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Biomedical subjects

T Cooper

Publications and source records attributed to T Cooper.

At least 19 recordsLinked to original sources

Cloning of a mu-class glutathione S-transferase gene and identification of the glucocorticoid regulatory domains in its 5' flanking sequence.

The expression of a mu-class glutathione S-transferase gene (hGSTYBX) isolated from hamster smooth muscle tumor cells (DDT1 MF-2) is transcriptionally up-regulated by glucocorticoids, and this hormonal regulation is dependent upon protein synthesis. To study the mechanism of regulation, we have cloned and sequenced hGSTYBX genomic DNA including its 5' flanking region. The hGSTYBX gene contains nine exons dispersed over a 6.3-kilobase region. When linked to a chloramphenicol acetyltransferase (CAT) reporter gene, the 5' flanking region was able to direct transcription of the reporter gene. With 5' deletion studies, we have localized the major glucocorticoid-inducible regulatory element between nucleotides -353 and -239. Within this region no classic glucocorticoid response element (TGTTCT) was identified, but four potential helix-loop-helix binding domains are embedded in two 16-base-pair repeats. Another glucocorticoid regulatory domain has been localized between nucleotides -239 and -136. Cycloheximide blocks glucocorticoid-induced transcription of both the -353CAT and -239CAT reporter genes (nucleotides -447 to -12 and nucleotides -239 to -12 of hGSTYBX, respectively, ligated to a CAT reporter gene); therefore, our observations support previous results suggesting that hGSTYBX induction by glucocorticoids is a secondary response.

Amino Acid Sequence

Haloperidol blood levels and clinical effects.

This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients.

Acute Disease

Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium.

Anticholinergic effects of the 25 drugs most commonly prescribed for the elderly were measured by radioreceptor assay. Fourteen had detectable anticholinergic drug levels; 10 of these had levels that have been associated with impairments in memory and attention in normal elderly subjects. These data indicate that patients taking multiple medications may be at increased risk for side effects from psychotropic drugs, most of which have anticholinergic effects.

Age Factors

Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression.

Prolactin release in response to fenfluramine hydrochloride (60 mg orally) and placebo was evaluated in 18 medication-free patients with RDC major depressive disorder, endogenous subtype, before and after a series of bilateral treatments with ECT. Before ECT, fenfluramine induced a twofold increase in plasma prolactin levels. This response was significantly enhanced after the ECT series, while baseline prolactin levels and response to the placebo challenge were not altered. There was no significant difference in plasma fenfluramine and norfenfluramine levels during the pre- and post-ECT challenges. These findings suggest that ECT enhances central serotonergic responsivity and extend to depressed patients pre-clinical observations regarding the effect of electroconvulsive shock on serotonergic function.

Depressive Disorder

Impedance plethysmography and thrombo-embolic disease.

This study compares the results of impedance plethysmography with lower limb venography in 68 patients referred for investigation of clinical deep vein thrombosis, and with the results of ventilation/perfusion isotope scans in 125 patients with suspected pulmonary embolism. Impedance plethysmography had a sensitivity of 100% and a specificity of 61% for the detection of thromboses involving popliteal or more proximal veins (30 patients), but a sensitivity of 90% and a specificity of 68% in the detection of thrombosis at any level, because of a low sensitivity in the detection of isolated calf vein thrombosis (60% in 10 patients). It is a non-invasive, portable and low-cost technique and, in centres where anticoagulation is only given to patients with popliteal or more proximal thrombosis, venography may only be necessary if impedance plethysmography is positive. It may also be of value in the assessment of patients with suspected pulmonary embolic disease and an indeterminate ventilation/perfusion lung scan.

Humans

Low dose oral haloperidol and blood levels in Alzheimer's disease: a preliminary study.

Nineteen patients with probable Alzheimer's disease who manifested psychosis or behavioral disturbance received 0.5 to 5 mg per day of oral haloperidol, with blood levels drawn on a stable daily dose. Oral dose correlated strongly with haloperidol blood levels assessed by radioimmunoassay (r = 0.82, p = .0001). The stronger correlation observed between oral dose and blood level compared with most studies in schizophrenia may be related to the fact that virtually all the Alzheimer's patients were neuroleptic naive, without the alterations in absorption and metabolism known to occur in schizophrenics receiving long-term neuroleptic treatment. Compared with oral dose, blood levels showed stronger relations to changes in symptoms and to changes in severity of extrapyramidal side effects. These preliminary data suggest that the utility of monitoring haloperidol blood levels in patients with Alzheimer's disease merits further investigation.

