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1.
Cerebrovasc Dis ; 34(1): 48-54, 2012.
Article in English | MEDLINE | ID: mdl-22759627

ABSTRACT

BACKGROUND: The Montreal Cognitive Assessment (MoCA) appears more sensitive to mild cognitive impairment (MCI) than the Mini-Mental State Examination (MMSE): over 50% of TIA and stroke patients with an MMSE score of ≥27 ('normal' cognitive function) at ≥6 months after index event, score <26 on the MoCA, a cutoff which has good sensitivity and specificity for MCI in this population. We hypothesized that sensitivity of the MoCA to MCI might in part be due to detection of different patterns of cognitive domain impairment. We therefore compared performance on the MMSE and MoCA in subjects without major cognitive impairment (MMSE score of ≥24) with differing clinical characteristics: a TIA and stroke cohort in which frontal/executive deficits were expected to be prevalent and a memory research cohort. METHODS: The MMSE and MoCA were done on consecutive patients with TIA or stroke in a population-based study (Oxford Vascular Study) 6 months or more after the index event and on consecutive subjects enrolled in a memory research cohort (the Oxford Project to Investigate Memory and Ageing). Patients with moderate-to-severe cognitive impairment (MMSE score of <24), dysphasia or inability to use the dominant arm were excluded. RESULTS: Of 207 stroke patients (mean age ± SD: 72 ± 11.5 years, 54% male), 156 TIA patients (mean age 71 ± 12.1 years, 53% male) and 107 memory research subjects (mean age 76 ± 6.6 years, 46% male), stroke patients had the lowest mean ± SD cognitive scores (MMSE score of 27.7 ± 1.84 and MoCA score of 22.9 ± 3.6), whereas TIA (MMSE score of 28.4 ± 1.7 and MoCA score of 24.9 ± 3.3) and memory subject scores (MMSE score of 28.5 ± 1.7 and MoCA score of 25.5 ± 3.0) were more similar. Rates of MoCA score of <26 in subjects with normal MMSE ( ≥27) were lowest in memory subjects, intermediate in TIA and highest after stroke (34 vs. 48 vs. 67%, p < 0.001). The cerebrovascular patients scored lower than the memory subjects on all MoCA frontal/executive subtests with differences being most marked in visuoexecutive function, verbal fluency and sustained attention (all p < 0.0001) and in stroke versus TIA (after adjustment for age and education). Stroke patients performed worse than TIA patients only on MMSE orientation in contrast to 6/10 subtests of the MoCA. Results were similar after restricting analyses to those with an MMSE score of ≥27. CONCLUSIONS: The MoCA demonstrated more differences in cognitive profile between TIA, stroke and memory research subjects without major cognitive impairment than the MMSE. The MoCA showed between-group differences even in those with normal MMSE and would thus appear to be a useful brief tool to assess cognition in those with MCI, particularly where the ceiling effect of the MMSE is problematic.


Subject(s)
Cognition/physiology , Cognitive Dysfunction/physiopathology , Ischemic Attack, Transient/physiopathology , Memory/physiology , Stroke/physiopathology , Aged , Aged, 80 and over , Cognition Disorders/psychology , Humans , Mental Status Schedule , Middle Aged , Neuropsychological Tests
2.
Br J Psychiatry ; 191: 14-22, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17602120

ABSTRACT

BACKGROUND: There are claims that the extra costs of atypical (second-generation) antipsychotic drugs over conventional (first-generation) drugs are offset by improved health-related quality of life. AIMS: To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia. METHOD: Cost-effectiveness acceptability analysis integrated clinical and economic randomised controlled trial data of conventional and atypical antipsychotics in routine practice. RESULTS: Conventional antipsychotics had lower costs and higher quality-adjusted life-years (QALYs) than atypical antipsychotics and were more than 50% likely to be cost-effective. CONCLUSIONS: The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics.


