamics of disturbed adult interpersonal relationships. The purpose of this study was to examine the relevance of anxious attachment to the differentiation of psychiatric outpatients from nonpatients. Empirically, three scales (feared loss of the attachment figure, proximity seeking, and separation protest) measure the components of anxious attachment as defined by Bowlby. The scales were administered to two research samples. Sample 1 was composed of 136 respondents to a survey within the Calgary community. Sample 2 consisted of 110 psychiatric outpatients drawn from the psychotherapy clinic of the Calgary General Hospital. The results indicate that the three components of anxious attachment offer a clinically relevant system for differentiating between psychiatric outpatients and nonpatients. Of these three components, feared loss has the predominant effect. The implications of this finding for the delineation of disturbed interpersonal relationships in adults is discussed.
Disturbed or impoverished relationships have been identified as a predominant feature of adult children of alcoholics (ACOAs). Recently, the concept of co-dependency has been advanced to depict the interpersonal difficulties of these individuals, but lacks definitional rigor. The notion that childhood experiences with parents are 'carried forward' to affect attitudes and behaviors relevant to later intimate relationships is also consistent with attachment theory. This study examined the patterns of attachment of ACOAs as compared to adult children of non alcoholics (ACONAs). A cross-sectional sample of 203 individuals attending either a short term hospital based outpatient psychiatric program or a community based alcoholism treatment program was included in this study. Results supported the hypothesis that female ACOAs had a distinctive dysfunctional attachment profile. There were no significant differences in the attachment styles of male ACOAs as compared to ACONAs, or male substance abusers as compared to non-abusers.
In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder.
This study investigated the characteristics related to attachment of 42 depressed psychiatric patients and 42 non-depressed psychiatric controls. The depressed subjects demonstrated an anxious pattern of attachment, characterized by either intense care-seeking in relation to their attachment figure or angry withdrawal from their attachment figure when their desire for security was frustrated. The results are discussed in terms of Bowlby's attachment construct.
Cellular transcription factors play critical roles in regulating human immunodeficiency virus (HIV) gene transcription, although the precise mechanism(s) defining their roles are not well established. Primarily it has been suggested that sequence-specific interaction of trans-activating proteins with cis-acting DNA elements plays a crucial role in regulating the target genes. The negative regulatory element (NRE) of HIV-1 long terminal repeat (LTR) is one such defined region that has been reported to down-regulate LTR-directed HIV gene expression. Information regarding the role of this region in the regulation of HIV expression is lacking. Here we describe an attempt to further characterize the role of NRE cis-elements and define any sequence-specific interaction with cellular factors. Using gel mobility shift DNA-binding and Southwestern blot assays, we have mapped a distinct region of NRE (-290 to -260, a 30-base pair (bp) domain of NRE-A) sequences of HIV-1 LTR, which recognizes a specific DNA-binding protein from HeLa cell nuclear extracts. This factor is a 38-kDa polypeptide which can be affinity-purified to near homogeneity by this 30-bp specific oligonucleotide in affinity chromatography. The cellular factor from HeLa cell nuclear extract exhibits specific interaction only with the 30-bp NRE-A domain of HIV-1 LTR and acts as a strong transcriptional repressor/inhibitor molecule in the DNA-protein gel binding, as well as in vitro transcriptional studies with the nuclear extracts from cells with productive HIV-1 infection. To our knowledge, this is the first report of a factor recognizing a distinct segment within NRE that has been shown to exert an inhibitory effect on transcriptionally active DNA-protein "pre-initiation" complex formation, suggesting a possible role in HIV-1 gene regulation.
Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.
Long-term follow-up data are provided for a previously reported study of patients with membranous glomerulonephritis (MGN), nephrotic syndrome, and renal function impairment. Nine patients were treated with cyclophosphamide (1 to 2 mg/kg) and six of these received concurrent prednisone; they are compared with 17 concurrent controls (14 of whom had received prednisone at some time). The mean follow-up is 83 +/- 13 months in the treated patients and 64 +/- 7 months in the controls. Of the nine treated patients, four achieved a complete remission from the nephrotic syndrome (proteinuria less than 0.5 g/d), and five a partial remission (proteinuria decreased by at least 50% and to less than 3.5 g/d). One of the nine treated patients and 10 of the 17 controls have reached end-stage renal disease (ESRD) (P less than 0.05). Nine of the controls reaching ESRD had persistent nephrotic syndrome, whereas of the seven controls who have not yet reached ESRD, only two have persistent nephrotic syndrome (chi 2, P less than 0.02). There have been four relapses in three treated patients, and three of the four have responded to repeat therapy. One patient refused full therapy and remains nephrotic. Life-table analysis demonstrates significantly increased survival from ESRD in treated patients as compared with controls (P = 0.04).
This report is a prospective study of 33 male patients who underwent both contrast ventriculography (CVG) and radionuclide ventriculography (RVG) within a 24-hour period. Expert, blinded observers graded the left ventricle's regional wall motion (RWM) in the left anterior descending (LAD), left circumflex (LCx), and posterior descending arterial (PDA) distributions on right anterior oblique (RAO), and left anterior oblique (LAO) CVGs, and on anterior (ANT), LAO, 70 degrees left anterior oblique (LAO70), and left posterior oblique (LPO) RVGs. When statistically compared with CVG RWM standard data, RVG studies composed of LAO and LPO views were equal to the RVG studies composed of ANT, LAO, and LAO70 views in assessment of the LAD and LCx distributions. The RVG with LAO and LPO views was superior to the RVG with ANT, LAO, LAO70 in the detection of the posterior descending artery RWM. The authors conclude that accurate assessment of RWM is efficiently performed with the RVG composed of LAO and LPO views.