Aged

Mood responses of remitted schizophrenics to methylphenidate infusion.

To investigate the mood response of schizophrenic subjects to psychostimulant challenge, 29 neuroleptic-treated subjects (22 with schizophrenia and 7 with schizoaffective disorder) in clinical remission received two infusions, one with methylphenidate 0.5 mg/kg and the other with normal saline, under double-blind conditions. Twenty-five of these subjects were withdrawn from neuroleptics and given a second set of double-blind infusions. Infusion mood responses were classified as euphoric, neutral, mixed or dysphoric. Subjects were also rated as either psychotic symptom activators to the infusion or no change in psychotic symptoms. Overall response by mood category was as follows: 35.2% euphoric, 50% neutral, 5.6% mixed and 9.3% dysphoric. Mood responses were not correlated with sex, methylphenidate plasma levels or diagnostic distinctions between schizophrenia and schizoaffective disorder. Although they occurred infrequently, dysphoric and mixed mood responses were associated with high rates of psychotic activation. Comparing subjects on and off neuroleptics, subjects on neuroleptics had more euphoric responses than the same subjects off neuroleptics. This increased number of euphoric responses in subjects taking neuroleptics compared to off neuroleptics suggests that neuroleptic treatment status may be an important factor in assessing psychostimulant use in schizophrenia patients.

Adolescent

Glucocorticoid level and neuropsychiatric symptoms in homosexual men with HIV infection.

OBJECTIVE: There is a controversial literature suggesting that stress, anxiety, and depression are harmful to the immune system and therefore to health. Preclinical studies indicate that activation of the hypothalamic-pituitary-adrenal (HPA) axis by stress may be responsible for immunocompromise. The goal of this study was to assess this phenomenon in human immunodeficiency virus (HIV) infection. METHOD: Homosexual men in the community who did not meet modified Centers for Disease Control criteria for acquired immune deficiency syndrome (AIDS) were recruited for the study; 113 of the men were HIV positive and 77 were HIV negative. Very few of the men studied suffered from depression or anxiety disorder at the time of the first assessment. Twenty-four-hour urinary free cortisol levels were obtained from the 112 HIV-positive and 75 HIV-negative men whose 24-hour urine volumes were 500 ml or more. Cortisol levels were correlated with measures of medical, immunological, neurological, and psychiatric status. RESULTS: Small but significant correlations between 24-hour urinary free cortisol and medical status, level of depression, and level of anxiety were found in the HIV-positive group. There was no relationship between cortisol level and the number of CD4+ or CD8+ T lymphocytes or the CD4-CD8 ratio. CONCLUSIONS: Although HPA activation may be associated with stress in cases of HIV infection, it does not seem to be associated with further loss of CD4+ T lymphocytes. Subjects with HIV infection with the most evidence of medical complications may also be the most anxious and depressed.

Adult

Relationships between milk yield and fertility in dairy cattle.

In three studies of 51,618 Holstein, 6,630 Jersey, and 1,524 Guernsey records, correlation was .07 between 120-day milk yield and number of services required for probable conception, independent of days postpartum. The partial regression coefficient for Holsteins was .014 +/- .001 more services for each additional 100 kg of 120-day milk. For Jerseys and Guernseys, .028 +/- .008 more services were required for each additional 100 kg of 120-day milk.

Animals

Your future.

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Delivery of Health Care

Undergraduate self-perceptions of creativity and independence.

596 undergraduate students from 7 schools of a major university responded to a group of 20 questions relating to self-perceptions of creativity and independence employed in earlier studies of graduate faculty members and industrial inventors and producers. The hypothesis was that these students would tend to perceive of themselves in terms of popular expectations relating to the schools of their choice. The results indicated that students of architecture, engineering, liberal arts, and science tend to see themselves as significantly more independent, individualistic, and creative than students of business, education, and to some extent, agriculture.

Achievement