Subject(s)
Antipsychotic Agents/economics , Antipsychotic Agents/therapeutic use , Quality-Adjusted Life Years , Schizophrenia/drug therapy , Adult , Cost-Benefit Analysis , Female , Humans , Male , Schizophrenia/economics , Statistics as Topic , United Kingdom
3.
Int J Obes (Lond) ; 30(10): 1463-75, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17003807

ABSTRACT

OBJECTIVE: To report on a new modelling approach developed for the assessing cost-effectiveness in obesity (ACE-Obesity) project and the likely population health benefit and strength of evidence for 13 potential obesity prevention interventions in children and adolescents in Australia. METHODS: We used the best available evidence, including evidence from non-traditional epidemiological study designs, to determine the health benefits as body mass index (BMI) units saved and disability-adjusted life years (DALYs) saved. We developed new methods to model the impact of behaviours on BMI post-intervention where this was not measured and the impacts on DALYs over the child's lifetime (on the assumption that changes in BMI were maintained into adulthood). A working group of stakeholders provided input into decisions on the selection of interventions, the assumptions for modelling and the strength of the evidence. RESULTS: The likely health benefit varied considerably, as did the strength of the evidence from which that health benefit was calculated. The greatest health benefit is likely to be achieved by the 'Reduction of TV advertising of high fat and/or high sugar foods and drinks to children', 'Laparoscopic adjustable gastric banding' and the 'multi-faceted school-based programme with an active physical education component' interventions. CONCLUSIONS: The use of consistent methods and common health outcome measures enables valid comparison of the potential impact of interventions, but comparisons must take into account the strength of the evidence used. Other considerations, including cost-effectiveness and acceptability to stakeholders, will be presented in future ACE-Obesity papers. Information gaps identified include the need for new and more effective initiatives for the prevention of overweight and obesity and for better evaluations of public health interventions.


Subject(s)
Models, Econometric , Obesity/economics , Obesity/prevention & control , Adolescent , Australia , Behavior Therapy , Body Mass Index , Child , Cost-Benefit Analysis/methods , Energy Intake , Evidence-Based Medicine , Health Priorities , Humans , Obesity/physiopathology , Quality-Adjusted Life Years , Treatment Outcome
4.
Health Technol Assess ; 10(17): iii-iv, ix-xi, 1-165, 2006 May.
Article in English | MEDLINE | ID: mdl-16707074

