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J Haycock

Publications and source records attributed to J Haycock.

17 recordsLinked to original sources

Dopamine D(2) receptors regulate tyrosine hydroxylase activity and phosphorylation at Ser40 in rat striatum.

In the striatum, dopamine release is inhibited by activation of dopamine D(2) autoreceptors. Changes in dopamine release have been attributed to changes in the synthesis of dopamine, which is regulated via phosphorylation of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines. Here, we have studied the involvement of dopamine D(2) receptors in the regulation of TH phosphorylation at distinct seryl residues, using phosphorylation site-specific antibodies and a preparation of rat striatal slices. The D(2) receptor agonist, quinpirole, reduced basal TH phosphorylation at Ser40 but not at Ser19 or Ser31. Quinpirole was also able to reduce the increase in Ser40 phosphorylation caused by forskolin, an activator of adenylyl cyclase, without affecting the increase in Ser19 phosphorylation produced by the glutamate receptor agonist, N-methyl-D-aspartate (NMDA). In addition, the dopamine D(2) receptor agonist reduced both basal and forskolin-stimulated activity of TH, measured as 3,4-dihydroxyphenylalanine (DOPA) accumulation. Quinpirole decreased phosphorylation of Ser40 induced by okadaic acid, an inhibitor of protein phosphatase 1 and 2A and Ro-20-1724, a phosphodiesterase inhibitor. In contrast, quinpirole did not affect the increase in Ser40 phosphorylation caused by the cAMP analogue, 8-Br-cAMP. These data indicate that, in the striatum, activation of dopamine D(2) receptors results in selective inhibition of TH phosphorylation at Ser40 via reduction of the activity of adenylyl cyclase. They also provide a molecular mechanism accounting for the ability of dopamine D(2) autoreceptors to inhibit dopamine synthesis and release from nigrostriatal nerve terminals.

8-Bromo Cyclic Adenosine Monophosphate↗

Regulation of tyrosine hydroxylase activity and phosphorylation at Ser(19) and Ser(40) via activation of glutamate NMDA receptors in rat striatum.

The activity of tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of dopamine, is stimulated by phosphorylation. In this study, we examined the effects of activation of NMDA receptors on the state of phosphorylation and activity of tyrosine hydroxylase in rat striatal slices. NMDA produced a time-and concentration-dependent increase in the levels of phospho-Ser(19)-tyrosine hydroxylase in nigrostriatal nerve terminals. This increase was not associated with any changes in the basal activity of tyrosine hydroxylase, measured as DOPA accumulation. Forskolin, an activator of adenylyl cyclase, stimulated tyrosine hydroxylase phosphorylation at Ser(40) and caused a significant increase in DOPA accumulation. NMDA reduced forskolin-mediated increases in both Ser(40) phosphorylation and DOPA accumulation. In addition, NMDA reduced the increase in phospho-Ser(40)-tyrosine hydroxylase produced by okadaic acid, an inhibitor of protein phosphatase 1 and 2A, but not by a cyclic AMP analogue, 8-bromo-cyclic AMP. These results indicate that, in the striatum, glutamate decreases tyrosine hydroxylase phosphorylation at Ser(40) via activation of NMDA receptors by reducing cyclic AMP production. They also provide a mechanism for the demonstrated ability of NMDA to decrease tyrosine hydroxylase activity and dopamine synthesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Changing hospitals.

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Economics, Hospital↗

The economic consequences of reorganizing hospital services in Bishkek, Kyrgyzstan.

Kyrgyzstan gained independence from the Soviet Union in 1991 and has since been thrown into severe financial crisis. All public sector funding has been significantly reduced and international aid agencies are supporting the government in rebuilding the economy. The health sector requires a radical overhaul and a major part of this process involves rationalization of existing facilities, particularly in the capital Bishkek, where 26 secondary and tertiary hospitals support a population of approximately 800000 people. This paper describes the development of a plan for rationalization with particular emphasis on the economic aspects of the process. This involved calculating future hospital requirements by modelling a variety of policy options, ranging from changes to clinical practice to hospital closures. The model generates estimates of resource requirements at each hospital, from which the costs falling on the health budget and patients are derived.

Adult↗

Competence to stand trial: a neuropsychological inquiry.

