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Biomedical subjects

J L Price

Publications and source records attributed to J L Price.

At least 37 records · Page 2Linked to original sources
PubMed2000

Isolation and analysis of six timeless alleles that cause short- or long-period circadian rhythms in Drosophila.

In genetic screens for Drosophila mutations affecting circadian locomotion rhythms, we have isolated six new alleles of the timeless (tim) gene. Two of these mutations cause short-period rhythms of 21-22 hr in constant darkness, and four result in long-period cycles of 26-28 hr. All alleles are semidominant. Studies of the genetic interactions of some of the tim alleles with period-altering period (per) mutations indicate that these interactions are close to multiplicative; a given allele changes the period length of the genetic background by a fixed percentage, rather than by a fixed number of hours. The tim(L1) allele was studied in molecular detail. The long behavioral period of tim(L1) is reflected in a lengthened molecular oscillation of per and tim RNA and protein levels. The lengthened period is partly caused by delayed nuclear translocation of TIM(L1) protein, shown directly by immunocytochemistry and indirectly by an analysis of the phase response curve of tim(L1) flies.

Alleles↗
PubMed2000

Reliability and validity of DSM-IV axis V.

OBJECTIVE: The authors investigated the reliability and convergent and discriminant validity of the DSM-IV Global Assessment of Functioning Scale and two experimental DSM-IV axis V global rating scales, the Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale. METHOD: Forty-four patients admitted to a university-based outpatient community clinic were rated by trained clinicians on the three DSM-IV axis V scales. Patients also completed self-report measures of DSM-IV symptoms as well as measures of relational, social, and occupational functioning. RESULTS: The Global Assessment of Functioning Scale, Global Assessment of Relational Functioning Scale, and Social and Occupational Functioning Assessment Scale all exhibited very high levels of interrater reliability. Factor analysis revealed that the Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale are each more related to the Global Assessment of Functioning Scale individually than they are to each other. The Global Assessment of Functioning Scale was significantly related to concurrent patient responses on the SCL-90-R global severity index. The Social and Occupational Functioning Assessment Scale was significantly related to concurrent patient responses on the SCL-90-R global severity index and to a greater degree with both the Social Adjustment Scale global score and the Inventory of Interpersonal Problems total score. Although the Global Assessment of Relational Functioning Scale was not significantly related to any of the three self-report measures, it was related to the presence of clinician-rated axis II pathology. CONCLUSIONS: The three axis V scales can be scored reliably. The Global Assessment of Relational Functioning Scale and the Social and Occupational Functioning Assessment Scale evaluate different constructs. These findings support the validity of the Global Assessment of Functioning Scale as a scale of global psychopathology; the Social and Occupational Functioning Assessment Scale as a measure of problems in social, occupational, and interpersonal functioning; and the Global Assessment of Relational Functioning Scale as an index of personality pathology. The authors discuss further refinement and use of the three axis V measures in treatment research.

Adult↗
PubMed1999

Prefrontal cortical networks related to visceral function and mood.

At least twenty-two architectonic areas can be distinguished within the orbital and medial prefrontal cortex (OMPFC). Although each of these areas has a distinct structure and connections, they can be grouped into two "networks," defined by cortico-cortical connections that primarily interconnect areas within each network. The networks also have different connections to the striatum, medial thalamus, and other brain regions. The orbital network consists of most of the areas in the orbital cortex. It receives several sensory inputs (olfactory, gustatory, visceral afferent, somatic sensory, and visual) that appear to be related to feeding. It also receives many limbic inputs from the amygdala, entorhinal and perirhinal cortex, and subiculum, including a specific projection from the ventrolateral part of the basal amygdaloid nucleus. The orbital network may therefore serve as a substrate to integrate viscerosensory information with affective signals. The medial network consists of areas on the medial frontal surface together with a few select areas in the orbital cortex. These areas have few direct sensory inputs, and their limbic inputs are somewhat different than those to the orbital network (e.g., from the ventromedial part of the basal amygdaloid nucleus). However, they provide the major output from the OMPFC to the hypothalamus and brain stem (especially the periaqueductal gray). The medial network may therefore serve as a visceromotor system to provide frontal cortical influence over autonomic and endocrine function. Connections between the networks presumably allow information flow from viscerosensory to visceromotor systems. In addition to a probable role in eating behavior, this system appears to be involved in guiding behavior and regulation of mood. Lesions of the ventromedial prefrontal cortex result in sociopathic behavior and difficulty in making appropriate choices, whereas functional imaging studies indicate that subjects with unipolar and bipolar depression have abnormal activity in medial and orbital prefrontal areas. Many of these areas also show volume changes and decreased glial number and density in mood-disordered subjects.