ABSTRACT

OBJECTIVES: To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to, or having unacceptable side-effects from, their current medication. DESIGN: Two pragmatic, randomised controlled trials (RCTs) were undertaken. The first RCT (band 1) compared the class of older, inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders, whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects. The second RCT (band 2) compared the new (non-clozapine) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs. Both RCTs were four-centre trials with concealed randomisation and three follow-up assessments over 1 year, blind to treatment. SETTING: Adult mental health settings in England. PARTICIPANTS: In total, 227 participants aged 18-65 years (40% of the planned sample) were randomised to band 1 and 136 (98% of the planned sample) to band 2. INTERVENTIONS: Participants were randomised to a class of drug. The managing clinician selected the individual drug within that class, except for the clozapine arm in band 2. The new atypical drugs included risperidone, olanzapine, quetiapine and amisulpride. The conventional drugs included older drugs, including depot preparations. As in routine practice, clinicians and participants were aware of the identity of the prescribed drug, but clinicians were asked to keep their participating patient on the randomised medication for at least the first 12 weeks. If the medication needed to be changed, the clinician was asked to prescribe another drug within the same class, if possible. MAIN OUTCOME MEASURES: The primary outcome was the Quality of Life Scale (QLS). Secondary clinical outcomes included symptoms [Positive and Negative Syndrome Scale (PANSS)], side-effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. RESULTS: Recruitment to band 1 was less than anticipated (40%) and diminished over the trial. This appeared largely due to loss of perceived clinical equipoise (clinicians progressively becoming more convinced of the superiority of new atypicals). Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75% power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks. The recruitment to band 2 was approximately as planned. Follow-up assessments were completed at week 52 in 81% of band 1 and 87% of band 2 participants. Band 1 data showed that, on the QLS and symptom measures, those participants in the conventional arm tended towards greater improvements. This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample. Participants reported no clear preference for either class of drug. There were no statistically significant differential outcomes for participants entering band 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance. Net costs over the year varied widely, with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group, not a statistically significant difference. Of these costs, 2.1% and 3.8% were due to antipsychotic drug costs in the conventional and atypical group, respectively. There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year. The results for band 2 showed an advantage for commencing clozapine in quality of life (QLS) at trend level (p = 0.08) and in symptoms (PANSS), which was statistically significant (p = 0.01), at 1 year. Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects. Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals (p < 0.05). Net costs of care varied widely, but were higher than in band 1, with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group. Of these costs, 4.0% and 3.3%, respectively, were due to antipsychotic drug costs. The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug. There was a trend towards higher mean participant utility scores in the clozapine group. CONCLUSIONS: For band 1, there is no disadvantage in terms of quality of life and symptoms, or associated costs of care, over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs. Conventional drugs were associated with non-significantly better outcomes and lower costs. Drug costs represented a small proportion of the overall costs of care (<5%). For band 2, there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs, but with increased associated costs of care. The results suggest that conventional antipsychotic drugs, which are substantially cheaper, still have a place in the treatment of patients unresponsive to, or intolerant of, current medication. Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance, valid measures of utility in serious mental illness, low-dose 'conventional' treatment in first episode schizophrenia, QLS validity and determinants of QLS score in schizophrenia, and into the possible financial and other mechanisms of rewarding clinician participation in trials.


Subject(s)
Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Schizophrenia/drug therapy , Adolescent , Adult , Aged , Antipsychotic Agents/adverse effects , Antipsychotic Agents/economics , Clozapine/adverse effects , Female , Humans , International Classification of Diseases , Male , Middle Aged , Patient Satisfaction , Quality of Life , Schizophrenia/classification , Schizophrenia/economics , Treatment Outcome
5.
Pediatr Infect Dis J ; 17(10): 913-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9802635

ABSTRACT

AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens. METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age. Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo. Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose. RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H. influenzae type b were not statistically different between RV-TV and placebo recipients. The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found. The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients. There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients. CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines. Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age.


Subject(s)
Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Haemophilus Vaccines/administration & dosage , Poliovirus Vaccine, Oral/administration & dosage , Rotavirus Vaccines , Rotavirus/immunology , Viral Vaccines/administration & dosage , Antibodies, Bacterial/biosynthesis , Antibodies, Viral/biosynthesis , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Double-Blind Method , Female , Haemophilus Vaccines/immunology , Humans , Immunization Schedule , Infant , Male , Poliovirus Vaccine, Oral/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Vaccines, Combined/immunology , Viral Vaccines/immunology
7.
Br J Nurs ; 7(2): 92-6, 1998.
Article in English | MEDLINE | ID: mdl-9510684

ABSTRACT

The increased expectation for women with learning disabilities to become more autonomous and independent is generally a positive and dynamic force. However, care must be taken to ensure that, within this environment, women with learning disabilities are not isolated or lack support as this increases their vulnerability. These issues exist for all women within our society, but women with learning disabilities are more vulnerable because of their lack of voice both individually and politically. Within this new culture of independence and rights for women with learning disabilities, nurses must ensure that they address their own accountability and responsibility.