How might the deconstruction of the legal theory of competence be related to modern neuropsychological models of cognition? To address this question, we examined retrospectively the relationship between clinical judgments of competence of defendants committed to a maximum security psychiatric facility and their neuropsychological test scores on measures of intelligence, memory, attention, academics, and executive function. In addition, based on both neuropsychological and legal theory, we examined whether subtypes of memory, namely episodic and semantic, and intelligence, specifically social intelligence, would have special relevance to these clinical judgements of competence. Results indicated that in relation to the defendants recommended as incompetent to stand trial (IST), defendants recommended as competent to stand trial (CST) scored significantly higher on summary indexes of psychometric intelligence, attention, and memory, especially verbal memory, but not significantly higher on tests of academics or executive function. Moreover, CST defendants scored significantly higher than did IST defendants on selective tests of episodic memory and social intelligence, but not on measures of semantic memory. Partial correlation also revealed a significant relationship between the likelihood of an IST recommendation and lower scores on tests of episodic memory and social intelligence, but not on measures of semantic memory. These findings illustrate the theoretical import of neuropsychological methods and concepts to the burgeoning nomological net known as competence.

Adolescent↗

L-Dopa and dopamine-producing gene cassettes for gene therapy approaches to Parkinson's disease.

As an aid in the development of vector systems for use in gene therapy paradigms of central nervous system disorders such as Parkinson's disease, we have developed L-Dopa or dopamine-producing gene cassettes. Specifically, a human tyrosine hydroxylase cDNA (HTH-2) was rendered constitutively active by truncation of the N-terminal regulatory domain (tHTH). In addition, a bicistronic construct capable of directing the production of dopamine was created by inserting an internal ribosome entry site downstream of tHTH followed by the coding sequences of aromatic amino acid decarboxylase. All three constructs generated immunoreactive peptides of the predicted size, were enzymatically active, and produced L-Dopa (HTH-2, tHTH) or dopamine (bicistronic construct) following transient transfection of COS-7 cells. These constructs, in conjunction with viral or nonviral expression systems, may be efficacious in gene therapy approaches to Parkinson's disease.

Animals↗

Not guilty by reason of insanity of murder: clinical and neuropsychological characteristics.

We examined archivally clinical status, neuropsychological functioning, and perpetrator-victim relationships of 28 adult patients who had committed homicide and had been subsequently involuntarily committed to a forensic hospital. We divided patients into two groups: (1) not guilty by reason of insanity (NGRI) acquittees (n = 13) and (2) convicted murderers (n = 15). In comparison with convicted murderers, NGRI acquittees were more likely to be seen as psychotic at the time of the index offense and also were more likely to have killed blood relatives, especially a parent. By contrast, convicted murderers were more likely to have killed a significant other, mainly a spouse or lover. At the time of the index offense, substance abuse was more likely to have occurred in the convicted murderers than in the NGRI acquittees. NGRI acquittees and convicted murderers did not differ on neuropsychological tests, with both groups generally scoring within normal limits on all tests. Taken together, these results suggested that NGRI murderers may be driven by acute psychosis directed toward blood relatives and occurring against a backdrop of relatively preserved neuropsychological functioning.

Adult↗

Inhibition by halothane of potassium-stimulated acetylcholine release from rat cortical slices.

1. Cholinergic neurones in the basal forebrain are linked to cortical activation and arousal. 2. The present study was designed to examine the hypothesis that clinically relevant doses of halothane (0.1 to 5%) would significantly reduce depolarization-evoked acetylcholine (ACh) release from rat cortical slices. 3. ACh release was measured from rat cortical slices by a chemiluminescent technique. 4. Depolarization-evoked ACh release was inhibited significantly by halothane with an IC50 of 0.38%. This value equates to 0.3 MAC (the minimum alveolar concentration at which no movement occurs to a standard surgical stimulus in 50% of subjects) for the rat. 5. The potent effect of halothane on ACh release suggests that this mechanism may be a target for the action of volatile anaesthetic agents. This in vitro effect on ACh release is consistent with effects of halothane reported in vivo.

Acetylcholine↗

Lethal violence and psychosis: a clinical profile.