Affect↗
PubMed1999

Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease.

The distribution and density of neurofibrillary tangles and amyloid plaques was studied in a unique series of cases whose premortem cognitive status had been assessed with the Clinical Dementia Rating (CDR), including 39 nondemented cases (CDR = 0; age, 51-88 years), 15 very mildly demented cases (CDR = 0.5), and 8 severely demented (CDR = 3) cases. The initial formation of tangles and plaques in healthy aging appeared to be independent of each other. Tangles were found in all the nondemented cases, especially in hippocampal and parahippocampal areas; the average tangle concentration increased exponentially with age. In contrast, plaques were absent in some brains up to age 88, and the earliest plaque formation in other cases occurred in the neocortex, in patches of diffuse plaques. Widely distributed neuritic as well as diffuse plaques throughout neocortex and limbic structures characterized a further group of nondemented cases. In these cases there was also a substantial increase over other nondemented cases, both in the number of tangles and in the rate of increase in tangles with age, suggesting an interaction between amyloid and neurofibrillary change at this stage. Such cases closely resemble CDR = 0.5 cases, and it is proposed they represent "preclinical" Alzheimer's disease.

Age Distribution↗
PubMed1999

Resident resistance.

Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident.

Family Practice↗
PubMed1998

Prefrontal cortical projections to longitudinal columns in the midbrain periaqueductal gray in macaque monkeys.

The origin and termination of prefrontal cortical projections to the periaqueductal gray (PAG) were defined with retrograde axonal tracers injected into the PAG and anterograde axonal tracers injected into the prefrontal cortex (PFC). The retrograde tracer experiments demonstrate projections to the PAG that arise primarily from the medial prefrontal areas 25, 32, and 10m, anterior cingulate, and dorsomedial areas 24b and 9, select orbital areas 14c, 13a, Iai, 12o, and caudal 12l, and ventrolateral area 6v. Only scattered cells were retrogradely labeled in other areas in the PFC. Caudal to the PFC, projections to the PAG also arise from the posterior cingulate cortex, the dorsal dysgranular, and granular parts of the temporal polar cortex, the ventral insula, and the dorsal bank of the superior temporal sulcus. Cells were also labeled in subcortical structures, including the central nucleus and ventrolateral part of the basal nucleus of the amygdala. The anterograde tracer experiments indicate that projections from distinct cortical areas terminate primarily in individual longitudinal PAG columns. The projections from medial prefrontal areas 10m, 25, and 32 end predominantly in the dorsolateral columns, bilaterally. Fibers from orbital areas 13a, Iai, 12o, and caudal 12l terminate primarily in the ventrolateral column, whereas fibers from dorsomedial areas 9 and 24b terminate mainly in the lateral column. The PFC areas that project to the PAG include most of the areas previously defined as the "medial prefrontal network." The areas that comprise this network represent a visceromotor system, distinct from the sensory related "orbital network."

Amidines↗
PubMed1998

Prefrontal cortical projections to the hypothalamus in macaque monkeys.