Subject(s)
Health Services Accessibility/standards , Intellectual Disability/therapy , Patient Advocacy , Women's Health , Female , Humans , Social Support
8.
Br J Nurs ; 6(2): 99-102, 1997.
Article in English | MEDLINE | ID: mdl-9116446

ABSTRACT

Self-image arises from a complex interaction of intrinsic and extrinsic factors. This article explores the importance of people with a learning disability attaining a positive self-image. It discusses the effect of society's perception of people with learning disabilities, and questions the willingness of the community to accept such people in a non-judgmental way. It argues that staff caring for this client group have a vital role to play in how people with learning disabilities are perceived by others and discusses the effects that a market philosophy (Fromm, 1978) and the popular media have on society regarding people with learning disabilities. Self-worth is important to everyone; however, the article concludes that a person with a learning disability is seriously disadvantaged in this respect. This aspect of care therefore requires insight, support and skills on the part of those healthcare professionals caring for this client group.


Subject(s)
Attitude of Health Personnel , Intellectual Disability/nursing , Intellectual Disability/psychology , Self Concept , Humans , Marketing of Health Services , Social Perception , Social Support
9.
Pediatr Infect Dis J ; 15(11): 1012-8, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8933551

ABSTRACT

OBJECTIVE: To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing. METHODS: A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination. RESULTS: Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups. CONCLUSIONS: RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.


Subject(s)
Antibodies, Viral/biosynthesis , Rotavirus Vaccines , Rotavirus/immunology , Vaccines, Attenuated/administration & dosage , Viral Vaccines/administration & dosage , Administration, Oral , Double-Blind Method , Drug Administration Schedule , Humans , Immunoglobulin A/immunology , Infant , Vaccination , Vaccines, Attenuated/immunology , Viral Vaccines/immunology
10.
J Mol Endocrinol ; 7(2): 89-96, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1930628

ABSTRACT

The neotropical cotton-top marmoset (Saguinus oedipus) is a New World primate known to have markedly increased total and free plasma cortisol concentrations when compared with Old World primates including man. The relative end-organ 'resistance' to glucocorticoids found in various New World primates has been attributed to a glucocorticoid receptor (GR) with diminished affinity for glucocorticoids. It has been demonstrated that the marmoset GR has approximately tenfold lower binding affinity for dexamethasone when compared with the human GR. We have examined the primary structure of the marmoset GR by molecular cloning and sequencing of GR functional domains. A library of cDNA clones was constructed in the phage vector gamma gt10 using poly(A)+ RNA from a marmoset-derived lymphoid cell line, and screened using the human GR cDNA. DNA sequencing determined 76 individual nucleotide substitutions in the coding region of the marmoset GR. Comparison of the marmoset GR nucleotide sequence with the human GR cDNA coding region indicated an overall sequence homology of about 97%. Thirty of the nucleotide substitutions lead to alterations in the predicted amino acid sequence (28 amino acid substitutions) of the marmoset GR. The size of the marmoset GR predicted from the 778 amino acids is approximately 90,000 which is in agreement with previous size estimates of the human and marmoset GRs. Alterations of amino acid sequence in the marmoset GR were greatest towards the amino terminus, including the tau 1 domain putatively involved in transcriptional activation. The DNA-binding domain contained an additional codon (arginine).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Glucocorticoids/metabolism , Receptors, Glucocorticoid/genetics , Saguinus/genetics , Amino Acid Sequence , Amino Acids/analysis , Animals , Base Sequence , Binding Sites , Cell Line , DNA/metabolism , Glucocorticoids/pharmacology , Humans , Hydrocortisone/blood , Molecular Sequence Data , Nucleic Acid Hybridization , Receptors, Glucocorticoid/chemistry , Receptors, Glucocorticoid/metabolism , Sequence Homology, Nucleic Acid
11.
Science ; 249(4966): 298-301, 1990 Jul 20.
Article in English | MEDLINE | ID: mdl-2374929

ABSTRACT

Angiotensin II (AII) stimulates rapid increases in the concentration of cytosolic calcium in follicular oocytes from Xenopus laevis. This calcium response was not present in denuded oocytes, indicating that it is mediated by AII receptors on the adherent follicular cells. The endogenous AII receptors differed in their binding properties from mammalian AII receptors expressed on the oocyte surface after injection of rat adrenal messenger RNA. Also, the calcium responses to activation of the amphibian AII receptor, but not the expressed mammalian AII receptor, were blocked reversibly by octanol and intracellular acidification, treatments that inhibit cell coupling through gap junctions. In addition, AII increased the rate of progesterone-induced maturation. Thus, an AII-induced calcium-mobilizing signal is transferred from follicle cells to the oocyte through gap junctions and may play a physiological role in oocyte maturation.


