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Biomedical subjects

R E Powers

Publications and source records attributed to R E Powers.

At least 19 recordsLinked to original sources
PubMed2001

Design, formation and properties of tetrahedral M(4)L(4) and M(4)L(6) supramolecular clusters.

The rigid tris- and bis(catecholamide) ligands H(6)A, H(4)B and H(4)C form tetrahedral clusters of the type M(4)L(4) and M(4)L(6) through self-assembly reactions with tri- and tetravalent metal ions such as Ga(III), Fe(III), Ti(IV) and Sn(IV). General design principles for the synthesis of such clusters are presented with an emphasis on geometric requirements and kinetic and thermodynamic considerations. The solution and solid-state characterization of these complexes is presented, and their dynamic solution behavior is described. The tris-catecholamide H(6)A forms M(4)L(4) tetrahedra with Ga(III), Ti(IV), and Sn(IV); (Et(3)N)(8)[Ti(4)A(4)] crystallizes in R3(-)c (No. 167), with a = 22.6143(5) A, c = 106.038(2) A. The cluster is a racemic mixture of homoconfigurational tetrahedra (all Delta or all Lambda at the metal centers within a given cluster). Though the synthetic procedure for synthesis of the cluster is markedly metal-dependent, extensive electrospray mass spectrometry investigations show that the M(4)A(4) (M = Ga(III), Ti(IV), and Sn(IV)) clusters are remarkably stable once formed. Two approaches are presented for the formation of M(4)L(6) tetrahedral clusters. Of the bis(catecholamide) ligands, H(4)B forms an M(4)L(6) tetrahedron (M = Ga(III)) based on an "edge-on" design, while H(4)C forms an M(4)L(6) tetrahedron (M = Ga(III), Fe(III)) based on a "face-on" strategy. K(5)[Et(4)N](7)[Fe(4)C(6)] crystallizes in I43(-)d (No. 220) with a = 43.706(8) A. This M(4)L(6) tetrahedral cluster is also a racemic mixture of homoconfigurational tetrahedra and has a cavity large enough to encapsulate a molecule of Et(4)N(+). This host-guest interaction is maintained in solution as revealed by NMR investigations of the Ga(III) complex.

Algorithms↗
PubMed2001

MSHAKE. A tool for measuring staff knowledge related to geriatric mental health.

This article describes the development of a knowledge-screening instrument used with staff caring for elderly patients with neuropsychiatric disability. A 25-item tool, referred to as the Mary Starke Harper Aging Knowledge Exam (MSHAKE), was developed to verify knowledge competencies of 171 employees at a geropsychiatric center in the Southeastern United States. The MSHAKE assesses basic geriatric mental health knowledge in an educationally diverse health care work force. A variety of descriptive and inferential statistics provide preliminary evidence supporting the use of the MSHAKE as an effective measure of staff members' essential knowledge of aging and neuropsychiatric disorders. This tool has practical application in the clinical setting as part of a competency verification system or in-service evaluation.

Administrative Personnel↗
PubMed1999

The neuropathology of schizophrenia.

This review of brain changes in schizophrenia provides the neuropathologist with a conceptual framework to understand this disease. Numerous conflicting reports describe structural, functional, neurochemical, and neuropathological alterations in brains of schizophrenic patients. A core clinical manifestation of schizophrenia is disruption of thought; a mental process that is poorly localized in the brain and influenced by multiple neural systems. Schizophrenia has variable clinical presentations, natural history, and response to medication that imply a pathologically heterogenous group of diseases. Recent studies suggest that schizophrenia may involve cortical, limbic, and subcortical structures as well as multiple neurotransmitter systems. Schizophrenia may result from a perinatal insult in a genetically predisposed individual that produces neuronal alterations that manifest during final synaptic reorganization and myelination of early adulthood.

Aging↗
PubMed1999

Anatomic asymmetries of the posterior superior temporal lobes: a postmortem study.

