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Biomedical subjects

J Russell

Publications and source records attributed to J Russell.

At least 55 records · Page 3Linked to original sources

Deregulated expression of DP1 induces epidermal proliferation and enhances skin carcinogenesis.

E2F transcription factors have been implicated in several cellular processes, including proliferation, apoptosis, and oncogenic transformation. A functional E2F factor consists of a heterodimer containing an E2F polypeptide (E2F1-E2F6) and a DRTF1-polypeptide (DRTF1-polypeptide-1 (DP1) or DRTF1-polypeptide-2). It is the E2F subunit that supplies the transcriptional activation domain and the motif involved in binding to members of the retinoblastoma tumor suppressor family. The role of the DP subunit in regulating E2F-dependent activities is not completely understood. To examine the properties of DP1 in vivo, we generated transgenic mouse lines expressing DP1 under the control of a keratin 5 (K5) promoter. Overexpression of DP1 in basal layer keratinocytes caused mild hyperplasia and hyperproliferation of the epidermis but did not result in increased apoptosis or spontaneous tumor development. Coexpression of DP1 with E2F1 or E2F4 in the epidermis of bigenic mice modestly enhanced proliferation and apoptosis over the levels induced by E2F1 or E2F4 expression alone. In a two-stage chemical carcinogenesis assay, more and larger skin tumors developed in K5 DP1 transgenic mice than in nontransgenic mice. These findings show that in this in vivo model, deregulated expression of DP1 on its own induced proliferation and enhanced carcinogenesis.

Animals↗

Executive control within strategic deception: a window on early cognitive development?

Recently it has been claimed that the difficulty young children have with tests of strategic deception may be due to limitations in executive control rather than lack of insight into mental concepts. In the studies reported here we asked how reducing the executive demands of one measure of strategic deception, the windows task (J. Russell, N. Mauthner, S. Sharpe, & T. Tidswell, 1991), would affect performance. Study 1 demonstrated that both providing an artificial response medium and having children play in partnership enabled 3-year-olds to adopt a successful strategy. Study 2 examined whether social or executive factors accounted for the good performance of children when they played in partnership. Study 3 ruled out the possibility that the effectiveness of the artificial media was a result of reducing social intimidation-the manipulations were effective even in the presence the opponent. These results argue for executive factors playing a substantial role in the development of strategic deception.

Child, Preschool↗

Altered energy metabolism in anorexia nervosa.

Optimal nutritional rehabilitation of anorexia nervosa requires more information concerning actual energy and substrate requirements. To this end, indirect calorimetry was performed in female patients (n=34, age 20.9+/-1.2 yr, body mass index [BMI] 15.6+/-0.2 kg/m(2); mean+/-SEM) soon after commencement of refeeding and at the time of discharge from hospital (n=18, BMI 19.0+/-0.3 kg/m(2)). Healthy female controls (n=18, age 24.6+/-1.3 yr, BMI 21.6+/-0.6 kg/m(2)) were also tested. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured in the fasting state, followed by diet-induced thermogenesis (DIT) and RQ over a 4 h period following a 100 g oral glucose load. Compared with post-refeeding patients and controls, pre-refeeding patients had a high basal RQ and a low REE, with a paradoxically higher DIT (13.2+/-0.9% of REE vs. 8.3+/-1.2% and 8.6+/-0.9% in post-refeeding patients and controls, respectively). RQ values in pre-refeeding patients exceeded unity following the glucose load, probably reflecting net lipogenesis, whereas in the post-refeeding patients, post-glucose RQ was similar to that of controls, suggesting premature curtailment of lipogenesis. These data demonstrate energy wasting in emaciated patients with anorexia nervosa. Biological repair processes could account for disproportionate energy loss early in refeeding and there may be some later impediment to full restoration of fat stores.

Adolescent↗

The execution of arbitrary procedures by children with autism.

Executive tasks typically contain a prepotent lure. In addition, they require individuals either to (a) follow arbitrary procedures or (b) update their model of the physical world. Recent research suggests that children with autism may be challenged only by executive tasks of the former kind (containing arbitrary rules). We asked whether this continues to be true when there is no prepotent lure, comparing performance on (a) a task with arbitrariness but without prepotency with (b) a task with both features and (c) a task with neither. The participants with autism performed at a lower level than comparison groups on the first and second task but not on the third task. This outcome is consistent with the view that autism is associated with difficulties in following arbitrary procedures per se. We try to locate difficulties with acting on the basis arbitrary rules in relation to more mainstream ideas about autistic executive dysfunction.

Adolescent↗

PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation.