Subject(s)
Angiotensin II/analogs & derivatives , Angiotensin II/pharmacology , Calcium/metabolism , Intercellular Junctions/physiology , Oocytes/physiology , Signal Transduction , Aequorin , Angiotensin II/metabolism , Animals , Cytosol/drug effects , Cytosol/metabolism , Female , Intercellular Junctions/drug effects , Kinetics , Luminescence , Oocytes/drug effects , Progesterone/pharmacology , Receptors, Angiotensin/metabolism , Signal Transduction/drug effects , Structure-Activity Relationship , Xenopus laevis
12.
Cancer Res ; 49(8 Suppl): 2203s-2213s, 1989 Apr 15.
Article in English | MEDLINE | ID: mdl-2649236

ABSTRACT

In humans, the syndrome of cortisol resistance is characterized by the absence of signs and symptoms of Cushing's syndrome, elevated total and unbound plasma cortisol concentrations, and increases in urinary free cortisol excretion and plasma adrenocorticotropic hormone. In one family, a severely affected member had hypertension and hypokalemic alkalosis associated with increased plasma concentrations of corticosterone and deoxycorticosterone. These patients are resistant to suppression of the pituitary-adrenal axis by dexamethasone. Dexamethasone therapy, however, effectively corrected hypertension and hypokalemic alkalosis in the severely affected patient, without causing signs of glucocorticoid excess. The glucocorticoid receptor from these patients has a low affinity for glucocorticoids and is unstable during thermal activation. Both the molecular weight of the glucocorticoid receptor and the size of the corresponding mRNA are similar to those of normal controls. Transformation of B-lymphocytes with Epstein-Barr virus leads to induction of glucocorticoid receptors. Receptor induction, however, is lower in patient cells than those obtained from normal controls. This decreased induction parallels decreased expression of glucocorticoid receptor mRNA. Thus, in this form of glucocorticoid resistance the glucocorticoid receptor is abnormal and leads to diminished target organ responsiveness. Many New World primates exhibit glucocorticoid "resistance," without apparent pathology. These species have markedly elevated plasma cortisol, both total and unbound concentrations, increased urinary free cortisol excretion, and marked increases in plasma adrenocorticotropic hormone and beta-endorphin. The glucocorticoid receptors of these primates have decreased affinity for glucocorticoids, are thermolabile, and are not induced by Epstein-Barr virus transformation as indicated by specific binding and mRNA expression. Both the molecular weight of the glucocorticoid receptor and the size of the corresponding mRNA are similar to those of normal controls. Despite the high plasma cortisol concentrations in these primates, there is no sodium retention and aldosterone levels are actually increased. The kidney aldosterone receptor cross-reacts poorly with cortisol, explaining the absence of sodium retention. New World primates also have progesterone, estrogen, aldosterone, and vitamin D insensitivity, suggesting a common factor linking steroid hormone receptors.


Subject(s)
Glucocorticoids/pharmacology , Animals , Biological Evolution , Drug Resistance , Gonadal Steroid Hormones/physiology , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/physiology , Pituitary-Adrenal System/physiology , Primates , RNA, Messenger/analysis , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism
13.
FEBS Lett ; 241(1-2): 177-80, 1988 Dec 05.
Article in English | MEDLINE | ID: mdl-2848720

ABSTRACT

Specific receptors for angiotensin II (AII) were expressed in albino Xenopus laevis oocytes co-injected with poly(A)+ mRNA isolated from rat adrenal cortex and the calcium-specific photoprotein, aequorin. In such oocytes, AII elicited rapid, dose-dependent rises in cytosolic free calcium with light emission responses up to 100-fold above basal levels. Ligand-induced light emission was also observed in oocytes injected with rat brain mRNA and stimulated with acetylcholine and glutamate. These findings demonstrate that mammalian AII receptors expressed in Xenopus oocytes are functionally linked to intracellular Ca2+ mobilization, and indicate the potential value of aequorin-injected oocytes for rapid and specific screening of mRNAs transcribed from expression libraries containing cloned receptor cDNAs.