OBJECTIVE: To examine for structural asymmetries in the posterior superior temporal lobe at the microscopic level in an effort to explain the gross anatomical and functional asymmetries of this brain region. BACKGROUND: The posterior superior temporal lobe is typically larger on the left and damage to this area frequently results in an aphasia. This has led to the hypothesis that the structural asymmetry determines the functional asymmetry, but no definite confirmation of this hypothesis exists. METHODS: Sixteen men were studied at postmortem. Posterior superior temporal lobe dimensions, gray matter volume, white matter volume, SMI-32 immunopositive neuronal density, and glia cell volume were measured for both the left and right hemispheres. In a subset of eight subjects, myelin sheath and axon diameters were measured with electron microscopy. RESULTS: Posterior superior temporal lobe white matter volume was greater on the left (p = 0.003, t test for dependent samples). This asymmetry did not appear to be the result of an isolated proliferation of glia (p = 0.46, t test for dependent samples), nor the density of cortical to cortical projections neurons in the overlying cortex (p = 0.71, t test for dependent samples). In a subset of eight subjects studied with electron microscopy, axons of the left posterior superior temporal lobe were more thickly myelinated (57 nm [SD = 27] left, 46 nm [SD = 24], p < 0.001, ANOVA). CONCLUSIONS: As axons with thicker myelin sheaths conduct faster and require a greater volume, these results suggest asymmetry of myelination as an explanation for both a left hemisphere dominance for rapid sensory signal processing, leading to a functional asymmetry for language, and a larger left planum temporale.

Axons↗
PubMed1997

Transglutaminase activity is increased in Alzheimer's disease brain.

Transglutaminase is a calcium-activated enzyme that crosslinks substrate proteins into insoluble, often filamentous aggregates resistant to proteases. Because the neurofibrillary tangles in Alzheimer's disease have similar characteristics, and because tau protein, the major component of these tangles is an excellent substrate of transglutaminase in vitro, transglutaminase activity and levels were measured in control and Alzheimer's disease brain. Frozen prefrontal cortex and cerebellum samples from Alzheimer's disease and control cases matched for age and postmortem interval were used in the analyses. Total transglutaminase activity was significantly higher in the Alzheimer's disease prefrontal cortex compared to control. In addition the levels of tissue transglutaminase, as determined by quantitative immunoblotting, were elevated approximately 3-fold in Alzheimer's disease prefrontal cortex compared to control. To our knowledge, this is the first demonstration that transglutaminase is increased in Alzheimer's disease brain. There were no significant differences in transglutaminase activity or levels in the cerebellum between control and Alzheimer's disease cases. Because the elevation of transglutaminase in the Alzheimer's disease samples occurred in the prefrontal cortex, where neurofibrillary pathology is usually abundant, and not in the cerebellum, which is usually spared in Alzheimer's disease, it can be suggested that transglutaminase could be a contributing factor in neurofibrillary tangle formation.

Aged↗
PubMed1997

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls.

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups had smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.

Age of Onset↗
PubMed1997

Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder.

Prior magnetic resonance imaging (MRI) studies report both medial and lateral cortical temporal changes and disturbed temporal lobe asymmetries in schizophrenic patients compared with healthy controls. The specificity of temporal lobe (TL) changes in schizophrenia is unknown. We determined the occurrence and specificity of these TL changes. Forty-six schizophrenic patients were compared to 60 normal controls and 27 bipolar subjects on MRI measures of bilateral volumes of anterior and posterior superior temporal gyrus (STG), amygdala, entorhinal cortex, and multiple medial temporal structures, as well as global brain measures. Several regional comparisons distinguished schizophrenia from bipolar disorder. Entorhinal cortex, not previously assessed using MRI in schizophrenia, was bilaterally smaller than normal in schizophrenia but not in bipolar disorder. Schizophrenic but not bipolar patients had an alteration of normal posterior STG asymmetry. Additionally, left anterior STG and right amygdala were smaller than predicted in schizophrenia but not bipolar disorder. Left amygdala was smaller and right anterior STG larger in bipolar disorder but not schizophrenia.

Adolescent↗
PubMed1997

Knowledge about Alzheimer disease among primary care physicians, psychologists, nurses, and social workers.