Signaling mechanisms underlying neurotrophic regulation of synaptic transmission are not fully understood. Here we show that neurotrophin-3 (NT3)-induced potentiation of synaptic transmission at the neuromuscular synapses is blocked by inhibition of phosphoinositide-3 kinase, phospholipase C-gamma or the downstream IP3 receptors of phospholipase C-gamma, but not by inhibition of MAP kinase. However, neither stimulation of Ca2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase (PI3K*) in presynaptic motoneurons alone is sufficient to enhance transmission. Photo-uncaging of IP3 in neurons expressing PI3K* elicits a marked synaptic potentiation, mimicking the NT3 effect. These results reveal an involvement of PI3 kinase in transmitter release, and suggest that concomitant activation of PI3 kinase and IP3 receptors is both necessary and sufficient to mediate the NT3-induced synaptic potentiation.

Animals↗

The regulation of FasL expression during activation-induced cell death (AICD).

Activation-induced cell death (AICD), a Fas ligand (FasL)-dependent pathway, is important for maintaining T-cell homeostasis. Interleukin-2 (IL-2), an enhancer of AICD, can also enhance FasL expression. However, we show that the level of FasL or FLIP protein did not correlate with the susceptibility to AICD. Some T cells expressed high levels of FasL yet failed to undergo AICD, while others expressed little FasL and were sensitive. AICD susceptibility did not correlate with the kinetics of FasL up-regulation or down-regulation. The down-regulation of FasL can be mediated by a metalloprotease. However, we describe an alternative mechanism for the loss of FasL by endocytosis. Endocytosis inhibitors such as cytochalasins, sodium azide, deoxyglucose, or low temperatures prevented the loss of FasL. KB8301, a metalloprotease inhibitor had no effect on the loss of FasL or AICD in the T cells. Enhancing FasL expression was not crucial for AICD and the down-regulation of FasL proceeded via endocytosis.

Animals↗

Visitation in critical care: processes and outcomes of a performance improvement initiative.

When family members became dissatisfied with a restrictive visiting policy in a combined coronary and medical intensive care unit, this situation was seen as an opportunity to better meet patient and family needs. A review of the literature indicated that open visitation policies enhance patient and family satisfaction, while a survey of patients, families, and health care team members revealed a desire for a more open visitation policy. Nursing staff, with input from other disciplines, developed and implemented a less restrictive visitation policy. Post-intervention surveys revealed higher patient and family satisfaction and a marked decrease in formal complaints.

Aged↗

SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2.

We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimethylbenzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 x 10(6). The efficacy and toxicity of SJ-3366 are consistent when evaluated with established or fresh human cells, and the compound is equipotent against all strains of HIV-1 evaluated, including syncytium-inducing, non-syncytium-inducing, monocyte/macrophage-tropic, and subtype virus strains. Distinct from other members of the pharmacologic class of NNRTIs, SJ-3366 inhibited laboratory and clinical strains of HIV-2 at a concentration of approximately 150 nM, yielding a therapeutic index of approximately 20,000. Like most NNRTIs, the compound was less active when challenged with HIV-1 strains possessing the Y181C, K103N, and Y188C amino acid changes in the RT and selected for a virus with a Y181C amino acid change in the RT after five tissue culture passages in the presence of the compound. In combination anti-HIV assays with nucleoside and nonnucleoside RT and protease inhibitors, additive interactions occurred with all compounds tested with the exception of dideoxyinosine, with which a synergistic interaction was found. Biochemically, SJ-3366 exhibited a K(i) value of 3.2 nM, with a mixed mechanism of inhibition against HIV-1 RT, but it did not inhibit HIV-2 RT. SJ-3366 also inhibited the entry of both HIV-1 and HIV-2 into target cells. On the basis of its therapeutic index and multiple mechanisms of anti-HIV action, SJ-3366 represents an exciting new compound for use in HIV-infected individuals.

Drug Resistance, Microbial↗

Uterine contractile activity stimulates supraoptic neurons in term pregnant rats via a noradrenergic pathway.

Oxytocin secretion is important for the normal progress of parturition in the rat. We tested the hypotheses that contractions of the uterus before pup delivery activate oxytocin neurons, and that they do so via a noradrenergic projection. In anesthetized 22-day (term) pregnant rats, i.v. oxytocin pulses enhanced both uterine contractile activity and the firing rate of oxytocin and vasopressin neurons in the supraoptic nucleus, and these were significantly correlated. The same oxytocin treatment also increased the expression of Fos in both the supraoptic nucleus and the nucleus of the tractus solitarius, but not in 21-day pregnant or virgin rats. In five of eight rats on the day of expected parturition, noradrenaline release in the supraoptic nucleus (sampled by microdialysis) exhibited sudden peaks during oxytocin administration, seen in only one of nine rats given vehicle pulses. Noradrenaline release was significantly greater in rats that went into labor or gave birth to a pup than in rats not in labor. In rats infused with the alpha(1)-noradrenergic receptor antagonist, benoxathian, into the supraoptic nucleus before and during iv oxytocin administration, Fos expression in supraoptic neurons was significantly less than that in vehicle controls. Thus, at term pregnancy, uterine contractions activate both oxytocin and vasopressin neurons in the SON, and this activation involves a noradrenergic pathway.