The organization of projections from the macaque orbital and medial prefrontal cortex (OMPFC) to the hypothalamus and related regions of the diencephalon and midbrain was studied with retrograde and anterograde tracing techniques. Almost all of the prefrontal cortical projections to the hypothalamus arise from areas within the "medial prefrontal network," as defined previously by Carmichael and Price ([1996] J. Comp. Neurol. 371:179-207). Outside of the OMPFC, only a few neurons in the temporal pole, anterior cingulate and insular cortex project to the hypothalamus. Axons from the OMPFC also innervate the basal forebrain, zona incerta, and ventral midbrain. Within the medial prefrontal network, different regions project to distinct parts of the hypothalamus. The medial wall areas 25 and 32 send the heaviest projections to the hypothalamus; axons from these areas are especially concentrated in the anterior hypothalamic area and the ventromedial hypothalamic nucleus. Orbital areas 13a, 12o, and Iai, which are related to the medial prefrontal network, selectively innervate the lateral hypothalamic area, especially its posterior part. The cellular regions of the paraventricular, supraoptic, suprachiasmatic, arcuate, and mammillary nuclei are conspicuously devoid of cortical axons, but many axons abut the borders of these nuclei and may contact dendrites that extend from them. Areas within the orbital prefrontal network on the posterior orbital surface and agranular insula send only weak projections to the posterior lateral hypothalamic area. The rostral orbital surface does not contribute to the cortico-hypothalamic projection.

Amidines↗
PubMed1998

Glial reduction in the subgenual prefrontal cortex in mood disorders.

Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann's area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD). In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and BD. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24%, P = 0.01) or BD (41%, P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.

Adult↗
PubMed1998

double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation.

We have isolated three alleles of a novel Drosophila clock gene, double-time (dbt). Short- (dbtS) and long-period (dbtL) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbtP, causes pupal lethality and eliminates circadian cycling of per and tim gene products in larvae. In dbtP mutants, PER proteins constitutively accumulate, remain hypophosphorylated, and no longer depend on TIM proteins for their accumulation. We propose that the normal function of DOUBLETIME protein is to reduce the stability and thus the level of accumulation of monomeric PER proteins. This would promote a delay between per/tim transcription and PER/TIM complex function, which is essential for molecular rhythmicity.

Alleles↗
PubMed1998

The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon.

The cloning of double-time (dbt) is reported. DOUBLETIME protein (DBT) is most closely related to human casein kinase Iepsilon. dbtS and dbtL mutations, which alter period length of Drosophila circadian rhythms, produce single amino acid changes in conserved regions of the predicted kinase. dbtP mutants, which eliminate rhythms of per and tim expression and constitutively overproduce hypophosphorylated PER proteins, abolish most dbt expression. dbt mRNA appears to be expressed in the same cell types as are per and tim and shows no evident oscillation in wild-type heads. DBT is capable of binding to PER in vitro and in Drosophila cells, suggesting that a physical association of PER and DBT regulates PER phosphorylation and accumulation in vivo.

Amino Acid Sequence↗
PubMed1998

Amygdala core nuclei volumes are decreased in recurrent major depression.

The amygdala is a key structure in the brain's integration of emotional meaning with perception and experience. Patients with depression have impaired functioning in emotional tasks involving the amygdala, and have abnormal resting amygdala blood flow. To better understand the anatomical basis for these functional changes we measured the volumes of the total amygdala and of the core amygdala nuclei in 20 patients with a history of depression and 20 pair-wise matched controls. Depressed subjects had bilaterally reduced amygdala core nuclei volumes and no significant differences in total amygdala volumes or in whole brain volumes. Since patients with a depression history have bilateral hippocampal volume reduction the volume loss in this closely related structure suggests a shared effect on both structures, potentially glucocorticoid-induced neurotoxicity mediated by the extensive reciprocal glutamatergic connections.

Adult↗
PubMed1998

Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype.

