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Biomedical subjects

P Pratt

Publications and source records attributed to P Pratt.

At least 19 recordsLinked to original sources

Regulator of G protein signaling RGS3T is localized to the nucleus and induces apoptosis.

RGS3 belongs to a family of the regulators of G protein signaling (RGS). We previously demonstrated that cytosolic RGS3 translocates to the membrane to inhibit G(q/11) signaling (Dulin, N. O., Sorokin, A., Reed, E., Elliott, S., Kehrl, J., and Dunn, M. J. (1999) Mol. Cell. Biol. 19, 714-723). This study examines the properties of a recently identified truncated variant termed RGS3T. Both RGS3 and RGS3T bound to endogenous Galpha(q/11) and inhibited endothelin-1-stimulated calcium mobilization and mitogen-activated protein kinase activity to a similar extent. However, unlike cytosolically localized RGS3, RGS3T was found predominantly in the nucleus and partially in the plasma membrane. Furthermore, RGS3T, but not RGS3, caused cell rounding and membrane blebbing. Finally, 44% of RGS3T-transfected cells underwent apoptosis after serum withdrawal, which was significantly higher than that of RGS3-transfected cells (7%). Peptide sequence analysis revealed two potential nuclear localization signal (NLS) sequences in RGS3T. Further truncation of the RGS3T N terminus containing putative NLSs resulted in a significant reduction of nuclear versus cytoplasmic staining of the protein. Moreover, this truncated RGS3T no longer induced apoptosis. In summary, RGS3 and its truncated variant RGS3T are similar in their ability to inhibit G(q/11) signaling but are different in their intracellular distribution. These data suggest that, in addition to being a GTPase-activating protein, RGS3T has other distinct functions in the nucleus of the cell.

Animals↗

Obsessive compulsive disorder, checking, and non-verbal memory: a neuropsychological investigation.

There is considerable evidence in the literature for the presence of non-verbal and praxic memory deficits in OCD. Such deficits may represent the cognitive substrate of doubt-related phenomenon such as checking. Neuropsychological tests of non-verbal memory functioning and memory for actions were administered to patients with OCD (whose predominant symptom was checking) and a group of matched healthy controls. Significant differences were found between the experimental and control groups, suggesting some memory impairment in the OCD group; however, no significant relationship was found linking neuropsychological test indices with checking. Significant relationships were found linking recognition memory problems and immediate memory for actions with general symptom severity.

Adult↗

The characteristics of asthma education programs within New South Wales.

The aim of the study was to examine the characteristics of asthma education programs within NSW. A cross-sectional questionnaire survey concerning the aims and characteristics of 42 asthma education programs was administered to members of the Asthma Educators Association (AEA) of NSW. While most programs sought to improve asthma knowledge (78%), only a small number sought to improve asthma management skills (38%), asthma control (33%) and attitudes (10%). Most programs performed one-to-one (69%) education. Medical intervention was under-utilized by most programs and only 4% gave feedback to the referring doctor. Program evaluation was incompletely linked to program aims. There was incomplete evaluation of knowledge gain as an outcome. The study reviewed the characteristics of education programs within NSW Existing programs appropriately employ a variety of educational methods and target a broad range of people with asthma. There remains a need to use a combined approach utilizing education and medical management, and to employ methods to evaluate programs.

Adolescent↗

Get plugged in. East Central Michigan hospitals restore public trust through better communication.

Hoping to regain the confidence of their communities, members of the Hospital Council of East Central Michigan convened a task force of community leaders and hospital representatives, including trustees. One of the task force's first recommendations was to hold focus groups with citizens from around the region. Task force members listened and acted upon their neighbors' concerns.

Community-Institutional Relations↗

Information-processing, storage characteristics and worry.

Eysenck (1984, Bulletin of the Psychonomic Society, 22, 545-548) suggested that storage characteristics may be an important determinant of worry, and postulated that prolonged worry occurs in individuals who have tightly organised clusters of worry-related information stored in long-term memory. These clusters reflect areas or domains of worry. Because the information is stored in tight clusters, it becomes more accessible, more rapidly activated and therefore retrieved more quickly. The Worry Domains Questionnaire (WDQ) (Tallis, 1991c) is used to determine which domain worried subjects most (Primary) and least (Secondary). Two experiments are reported using a word allocation task, which requires subjects to make categorical decisions, based on these worry domains. It is reported that priming facilitates the emergence of domain effects, thus providing support for a structural hypothesis. High worries take longer to reject negative words if they are from the Primary domain and have difficulty rejecting Primary domain words when they are under a congruent heading. In addition, high worriers are reported to show retarded latencies when attempting to process ambiguous information, consistent with Metzger et al.'s studies (1990, Journal of Clinical Psychology, 48, 76-88). It is suggested that the initiation and maintenance of worry is largely attributable to an elevated evidence requirement and this may link to the personality trait of perfectionism.

Adolescent↗

Zaprinast, but not dipyridamole, reverses hemodynamic tolerance to nitroglycerin in vivo.