Although much of the care of Alzheimer disease (AD) patients and their families is carried out by health professionals who are not specialists in AD or geriatrics, little is known about how knowledgeable these health professionals are about AD. An AD knowledge test was constructed through careful instrument development procedures and then administered through a mail survey. Subjects were 693 individuals, including experts in AD care, generalist health care professionals (primary care physicians, psychologists, social workers, and nurses), nursing students, hospital staff nurses, and assorted health professionals. A 12-item scale with excellent psychometric properties was developed. Experts in AD care performed significantly better than generalist health care professionals on all items. All four groups of generalist health care professionals showed important deficits in fundamental knowledge about AD; for example, only 40% of generalists (vs. 97% of experts) knew that AD is the most common cause of severe memory loss in people over age 65. Results suggest that, although knowledge about assessment and management of AD has increased and has been widely disseminated, many health care professionals remain uninformed about AD. Suggestions for professional education and for use of the UAB AD Knowledge Test for Health Professionals are discussed.

Alzheimer Disease↗
PubMed1997

Planum temporale asymmetry reversal in schizophrenia: replication and relationship to gray matter abnormalities.

OBJECTIVE: The planum temporale, the posterior superior surface of the superior temporal gyrus, is a highly lateralized brain structure involved with language. In schizophrenic patients the authors previously found consistent reversal of the normal left-larger-than-right asymmetry of planum temporale surface area. The original subjects plus new patients and comparison subjects participated in this effort to replicate and extend the prior study. METHOD: High-resolution magnetic resonance imaging of 28 schizophrenic patients and 32 group-matched normal subjects was performed. The authors measured planum temporale surface area, gray matter volume underlying the planum temporale, and gray matter thickness. Asymmetry indices for areas and volumes were calculated. RESULTS: Overall gray matter and total brain volume were not significantly smaller in the patients than in the comparison subjects. As previously reported, there was striking reversal of the normal asymmetry for planum temporale surface area in the male and female schizophrenic subjects. Bilaterally, gray matter volume beneath the planum temporale was smaller in the schizophrenic patients, and the gray matter thickness of the right planum temporale was only 50% of the comparison value. Volume of planum temporale gray matter did not show significant asymmetry in either group. CONCLUSIONS: This study extends the finding of reversed planum temporale surface area asymmetry in schizophrenic patients and clarifies its relationship to underlying gray matter volume. Although right planum temporale surface area is larger than normal in schizophrenia, gray matter volume is less than the comparison value; thus, gray matter thickness is substantially less than normal.

Adult↗
PubMed1996

Striatal dopamine D2 receptor quantification and superior temporal gyrus: volume determination in 14 chronic schizophrenic subjects.

Chronic schizophrenic (n = 14) and normal subjects (n = 15) were studied with resonance imaging (MRI) and positron emission tomography (PET). Two PET scans were carried out to estimate caudate dopamine D2 receptor densities. MRI was used to measure the volume of the superior temporal gyrus. Average striatal D2 receptor density (Bmax) was significantly higher in the schizophrenic group than in the normal group. Average left superior temporal gyral volume was significantly smaller in the schizophrenic group than in the normal group, and the same tendency was found for the right superior temporal gyrus. Thus, the main finding of this combined analysis of functional and structural neuroimaging techniques was an inverse relationship between reduced superior temporal gyral volume and elevated striatal D2 receptor Bmax values. These preliminary findings require confirmation in larger groups of patients and control subjects.

Adult↗
PubMed1996

Altered brain sodium channel transcript levels in human epilepsy.

Normal, and perhaps pathological, characteristics of neuronal excitability are related to the distribution and density of voltage-gated ion channels such as the sodium channel. We studied normal and epileptic human brain using the ligase detection reaction to measure the relative quantities of mRNAs encoding sodium channel subtypes 1 and 2. Normal brains exhibited characteristic 1:2 ratios which varied by brain region, but the ratios were invariate among individuals. These normal values were altered as much as threefold in anatomically corresponding regions of epileptic brain tissues. Changes of this magnitude in such a highly conserved value support a potential role for sodium channels in the pathophysiology of epilepsy.