OBJECTIVE: To study differences between subjects with Alzheimer disease (AD) and cognitively intact control subjects, with respect to brain histologic markers of AD, and the relationship of those markers in the AD group to severity of dementia, age at death, sex, and apolipoprotein E genotype. SETTING: Washington University Alzheimer's Disease Research Center, St Louis, Mo. DESIGN AND SUBJECTS: Consecutive neuropathologic series of 224 prospectively studied volunteer research subjects, 186 with dementia of the Alzheimer type (DAT) or "incipient" DAT and confirmed to have AD by postmortem examination and 13 cognitively intact subjects, confirmed to lack postmortem findings of AD. MAIN OUTCOME MEASURES: Brain densities (number per square millimeter) of senile plaques and neurofibrillary tangles, extent of cerebral amyloid angiopathy, cortical Lewy bodies, and apolipoprotein E genotype. RESULTS: Neocortical neurofibrillary tangle densities were substantially correlated with dementia severity, and to a greater degree than was true for senile plaque densities. When infarcts, hemorrhages, and Parkinson disease changes coexisted with AD, neurofibrillary tangle and senile plaque densities were lower. Plaque-predominant AD was found in a greater proportion of subjects with milder than more severe dementia. Entorhinal cortical Lewy bodies were no more frequent in plaque-predominant AD than in the remaining AD cases. Increasing age at death was negatively correlated with dementia severity and densities of senile plaques and neurofibrillary tangles. The apolipoprotein E epsilon4 allele frequency was greater in AD than in control subjects but decreased with increasing age. After controlling for dementia severity, senile plaque densities were only weakly related to epsilon4 allele frequency, and only in hippocampus. However, the degree of cerebral amyloid angiopathy was clearly related to epsilon4 allele frequency. Among subjects diagnosed during life as having DAT or incipient DAT, only 7% were found to have a neuropathologic disorder other than AD causing their dementia. CONCLUSIONS: (1) The order of the strength of relationships between densities of histologic markers and dementia severity in AD is neurofibrillary tangles greater than cored senile plaques greater than total senile plaques. (2) Advanced age at death is associated with somewhat less severe dementia and fewer senile plaques and neurofibrillary tangles. (3) Plaque-predominant AD may represent a developmental stage in AD. (4) Despite a substantial effect of apolipoprotein E epsilon4 as a risk factor for AD, on decreasing the age at AD onset, and increasing the amount of cerebral amyloid angiopathy, its effect on senile plaque densities is variable and complex, being confounded with age, dementia severity, and methodologic differences. (5) Stringent clinical diagnostic criteria for DAT, even in the very mild stage, and senile plaque-based neuropathologic criteria for AD are highly accurate.

Aged↗
PubMed1998

Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders.

The prefrontal cortex (PFC) ventral to the genu of the corpus callosum has been implicated in the modulation of visceral responses to stressful and emotionally provocative stimuli, based upon analysis of lesion effects involving this area in humans and experimental animals. In a recent magnetic resonance imaging (MRI) study of familial mood disorders, we demonstrated that the mean grey matter volume of this cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of their treatment status or current mood state. Moreover, in preliminary histopathological assessments of subgenual PFC tissue taken post mortem from subjects with MDD and bipolar disorder we obtained results suggesting that this decrement in grey matter volume is associated with a reduction in glia without an equivalent loss of neurons. The potential functional significance of these neuroimaging and microscopic abnormalities is discussed with respect to evidence that subgenual PFC dysfunction may disturb stress-related autonomic and neuroendocrine responses and reward-related mesolimbic dopamine function. These data may thus hold important implications for the development of neural models of mood disorders that can account for the abnormal hedonic, motivational, neuroendocrine, and autonomic manifestations evident in these idiopathic conditions.

Bipolar Disorder↗
PubMed1998

A reflective approach to career trajectory in advanced practice nursing.

Opportunities in nursing continue to expand. Advanced practice nurses today have greater control over the scope of their practice and can look forward to mapping a career pathway using personal and professional talents and interests. This article offers a reflective process approach to evaluating and relating career satisfaction and satisfactoriness to personal development needs. Through implementation of the suggested reflective exercise, a 3- to 5-year career plan can be constructed that will guide change and affect growth for the advanced practice nurse.

Career Mobility↗