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Biomedical subjects

R P Hart

Publications and source records attributed to R P Hart.

At least 19 recordsLinked to original sources

Recall of clustered and unclustered word lists in elderly adults.

We present descriptive data for alternate forms of clustered and unclustered word list recall in 102 healthy elderly adults and test results for 11 patients with Parkinson's disease. The word list test provided a relatively stable measure of verbal memory. Alternate forms were equivalent except for a tendency of the unclustered list of Form 1 to be easier than those of the other three forms. Verbal intelligence, total word recall, and the ability to cluster related words at recall were related significantly. There were modest effects of education on word recall; female subjects tended to recall more words than males.

Aged

Serotonin regulation of neostriatal tachykinins following neonatal 6-hydroxydopamine lesions.

In order to determine whether dopamine mediates the effects of serotonin on tachykinin biosynthesis in the neostriatum, serotonin neurotransmission was altered following depletion of dopamine. Neonatal rats received intracisternal injections of saline or the dopamine neurotoxin 6-hydroxydopamine (6HD). This lesion caused significant reductions in the neostriatum of substance P-like immunoreactivity as well as levels of mRNA coding for preprotachykinin (PPT; the prohormone precursor to tachykinins substance P, neurokinin A and related peptides). Two months later, rats were treated for 5-6 days with saline or the serotonin-uptake inhibitor, zimelidine. Zimelidine treatment of unlesioned animals significantly increased PPT mRNA levels in the neostriatum. However, zimelidine treatment failed to increase PPT mRNA content in 6HD-treated animals. By contrast, neostriatal substance P-like immunoreactivity was restored by zimelidine treatment of 6HD-lesioned animals. These results suggest that an intact nigrostriatal pathway may be required for serotonin neurotransmission to alter PPT mRNA levels in the neostriatum. However, neostriatal tachykinins may be regulated by direct serotonin innervation.

Animals

Serotonin regulation of tachykinin biosynthesis in the rat neostriatum.

Serotonin (5-HT) neurotransmission was altered to determine its role in regulating the biosynthesis of tachykinins in the neostriatum (NS). Depletion of 5-HT with subchronic p-chlorophenylalanine (pCPA) treatment decreased preprotachykinin (PPT, the prohormone precursor to SP) mRNA levels in the NS. By contrast, raising extracellular 5-HT levels with zimelidine (a 5-HT uptake inhibitor) or clorgyline (a monoamine oxidase inhibitor) resulted in increased levels of PPT mRNA. To determine whether 5-HT receptors played a role in mediating the changes in PPT mRNA, animals were treated with the 5-HT2 agonist DOI. This drug significantly increased both PPT mRNA and SP-like immunoreactivity in the NS. These results together indicate that neostriatal tachykinin biosynthesis is sensitive to alterations in 5-HT neurotransmission.

Animals

Substance P gene expression is regulated by interleukin-1 in cultured sympathetic ganglia.

We have investigated the effects of interleukin-1 beta (IL-1 beta) on the induction of substance P (SP) in cultured sympathetic ganglia. Northern blot analysis reveals that SP increases are secondary to an increase in mRNA coding for the preprotachykinin (PPT) precursor of SP. Nuclear transcription assays detect an early increase in PPT-specific nascent transcripts, suggesting that the ultimate effect of IL-1 is on transcription itself. Depolarizing agents, interferon-gamma, glucocorticoid hormones, and prostaglandin synthesis inhibitors all diminish the induction of SP and PPT mRNA by IL-1. Since SP has stimulatory effects on the immune system, the IL-1-induced increase in ganglionic SP may be one means by which the nervous and immune systems interact during an acute response to ganglionic injury.

Animals

A comparison of substance P peptide and preprotachykinin mRNA levels during development of rat medullary raphe and neostriatum.

Substance P (SP) and the mRNA coding for its precursor peptide, preprotachykinin (PPT), were measured in medullary raphe nuclei (MRN) and neostriatum (NS) over development in order to determine (1) whether PPT mRNA levels correlate with peptide development, and (2) whether changes in PPT mRNA might help to account for the apparent decline in SP seen immunohistochemically in certain brain areas postnatally. Total RNA was quantified in dissected tissue pieces using the sensitive orcinol reaction. When MRN PPT mRNA levels measured by Northern blot analysis were adjusted to total RNA levels, PPT mRNA per MRN increased over development with a profile similar to that seen for SP peptide. Moreover, both peptide and mRNA levels exhibited a similar decline after postnatal day 15. Therefore, developmental regulation of SP biosynthesis in the MRN may, in part, explain previous evidence documenting a postnatal decline in SP there. In the NS, SP peptide and PPT mRNA increased with a similar profile from E18 through the first postnatal week. Thereafter, SP increased less rapidly than its mRNA, indicating incongruities in prohormone message and processed peptide in the NS.

Animals

Mirror phenomena in language and nonverbal activities--a case report.

A case is described of a 38-year-old, left-handed female who demonstrated mirror phenomena for both language and non-motor, nonverbal material. She mirror-wrote with her left hand with normal right-hand writing. Mirror-reading as well as object and spatial reversals were revealed. These data are consistent with bilateral representation of visual engrams, with one hemisphere containing a mirror-reversed representation of the other.

Adult

Effects of buspirone and alprazolam on the cognitive performance of normal elderly subjects.