Adrenergic alpha-Antagonists↗

Tardive dystonia of the larynx in a quadriplegic patient: an unusual cause of stridor.

We describe a case of a quadriplegic brain-damaged man with severe upper airway obstruction. A diagnosis of tardive dystonia affecting the vocal folds was made and confirmed by flexible nasopharyngoscopy. Emergency tracheotomy was required. The tardive movement disorder resolved with discontinuation of thioridazine. This case serves to heighten awareness of potentially serious airway complications associated with the use of anti-psychotics and anti-emetics particularly in those with organic brain disease.

Antipsychotic Agents↗

Action-monitoring and intention reporting in children with autism.

The " mindblindness" theory of core cognitive impairment in autism and at least one of the executive theories of the core cognitive deficit both predict that children with autism should find it difficult to report what their intention was when it diverged from an outcome. The former predicts this because it takes intention reporting to require a " theory of mind " and the latter predicts it because the theory posits an impairment in the monitoring of goal-directed actions. The latter also predicts impairments in the ability to monitor basic actions. Our three studies failed to support either of these views. Experiment 1 demonstrated intact abilities in the monitoring of basic actions (detecting which stimulus of a number of stimuli one is controlling). Experiment 2 demonstrated intact abilities in reporting an intention, both for self and for another agent, when the outcome was unintended but desired. In Experiment 3, using the novel "transparent intentions task", we found (with a minor qualification) intact ability in reporting on nonballistic intended actions when the result that the action achieved was unexpected. The implications of these results for views of the relation between theory of mind and executive difficulties in autism are discussed.

Autistic Disorder↗

Case report: an unusal cause of stridor in a post-liver transplant 6-year old.

Polymorphic lymphoproliferative disorder is a recognised cause of upper airway obstruction in children [N. Sculerati, M. Arriga, Ann. Otol. Rhinol. Laryngol 99 (1990) 445-450]. It is associated with long-term immunosuppression therapy and frequently with Epstein-Barr virus (EBV) infection [D.W. Hanto, Annu. Rev. Med. 46 (1995) 381-394; B.D. Fletcher, H.E. Heslop, H.C. Kaste, S. Bodner, Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children, Pediatr. Radiol. 28 (1998) 492-496]. The prevalence in reported series ranges from 4 to 13% among post-transplant children [M. Ho, R. Jaffe, G. Miller, Transplantation 45 (1988) 719-727; G.B. Hammer, S. Cao, M.G. Boltz, A. Messner, Anesthesiology 89 (1998) 263-265; B.V. Lattyak, P. Rosenthal, Post-transplant lymphoproliferative disorder presenting in the head and neck, Laryngoscope 108 (1998) 1195-1198]. This condition may present in the transplanted allograft, the gastrointestinal tract, the head and neck, and in particular in the upper airway. Previously reported cases of upper airway obstruction have been in the supraglottis, Waldeyer's ring, the glottis, and one case of an intra tracheal mass [M. Ho, R. Jaffe, G. Miller, Transplantation 45 (1988) 719-727; G.B. Hammer, S. Cao, M.G. Boltz, A. Messner, Anesthesiology 89 (1998) 263-265]. We report a case of post-transplant lymphoproliferative disorder in the sub-glottis causing acute upper airway obstruction with negative (EBV) serology.

Acyclovir↗

Perceived expressed emotion in the siblings and parents of hospitalized patients with anorexia nervosa.

OBJECTIVE: The present study investigated the relationship between the level of perceived Expressed Emotion (EE) of the siblings and parents of patients hospitalized with anorexia nervosa and its effect on weight gain and psychological functioning. METHOD: The Level of Expressed Emotion (LEE) Scale was administered on admission to 19 patients with anorexia nervosa who completed the LEE three times so as to identify their perceptions of their relationship with their closest age sibling, mother, and father. They were also required to complete the Eating Disorder Inventory 2 (EDI-2). Patients' closest age sibling completed the Family Attitude Scale (FAS). The patients' body mass index (BMI) was calculated 6 weeks later, and the EDI-2 readministered. RESULTS: Perceived EE was not predictive of BMI change after 6 weeks of hospitalization. A composite perceived family EE score was a significant predictor of change on the Interpersonal Distrust, Maturity Fears, and Perfectionism subscales of the EDI-2. DISCUSSION: These findings suggest that patients' perceptions of their relationships with their closest aged sibling, mother, and father are poor predictors of weight gain and improvement in psychological functioning following 6 weeks of inpatient treatment.