Adult↗
PubMed1996

Alzheimer's disease patients and their caregivers: medical care issues for the primary care physician.

Alzheimer's disease (AD) is a common problem with complex challenges in assessment and management for the primary care physician. We present a practical, six-step strategy for physicians to use in AD care, summarized by the acronym ACROSS: assessment of AD, communication of the diagnosis, referral to appropriate community resources, ongoing evaluation, providing solutions to patient and caregiver problems, and maintaining sensitivity to family caregiver issues. The family caregiver of the patient with AD provides the physician with essential diagnostic information and implements physician recommendations for AD care. Advice and support from the physician are essential for the family caregiver to withstand the relentless strain of caring for a loved one with a progressive dementia. We provide practical suggestions for management of common patient and caregiver problems across the stages of AD.

Alzheimer Disease↗
PubMed1996

Evidence for a regulatory role for histamine in gastric enterochromaffin-like cell proliferation induced by hypergastrinemia.

BACKGROUND/AIMS: Hypergastrinemia, induced by sustained suppression of gastric acid secretion, is associated with gastric enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumor formation. We examined the effect of a selective H1-histamine antagonist, terfenadine, on gastric mucosal cell proliferation to determine whether histamine might modulate ECL cell generation. METHODS: The rodent mastomys received the H2-antagonist loxtidine (2 g/l drinking water) alone or in combination with terfenadine (0.5 g/l or 35 mg/l drinking water) for 120 days. Controls received water or terfenadine alone. Serum gastrin levels and tissue histamine content were assayed by radioimmunoassays, and tissue chromogranin levels determined (Western blot analysis). In vivo cell proliferation was measured by bromodeoxyuridine (BrdU, 200 mg/kg/day, 3 days) incorporation. Gastric mucosal thickness was determined, ECL cell number was assessed, and the percentage of proliferating ECL cells quantitated. To evaluate the direct action on ECL cells we then studied the effect of terfenadine on histamine secretion and DNA synthesis (BrdU uptake) in an isolated preparation (approximately 90% pure) of ECL cells. RESULTS: Loxtidine increased serum gastrin levels, mucosal thickness, tissue chromogranin levels, tissue histamine content, BrdU incorporation, ECL cell number, and proliferating ECL cells (all parameters p < 0.05). Terfenadine alone, irrespective of dosage, had no significant effect. The high dose in combination with loxtidine significantly inhibited the increase in tissue chromogranin levels, tissue histamine content, ECL cell number and proliferating ECL cells (p < 0.05), but did not alter other parameters, compared to loxtidine alone. The low does did not alter the loxtidine-induced changes. In pure isolated ECL cells, terfenadine did not alter histamine secretion either alone or in combination with gastrin (10 nM). DNA synthesis was significantly inhibited by terfenadine (IC50 10(-10) M). CONCLUSIONS: Terfenadine specifically inhibited the effect of loxtidine-induced ECL cell proliferation in vivo and significantly inhibited ECL cell DNA synthesis in vitro. We postulate that histamine, through an H1 receptor, positively modulates gastric ECL cell proliferation.

Animals↗
PubMed1995

Asymmetry of the planum temporale: methodological considerations and clinical associations.

Asymmetry of the planum temporale, a region on the posterosuperior surface of the temporal lobe involved in the production and comprehension of language, is a notable feature of the normal human brain. Several attempts have been made to measure it using both post-mortem and magnetic resonance imaging (MRI) methods, but previous approaches made inadequate allowance for the convoluted nature of the structure. The current study used rigorous criteria to define the planum and examined three separate approaches for its measurement on MRI scans. A method involving triangulation of the surface consistently gave larger values for the surface area of the planum, suggesting that this method takes account of the convoluted nature of the structure.

Adult↗
PubMed1995

Genotoxicity, carcinogenicity and acid-suppressing medications.