OBJECTIVE: To increase understanding of the potential in elderly persons for disability related to behavioral side effects of anxiolytic medications, cognitive and psychomotor effects of clinical doses of buspirone and a popular intermediate-acting benzodiazepine, alprazolam, were examined in carefully screened, healthy elderly subjects. METHOD: Sixty subjects recruited through community organizations and newspaper advertisements and screened on the basis of history, physical examination, and laboratory studies were randomly assigned to one of three drug treatment groups. After 2 days of washout placebo, subjects were given 0.25 mg t.i.d. of alprazolam, 5 mg t.i.d. of buspirone, or placebo three times a day for a total of 14 days in a double-blind design. Behavioral assessments were completed beginning 1 hour after ingestion of medication on the second washout placebo day, day 1 of the treatment period, and day 14 of the treatment period. Tests included the continuous performance test, recall memory for word lists, digit-symbol substitution, retention of pictorial stimuli over 1 hour, the Profile of Mood States, and subjective ratings of mental status. RESULTS: Buspirone did not affect reaction time, vigilance, psychomotor speed, or memory function. Alprazolam had minimal effects on vigilance, psychomotor speed, and memory on the first treatment day and had no effects after repeated doses. CONCLUSIONS: Buspirone did not produce behavioral side effects that could lead to disability, and alprazolam had minimal side effects. Because the patients were carefully screened, it is unclear whether these medications in the doses used would have more side effects in less healthy elderly patients.

Aged

Tryptophan hydroxylase inhibition increases preprotachykinin mRNA in developing and adult medullary raphe nuclei.

In order to study the regulation of co-localized monoamine and peptide neurotransmitters in the medullary raphe nuclei (MRN), we determined whether inhibition of serotonin (5-HT) synthesis affected levels of preprotachykinin (PPT; the prohormone precursor of substance P) mRNA in the MRN. Adult rats received p-chlorophenylalanine (pCPA), an irreversible inhibitor of tryptophan hydroxylase (TPH), via Alzet minipumps. TPH activity was inhibited by 70-80% for 3 weeks following pump implantation. During this period Northern mRNA analysis revealed that PPT mRNA levels in the MRN were increased 1.5-2-fold. The pCPA-induced increase was specific for PPT mRNA since no change was detected in mRNA coding for neuron-specific enolase (NSE; a constitutive neuronal protein) or 28 S ribosomal RNA. To determine whether fetal inhibition of 5-HT synthesis affected development of PPT mRNA in the MRN, pregnant rats were administered pCPA via Alzet minipump implanted on embryonic day 8. In pCPA-treated litters TPH activity was decreased by 60-70% from E16 to postnatal day 3 (P3), returning to control levels by P8. Northern mRNA analysis revealed that PPT mRNA levels increased 2.4-fold of control levels at P1. Infusion of pCPA for one week resulted in an earlier increase in PPT mRNA levels, suggesting that birth was not required to elicit the surge in PPT message. These results support the hypothesis that alterations in 5-HT metabolism have regulatory consequences for co-localized substance P formation in the MRN.

Animals

Neuropsychological effects of occupational exposure to cadmium.

Neuropsychological functioning was measured in 31 male workers exposed to cadmium in a refrigerator coil manufacturing plant. Workers with high urinary cadmium levels performed less well than did those with low urinary cadmium levels on measures of attention, psychomotor speed, and memory. There were modest correlations between one of two biologic measures of cadmium exposure and neuropsychological performance. The neuropsychological impairments cannot readily be attributed to exposure to other neurotoxins, alcohol intake, CNS effects of renal dysfunction, or psychological distress. Cadmium body burden has previously been related to intelligence and school achievement of children; this study would appear to be the first to suggest that occupational exposure to cadmium is associated with cognitive impairment in adults. Cadmium interferes with several important nervous system functions, but the mechanisms of neurotoxicity remain uncertain.

Adult

Effects of protriptyline on vigilance and information processing in narcolepsy.

Vigilance, memory function, and response latency on the Sternberg short-term memory scanning task were examined in eight narcoleptic patients on and off medication. Off medication, half of the patients demonstrated reduced vigilance and all displayed diminished automatic memory encoding and longer response latencies on the Sternberg memory scanning procedure relative to the treated condition. Protriptyline normalized vigilance in half of the patients, while response latency and automatic information processing significantly improved in all. These findings are discussed with regard to the potential effect of the medication on central nervous system arousal.

Adult

Rate of forgetting in mild Alzheimer's-type dementia.

Patients with mild dementia of the Alzheimer's type (DAT) and matched controls were examined for rate of forgetting line drawings of common objects. DAT patients demonstrated rapid forgetting in the first 10 min after learning to criterion. This finding is discussed with respect to memory consolidation and neuropathologic changes in dementia of the Alzheimer's type.

Aged

Mutations in poly(A) site downstream elements affect in vitro cleavage activity.

Previous studies have shown that a sequence element downstream of the poly(A) addition site is required for efficient cleavage in vivo. We tested a group of downstream element point mutations in an in vitro reaction using HeLa cell nuclear extract as a source of cleavage activity. In close agreement with earlier studies (M. A. McDevitt, R. P. Hart, W. W. Wong, and J. R. Nevins, EMBO J. 5:2907-2913, 1986), a downstream element from the adenovirus E2a gene directed a higher level of cleavage activity than one from the simian virus 40 early gene. Furthermore, a single-base change in the downstream element could result in a decrease in cleavage activity of about 50-fold. That these mutations have similar effects in vivo and in vitro indicates that the HeLa cell nuclear extract system contains all of the factors required to study the mechanism of sequence recognition.

Adenovirus Early Proteins

Psychological factors predict symptoms of severe recurrent genital herpes infection.

In a group of patients with severe recurrent genital herpes infection, we measured symptoms (pain and itching), psychological factors (depression, anxiety, somatisation, interpersonal sensitivity, and life change) and objective indices of disease (number of recurrences in the previous year, total number of recurrences, duration of recurrences, number of lesions per recurrence). Psychological factors were more predictive of pain and itching than were somatic indices, even after correcting for sex.

Adult