Adult↗

Development of an instrument to assess readiness to recover in anorexia nervosa.

OBJECTIVE: The degree to which patients with anorexia nervosa demonstrate readiness to recover from their illness has received scant theoretical or empirical attention. Investigating the prevalence and degree of amotivation for recovery in anorexia nervosa, its role in outcome, and the effectiveness of interventions designed to enhance readiness to recover necessitates the existence of a reliable and valid measure of motivational issues relevant to the disorder. The present study aimed to develop and evaluate an instrument for assessing readiness to recover in anorexia nervosa, namely, the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ), a 23-item self-report questionnaire based on Prochaska and DiClemente's stages of change model. METHOD: Seventy-one inpatients with anorexia nervosa participated in the study. On several occasions during their admission, participants completed the ANSOCQ as well as questionnaires assessing readiness to recover, anorexic symptomatology, general distress, and social desirability. RESULTS: The ANSOCQ demonstrated good internal consistency (.90) and 1-week test-retest reliability (.89). Various aspects of validity were also supported, such as significant relationships with other instruments assessing readiness to recover and the prediction of weight gain during different periods of treatment. DISCUSSION: The results suggest that the ANSOCQ is a psychometrically sound instrument that may prove useful in investigating the role of readiness to recover in anorexia nervosa.

Adolescent↗

Effects of propofol on cerebral oxygenation during cardiopulmonary bypass in children.

PURPOSE: Neurologic complications occur following cardiopulmonary bypass surgery. We conducted a randomized, controlled, single-blind study to determine the effect of propofol on the redox status of cytaa3, and to evaluate its potential for decreasing neurologic complications. METHODS AND MATERIALS: Twenty-four children (median age: 3.3 yr; median weight: 14.4 kg) scheduled for elective cardiopulmonary bypass surgery were assigned to either the experimental group (Group P, given sufficient propofol to eliminate brain electrical activity as measured on EEG (i.e. burst suppression)) or the control group (Group C, no propofol). Near infrared spectroscopy data were collected at one-second intervals throughout the surgical procedures. Pre- and postoperative neurologic examinations were completed by a physician blinded to the group to which the patient was assigned. Change in cytochrome aa3 data at 10-min intervals (10, 20, 30, 40 min) following start of bypass were compared between groups by repeated measures analysis of variance. RESULTS: The patterns of change in redox state of cytochrome were different between the two groups (P < 0.002). The pattern of change within Group P was similar to that in hypothermic patients in Group C. There were correlations between change in cytaa3 redox status and temperature in the control subjects. There were no gross neurologic complications in either group. CONCLUSIONS: Propofol appears to stabilize the energy supply/demand equilibrium of the brain during cardiopulmonary bypass surgery and thus theoretically could reduce the incidence or severity of neurologic complications.

Anesthetics, Intravenous↗

Lack of association of lipoprotein(a) levels with coronary calcium deposits in asymptomatic postmenopausal women.

OBJECTIVES: This study sought to determine the relationship of lipoprotein(a) (Lp(a)) and other cardiac risk factors to coronary atherosclerosis as measured by calcification of coronary arteries in asymptomatic postmenopausal women. BACKGROUND: Lipoprotein(a) is considered a risk factor for coronary heart disease. Coronary calcium deposition is believed to be a useful noninvasive marker of coronary atherosclerosis in women. However, to our knowledge, there are no reports of the relationship of Lp(a) to coronary calcium in postmenopausal women. METHODS: In 178 asymptomatic postmenopausal women (64 +/- 8 years), we measured Lp(a) and other cardiac risk factors: age, hypertension, diabetes, low-density lipoprotein cholesterol, smoking status, body mass index, physical activity level and duration of hormone replacement therapy. Electron-beam computed tomography was done to measure coronary calcium (calcium score). We analyzed the relationship between calcium score and cardiac risk factors using multivariate analysis. RESULTS: Although calcium score correlated with traditional risk factors of age, diabetes, hypertension and smoking, it did not correlate with Lp(a) in the asymptomatic postmenopausal women. Similar multivariate analyses were done in the subjects age >60 years and in the subjects with significant coronary calcium deposit (calcium score > or =50). These analyses also have failed to show an association of levels of Lp(a) with coronary calcium deposits. CONCLUSIONS: We conclude that in asymptomatic postmenopausal women, Lp(a) levels do not correlate with coronary atherosclerosis as measured by coronary calcium deposits.

Adult↗