To investigate the relationship between lethal violence and psychosis, the authors examined symptomatology, neuropsychological functioning, and the nature of perpetrator-victim relationships of patients with psychotic disorders who were committed to a forensic psychiatric hospital following violent, primarily criminal behavior. A severely violent group, composed primarily of psychotic patients charged with murder, was compared with a less severely violent group that was composed primarily of psychotic patients involved with property crimes. As compared with the less violent group, the severely violent group was more likely to have delusional beliefs about specific personal targets and to have delusions about significant others being replaced by impostors. These beliefs were accompanied by higher scores on neuropsychological tests of intellectual and academic abilities. A high number of their blood relatives were victims of psychotic murder. These results indicated that a higher incidence of lethal or near lethal acts of violence may characterize intellectually intact but psychotic individuals with organize delusions involving personal, accessible targets.

Adult↗

Comparative suicide rates in different types of involuntary confinement.

In the past decade especially, a number of studies have appeared on suicide among court-involved persons, chiefly in jail and prison remand settings, and to a lesser degree among longer-term prisoners. Confinement is not everywhere equally suicidogenic, and the types of people who find themselves confined do not represent uniformly high risk groups. This article reports on rates of completed suicides over long periods of time in two very different US institutions operated by the Massachusetts Department of Correction: the Addiction Centre and its antecedent facilities (1886-1990); and the Defective Delinquent Department (1922-1971). For perspective, the paper compares suicide rates among its two populations to rates for other very distinctive institutions operated by the Massachusetts Department of Correction, the Bridgewater State Hospital and the Massachusetts Treatment Centre for Sexually Dangerous Persons. The results are remarkable for the rarity of suicide in three distinct populations--the Addiction Center, the Defective Delinquent Department and the Treatment Center for Sexually Dangerous Persons--but considerably higher rates in the State Hospital, a population often dismissed as 'criminally insane.' The possible significance of these results for debates about 'importation' versus 'deprivation' explanations of custodial suicide is discussed.

Female↗

Double jeopardy: suicide rates in forensic hospitals.

While a number of studies have described high and increasing rates of completed suicide among psychiatric patients, the suicide risk of forensic hospital patients is virtually unknown. This paper reports on the suicides that have taken place in the country's oldest continually operating institution housing persons formerly labeled "criminally insane," the Bridgewater State Hospital. The results show considerable variation in the suicide rate by historical period, with suicide prior to 1968 a considerably more infrequent event. By contrast, the post-'68 rate of 232 per 100,000 is comparable to data reported in a series of studies of psychiatric suicides, and significantly higher than that found in U.S. studies of correctional populations. These differences are discussed. The results strongly suggest that forensic hospital populations have suicide rates broadly comparable to other psychiatric populations.

Dangerous Behavior↗

A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma.

BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.

Adolescent↗

Preparative peptide purification by cation-exchange and reversed-phase perfusion chromatography.

Cation exchange was compared to reversed-phase chromatography for the preparative purification of a 28-residue peptide (vasoactive intestinal polypeptide) on the 100-mg scale. Optimized high-speed, high-resolution methods were developed for both chromatographic modes on POROS Perfusion Chromatography flow-through particle chromatography columns. While both methods appeared to provide similar purity, the cation exchange column had approximately ten times the loading capacity per unit column volume as the reversed-phase column. Five-minute methods for desalting the cation exchange-purified peptide and analysis of fractions were developed using small reversed-phase columns. The cation-exchange method was scaled up to process 95 mg of crude peptide in a 12-min run.

Amino Acid Sequence↗

Race and suicide in jails and prisons.

Jails and prison populations are unique in the incidence of deliberate self-harm, but the phenomenon is not well understood. One of the few generally accepted findings about suicidal behavior among the incarcerated is that white prisoners are overrepresented among both completed and attempted suicides, whereas black prisoners are underrepresented. This article examines the explanations two books have advanced for racial differences in rate of self-injury. The article argues that the overrepresentation of white and Hispanic prisoners and the underrepresentation of black prisoners does not warrant those books' conclusion that prison brings greater pain or intolerable stress to white and Hispanic inmates. The interpretation that black free-world life prepares blacks better for prison, whereas white and Hispanic experiences render them more crisis-prone, ignores institutional and interpersonal factors that may affect inmate behavior. That interpretation also carries potentially insidious implications for the care and management of different ethnic groups in prison. The idea that white prisoners suffer more pain from imprisonment and merit more staff attention can affect recommendations for prevention and intervention approaches to prisoners.

Black or African American↗