Hemodynamic tolerance to nitroglycerin was developed in spontaneously hypertensive rats following 2-3 days of pretreatment with 100 mg/kg of nitroglycerin administered s.c. 3 times/day. Tolerance was evaluated both in vivo, by administering ascending bolus doses of nitroglycerin of 1-300 micrograms/kg i.v., and ex vivo in isolated, denuded aortic vascular rings by exposure to ascending concentrations of nitroglycerin of 0.0003-100 microM. Tolerance was observed as a significant blunting of the hypotensive and vasorelaxant effect of nitroglycerin. Co-incubation of tolerant aortic rings and pretreatment of tolerant SHR with 10 microM and 0.1-10 mg/kg zaprinast, respectively, resulted in full restoration of the vasorelaxant and hypotensive effect of nitroglycerin. Zaprinast partially reversed hemodynamic tolerance at 0.01 mg/kg. Conversely, dipyridamole (10 microM) reversed tolerance ex vivo, but was ineffective in reversing tolerance in vivo at pretreatment doses of 30 and 60 mg/kg. Following a 100-micrograms/kg i.v. challenge dose of nitroglycerin, aortic cyclic guanosine monophosphate (cGMP) levels were lower in nitroglycerin tolerant SHR when compared to non-tolerant SHR. Pretreatment of tolerant SHR with 10 mg/kg zaprinast restored the increase in cGMP levels to nitroglycerin to that seen in non-tolerant SHR. Conversely, dipyridamole (30 mg/kg) pretreatment was not effective in restoring cGMP levels. These data therefore suggest that reversal of hemodynamic tolerance in vivo is related to restoration of changes in vascular cGMP levels. Zaprinast, a selective cGMP phosphodiesterase inhibitor, effectively reverses tolerance and dipyridamole, a rather non-selective inhibitor, does not.

3',5'-Cyclic-GMP Phosphodiesterases↗

Following in the right footsteps.

An initiative which targets resources towards chiropody patients with the greatest needs has been taking place in Nottinghamshire during the past three years. Ian Morton and Peter Pratt describe its progress and outline its new goals.

Costs and Cost Analysis↗

Olfactory acuity in the positive and negative syndromes of schizophrenia.

The olfactory thresholds of 46 schizophrenic subjects were measured. This group yielded 11 patients with a stringently defined positive syndrome and 12 with a negative syndrome when rated with the Positive and Negative Syndrome Scale. The negative group had a significantly (p less than 0.01) higher olfactory threshold than the positive group although neither of the groups differed significantly from a control group. Implications of this finding are discussed.

Adolescent↗

Prevention of detrimental effect of cyclosporin A on vascular ingrowth of transplanted pancreatic islets with verapamil.

The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20-30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P less than .02). Verapamil prevented the detrimental effect of CsA (P less than .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.

Animals↗

Selection of the nuclear gene for the mitochondrial adenine nucleotide translocator by genetic complementation of the op1 mutation in yeast.

Oxidative phosphorylation 1 (OP1), a nuclear gene of yeast Saccharomyces cerevisiae which is required for the expression of a functional mitochondria, has been isolated on a recombinant plasmid. The gene was selected from a recombinant plasmid pool which contained wild type yeast genomic DNA by transformation of the yeast nuclear mutant (op1) followed by a two-stage screening procedure. A recombinant plasmid containing a 2.6 kilobase Bam HI fragment of genomic yeast DNA inserted in either orientation into the single Bam HI site of yeast vector YEp 13 could complement the op1 mutation. Analysis of the gene product of this inserted DNA by three independent methods, 1) in vivo expression in Escherichia coli maxicells, 2) cell-free translation of plasmid selected RNA, and 3) expression analysis in yeast, revealed that its gene product is a protein of Mr = 30,000-32,000, which cross-reacts with specific anti-serum to the adenine nucleotide translocator of the mitochondrial inner membrane. The selection procedure is efficient and can be used for the isolation of any defined yeast nuclear gene which participates in mitochondrial development.

Cell Nucleus↗

Antituberculosis activity of 6 cyclo-octylamino-5,8-quinolinequinone (CQQ).

A new compound, 6 cyclo-octylamino-5,8-quinolinequinone (CQQ), a dual analogue of vitamin K and coenzyme Q, was effective against several drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis. In vitro studies indicated the bactericidal nature of its action at 1 microgram/ml. Pulse exposure studies using M. tuberculosis H37Rv showed that a growth lag period of 96 hours resulted with exposure to 1 microgram/ml for 24 hours or longer.

Mycobacterium tuberculosis↗

Betel quid and reaction time.

Fifteen male Yapese students participated in an experiment to see if the betel quid (betel nut, piper leaf, and calcium hydroxide) has overt effects on simple reaction time latencies. The data indicate that the entire quid produces discernible behavioral effects that are manifested in a relatively short time period following quid ingestion. Reaction time latencies lengthened following quid ingestion during the first 20 reaction time trials or within an apparent initial 5 minute interval.

Areca↗