Subject(s)
Angiotensin II/pharmacology , Calcium/metabolism , Oocytes/metabolism , RNA, Messenger/genetics , Receptors, Angiotensin/physiology , Receptors, Cholinergic/physiology , Receptors, Neurotransmitter/physiology , Acetylcholine/pharmacology , Adrenal Cortex/metabolism , Aequorin , Animals , Brain/metabolism , Female , Glutamates/pharmacology , Light , Oocytes/drug effects , Rabbits , Receptors, Angiotensin/genetics , Receptors, Cholinergic/genetics , Receptors, Glutamate , Receptors, Neurotransmitter/genetics
14.
Endocrinology ; 119(4): 1690-6, 1986 Oct.
Article in English | MEDLINE | ID: mdl-3530722

ABSTRACT

Immunoreactive arginine vasopressin (ir-AVP), coeluting with authentic nonapeptide on reverse phase HPLC, is present in the thymus of Sprague-Dawley, Long-Evans, and homozygous (di/di) Brattleboro rats, and BALB/c mice. By immunohistochemistry, ir-AVP positive cells are sparse, and do not appear to be lymphocytes. Adrenalectomy and dexamethasone administration to intact rats produces an identical response in terms of thymic ir-AVP, with a rise after 1-2 days followed by a fall to levels below baseline after 8 days. The rise 2 days after adrenalectomy, and the fall 8 days later, were both prevented by administration of aldosterone, but not by corticosterone or dexamethasone to adrenalectomized animals. The role(s) of thymic ir-AVP, and the physiological significance of its mineralocorticoid dependence, remain to be established.


Subject(s)
Arginine Vasopressin/metabolism , Thymus Gland/metabolism , Adrenalectomy , Aldosterone/pharmacology , Animals , Chromatography, High Pressure Liquid , Corticosterone/pharmacology , Dexamethasone/pharmacology , Histocytochemistry , Immunoenzyme Techniques , Male , Mice , Mice, Inbred BALB C , Rats , Rats, Brattleboro , Rats, Inbred Strains , Thymus Gland/drug effects
15.
J Clin Invest ; 77(6): 1776-9, 1986 Jun.
Article in English | MEDLINE | ID: mdl-2423557

ABSTRACT

We have previously demonstrated low levels of immunoreactive (ir)-beta-endorphin (beta-EP) and ir-ACTH in a subpopulation of mouse spleen macrophages, which is consistent with an involvement of opioid peptides in modulation of immune responses. Gel chromatography studies suggested the presence of an approximately 3.5,000-molecular weight (mol wt) species, putatively beta-EP, an approximately 11.5,000-mol-wt species, putatively beta-lipotropin, and a higher molecular weight species (putative beta-EP precursor, pro-opiomelanocortin (POMC). In this study we have extended our original findings by demonstrating the presence of messenger RNA for POMC by the use of a complementary DNA probe and Northern blot analysis of extracts of mouse and rat spleen. In addition, using high performance liquid chromatography (HPLC), we have shown that the major endorphin species in mouse spleen macrophages is beta-EP1-31, and that there are smaller amounts of each of the acetylated forms, N-acetyl-beta-EP1-16 (alpha-endorphin), N-acetyl-beta-EP1-17 (gamma-endorphin), N-acetyl-beta-EP1-27, and N-acetyl-beta-EP1-31. We interpret these studies as showing that (a) the spleen is an organ of POMC synthesis and that (b) the predominant COOH-terminal product of macrophage POMC is the opiate-receptor active species beta-EP1-31.