With the availability of increasingly potent acid-suppressing medications, questions continue to rise concerning the safety of these compounds in regards to carcinogenetic potential. In this review, we examine current concepts and procedures relating to genotoxicity, the potential for a chemical agent to interact with and alter the genomic information of the cell, and carcinogenesis. A description and discussion of commonly utilized techniques for the determination of (a) in vitro mutagenicity, (b) in vitro and in vivo DNA damage and repair, (c) in vitro and in vivo chromosomal damage and (d) chronically dosed animal tumorigenesis development is presented. Observations from these procedures as they have been applied to a review of the safety of acid-suppressing medications will be discussed. An evaluation of reports relating to potential genotoxic and carcinogenic hazards of therapeutically relevant acid-suppressing medications (cimetidine, ranitidine, omeprazole) is presented. Information related to the effect of prolonged administration of acid-suppressing medications, alterations of serum gastrin levels, and the potential for tumor promotion is discussed.

Animals↗
PubMed1995

Phosphoinositide hydrolysis, G alpha q, phospholipase C, and protein kinase C in post mortem human brain: effects of post mortem interval, subject age, and Alzheimer's disease.

Influences of post mortem time interval, subject age and Alzheimer's disease were investigated on several components of the phosphoinositide second messenger system, including stimulation of [3H]phosphatidylinositol hydrolysis by GTP[S] and several receptor agonists and the levels of Galphaq, beta, delta and gamma subtypes of phospholipase C, and five protein kinase C isoforms, in membranes prepared from post mortem human prefrontal cortex. Most of these components were stable with post mortem delays in the range of 5-21 h, but decreases of Galphaq and the alpha and xi protein kinase C subtypes were detected. Within the subject age range of 19-100 years, G-protein- and agonist-induced [3H]phosphatidylinositol hydrolysis decreased, as did levels of Galphaq, but the levels of phospholipase C and protein kinase C subtypes were generally unchanged. In Alzheimer's disease, compared with age- and post mortem interval-matched controls, there was a decrease in [3H]phosphatidylinositol hydrolysis stimulated by G-proteins and by several receptor agonists, but the levels of Galphaq and most of the phospholipase C and protein kinase C isoforms were unaffected. The greatest deficits, which were >50%, occurred with GTP[S]- and carbachol-induced [3H]phosphatidylinositol hydrolysis, indicating that this G-protein function and the response to cholinergic stimulation are significantly impaired in Alzheimer's disease. In summary a comprehensive assessment of several components of the phosphoinositide second messenger system was made in post mortem human brain. Most elements were stable within the post mortem interval range of 5-21 h, lending validity to measurements using these tissues. Significant age-related reductions in several components were identified, indicating loss of responses with increasing age. Most importantly, severe reductions in responses to several stimuli were found in Alzheimer's disease brain, deficits in signal transduction which may contribute to impaired cognition and to the limited therapeutic responses to drugs, such as those used to activate cholinergic receptors coupled with the phosphoinositide system.

Adult↗
PubMed1995

Reversal of asymmetry of the planum temporale in schizophrenia.

OBJECTIVE: The planum temporale is intimately involved in the generation and understanding of language and has been suggested to be a key area affected in schizophrenia. To explore temporal lobe abnormalities in schizophrenia, the authors measured the planum temporale, a normally asymmetric area lying on the superior part of the temporal lobe, in schizophrenic patients. METHOD: High-resolution magnetic resonance imaging (MRI) scans were obtained for 14 right-handed schizophrenic patients and 14 healthy comparison subjects individually matched for age, sex, handedness, race, and parental socioeconomic status. The surface area of the planum temporale was measured by using MRI reconstruction techniques. RESULTS: There was striking reversal of the normal asymmetry (left larger than right) in planum temporale surface area in 13 of the schizophrenic patients but in only two of the comparison subjects. However, Heschl's gyrus (primary sensory cortex), which served as an anatomically contiguous nonheteromodal cortical comparison region, showed no difference between the left and right sides in either group. Severity of thought disorder in the patients was related to asymmetry. CONCLUSIONS: This is a clear demonstration of a reversal of expected symmetry in the brains of right-handed schizophrenic patients, which involves a region of key importance in normal human behavior. The nature of the abnormality strongly suggests that schizophrenia is a neurodevelopmental disorder.

Adult↗