Subject(s)
Endorphins/biosynthesis , Macrophages/metabolism , Pro-Opiomelanocortin/genetics , Protein Processing, Post-Translational , RNA, Messenger/metabolism , Spleen/cytology , Animals , Chromatography, High Pressure Liquid , DNA/analysis , Male , Mice , Mice, Inbred BALB C , Nucleic Acid Hybridization , Poly A/metabolism , RNA/metabolism , beta-Endorphin
16.
Peptides ; 7(2): 267-76, 1986.
Article in English | MEDLINE | ID: mdl-2874549

ABSTRACT

The distribution of arginine-vasopressin (AVP)-, oxytocin-, beta-endorphin (beta-EP)- and dynorphin-immunoreactive cells was examined by peroxidase-antiperoxidase (PAP) immunocytochemistry in the ovaries of Brattleboro and Long-Evans (LE) rats. The ovarian distribution of the peptide-immunoreactivity is indistinguishable between the two strains. AVP- and beta-EP-immunoreactivity is co-localized in the majority of luteal cells, and in some cells scattered in the interstitial tissue. Of the AVP/beta-EP-positive cells, 1-2% also contained immunoreactive (ir)-dynorphin. Some cells in the interstitium contained only ir-AVP (approximately 50%) or only ir-dynorphin (approximately 5%); in the corpora lutea, however, no luteal cells appeared to contain only one peptide. AVP-immunoreactivity is also present in theca cells surrounding secondary and large, antral follicles; ir-oxytocin was not observed in any ovarian cell type in the rat. These data suggest that most luteal, and some interstitial, cells in the ovary have the capacity to produce and store up to three different neuropeptides.


Subject(s)
Arginine Vasopressin/analysis , Dynorphins/analysis , Endorphins/analysis , Ovary/cytology , Oxytocin/analysis , Animals , Female , Immunoenzyme Techniques , Rats , Rats, Brattleboro , Species Specificity , beta-Endorphin
17.
Neuroendocrinology ; 43(5): 577-83, 1986.
Article in English | MEDLINE | ID: mdl-3528899

ABSTRACT

A radioimmunoassay specific for arginine-vasopressin (AVP) was used to establish the presence of immunoreactive (ir)-AVP in extracts of anterior pituitary glands from Sprague-Dawley (SD) and Long-Evans (LE) rats (3.05 +/- 1.0 and 1.66 +/- 0.9 ng/gland, respectively). Lower levels of ir-AVP (0.56 +/- 0.26 ng/gland) were detected in anterior pituitary gland extracts from rats with hereditary diabetes insipidus (Brattleboro; di/di). The anterior pituitary gland ir-AVP from each rat strain was further characterized by reverse-phase high-performance liquid chromatography (RP-HPLC). In each case the major peak of immunoreactivity co-migrated with synthetic AVP. By peroxidase-antiperoxidase immunocytochemistry, sparsely distributed cells containing ir-AVP were localized in anterior pituitary sections. Levels of ir-AVP in primary cultures of anterior pituitary cells (from SD rats) increased from 52 +/- 5 pg/10(6) cells at 2 days in vitro to 152 +/- 17 pg/10(6) cells at 3 days; during this period 56 +/- 6 pg/ml ir-AVP was secreted into the culture medium. Fewer than 1% of the cells in these cultures were immunostainable for AVP. These data indicate that the anterior pituitary gland of the Brattleboro, Long-Evans and Sprague-Dawley rat contains ir-AVP, and that there is synthesis and secretion of this peptide in primary cultures of anterior pituitary cells in vitro.


Subject(s)
Arginine Vasopressin/analysis , Pituitary Gland, Anterior/cytology , Animals , Cells, Cultured , Female , Immunoenzyme Techniques , Radioimmunoassay , Rats , Rats, Brattleboro , Rats, Inbred Strains , Species Specificity
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